10 Biocrisis and Resplendence: Fermi Extinction and Planetary Reflowering

Planet Earth is heading into multiple serious human-caused self-extinction scenarios – habitat destruction planet wide, climate crisis that may become irreversible, mass extinction of biodiversity, exponential population instability, cumulative risk of nuclear holocaust, generalised AI takeover due to materialist physicalism failing to recognise we are NOT just machines, excessive brittle dependence on technology to feed ourselves, failure to protect our food species, failure to protect the genetic diversity of the planet, the failure of collective leadership and decision-making processes to address or protect human viability in a tragedy of the commons. If this doesn't actually cause our extinction as a species, it will certainly destroy our blue-green paradise and make human culture perilous to unliveable. There is no technofix for this. We should be envisaging another 500 million years of sanctuary to discover the ultimate mysteries of existence. No utopian pretence will save us. These are the hard facts of life we are failing to address.

Protecting the biospheric diversity of life is critical for our own survival, as is avoiding climate crisis and unravelling the ever-present risk of nuclear Armageddon. The rape of Gaia – "Mother Earth" by the patriarchal imperatives of dominion over nature and business-as-usual competitive exploitation is a suicidal insanity running through our cultural mind set, which humanity currently lacks the collective insight to alleviate. Intervention in the common good is urgently necessary. This is precisely what I experienced in being galvanised to write this work after a quantum change experience on sacred mushrooms, following a seven year karmic drought due to acute closed angle glaucoma, risking blindness if my pupils became dilated. For the "mind at large" to awaken even for a moment and become acutely aware of the carnage wrought upon the planet through the relentless exploitative impact of a single species Homo sapiens, it is obvious that, by its very compassion for the mortal coil, it will impart to the beholder an urgent tenacity to protect the living planet.

The Full Scope: Climate Crisis, Mass Extinction. Population and Nuclear Holocaust

Fig 19: (1) World population is predicted to continue to rise through to 2100 (Gerland et al. 2014), with the majority of the increase in sub-Saharan Africa (inset). This will increase the world population to 10 billion, with immense pressure on the African continent's carrying capacity and pressure of migration on all continents. (2) Predicted long term effects of climate change (Burke et al. 2018) could lead to a catastrophic cumulative heating over millennia, taking the planet back to the previous Eocene peak hot period 50 million years ago, placing many of the plant and animal species on which we depend well out of their evolved climate zone, potentially leading to human extinction because of our continuing dependence on highly evolved plant and animal species (Burke et al. 2018). (3) Threatened species by group (Guardian). (4) This situation is unsustainable and leads directly to mass extinctions of biodiversity, which would take up to 50 million years to be addressed by subsequent evolution, as exemplified by previous mass extinctions. (5) Species losses of a variety of animal and plant phyla. The incipient sixth mass extinction that started in the Late Pleistocene has already put over a quarter of mammal species under acute risk of extinction (Leakey & Lewin 1995, Kolbert 2014, 2021, Davis et al. 2018, Dawson 2016). Detailed calculations of mammalian species indicate a time frame of millions of years to recover from the current mass extinctions, by evolving new life forms, but those lost will never be recovered. Insects are also suffering catastrophic population decline due to habitat destruction. (7) Protected areas are manifestly insufficient to protect biological and genetic diversity. International agreement is urgently needed to extend these areas. (8) Scorched-earth clear felling for palm oil plantations has felled a third of Borneo's forest almost overnight. Such wholesale habitat destruction is even worse than burning the rainforest because all living diversity is eradicated in favour of one monoclonal species. (8) Coral bleaching shows how climate change can lead to wholesale mass extinction of species in some of the most intense oceanic biodiversity hotspots, leading to a barren ocean.

The global biomass of biodiversity

Human intrusion into all available habitats causing wholesale natural habitat destruction means that the biomass of livestock is over 14 times that of all wild mammals and the biomass of humans is over 8.5 times that of all wild mammals. Bar-On et al. (2018) assemble the overall biomass composition of the biosphere, establishing a census of the ≈550 gigatons of carbon (Gt C) of biomass distributed among all of the kingdoms of life. We show that terrestrial biomass is about two orders of magnitude higher than marine biomass and estimate a total of ≈6 Gt C of marine biota, doubling the previous estimated quantity. The global marine biomass pyramid contains more consumers than producers. Finally, we highlight that the mass of humans is an order of magnitude higher than that of all wild mammals combined and report the historical impact of humanity on the global biomass of prominent taxa, including mammals, fish, and plants.

Fig 19b: The biomass of humans plus livestock as of 2018 is 22.5 times that of all wild mammals. Graphical representation of the global biomass distribution by taxa. (A) Absolute biomasses of different taxa are represented with the area of each cell being proportional to that taxa global biomass.  (B) Absolute biomass of different animal taxa. Related groups such as vertebrates are located next to each other.

The global biomass of wild mammals

A study by scientists at Israel’s Weizmann Institute of Science (Greenspoon et al. (2023) concludes that wild land mammals alive today have a total mass of 22m tonnes. Humanity now weighs in at a total of around 390m tonnes. Domesticated species, such as sheep and cattle, in addition to other hangers-on such as urban rodents, add a further 630m tonnes. Thus as of 2023 wild land mammals represent only 22/(390+630)=0.02 or 2%. So the figure has risen to 46 times from 2018. The team led by Ron Milo has updated the biomass of world mammals. Biomass as a metric allows us to compare species with very different body sizes, and can serve as an indicator of wild mammal presence, trends, and impacts, on a global scale. Here, we compiled estimates of the total abundance (i.e., the number of individuals) of several hundred mammal species from the available data, and used these to build a model that infers the total biomass of terrestrial mammal species for which the global abundance is unknown. We present a total wet biomass of ≈20 million tonnes (Mt) for all terrestrial wild mammals (95% CI 13-38 Mt), i.e., ≈3 kg per person on earth.

Fig 19c: Left Top: The global mammalian biomass distribution is dominated by humans and domesticated mammals, including livestock and pets. Bottom: enlarged view of the biomass of wild terrestrial (Left, grouped by order) and marine mammals (Right, grouped by family, or few families). Top right: The relative number of species, individuals, and total biomass of each taxonomic order of wild land mammals. The relative biomass contribution of each order is also indicated by the animal silhouette sizes and corresponding percentages.  Lower right: The estimated total biomass is noted for each continent, together with the name of the top mass contributor and its relative biomass contribution to the said continent.

The universe as we know it has been in existence for some 13 billion years, but for over around a quarter of this cosmic lifetime, around 3.6 billion years, life and its diversity and complexity has continued to evolve to the point of human emergence amid climax diversity, which has taken around 66 million years to recover from the mass extinction caused by the Chicxulub asteroid that extinguished the dinosaurs. Our impact is rapidly becoming worse and setting us for a warming taking us back 50 million and yet we remain unable to give the priority to correct it due to our own folly. More troubling, it runs the risk of a Permian type extinction, the most catastrophic mass extinction of multicellular life ever, which like our own climate crisis, was caused by extreme global warming.

Fig 20: (a) The five mass extinctions dominated by the Permian, in which up to 95% of marine fauna expired. ( b) The Permian was not caused by an incoming asteroid but a huge peak in atmospheric CO₂, precipitated by massive eruptions which resulted in the Siberian Traps. The eruptions continued for roughly two million years and spanned the Permian–Triassic boundary, around 251.9 million years ago. (b, c) Historic temperatures and atmospheric CO₂ since the Cambrian, 500 million years ago both show a massive peak at the boundary (marked * in (c) and (d)) (Mulhern 2021). This resulted in the oceans becoming depleted in oxygen, making them oceans uninhabitable particularly to more temperate species, likely exacerbated by lethal H₂S contamination. (e) A 1.5-foot slab of rock from southern China shows the Permian-Triassic boundary. The bottom section is pre-extinction limestone. The upper section is microbial limestone deposited after the extinction. Three species that became extinct. (f) A fossilised spiralling shark tooth from Helicoprion, an extinct Permian shark species. (g) Diademaproetus, one of the trilobites that were plentiful in the world’s oceans but went extinct at the end of the Permian. (h) Paramblypterus, a species of fish that became extinct during the Permian.

During the end-Permian (P-T) extinction, 95 percent of all species on Earth became extinct, compared to only 75 percent during the Cretaceous-Tertiary (K-T) extinction, when a large asteroid impact, possibly exacerbated by ensuing volcanic activity, caused the dinosaurs to disappear. The impact of Homo sapiens on our planet is a striking example of how life can evolve to evoke existential crisis on a planetary scale, threatening both a mass extinction of living diversity by habitat destruction, runaway global heating from fossil fuel consumption and a possible nuclear holocaust, but there are others. Severe global heating can lead to the oceans becoming anoxic, resulting in oceanic bacteria using sulphate to poison the oceans and atmosphere with hydrogen sulphide.

We are used to the idea of the Gaia Hypothesis – that life is an integral part of a self-correcting global biochemical and geochemical process that keeps Earth conducive and habitable for life provided critical tipping points are not transgressed, to push this system beyond a point of no return. But what happens if things go too far? There is a known counterpoint to Gaia, and that is the Medea Hypothesis (Ward 2008) that under certain circumstances, living systems can also precipitate biochemical and geochemical feedback process that can bring about the mass extinction of life, like a mother killing her children.

Fig 20a: Levels of CO2 over the last 50 mya (compare fig 19(2)) compared with
global mean surface temperature, inset and colour bands (Hönisch et al. 2023).

The central cause of the Permian extinction is temperature-dependent hypoxia (Penn et al. 2018):

The conventional wisdom in the paleontological community has been that the Permian extinction was especially severe in tropical waters.” Yet the model shows the hardest hit were organisms most sensitive to oxygen found far from the tropics. Many species that lived in the tropics also went extinct in the model, but it predicts that high-latitude species, especially those with high oxygen demands, were nearly completely wiped out ( study co-author Jonathan Payne).

Since tropical organisms’ metabolisms were already adapted to fairly warm, lower-oxygen conditions, they could move away from the tropics and find the same conditions somewhere else,” Deutsch said. “But if an organism was adapted for a cold, oxygen-rich environment, then those conditions ceased to exist in the shallow oceans (study co-author Curtis Deutsch).

The huge igneous layers of the Siberian Traps (about 7 million km² (3 million sq mi) of basaltic rock, with a volume of around 4 million km³ (1 million cu mi)) were formed by flood basalt volcanism from a mantle plume, as in Iceland and Hawaii which rose until it impacted against the bottom of the Earth's crust pouring from great cracks in the land itself. As the magma rushed out into the air from its deep Earth origin, it carried enormous volumes of volcanic gas into the atmosphere, including hydrogen sulphide, methane and particularly carbon dioxide. If flood basalts are combined on a global scale with the more explosive volcanism that in addition, throws great quantities of ash and volcanic dust into the atmosphere, one might expect major effects on animals and plants.

Although the global heating caused by the erupted CO2 would not necessarily be enough on its own to cause a mass extinction of this scale, it could have set off a diabolical series of events that led to mass extinction. The Warner the tropical oceans the more the animal oxygen consumption. Normally, the deep ocean gets its oxygen from the atmosphere at the poles. Cold water there soaks up oxygen from the air and because cold water is dense, it sinks and slowly moves equator-ward, taking oxygen with it. The warmer the water, the less oxygen can dissolve and the slower the water sinks and moves toward the equator. The resulting atmospheric warming would in turn, warm surface ocean water enough to cause oceanic oxygen starvation by disrupting this conveyor belt flow, thus bringing less oxygen into the deep oceans. Once the oxygen is gone, the oceans become the realm of oceanic bacteria that obtain their oxygen stripping oxygen from sulphur oxide compounds such as sulphate, producing hydrogen sulphide, which kills aerobic organisms, as well as destroying the ozone layer protecting terrestrial plants. Methane produced in the ample swamps of this time period then has little to destroy it, so the atmosphere becomes laden with hydrogen sulphide, methane and ultra-violet radiation (Ward 2007, 2008). This scenario has been applied both to the Permian and succeeding Triassic-Jurassic (T-J) extinction (Kump, Pavlov & Arthur 2005, Richoz et al. (2012).

CO₂ levels are determined by the imbalance between carbon sequestration (burial in sediments, capture by plants), and carbon emissions (decomposition and volcanic activity). Imbalances in this system created a downward trend in CO₂ levels, leading to a glaciation period around 300 million years ago. This was followed by a period of intense volcanic activity, doubling CO₂ concentration to about 1000 ppm. Levels then dropped until they reached today’s concentrations during the [peak Eocene to] Oligocene era, 33 to 23 million years ago, when temperatures were still 4 to 6 degrees C higher than today. It can be said that history was shaped by CO₂ levels, and the types of climates they would allow. Looking back at the 2 extra degrees of warmth last time CO2 levels were this high (Pliocene era, 3 million years ago), should be enough of a call to action, considering the damage two more degrees would cause today. (Mulhern 2021). 

Under a business-as-usual emissions scenarios, by 2100 warming in the upper ocean will have approached 20 percent of warming in the late Permian, and by the year 2300 it will reach between 35 and 50 percent. This study (Penn et al. 2018) highlights the potential for a mass extinction arising from a similar mechanism under anthropogenic climate change (Justin Penn).

Global strategies to Halt the Dual Crises of Biodiversity loss and Climate Change

These are often formulated separately, even though they are interdependent and risk failure if pursued in isolation. The Global Safety Net maps (Dinerstein et al. 2022) show how expanded nature conservation addresses both overarching threats. We identify 50% of the terrestrial realm that, if conserved, would reverse further biodiversity loss, prevent CO2 emissions from land conversion, and enhance natural carbon removal. This framework shows that, beyond the 15.1% land area currently protected, 35.3% of land area is needed to conserve additional sites of particular importance for biodiversity and stabilize the climate. Fifty ecoregions and 20 countries contribute disproportionately to proposed targets. Indigenous lands overlap extensively with the Global Safety Net. Conserving the Global Safety Net could support public health by reducing the potential for zoonotic diseases like COVID-19 from emerging in the future.

Fig 20b: (Top) Areas of the terrestrial realm where increased conservation action is needed to protect biodiversity and store carbon. Numbers in parentheses show the percentage of total land area of Earth contributed by each set of layers. (Bottom) Interdependence of carbon and biodiversity. Currently unprotected high-carbon areas with median total carbon >215 MT/ha overlap extensively (92.0%) with areas selected under target 1, highlighting the importance of these lands for biodiversity conservation and climate stabilization. Other areas important for biodiversity but of lower carbon value, i.e., <215 MT/ha, are also shown. Additional CSAs, including tier 1 and tier 2 CSAs, are also selected to bridge the gap for adequate carbon storage beyond areas identified in target 1 (Dinerstein et al. 2022).

The minimum land area requiring conservation attention to safeguard biodiversity

Fig 21: Minimum land area for conserving terrestrial biodiversity. Components include PAs (light blue), KBAs (purple), and ecologically intact areas (dark blue). Where they overlap, PAs are shown above KBAs, which are shown above ecologically intact areas. New conservation priorities are in green. The Venn diagram shows the proportional overlap between features.

Ambitious conservation efforts are needed to stop the global biodiversity crisis (Allan et al. 2022). We estimate the minimum land area to secure important biodiversity areas, ecologically intact areas, and optimal locations for representation of species ranges and ecoregions. At least 64 million square kilometers (44% of terrestrial area) would require conservation attention (ranging from protected areas to land-use policies) to meet this goal.

Fig 22: Gap analyses of species and ecoregion coverage within areas above. (A) Percentage of the distribution of each species (in different taxonomic groups; freshwater includes crabs, shrimp, and crayfish) and ecoregion area that overlaps. Boxplots show the median and 25th and 75th percentiles. (B) Percentage of species and ecoregions with an adequate proportion of their distribution overlapping existing conservation areas to meet specific coverage targets for species or ecoregions (orange).

More than 1.8 billion people live on these lands, so responses that promote autonomy, self-determination, equity, and sustainable management for safeguarding biodiversity are essential. Spatially explicit land-use scenarios suggest that 1.3 million square kilometers of this land is at risk of being converted for intensive human land uses by 2030, which requires immediate attention. However, a sevenfold difference exists between the amount of habitat converted in optimistic and pessimistic land-use scenarios, highlighting an opportunity to avert this crisis. Appropriate targets in the Post-2020 Global Biodiversity Framework to encourage conservation of the identified land would contribute substantially to safeguarding biodiversity.

Fig 23: National-level land area for conservation and projected habitat loss. Estimated proportion of each country requiring effective conservation attention to safeguard biodiversity that is projected to suffer habitat conversion by 2030 (orange) and 2050 (red) or that is projected not to be converted (blue), according to SSP3 (a worst-case scenario). Gray areas are outside the land identified for conservation. We excluded 85 countries with a land area <10,000 km²  from the figure.

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Fig 24: Evolutionary tree of life (King 2021c), with entheogenic molecules. Preserving the diversity of life and of conscious life in evolutionary time scales
is the prime responsibility of our sentient incarnation. Background: Amazon burning.

Fig 25:  Scenario maps Half Earth Project show (1) protected areas, (2) protected+community, (3) human pressures (4) biodiversity priority, (5) biodiversity richness and (6) biodiversity rarity. These show the difficulty of planning for a half-Earth scenario because some countries have high value habitats which urgently need conserving while others lack any significant protected areas. Furthermore protected areas are not identical with the biodiversity priorities. Habitats involving priority species and rare species are quite distinct from areas with the greatest richness (Rinnan & Jetz 2020). This means that protecting half Earth is going to require massive funding of some developing countries and wide scale consent and economic motivation on the part of developed countries  to resolve these questions. The science is critical to make the process as effective as possible but this is also going to take a huge change in the human world view to upgrade its urgency sufficiently.

If you look at the Amazon Basin it looks as though there is little overlap between biodiversity richness and human pressure, but we know that's not true because the Amazon is being ravaged by fire, mining and agriculture. Moreover The priorities for biodiversity also lie, prominently lie along the Andes, with high overlap with human impact.

Turn now to Africa and you will see a big conflict between human pressure and biodiversity priorities in the North East Congo and south to the Cape of Good Hope.  This means that stopping a serious mass extinction is going to have to involve a new kind of global planning and financing to compensate affected parties and to ensure consistent standards of protection and mitigation. Predictions of biodiversity at 2100 remain contradictory depending on how the driving factors interact (Sala et al. 2000). Wilderness areas halve the extinction risk of terrestrial biodiversity (Di Marco 2019).

Fig 26: Top left: Predicted loss of mitochondrial cytochrome c oxidase subunit I haplotypes for nine montane aquatic insect species in Europe under business as usual IPCC 2080 CO2 emission scenario (Bálint et al. 2011).  Top right: Comparison of recent and distant past extinction rates with rates at which species are “committed to extinction” during the 21st century (Pereira et al. 2010). Bottom left: Map of expected change in biodiversity for the year 2100 under antagonistic interaction between drivers such as climate and habitat loss when the total biodiversity change equals the change resulting from the driver that is expected to have the largest effect and is calculated as the maximum of the effects of all the drivers (Sala et al. 2000).  All of the key tropical rainforest would be seriously affected. Bottom right: Estimated recent and future global biodiversity trends resulting from land-use change, with and without coordinated efforts to reverse trends (Leclère et al. 2020).  Habitat effects on their own contribute up to 20% loss in diversity (grey) unless adequate measures are taken (ochre). Mean extinction probability across studies making predictions of the future effects of climate change suggest a mean extinction probability of 10% across taxa and regions, whereas empirical evidence gave a mean probability of 14% (MacLean et al. 2011).

Davis et al. (2018) note that the incipient sixth mass extinction that started in the Late Pleistocene has already erased over 300 mammal species and, with them, more than 2.5 billion y of unique evolutionary history. At the global scale, this lost phylogenetic diversity (PD) can only be restored with time as lineages evolve and create new evolutionary history. Given the increasing rate of extinctions however, can mammals evolve fast enough to recover their lost PD on a human time scale? We use a birth–death tree framework to show that even if extinction rates slow to pre-anthropogenic background levels, recovery of lost PD will likely take millions of years.

This is going to take a paradigm shift in world views to get anywhere in time. It needs to convey an urgency and a sense of cosmological meaning to support the undertaking both scientifically and religiously to actually get there. There has to be some sheer inspiration and conviction to do this.

Fig 27: Left: Summary of major environmental-change categories expressed as a percentage change relative to the baseline given in the text. Red indicates the percentage of the category that is damaged, lost, or otherwise affected, whereas blue indicates the percentage that is intact, remaining, or otherwise unaffected (Bradshaw et al. 2021). Right: Loss of evolutionary history is variable across mammalian orders. The heights of the bars show the amount of unique evolutionary history attributable to each mammal order at a preanthropogenic baseline (130,000 y ago). The right-hand y axis shows this same value as a percentage of global mammal PD at this baseline. The heights of the colored bars show the contribution to global PD projected to remain after 50 y of status quo conservation. Warm colors represent proportional contributions that are high for an order’s SR; cool colors show the reverse. The orders Didelphimorpha to Microbiotheria are shown at standard (A) and enlarged (B) scales (Davis et al. 2018).

Human impact is causing a mass extinction of biodiversity on a time scale that is almost as acute in terms of the adaption of life as the Dinosaur extinction and is rapidly approaching a series of tipping points that could throw the entire planet into a far less hospitable state, not just for the diversity of life but for our own survival. As the Earth heats due to CO₂ and methane emissions, the albedo ^[73] of the white, light-reflecting poles shrinks, so that it absorbs more light increasing the heating. Destabilising the methane hydrates on the ocean floor can lead to a world-wide eruption of CH₄ which is 20 times more active in solar heating than CO₂. At the same time the entire forested areas of the planet that fix carbon are being replaced by pasture and agriculture, compounded by massive fires both lit intentionally to clear forest and arising naturally from lightning strikes due to increased heat and the drying out of forest areas.

 
Fig 27b: Statistical early-warning signals that the Amazon monsoon is approaching a critical transition in response to deforestation and could continue to fail due to deforestation, resulting in cumulative desiccation. Large parts of southwestern Amazonia show a simultaneous increase in variance and autocorrelation. Regions with high autocorrelation correspond well with the main atmospheric moisture transport routes and the aerial river across the Amazon to the subtropics (Bochow & Boers 2023).

As I was completing this work on on Boxing Day 2021, E O Wilson regarded as Darwin’s heir passed away. Here are three statements he made about Biodiversity in interview about his book “The Meaning of Human Existence”:

We are by instinct related closely to the survival of our distant ancestors by a driving need to strike nature as hard as we could, and to draw as much as we could from it. And we haven’t lost that at all. And now we come to a higher-level recognition that we struck too hard, and too far, and we are threatening the world that we first entered so aggressively and successfully in Africa. And we somehow have got to pull back our instincts to exploit and subordinate and convert to our immediate welfare—because if we take too much more of the Earth’s biodiversity we render the biosphere unstable. And we could, in the worst of circumstances, reach a tipping point in which the whole thing collapses—and we with it.

The living world the biosphere is a razor thin layer of organisms that have evolved over billions of years to create close to exactly the right combination of species and their interactions to maintain the conditions that they live in. Our minds and our bodies are particularly well designed by natural selection to live in those exact conditions and if we change it in any significant way, we die quickly, and so we should keep in mind that, when we destroy the living world by allowing species to go extinct, you're weakening the biosphere and eventually, you may reach a tipping point in which the whole thing starts to unravel, and when that happens pfuttt the end of everything.

Part of our problem is that we're a species that is narcissistic. We're intensely social and intensely interested in other people and that's how we keep our groups united and well coordinated. The result is that we're geniuses at social intelligence and really stupid when it comes to understanding how to manage the environment. We are a  badly adapted species right now. We have created civilisations in which we lead and live on parts of the planet on our own. And we haven't gotten over our emphasis on forming groups and having groups compete with each other. IT's easy for us to think that the world was made for us and we don't really need to know about the 8 million or so species on this planet, even when we're told that keeping them intact and making sure they continue to live is probably necessary for our long-term existence.

Fig 28: (Left) Phylogenetic distribution of hidden mammalian diversity estimated from consensus of delimitation results. Each silhouette represents a mammalian order with its shadow reflecting the ratio of predicted species to recognised species. Striped silhouettes represent orders with conflicting delimitation results that were not included in the predictive analysis (Parsons et al. 2022). The uncertainties may be much larger in other groups e.g. arthropods. (Right) Mutilation of the animal tree of life: (1) Monotypic genera (2) Endangered genera (Ceballos & Erlich 2023)

The Covid-19 pandemic has shown us a world which cannot realistically modify business as usual exploitation to address the human impact on the biosphere that precipitated the pandemic through trafficking and exploitation of wild animals. This inability risks a  potentially irreversible planetary tipping point. The fact that we can even temporarily be stopped in our tracks by a mere virus underscores the vulnerability of the human population to misadventure and the fragility of technological civilisation. By comparison with dealing with a pandemic, the cumulative problems of human impact are far more deleterious to both future quality of life and to the world’s economic viability, and could result in the mortality of billions of people. The problems are made all the more intractable because action requires international cooperation to transform our energy and consumption economies, but this is mired by national and political interests and resolute will can be unravelled all too easily by a single populist defector in a position of power, disrupting the capacity of the world to act cogently and scientifically.

Underlying the climate crisis is a much more serious and potentially devastating one for humanity’s future quality of life, economic future and survival as a species, and that is the mass extinction (Leakey & Lewin 1996) of biodiversity, driven both by whiplash climate change and wholesale habitat destruction further exacerbated by deforestation and the burning of both the tropical rainforests and temperate forests of Earth, as well as the conversion of vast wilderness areas to monoculture. Whole geographical regions of the planet, both at cooler poles where temperatures changes are magnified and in the hotter drier tropics are likely to devastate their plant and animal diversity. The issues of biocrisis (King 2006-2020) and mass extinction are more serious than climate change or human induced pandemics and require a combined strategy of mitigation of habitat destruction, replanting of wilderness areas, conversion of food production and consumption to less polluting and carbon-intensive practices and collecting as much genetic diversity as possible in gene banks to conserve plant, bacterial, and fungal diversity. The fate of insects and other small multi-celled animals is also highly important for overall planetary fertility, as exemplified from honey bees to humming birds.

(a) Half Earth The biosphere needs immediate protection from human impact over a full half its surface and restoration by a clear dedicated program (Wilson 2016, Le Page 2018, Baillie & Zhang 2018, Dinerstein et al. 2019, Lambert 2020, Convention on Biological Diversity), and assisting diversity to replenish in the wilderness is essential for the long-term robustness of the biosphere’s diversity and of human species over evolutionary time scales. Although we are stripping the biosphere, we are very small on the face of the planet and dependent on stable food supplies. Planetary changes crossing tipping points, would have a much more serious long term impact on the viability of human species, let alone the economy, than by adopting the precautionary principle. Climate change remains a serious long term risk to biodiversity and the human population. Changes in the ocean level, once initiated will continue for up to 1000 years due to changes in the planetary albedo as the white polar caps melt. They could render vast land areas uninhabitable to humans and for food production reducing the economic carrying capacity of the planet for human life for millennia to come, with increasing destertification in some areas and flooding in others all impacting on biodiversity. Pollution, from estrogenic chemicals to ocean plastics, also needs urgent containment.

Fig 29: Left: Current state of world nuclear weapon stockpiles. Right: Tsar bomba 50 megatons video. Black rose video.

(b) Nuclear Holocaust  We remain in a situation of mutually-assured destruction due to a massive overkill of nuclear destructive power, which could also lead to a human and biodiversity genocide. This remains a key challenge and a dark comment on the patriarchal male-combat winner-take-all death-risking reproductive strategy, extrapolated to utopian proportions, which urgently needs to be addressed for the safety of the human species and the biosphere. This is human maleficence being appropriated to create a hair-trigger potential for mass destruction, rather than using this technology to avoid astronomical threats to biospheric survival. All sides are drawn into a Faustian pact, in which no one can agree to unwind the false security that the unilateral exercise of nuclear deterrent continues to have, leading to inexorable cumulative long-term risks of species extinction by accidental or malicious global holocaust.

The Federation of American Scientists notes: “Despite progress in reducing Cold War nuclear arsenals, the world’s combined inventory of nuclear warheads remains at a very high level: roughly 13,100 warheads as of early-2021. Of these, nearly 9,600 are in the military stockpiles (the rest are awaiting dismantlement), of which some 3,800 warheads are deployed with operational forces, of which up to 2,000 US, Russian, British and French warheads are on high alert, ready for use on short notice. … All the nuclear weapon states continue to modernise their remaining nuclear forces, adding new types, increasing the role they serve, and appear committed to retaining nuclear weapons for the indefinite future”.

(c) Population and Patriarchy Population also remains a critical issue.  As of 2023, the issues arising from rapid population decline in developed countries and increasing risks of global conflicts over extreme inequalities and disruptive migration are becoming as serious as the spectre of overpopulation in a boom and bust dilemma. The most recent predictions are for an earlier peak reaching 9 or 10 billion people (Watts 2023) rather than unrestrained growth through to 2100 (Gerland et al. 2014), however the implications for wilderness areas, both in increasingly heavily populated sub-Saharan Africa and the Congo Basin and in the impacts of agri-development in the Amazon, combined with major climatic shifts in viable habitats and productive areas are serious threats. Since the total mass of domestic animals is nearly twice that of humans, a shift away from avid meat consumption, particularly of methane generating beef, is essential.

Fig 30: Predicting population: (1) UN 2023 fertility rates by country indicate population growth in Sub-Saharan Africa leading to overpopulation with an accelerating trend towards potentially precipitous decline in developed countries. with unsustainably low fertility rates and ageing populations, confirmed by (2) Percentage of people over 65 in 2022 shows populations becoming critically aged due to longer lifespans and lower reproduction rates. (3) Overall population growth rates by country counting all factor, including births, deaths, and migration. (4) Current population densities showing extreme variations in densities between Bangladesh at 1331 and Australia at 3.4. (5) Predicted population densities modelled to be consistent with Watts (2023). In the business-as-usual case, it foresees existing policies being enough to limit global population growth to below 9 billion in 2046 and then decline to 7.3 billion in 2100. (6) Predicted population densities in 2083 consistent with the previous more severe population predictions of Gerland et al. (2014) illustrated in fig 19(1). Both models show a rise in population density in sub-Saharan Africa to peaks of 9.6 bn circa 2058 in (5) and 12.2 bn circa 2083 in (6), moderated by population declines in Asia, Europe, the US and Brazil. Heat maps are non-linear, reducing the apparent effects due to the extremes of density between countries. For example the densities for Nigeria in (4), (5) and (6) are 225, 420 and 717 million respectively, reflecting the more severe 2014 prediction.

This existential cosmology presents a perspective in which consciousness is not just a human faculty but is shared widely by the biota, conveying at its heart, a reverence for the continuity and sacredness of conscious life. Patriarchal religions and cultures claim to represent the sanctity of life, but have abused it, both by suppressing female reproductive choice to ensure male paternity certainty and by encouraging unrestrained reproduction of their adherents as a means to social and world dominance, accompanied by dire penalties, from stoning for adultery, through enforced female veiling, chaperoning by male relatives, female genital mutilation, limitations on female education, careers and freedom of the female race to associate, and choose their/our own futures and sexual partners.

As noted in Sexual Paradox: Complementarity, Reproductive Conflict and Human Emergence (Fielder & King 2017) this frustrates the evolutionary process towards higher intelligence we have experienced in our XY-chromosomal evolutionary emergence.

Inevitably, whatever the scenario modelled in fig 30, the data confirms that Muslim countries together have a current birth rate of 3.20 versus a worldwide rate of 2.26, , and consequently the Muslim countries’ share of the world population will rise from 21% to 27% in 2058, based independently on the growth rate projections, above, consistent with Pew Research (2017).

Christianity and Islam together comprise a majority of the world population with religious believers constituting 84.5% of people. Heaven and Hell cosmology, discarding the living planet and natural diversity, in favour of a reliance on the after life, is in frank contradiction to, and conflict with, ensuring a sustainable and  immortal Paradise on Earth. This is not just a crime against nature, it is a crime against humanity and reality itself.

Fig 30b: Recent and future population growth of world religions (Pew Research 2017, Wikipedia).

Therefore the main thrust of Symbiotic Existential Cosmology is to change the religious weltanshauung, to that of the living immortality of life as a whole because transforming the religious paradigm is precisely the point of highest remedial capacity.

Both contraception and abortion have been opposed as violating the patriarchal God’s invocation to go forth and multiply, playing a central role in driving the population explosion and hence planetary destabilisation. Muslim and secondly Christian birth rates are the highest on the planet. Abortion is opposed as a heinous sin, but the sanctity of life is not just for a single offspring but the viability of our species in a finite enclosed biosphere. Therefore upholding the sanctity of life depends on respecting the ability of the females of the species, who bear responsibility for the ongoing immortal continuity of human life, to make reproductive choices and choices whether to sustain a pregnancy in terms of their bodies, and their future responsibilities, as mothers of children they need to support. At the same time, beginnings of a severe downturn in reproduction rates insufficient to maintain the population are in some developed countries turning into a flood that is also going to cause a population bust and seriously ageing populations, so both rampant opposition to abortion and the employment and career pressures on women in developed countries need to be removed, so that  human population dynamics can become culturally and biologically sustainable.

The Fermi Paradox and Human Extinction

The Fermi paradox is the discrepancy between the lack of conclusive evidence of advanced extraterrestrial life and the apparently high likelihood of its existence.  Enrico Fermi's name is associated with it because of a casual conversation in the summer of 1950 with fellow physicists Edward Teller, Herbert York, and Emil Konopinski. While walking to lunch, the men discussed recent UFO reports and the possibility of faster-than-light travel. The conversation moved on to other topics, until during lunch Fermi blurted out, "But where is everybody?"

Fig 30b: (Left) The night lighting of Earth shows planetary evidence of human civilisation visible from space.  (Right) JWT galaxy survey shows many early-forming disc-like galaxies similar to the milky way, indicating that the circumstances for life are as favourable as in our own galaxy, but we have no evidence of life elsewhere in the universe other than life on Earth.

The following are some of the facts and hypotheses that together serve to highlight the apparent contradiction:

1.    There are billions of stars in the Milky Way similar to the Sun.
With high probability, some of these stars have Earth-like planets in a circumstellar habitable zone.

2.    Many of these stars, and hence their planets, are much older than the Sun. If Earth-like planets are typical, some may have developed intelligent life long ago.

3.    Some of these civilisations may have developed interstellar travel, a step humans are investigating now.

4.    Even at the slow pace of currently envisioned interstellar travel, the Milky Way galaxy could be completely traversed in a few million years.

5.    Since many of the Sun-like stars are billions of years older than the Sun, the Earth should have already been visited by extraterrestrial civilisations, or at least their probes.

6.    However, there is no convincing evidence that this has happened.

The Drake equation is an attempt to find a systematic means to evaluate the numerous probabilities involved in the existence of alien life where   is the number of technologically advanced civilisations in the Milky Way galaxy:  where  is the rate of formation of stars in the galaxy;  is  the fraction of those stars with planetary systems;  is  the number of planets, per solar system, with an environment suitable for organic life;  is  the fraction of those suitable planets whereon organic life actually appears;  is the fraction of habitable planets whereon intelligent life actually appears;  is the fraction of civilisations that reach the technological level whereby detectable signals may be dispatched; and  is the length of time that those civilisations dispatch their signals. However, the fundamental problem is that the last four terms are unknown, rendering statistical estimates impossible.

Theories for the lack of evidence of other life in the universe, fall into three major categories:

(1) Extreme rarity: Technological civilisations are extremely rare because extraterrestrial life or intelligence is rare or non-existent elsewhere, due to the extreme rarity of aboigenesis, eucayogrnesis and conscious intelligent organisms, or due to periodic extinction, by natural events, eliminating advanced civilisations as most vulnerable.

(2) Self-destructive culture: It is the nature of intelligent life to destroy itself, or to destroy others.

(3) Cosmic anonymity: Other life forms may prefer to remain undetected, have only colonised small parts of galaxies or be unable to assimilate the resources to display evidence of their existence on galactic scales.

The last point may be pivotal. Organismic life, despite its sentient complexity, is the last, lowest energy cumulative interaction of the symmetry-broken forces of nature and the very idea of a biological organism commanding control of energy sufficient to advertise itself across galaxies may be simply a product of human technological hubris and the failure of the out humility to recognise that biological life is a very small player in the cosmic energy equation, although the most complex and conscious phenomenon in the universe.

Nevertheless, we need to heed the warning that, in the absence of knowing there is life elsewhere in the universe, we need above all to respect the sanctity of life on Earth and protect it from a human-caused mass extinction of biodiversity. As Brian Cox on the BBC ahead of COP26 warned, Earth’s demise could rid galaxy of meaning  Brian notes on the BBC that ‘Unique events that led to civilisation mean its demise could ‘eliminate meaning in the galaxy for ever’.

The “Great Filter”, Hanson (1996), represents the variety natural phenomena that would make it unlikely for life to evolve from inanimate matter to an advanced civilisation. The most commonly agreed-upon low probability event is abiogenesis: a gradual process of increasing complexity of the first self-replicating molecules by a randomly occurring chemical process. Other proposed great filters are the emergence of eukaryotic cells or of meiosis or some of the steps involved in the evolution of a brain capable of complex logical deductions.

1.    A planet capable of harbouring life must form in a star’s habitable zone.

2.    Replicative life must develop on that planet, able to reproduce, using such molecules as DNA and RNA.

3.    Simple (prokaryotic) single-celled life must evolve

4.    Simple cells (prokaryotes (archaea and bacteria) must evolve into more complex cells (e.g. eukaryotes).

5.    Sexual reproduction, which greatly increases genetic diversity, must take hold.

6.    Multicellular organisms must develop.

7.    Complex organisms capable of using tools must evolve.

8.    Those organisms must create advanced technology needed for space colonisation.

9.    The spacefaring species must go on to colonise other worlds and star systems, while avoiding destroying itself.

Ward & Brownlee (2000) in their “Rare Earth” hypothesis state a series of worst case scenarios that may have made life on Earth vanishingly improbable and hence also explain why life elsewhere in the universe might not exist. They invoke a number of astronomical worst case claims that make Earth’s history exceptional and pivotally cite both abiogenesis – the prebiotic origin of life; and eucayrogenesis – the origin of complex nucleated eucaryote cells as roadblocks, suggesting that nearly all planets might proceed no further than bacterial life.

The processes invoking abiogenesis are a frontier area of scientific discovery hat remains to be fully resolved. Organics form a major component of galactic gas clouds such as the Orion Nebula, in which planetary star formation is occurring. Carbonaceous chondrites show presence of biological precursors such as amino acids and nucleotide bases and key steps in the biogenic pathway to replication have been elucidated.

However the endosymbiosis that gave rise to eucaryotes from species of archaea incorporating respiring bacteria in their cell interiors is a natural symbiotic interaction between the two primal cellular life forms that evolved on the planet. Kasting (2001) has refuted these claims of eucaryote improbability:

One point upon which virtually all molecular biologists agree is that the eukaryotic lineage is very ancient. ... The first unambiguously eukaryotic cells (identified by their large size and distinctive morphology) in the fossil record date back to only about 2.1 Gya, whereas molecular evidence for eukaryotes goes back to at least 2.7 Gya (Brocks et al. 1999). The paper also demonstrates that the 2.5-Gya Snowball Earth event (which probably occurred closer to 2.3 Gya) could not have triggered the origin of eukaryotes, as suggested. Eukaryotes appear to have evolved long before this putative catastrophe. So there is no reason to suppose that their appearance required an unusual climatic event.

Furthermore Brocks et al. (2022) note that:

Eukaryotic life appears to have flourished surprisingly late in the history of our planet. This view is based on the low diversity of diagnostic eukaryotic fossils in marine sediments of mid-Proterozoic age (around 1,600 to 800 million years ago) and an absence of steranes, the molecular fossils of eukaryotic membrane sterols. This scarcity of eukaryotic remains is difficult to reconcile with molecular clocks that suggest that the last eukaryotic common ancestor (LECA) had already emerged between around 1,200 and more than 1,800 million years ago. The protosteroids reveal an ecologically prominent 'protosterol biota' that was widespread and abundant in aquatic environments from at least 1,640 to around 800 million years ago and that probably comprised ancient protosterol-producing bacteria and deep-branching stem-group eukaryotes. Modern eukaryotes started to appear in the Tonian period (1,000 to 720 million years ago), fuelled by the proliferation of red algae (rhodophytes) by around 800 million years ago. This 'Tonian transformation' emerges as one of the most profound ecological turning points in the Earth's history.

This brings us to the intervention of destructive cycles, both natural and astronomical, and human self-destruct cycles induced by the sheer instability of rapidly evolving technological civilisations and their tendency towards exploitation and internal conflict.

Firstly, we know both the lighter elements of life on Earth along with the heavier elements are produced in cataclysmic events, including supernovae and neutron star collisions, which are themselves potential threats to existing life on nearby planets through intense radiation and black-hole formation. We also know that astronomical collisions are part of the chaotic many-body gravitational dynamics of the universe, resulting in huge collisions such as that which resulted in the Earth-Moon system from a putative collision between Earth and another early planet and which inundated the Earth with asteroid and cometary strikes in the early Hadean era.

Secondly, we know e.g. from fig 19(4) that there have been five great mass extinctions of the diversity of existing life in Earth’s geological history, confirming both astronomical impacts and massive atmosphere and ocean changing volcanism have all-but wiped life off the face of the planet.

Fig 30c:  (1, 2) Dynamical instabilities between population growth, resource demand and global temperature lead to collapse of society unless resource change sufficiently addresses impacts far enough in advance (Frank et al. 2018, Billings 2018). (3) Civilisation leads to burnout unless such resource awakening occurs effectively enough to reorient energy demands before blowout. (4) Growing urban populations can suffer multiple singularity crises requiring homeostatic reorientation , resulting in a bi-modal distribution of failed planetary burnouts and some homeostatic cultures surviving crises Wong & Bartlett 2022).

This brings us to the emergence of human culture and energy and habitat exploitation, resulting in rapid population growth in the wake of agriculture and animal husbandry, and ensuing human niche construction of urban cultures at the expense of both non-renewable energy resources and the planetary habitats sustaining the biosphere of Earth.

Homo sapiens can survive as a living species only in biospheric cooperation with the other species in the biosphere, particularly but not restricted to the species we rely on for food and medicine. We need the full robustness of the genetic and biological diversity of the biosphere to ensure the planet is in a robust enough condition to last over evolutionary time scales.

Just as the current investment cycle depends on the futures triple witching hour, not our long-term welfare, not only is our predictable investment horizon less than six months, but we currently lack full confidence of human survival of even a month at a stretch.

 (a) Nuclear Holocaust: We have a significant continuing chance at any time of al all-out nuclear war due to the sheer instability of massive first strike options and the hair trigger decision-making processes that would be set in motion in the event of a nuclear alert. As I write, the war continues in Ukraine, in which specific threats of the use of nuclear weapons have been made. We also know that, even in peace time, we have come very close to accidental hair-trigger mistaken launches. The logic of mutually-assured destruction does not protect us from nuclear war, but coverts the situation into a form of global Russian roulette where any mistake could lead to complete Fermi annihilation:

Fig 30d: Stanislav Petrov

On 26 September 1983, three weeks after the Soviet military had shot down Korean Air Lines Flight 007, Petrov was the duty officer at the command centre for the Oko nuclear early-warning system when the system reported that a missile had been launched from the United States, followed by up to five more. Petrov judged the reports to be a false alarm. His subsequent decision to disobey orders, against Soviet military protocol, is credited with having prevented an erroneous retaliatory nuclear attack on the United States and its NATO allies that could have resulted in a large-scale nuclear war which could have wiped out half of the population of the countries involved.

On January 25 1995, the Norwegian rocket incident occurred, when a team of scientists launched a four-stage sounding rocket to study the aurora borealis. The rocket eventually reached an altitude of 1,453 kilometres (903 mi), resembling a US Navy submarine-launched Trident missile. Fearing a high-altitude nuclear attack that could blind Russian radar, Russian nuclear forces went on high alert, and the "nuclear briefcase" was taken to Russian President Boris Yeltsin, who then had to decide whether to launch a retaliatory nuclear strike against the United States. Russian observers determined that there was no nuclear attack and no retaliation was ordered.

Fig 30: Greta Thunberg submerged by rising oceans. The older generation stealing the future of their offspring and all future generations.

(b) Climate Crisis: We are continuing to fail to meet the targets required to avoid Earth’s climate moving out of the temperature zone of the last million years and into an acutely accelerated warming that could take us back to the Eocene 50 million years ago (fig 19(2)) with a commensurate massive rise in ocean levels and unstoppable ecocrisis, in which major species can no longer survive in their existing habitats. Rather than making a rapid transition to renewable energy, we are supplementing oil and coal exploitation in a short-term economic vicious cycle, and instead we imagine utopian solutions, from massive scale carbon recapture, to geoengineering antarctic glaciers to imede the rising oceans and mining the moon. These are all desperate technological Fermi extinction scenarios.

Fig 30f: Borneo deforestation

(c) Wild Habitat exploitation: Wherever humanity reaches, particularly by road, the biodiverse wilderness is ruthlessly exploited for beef farms, for agricultural land and for palm oil plantations, and later for urban development This leads to the most pervasive form of biosphere destruction short of an astronomical impact, by systematic human conversion of the entire land surface area to human production and habitation. Again a Fermi extinction scenario.

Fig 30g: Giraffes die en mass during climate driven drought in Africa. An orangutan confronts a bulldozer deforesting land in Borneo for palm oil plantations. Over 100,000 have died as a result of this activity.

(d) Biodiversity crisis and Mass Extinction: Underlying the combined effects of climate crisis and habitat appropriation is the fact that the Anthropocene, defining Earth's most recent geologic time period as being human-influenced, or anthropogenic, based on overwhelming global evidence that atmospheric, geologic, hydrologic, biospheric and other earth system processes are now altered by humans. This is occurring in a climate of opinion where there is little understanding that human survival depends on a robust evolving biosphere. Our economic targets are so short that we can’t even comprehend of a sustainable future 5 years out, let alone a thousand years hence or the tens of millions of years of stable climate and evolving diversity we need to envisage if we are talking about the survival of humanity as a living species. Biodiversity itself while concerned words are expressed about the wonders of nature are far out on the back burner of economic urgency, despite the increasing vulnerability of monoclonal food species to epidemic disease and genetic attrition. This is clearly on its own our most serious cause of long-term Fermi extinction.

Fig 30h: Fig 30h: Technological utopias involve concepts like interstellar travel in "generation ships" where species and genetic diversity is minimal leaving the "late" planet Earth to an uncertain fate. Dystopias revolve around purely urban "civilisations" in which artificial intelligence dominates and there is no biosphere to support organismic life. None of these scenarios have stability over evolutionary time scales.

(e) AI takeover: At the same time our fixation with physical technologies and materialistic notions of cognition and intelligence makes it harder and harder for human beings to distinguish themselves from biological machines which can be superseded by generalised artificial intelligence, and robotic processes, leading to realistic concerns of humanity becoming dependent on AI and losing the autonomous agency to control our own fate as a species.

(f) Sheer cultural and technological instability Rather than existing in a living world of conscious agents, including other humans, animal predators and in our animistic origins in the gatherer hunter epoch, storms and floods as our existential survival threats, we have surrounded ourselves so completely by machines, and computational devices, that we have reduced the natural world around us to a potentially dystopian mechanism, in which critical infrastructure, from energy supplies to the very food production and supply and transport lanes we depend on in urban societies to survive are automated beyond our control. Even without a malicious AI takeover, we become a brittle, unstable techno-culture with so many avenues of short term instability, that survival prospects become no more viable than a casual breakdown on the technological highway, from which there is no escape and no return.

Humanity tends to envision future utopias which are purely technological and lack any form of stability over evolutionary time scales, when above all, we need to stop biosphere exploitation and engage sustainable enhancement of the diverse living species our food and medicinal supply and our climatic and biospheric survival depends on. We tend to treat other organisms as "dumb animals" driven by instincts, and see human intellectual achievements as superior and transformative towards a purely technological future, but this absolutely lacks any concept of the stability of life over evolutionary time scales. We see ourselves as moving beyond the evolutionary process, in forms of cultural, intellectual and technological innovation, but these remain tragically unstable on any cosmological time scale. The reality is that evolutionary diversification is the underlying creative process, from which new life forms emerge, and there is no guarantee that humanity will remain the dominant intellectual species, because of it's ill-fated evolutionary dominance. Thus species, from founding primates, to rodents, actually carry more future evolutionary potential than patriarchally dominant Homo sapiens, which is unstably prone to a self-destructive boom and bust "death wish".

Fig 30i: (above) Food supply chain adaption during the covid 19 pandemic (Marusak et al. 2021) (below) Comparing Adaptive Capacity in Simplifying and Diversifying Farming Systems (Petersen-Rockney et al. (2021).

On the wider front, we remain politically and strategically stymied by tribal politics amid the endless exponential growth of GDP economics, which is transparently unsustainable, and a complete inability as a world culture to address the key existential threats to our own survival on Earth as a species as our top existential priorities. We all know this and across the planet, people feel a sense of uncertainty about the future and whether the world is going to be a viable place in future for their children to survive, yet because of the global power structures and the way political decisions are made, we all feel too helpless to do anything decisive about it and bury our heads in the fog of delusion.

Humanity has evolved through Machiavellian intelligence to dominate and capitalistically, or militarily exploit one another. For males and male reproductive strategies to collectively dominate the entire female sex and control other living organisms as a dominant patriarchal species, turning to technology as a replacement for living systems is biospheric misadventure. To allow the males of a species, whose investment is principally in fertilisation, rather than the long-term female investment in sustainable child rearing, is committing evolutionary suicide because males risk death to compete for reproductive opportunities and their sole reproductive influence leads to boom and bust instability. We are politically and socially maladjusted to making constructive decisions for the welfare of humanity as a whole, let alone the other species with whom we co-exist and inter-depend. We are completely unaccustomed to living within our means and survive economically on the delusion that endless exponential growth is the solution to the world's problems. Our global decision-making is driven by authoritarian leadership of a tribal nature, in which populism is rife and Western society is a WEIRD (Western, Educated, Industrialised, Rich and Democratic) minority aberration (Henrich 2020), to the global rule.

Closing the Circle: Doughnut Economies

A revolutionary female-inspired economic antidote to the paradigm of the GDP and exponentiating growth imperatives, comes from Kate Raworth (2012), in her discussion paper "A safe and just space for humanity" , forming an interactive template for regenerating a fair, sustainable social dynamics in the closing circle of the natural planetary ecosystem and environment, originally prepared under the auspices of Oxfam in the run-up to Rio+20. This is built on "A safe operating space for humanity" in which Johan Rockström et al. (2009) propose numerical boundaries for seven parameters: climate change, ozone depletion, ocean acidification, biodiversity, freshwater use, the global nitrogen and phosphorus cycles, and change in land use. The authors argue that we must stay within all of these boundaries in order to avoid catastrophic environmental change.

Fig 31: (Left) Beyond the boundary: The inner green shading represents the proposed safe operating space for nine planetary systems. The red wedges represent an estimate of the current position for each variable. The boundaries in three systems (rate of biodiversity loss, climate change and human interference with the nitrogen cycle), have already been exceeded. (Right) The Doughnut Economics model forming a closing circle balancing the outer limits of the sustainable biosphere with the inner shortfalls of human society spanning health, education, energy, food gender equality and social equity.

In Kate Raworth’s words ^[74]:

The goal of the doughnut is to meet the needs of all people within the means of the planet. Sometimes when I present the idea of Doughnut Economics, people say. "Is this capitalism? Or is this communism? Or is it socialism?" And you think 'Really Are these the only choices we have?' The -isms of the last century? Can we not come up with some ideas of our own and create new names for them and see new patterns?

Governments in every country are almost addicted to citing GDP figures as if this was proof of success and yet it's so clearly not. Because we have climate breakdown and Covid lockdown and financial meltdown, we have to pursue something far richer to move from this pursuit of endless growth, which we can now see is hitting us with crisis after crisis, moving too a goal of thriving. And the doughnut is possible to turn not into a single number, but into a dashboard. We can hold policy makers to account and say every year you need to talk about how you are making progress on these different dimensions of the Doughnut.

The outside of the doughnut is created by leading Earth system scientists just a decade ago. These are the nine life-supporting systems of planet Earth. To have a stable climate, healthy oceans, recharging fresh water. And they drew these and called them the planetary boundaries.  But I thought if we go to the centre of the circle where we use hardly any of the Earth's resources, that's not thriving, that is actually death and destitution for billions of people. We need to convert Earth's lands for food, for water, for housing for energy. So I drew this inner circle and so just as there is an outer limit of humanity's pressure on the planet so too there must be an inner limit. o the hold in the middle is a place where people are left falling short on the essentials of life. It's where people don't have the food, water, energy, healthcare, housing, education, political voice that every person has a claim to meeting. We want to leave nobody in this hole. Get everybody into the green ring of the Doughnut itself.

And I think smart policy makers realised that they don't need a solution to financial crisis and a different one to climate crisis and a different one to health emergencies. They need a paradigm that no longer pushes for endless growth, but instead focuses on thriving, on resilience and on well-being within communities.

We began with downscaling in rich cities, in high-income nations because they are the ones that have the greatest obligation to transform, to come back within the planetary boundaries. But I believe the framework that we've created can absolutely be adapted and used in low income countries and cities.

Since 2012, there have been initiatives to downscale the Doughnut Economy, so it can apply to individual countries and cities, starting with developed economies where there is an impending need to face these realities, with projects in Amsterdam and “Regenerate Costa Rica” and the spinoff DASH project where researchers have applied the Doughnut to the needs of 150 countries.

In short: (1) Give half the Earth back to re-wilding the wilderness, so there is enough species diversity for the biosphere to evolve. (2) Transition immediately to renewable energy. (3) Decentralise the food supply chains to protect humanity.      (4) Ensure the genetic diversity of our food and medicinal species. (5) Eliminate nukes and consider how best to avoid a massive asteroid Earth strike and protection from a nearby supernova. (6) Teach people how to live in symbiotic urban culture. (7) Use technology for the benefit of life as a whole, not for humanity alone, or an artificial intelligence takeover (Werthner 2022). (8) Celebrate the perennial wonder of existence throughout our generations forever Amen.

“A human being is a part of the whole, called by us the 'Universe,’ a part limited in time and space. He experiences himself,

his thoughts and feelings as something separated from the rest — a kind of optical delusion of his consciousness.

This delusion is a kind of prison for us, restricting us to our personal desires and to affection for a few persons nearest to us.

Our task must be to free ourselves from this prison by widening our circle of compassion

to embrace all living creatures and the whole of nature in its beauty” (Einstein)

Symbiotic Existential Cosmology is written to fully sacralise nature and the diversity of life as the supreme spiritual meaning of existence, in a universe whose climax is conscious life immortal unfolding in ever deepening illumination.

Karen Armstrong (2022) in “Sacred Nature” notes the urgency of this reflecting Kate Raworth's statement above:

Today that link between nature and humanity has become even more poignant, as we consider the damage we have inflicted on our environment. We cannot delight in nature any more without knowing that we face the urgent task of saving it from human destruction. 

In the dynamic of concentric circles, of “The Great Learning” (Bloom 1999), the extension of each circle signifies a moment when we are compelled to transcend ourselves and our obsession with “me” and “mine.” The Chinese rituals of family life were painstakingly contrived to make this expansion of sympathy habitual. But to that we should add a new circle, which transcends our focus on humanity. When finally we realise that our very existence depends upon nature, it will be time to surrender our anthropocentrism and include the entire cosmos in our ultimate concern. The Confucian scholar Tu Weiming (1998) argues that we must go beyond the secular humanism that formed the anthropocentric ethos of the Enlightenment. We should develop an anthropocosmic mentality that unites the individual with the community and preserves the harmony between the human species and the non-human world.

Psychedelics and World Reflowering

This is the reason Symbiotic Existential Cosmology was written and why psychedelics have a key role in saving humanity from an apocalyptic extinction, or a slow decline back to an oblivion of dark ages from which culture cannot recover.

Fig 30g: Arbol de Ruben

The nascent reality connecting psychedelics and the Fermi paradox is that evolution climaxing to the emergence of a dominant cultural species like Homo, involves a narrowing of the experiential filters of conscious experience in the brain to promote species dominance, which then becomes a critical flaw, in a breakdown of coexistence into predatory exploitation, precipitating a mass extinction of the diversity of life through habitat destruction and the depletion of resources, in a non-renewable energy consumption and population burst, causing severe climatic change and disrupting planetary habitats on a global scale. This is the Fermi apocalypse catastrophe we are witnessing. 

The natural antidote to the destructive Fermi apocalypse is that the kind of climax driven by a dominant cultural species also occurs at peak biodiversity, after a long period of fecund prosperity, in our case since the Tertiary-Cretaceous extinction, and this results in a ‘salting’ of the biosphere with biomolecules which can modulate the neuronal activity of a dominant species in such a way as to carry its conscious neurodynamics closer to the climax edge of experiential chaos than its own evolutionary species selection became adapted for, thus opening the mind of humanity to the totality of existence that lies at the source of all spiritual experience of transcendence but in a way that is fully entangled with the diversity of life as a biospheric sacrament. This is then a way the fullness of evolutionary climax comes to reestablish the symbiotic biosphere, because changing the consciousness of the dominant species liberates it from its evolutionary constraints. Because any dominant cultural species seeks to understand what the hell it is doing in the universe, this becomes a catalyst for its own self-discovery.

Fig 31c: (Top) DMT-bearing plants are widespread. Phalaris arudinacia, Psychotria viridis and Acacia phlebophylla. (Bottom) Mescalin-bearing cacti Lophophora williamsii and Trichocereus pachanoi have no close taxonomic relationship nor overlapping locale, suggesting a similar defence to insect predation.

This is not a magic process of divine psychedelic intervention. Of the three classic psychedelics, dimethyl-tryptamine (DMT) and its related compounds such as 5MeO-DMT are widespread across species. DMT is an endogenous compound found in both animals (Saavedra and Axelrod, 1972; Christian et al., 1977) and a wide variety of plants around the globe spanning both moncot grasses and dicot lowering plants. Major plant genera containing DMT include Phalaris, Delosperma, Acacia, Desmodium, Mimosa, Virola, and Psychotria. It has even been proposed that it plays an endogenous role neurologically in human beings. Phalaris grass species for example are known to contain the alkaloids DMT, 5-MeO-DMT, and 5-OH-DMT (bufotenin), which also occurs in toads, but also toxic gramine.

The occurrence of mescaline is less widespread, confined to two unrelated cactus genera, the peyote cactus Lophophora williamsii and several Trichocereus species, including T. pachanoi, the  San Pedro cactus. This suggests that mescaline and the wider variety of bitter alkaloids in peyote have arisen through a response to insect predation.

The status of psilocin appears to be similar to mescaline and is even more intriguing. The incidence of psilocin activity is not taxonomic with the evolutionary tree, but is scattered across diverse genera of Agricales. The active species share both dung and a rotting wood habits and do not have a mycorrhizal symbiotic relationship with plant roots, as related non-active species do, indicating their activity is an adaptive  response to competition with insect varieties which also exploit these habitats. Reynolds et al. (2018) have established that a complex of five genes appears to have been horizontally transferred together from the wood decomposing species to the dung species. The phylogenies of PS genes suggest they originally served roles in the wood-decay niche among fungi, and more recently emerged through both vertical and horizontal transfer in dung-decay fungi, possibly in association with the rise of grasslands and megafauna in the Eocene at 50 mya. . Horizontal transfer and retention of PS clusters are evidence of selection on the PS pathway in the recipient lineage. This suggests that the genes form a complex that can be transferred together by a transposable element which confers resistance to predation. The lead author Jason  Slot notes: ”The psilocybin probably doesn't just poison predators or taste bad. These mushrooms are altering the insects' 'mind' – if they have minds – to meet their own needs.” Serotonin shares  psychodynamic survival function across all Bilateria, spanning arthropods and vertebrates, so it has been suggested that their role has been to deter insect consumption, possibly via a non-lethal psychoactive appetite suppressant based on the known olfactory role of 5HT2a receptors in fruit flies (Huser et al. (2017), although the spread of P. cubensis is also associated with Brahman cattle.

Fig 31d: Analysis of horizontal transfer of psilocin synthesis genes between fungi.

But this explanation reveals the other good half of the Fermi paradox. A dominant species which discovers its psychic species and learns to use their paradoxically disturbing properties, and begins to protect and even cherish its biosphere as sacred and integral to the evolving cosmic “design”, for the lack of a better word, and thus, instead of proudly announcing its dominant existence to all comers, or failing one of the many triple witching hours of its own cultural, political, economic and environmental instabilities, instead settles into discovering the abyss of its own conscious experience as a convergent symbiosis with the conscious universe as a whole.

This is what I term cosmological symbiosis, thereby settling into a much more cerebral perennially immortal existence, complemented by the use of renewable technology and adroit strategies to protect the biosphere from astronomical crises, such as massive impacts and nearby supernovae, by careful use of its solar system habitats to avoid putting all its eggs in one basket and to remain concealed in the universe at large, to avoid predatory exploitation from without. This is Fermi paradise on the cosmic equator in space-time.

Critical to addressing our existential threats to survival is the ability of subjective conscious volition to have efficacy over the physical universe. The history of neuroscience and consciousness research has been plagued by the notion of epiphenomenalism, in which the conscious mind is given the "ghost in the machine" status of an internal model of reality constructed by the physical brain, while subjective conscious volition over the physical universe is disregarded entirely as an impossible option to accept, because of the devotion of physical science to purely mechanistic principles, particularly  those expressed in physical behaviour.  This is why Symbiotic Existential Cosmology has a core empirical principle that subjective consciousness has efficacy of volition over the physical universe, which we can each affirm at once through simple physical affirmation, as is central in the law on both criminal and corporate intent..

The failure to accept this foundation feeds into our entire existential dilemma, because we then accept the abandonment of personal responsibility for our fates in all the existential threats facing our species. We have drifted into accepting the notion of nuclear deterrence, as tacit acceptance of the necessity for ever refined and more automated forms of nuclear weapons, when this just perpetuates humanity's genocidal tendencies, as the Mayor of Hiroshima lamented after the G7 summit. We accept climate crisis as a fact of economic existence, whatever the ultimate costs to the diversity of life, and human welfare and futures. We are ruthlessly exploiting all the wild habitats of the planet, leaving no room for life as a whole to flourish. We are now in the process of reinventing ourselves as biological forms of artificial intelligence, reducing our intentionality and creative insights to mere computational processes, and homeostatic mechanisms. All this is leaning towards Fermi extinction by cultural instability. That is why I am acting to heal the apocalypse of life and doing it now.

Self-mechanisation constitutes a complete abandonment of our essential being, and our sense of personal responsibility for our fates, both because existential issues seem too huge and all-embracing to address, but also because we have abandoned our very notion of being intentional beings able to alter our destiny for the future of life as a whole, in the pursuit of a degenerate mechanistic identity. At the centre of the cyclone is not consciousness, but the ability of subjective consciousness to change the physical world around us, through conscious volition, as clearly expressed in our intentional physical behaviour, so that we and our offspring and all the sentient living creatures we are surrounded by, can continue our struggle for illumination and transcendence together. Pure materialism seeks to deny subjective conscious autonomy as a key way to prove the rule of mechanism, by deconstructing volition as brain based purely physical neural outputs, when consciousness itself is too elusive to attack. This is root misadventure.

Over the last few weeks Christine and I have spent a lot of time watching David Attenborough narrating the last few years of his documentary programs and what was utterly striking was the unrelenting conscious volitional will and sheer determination of seemingly dumb animals, and the plants and fungi, to struggle, not just for their own survival, but the flowering of life in each species, caring with utter resourcefulness for their offspring and for the evolving future of life, through the web of their interactions, as plant and fungal producers, herbivores, and carnivores, amid the tooth and claw of predators and prey, and parasites and hosts, to form the climax network of living diversity.

What is gobsmacking – outstanding in its sheer intensity, is that all these supposedly dumb organisms are intentionally creating and perpetuating life around us under extreme stresses of near starvation, food searches over hundreds of kilometres for their young, new born offspring having to depart without food, to fly or swim in one stretch, half-way across the planet to seasonal feeding grounds with mothers struggling to avoid all their offspring being consumed by predators along the way. All these species have the will to live and to perpetuate life as a sine qua non, except we ourselves, who can't even accept we have any ability to do so because our mechanistically computational physical brains made us do it! Hence it is key to know that subjective conscious volition has efficacy over the physical universe.

I summoned this “gnosis”, without fear or favour, when I made my millennial vigil  to the Amazon and Jerusalem. I knew the odds and knew I was on the side of life against monotheistic doctrine, of dominion over nature and woman alike, as a catcher in the rye, passing right through the monotheistic throng, carrying the entheogenic sacramental holy grail of the Western religious tradition in my blood. I knew I was facing three major world religions with vested interests and violent tendencies. I didn't try to confront or argue fine points of law, and sought simply to to find common ground with liberal rabbis of both sexes, and perform a quick passage, as Jesus did, after preaching in the synagogue at Nazareth and passing cleanly through the crowds seeking to throw him off the cliffs for blasphemy. So I held simple rites of passage – to unfold the promised epoch of the Tree of Life, throw open the Gates of Mercy and celebrate the Hieros Gamos of woman and man, in the Song of Songs, fulfilled in my subsequent pilgrimage to pay my respects to Kali in Varanasi, completing my academic sabbatical. These are the three core principles of natural redemption that heal the apocalyptic tradition in a true unveiling of the immortal abundance of life.

Crisis and Resplendence

Communique on Preserving the Diversity of Life on Earth for our Survival as a Species

Affirmations: How to Reflower the Diversity of Life for our own Survival

William Blake – The Marriage of Heaven and Hell

5 Psychedelics in the Brain and Mind

While the brain is an electro-chemical organ, whose excitations are pulses and waves of electrical excitation, communication between neurons is predominantly chemical, via synaptic bulbs which release neurotransmitter molecules that bind to receptor proteins in the membrane of the target neuron that are either ionotropic and open ion channels, causing an electrical voltage, or metabotropic, activating proteins which alter the way the target neuron behaves.

There is widespread agreement that all neurotransmitters, like dopamine, can act as neuromodulators under certain conditions. Which role a molecule is playing in given circumstances tends to be defined by its function and activity. In general, neurotransmitters are released from one neuron into the synaptic space that connects it to another neuron; within milliseconds, they cause the gates of ionotropic receptor proteins to open and allow ions and other charged molecules to flood into a neuron, changing its internal voltage. Once the voltage passes a threshold value, the neuron fires an electrical signal to other neurons.

In contrast, neuromodulators are often released en masse at sites all over the cortex to seep through brain fluid and reach many more neurons. Binding to metabotropic receptors, whose protein cascades can affect both the nucleus and modulate neighbouring receptors, they act over seconds and minutes to make it more or less likely that the neuron will fire an electrical signal. They can alter the strength of connections between neurons, turn up the “volume” of certain neurons compared to others, and even affect which genes get turned on or off. These changes happen to individual neurons, but when a whole network is blanketed with neuromodulator molecules landing on the receptors of thousands or millions of neurons, due to major ascending pathways such as those of serotonin, nor-epinephrine, dopamine and acetyl-choline the molecules can “wash” into the intercellular fluid creating neurosystem-wide effects which influence every neural function, from sleep-wake cycles to attention and learning.

Fig 32: Left: Serotonin 5HT2a receptors are widely distributed across the cortex (Stein 2007). Centre: Ascending serotonin and nor-epinephrine pathways from basal brain centres fan out across layers of the cortex, modulating modes of sleep, wakefulness, mood, vigilance and drive. Right: 5HT2a receptors line pyramidal cells traversing the cortical layers.

Eve Marder, recognised for her pioneering studies on neuromodulators notes: By washing through the brain, neuromodulators allow you to govern the excitability of a large region of the brain more or less in the same way or at the same time. You’re basically creating either a local brain wash or more extended brain wash that is changing the state of a lot of networks simultaneously.

The primary excitatory neurotransmitter is the amino acid glutamate and the primary inhibitory one is gamma-amino-butyric acid or GABA, modulated by alcohol and sedatives. Their mutual interaction generates waves of excitation and inhibition identified with brain activity in the electroencephalogram.

Fig 33: Metabotropic and ionotropic actions of

neurotransmission and neuromodulation.

Other neurotransmitter molecules including serotonin (5-hydroxy-tryptamine derived from the amino acid tryptophan), nor-epinephrine and dopamine (derived from tyrosine) have a modal modulating effect on brain activity mostly through slower-acting metabotropic receptors. Serotonin and nor-epinephrine pathways regulate modes of organismic behaviour, including sleep and mood in serotonin, vigilance in nor-epinephrine, and reward seeking in dopamine. The level of neurotransmitters in the synaptic junction is also regulated by transporter proteins which mop up unused neurotransmitters after the event, to avoid the brain being flooded with effects that are now over.

Each of the classical neurotransmitters have both ionotropic and metabotropic receptors as targets with the exception of mono-amines, where only the serotonin 5HT3 receptor is ionotropic and differs structurally and functionally from all other metabotropic receptors which are hepta-helical G-protein-linked and all have a common evolutionary tree universal to life, fig 115.  Postsynaptic 5-HT3 receptors mediate fast excitatory synaptic transmission in neocortical interneurons, amygdala, and hippocampus. Nicotinic acetylcholine receptors are ionotropic. At the neuromuscular junction they are the primary receptor in muscle controlling muscular contraction.  Muscarinic acetylcholine receptors are metabotroic and modulate alertness. Glutamate has both ionotropic NMDA and AMPA receptors and metabotropic mGLu receptors. GABA A recptors are ionotropic while B are metabotropic. The 5-HT3, nicotinic and GABA A receptors all consist of five subunits arranged around a central ion conducting pore.

The term “psychedelic” has been eloquently (and compellingly) defined by Grinspoon and Bakalar (1979) to indicate “A drug which, without causing physical addiction, craving, major physiological disturbances, delirium, disorientation, or amnesia, more or less reliably produces thought, mood, and perceptual changes otherwise rarely experienced except in dreams, contemplative and religious exaltation, flashes of vivid involuntary memory, and acute psychosis.” The classic psychedelics, including psilocin, mescalin, dimethyl-tryptamine and LSD all have a common action on serotonin receptors in the brain. By interrupting psychedelic action with an inhibitor, Franz Vollenweider et al. (1998) established that the principal action of psychedelics was at the serotonin 2HT2a receptor, widely distributed in the cortex, fig 34(a), and densely expressed in layer 5 pyramidal neurons. Their detailed interaction with the spectrum of brain receptors can be seen in fig 34(h) and the close relationship between psilocin (4-hydroxy-dimethyl-tryptamine) and serotonin (5-hydroxy tryptamine) in fig 34(l).

Serotonin has multiple modal behavioural roles in the brain as a regulator of sleep and mood. The class of anti-depressants called  SSRIs, or selective serotonin reuptake inhibitors, increase the levels of serotonin by inhibiting its reuptake by transporter proteins. Entactogens such as MDMA, or ecstasy, go further and reverse the transporter, so as to dump an acute dose of serotonin, leading to the entactogenic high, accompanied by pleasurable and affectionate interpersonal contact. Both these agents can subsequently lead to serotonin depletion, the “Tuesday blues” or longer term withdrawal effects in antidepressants, but neither induce the psychedelic state. By contrast psychedelics have little physical dependence potential, because the acute effects rapidly wane if they are repeatedly dosed, until after a refractory period of days.

Fig 33b: Full psychedeic agonist psychedelic 25CN-NBOH — 5HT2a coupling
involving differential G q and -arrestin engagement (Kim et al. 2020).

Outlines of an understanding of how psychedelics act have required protracted investigation and are still under exploration. Psychedelics are agonists that turn on serotonin receptors, rather than blocking their action, just as is serotonin itself, but the way psychedelics do this seems to involve a distinct protein cascade. As shown in fig 34(b), while all serotonin agonists active the protein c-fos, psychedelics also active the developmental protein early growth response 2 or  egr-2. Fig 34(c) shows this is confirmed in vivo in mice. There has also been found from multiple researchers to be interactions between 5HT2a and metabotropic glutamate MgluR2 receptors, fig 34(d) involving psychedelics, which may explain how psychedelics, in addition to causing a standard serotonergic effect, also have the bizarre sensory and existential effects they are renowned for, by modulating excitatory glutamate activity. Kim et al. (2020) have further explored the relation between psychedelics and the G q subunit of the heterotrimeric G-protein responsible for psychedelic activation and its deactivation by -arrestin.

When we come to studying the effects on the brain in electrical and metabolic brain studies, the results are complex. There are two principal ways of studying brain activity, one is to place electrodes, or superconducting magnets on the scalp and record the electrical activity in electro- and magneto-encephalograms (EEG and MEG) and the other is to use metabolic measures using functional magnetic resonance imaging (fMRI), or positron emission tomography (PET) requiring a radio-active tracer. fMRI BOLD uses blood oxygen level dependent imaging and PET can sample for glucose.

Fig 34: (a) Left healthy person's excitatory 5HT2a receptors are widespread across the cortex. Mentally "at-risk" patient right shows lower activation (Hurlemann et al 2008). (b) In vitro and (c) in vivo investigation of protein activations caused by 5HT2a has shown a consistent differential activation of egr-2 (early growth response 2) transcription factor in psychedelics, as opposed to universal activation of c-fos (Nichols & Sanders-Bush 2002, González-Maeso & Sealfon 2003, González-Maeso et al 2007). (d) Serotonin agonism also appears to be linked to a pairing of 5HT2a with an adjacent glutamate mGluR2 metabotropic (G-protein-linked) receptor where egr-2 is blocked by an mGluR2 agonist (Bockaert et al, Fribourg et al, Kondo & Sawa, Uslaner et al, Gewirtz & Marek, Delille et al). (e) Persistence homological scaffolds for placebo (left) and psilocybin (right) showing greater inter-connective persistence (Petri et al). (f) PET study of 15-20 mg psilocybin taken orally over a 48 minute period 90 minutes after consumption, which shows frontal activation by comparison with a resting state (Vollenweider et al 1997).  (g) Reduction in amygdala activity in patients with treatment-resistant depression. Stabilisation of the DMN also occurred. Half of patients ceased to be depressed and experienced changes in their brain activity that lasted about five weeks (Carhart-Harris R et al. 2017). (h) Heat map of normalised receptor interactions (Ray 2010). Activity dark blue=0 to red=4 (orange for 2a and 2c, black no data). (i) LSD increases global functional connectivity of higher-level integrative cortical and sub-cortical regions (Tagliazucchi et al. 2016). (j) A recording during the 12 minutes after intravenous administration of psilocybin 2mg (~15 mg orally), which shows reduced activity in medial frontal cortex  (mPFC), posterior cingulate cortex (PCC) and other areas (Carhart-Harris et al 2012a, Lee & Roth). (k) PET study of 5HT2a sites where psilocybin acts, with red and yellow having highest density (Hasler & Quednow).  (l) Comparative electric fields of serotonin and psilocin. (m) Increases in activity associated with autobiographical memories on psilocybin. (n) Greater late phase activations during autobiographical recollection under psilocybin than placebo (Carhart-Harris et al. 2012b). (o) Changes in fMRI whole cerebral blood flow (CBF) on LSD, resting state functional connectivity (RSFC) increased between V1 and a large number of cortical and subcortical brain regions, but decreased between the parahippocampal  (PH) and the retrosplenial cortex (RSC) and PCC, although increased between the PH and dorsal mPFC and right dorsolateral prefrontal cortex (Carhart-Harris et al  2016a). (p) Reductions in alpha (8-15 Hz) and delta (1-4 Hz) MEG power with ego-dissolution on LSD attributed to cortical desynchronisation (Ibid). (q) Corresponding decreases in MEG for psilocybin (Muthukumaraswamy et al. 2013). (r) Source localisation of one of several networks with reduced power, again associated with desynchronisation (Ibid). (s) fMRI BOLD Variance time courses into the four regions of peak statistical significance for psilocybin and placebo. (t) Statistical significance for decreased low frequency power (LFP) and power spectrum scaling exponent α after psilocybin infusion. Statistical significance of increased power point rate (PPR) and decreased point process interval (PPI) after psilocybin infusion (Tagliazucchi et al. 2014). (u) Distinct receptor phosphorylation barcodes in psychedelics. (Vandermoere & Marin 2014). (v) Increased functional connectivity after psilocybin between the DMN and (i) r-fronto-parietal, (ii) DAN dorsal attention network, (iii) SAL salience network, (iv) TPN task positive network, (v) thalamus to TPN (Carhart-Harris et al. 2013), consistent with the “unconstrained mind” (Lifshitz et al. 2018).

While one might expect that something causing visions, or even hallucinations, might result in enhanced brain excitation, some aspects of the psychedelic state, such as ego loss might also arise from a reduction in activity. Early scans of subjects on psilocybin, fig 34(f) indeed showed increases, as has a later study on LSD when the visual areas are examined, fig 34(o), but the scientific community was surprised when a team led by Robin Carhart-Harris and David Nutt, fig 34(j), found that there was a significant and unexpected reduction in activity. At the time, Franz Vollenweider commented: “We have completed a number of similar studies and we always saw an activation of these same areas. We gave the drug orally and waited an hour, but they administered it intravenously just before the scans, so one explanation is that the effects were not that strong.”  Carhart-Harris et al. injected psilocybin and waited only a short period before the scans began. Psilocybin is a pro-drug, which is converted to psilocin, the active ingredient. The former is converted to the latter both by stomach acids and in the liver by alkaline phosphatase (Dinis-Oliveira 2017).

 Fig 35: LEFT (Above) MEG complexity measures are greater for waking consciousness than sedative-induced anaesthesia, but greater still for psychedelics. Increased complexity and correlations of measures. For all three there is reliably higher spontaneous signal diversity, than placebo even when controlling for spectral changes (Schartner et al. 2017).  Below left: Structural-functional similarity calculated as the Spearman correlation between vectorised structural and functional connectivity matrices. Below right: Brain networks of significant functional connectivity differences (r values) between placebo and LSD. LSD makes globally segregated brain sub-states more complex and more decoupled from structural constraints, as well as reducing functional connectivity of the anterior medial PFC, which is thought to subserve processes of reality monitoring (Luppi et al. 2021). RIGHT: Upper Left: Simulation of Lempel-Ziv complexity against Lyapunov exponent measured for a deterministic system. Lower left: The same measure in terms of the experimental K-statistic . Right: LSD, propofol anaesthesia and seizures normalised to the conscious state show that LSD enhances complexity, and brings the conscious brain state closer to criticality (Toker et al. 2022).

However Robin Carhart-Harris subsequently associated these results with a reduction in the activity of the default mode network (DFM). This was discovered a few years earlier from a pattern of apparent reductions in activity in certain areas during specific tasks that showed up as increased activity when resting (Raichle et al. 2001, Raichle & Snyder 2007). The DFM is thought to have a  critical survival role in formulating responses to actual or incipient crises, making active use of the brain during down times from activity to be better prepared. In fact there are many resting state networks and the fundamental idea is that the brain has two complementary modes of activity which can occur together, a passive role responding to incoming environmental or sensory priorities and an active role generating activity beneficial to the organism’s survival, with both of these processes superimposing during activities, so one or the other appears more prominent. Areas noted in these studies as having reductions were the medial frontal cortex  (mPFC), posterior cingulate cortex (PCC), parahippocampal  (PH) and the retrosplenial cortex (RSC). The PCC in particular is characterised in measuring how much you are “caught up” in your feelings and responses, as opposed to just having them. Carhart-Harris et al. (2013) also investigated (v) the connection between the DMN and other networks such as the saliency (SAL) and dorsal attention (DAN) networks and found psilocybin increased functional connectivity between several areas which normally have orthogonal non-interactive relationships confirming the increased functional connectivity of diverse regions under psychedelics.

Carhart-Harris cites the results as evidence of a reduction in default mode network activity consistent with silencing the internal dialogue and ego loss (Pollen 2018). A second researcher Justin Brewer has also found a similar reduction in people meditating (Brewer et al. 2011). This has led to the idea that stopping the internal dialogue of the default mode can result in ego dissolution, because the distinctions between self and other become blurred and the role of the ego as the strategic basis of the default mode network means that silencing it could induce a state of union, in which self and universe become one. Functional imaging has linked the precuneus, an integral component of the default mode network to the processes involved in self-consciousness, such as reflective self-awareness, that involve rating one's own personality traits compared to those judged of other people (Cavanna & Trimble 2006). This thesis supports the notion that both psychedelics and meditation can induce states of ego loss, but the effects of psychedelics are very profound and striking and experientially different from a meditative state of controlled repose, so quietening the resting state networks is a necessary gateway to both, but is not sufficient to explain the vast experiential territory of the psychedelic conscious state.

Carhart-Harris, Fortier, & Millière (2017) note the collapse of duality: The DMN is usually associated with mind-wandering, self-reflection and introspection while the Task Positive Network (TPN) is associated with the orientation of the mind towards the external world. Elaborating on this distinction, you notice that these two networks are anti-correlated in order to guarantee the functionally important distinction between the internal world and the external one. Now, with your colleagues, you have shown that the DMN/TPN anti-correlation is significantly decreased after psilocybin intake. You have proposed that the diminution of the orthogonality between the DMN and the TPN was a very plausible explanation as to why psychedelic experiences are characterized by a "collapse of dualities" and by the "disturbance in one's sense of self, and particularly one's sense of existing apart from one's environment" (Carhart-Harris et al., 2014, 16).

Millière R et al. (2018) express it this way: “even forms of putative “total” self-loss involving the radical disruption of both narrative and multisensory aspects of self-consciousness are best thought of as a family of states which can differ from a phenomenological perspective with respect to variables that are not directly related to self-consciousness. Indeed, strong forms of drug-induced ego dissolution may involve a very vivid and rich sensory phenomenology, perhaps as a result of decreased sensory gating, while available evidence on some “selfless” states induced by meditation suggests that their phenomenal content is very sparse (e.g., in states of so-called “pure consciousness” achieved in Samadhi practice).”

Carhart-Harris also compared the degree of reduction with subjects’ personal reports of the experience during the session and found that the reduction was greater in subjects who reported evidence of ego or subject-world dissolution such as “I existed only as an idea, or concept”, or “I didn't know where I ended and my surroundings began”, suggesting the effect is genuine. The result is also consistent with heightened activity in other brain areas, particularly those involved in the subjective effects of visions and synesthesia ^[30], which would tend to affect sensory areas rather than associative or frontal areas.

Subsequent studies, both on psilocybin and LSD using MEG fig 34(p, q), give further insights into this situation. The psilocybin study was again by injection but the listed subjective responses showed marked effect differences between subject and placebo, indicative of the psychedelic state. In both studies there was found to be a reduction in oscillatory power, which in the LSD study was strongly associated with ego loss.

Fig 36: Subjective responses within 15 mins of exiting the scanner (Muthukumaraswamy et al.2013).
Right: Increased global integration in the brain after psilocybin therapy for depression, but not for escitalopram (Daws 2022).

This reduction in overall power is consistent with increased desynchronisation in the signals, as in wave superposition of decoherent signals, which rise and fall at different instants are more likely to cancel one another, resulting in lower net oscillatory power.  This is consistent with diverse interacting signals arising from the stimulatory effects of the psychedelic on usually less associated areas, resulting in more information arising to the conscious level which would normally be filtered out, disrupting the usual flow of attention identifying and streamlining the ordered thought process. The psilocybin study also attempted to identify the source localisation of the resting state networks using independent component analysis (ICA) which determined up to seven, rather than just one, as illustrated in fig 34(r).

Evidence corroborating this interpretation came from a further ingenious experiment from another team led by Carhart-Harris, to analyse “homological scaffolds” of brain activity under psychedelics.  Fig 34(e) shows the result, in which there is a far richer network of homological scaffolds in play under psilocybin (right) with the “doors of perception” thrown open than in the normal mental state (left). This technique takes filtered correlations between the time series of the fMRI voxels, forms linkage graphs between each correlated series and then applies algebraic topology using the cliques of three or more to determine and weight the connections. Their evolution over time is also used to show that, while most of the population of psychedelic scaffolds have shorter duration than the fewer number in the placebo state, some psychedelic ones last significantly longer. This is also supported fig 34(s, t), by increased fMRI variance in the hippocampus and anterior cingulate and changes in power spectrum and other measures (Tagliazucchi et al. 2014). A further study (Lord et al. 2019) has explored recurrent BOLD phase-locking patterns (PL states). A similar result 5(i) shows LSD increases global functional connectivity of higher-level integrative cortical and sub-cortical regions (Tagliazucchi et al. 2016).

McNamara (2022) notes how psychedelics may alter the balance between intra and interconnectivity to induce mystical experiences:

Tagliazucchi et al. (2016) utilized fMRI to investigate global and local brain connectivity changes from the resting state following intravenous injection of LSD versus placebo to fifteen healthy volunteers. They found that the DMN, salience and FPN or fronto-parietal executive function network and the thalamus showed increased global connectivity under the drug but decreased within-network integrity. The increase in global connectivity observed under LSD correlated with subjective reports of ego dissolution. The authors suggested that increased cross talk between DMN, salience and FPN, when these individual networks are not functioning normally, could blur boundaries between self and world in such a way as to lead to ego dissolution and mystical experiences.

Fig 36b: (1) The principal cortical gradient of the transmodal association cortex pole (or “TOP”) of the human brain, expressed in a variety of measures, forming a hierarchical gradient down to primary sensory areas (Huntenburg et al. 2018). (2) Vatansever et al. (2017) used task-based fMRI to illustrate how the default mode network (DMN) and the fronto-parietal network (FPN), work collectively in cognition to guide complex behaviour. These demonstrate that the FPN is active after a rule change — the “acquisition phase”—suggesting its involvement in encoding the contingencies upon which the decision is based. Later, the “application phase” — when the individual understands the rule, activity within the FPN is reduced, and activity within the DMN increases (Margulies & Smallwood 2017). (3) Vidaurre et al. (2017) show that ongoing states are hierarchically organised, forming temporal groupings referred to as “metastates.” These reflect a dissociation between states anchored by regions of the cortex concerned with constrained neural processing (such as the sensorimotor systems), from those anchored by transmodal regions of the cortex. Spending time in states anchored in transmodal cortex, including those dominated by the DMN, predict better executive control and higher intelligence. (4) Subregions of the posterior cingulate cortex (PCC) within the white ellipse) and how each is functionally connected with (“echoes”) different whole brain intrinsic connectivity networks (shown by colour) (Braga & Leech 2015). The motor cortex has similar subdivisions sampling sensory and cognitive data (Gordon et al. 2023). (5) Timmermann et al. (2023) show increased global functional connectivity (GFC) under DMT, with corresponding decreased resting state between-network segregation in FPN, DMN, salience (SAL) and limbic (LIM). (6) Timmermann et al. (2023) show a compressed principal gradient under DMT consistent with dysregulation of the separation between abstract associate areas and sensory processing.

In a 2023 study to explore the changes induced by the psychedelic DMT on fundamental neurodynamic networks, including the default mode (DMN) and fronto-parietal (FPN), a them led by Robin Carhart-Harris has performed the first experiment combining combining concurrent fMRI and EEG investigations.

At dosages consistent with the study, they note:

DMT, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. The present findings advance on previous work by confirming a predominant action of DMT – and likely other 5-HT2AR agonist psychedelics – on the brain’s transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.

The transmodal association cortex pole (or “TOP”) of the human brain sits at the upper end of a hierarchical gradient of cortical organisation, while unimodal sensory areas sit at the lower end. The TOP is linked to abstract semantic representations, longer temporal windows of information processing, and is relatively more detached from sensory input, while also appearing later in primate cortical expansion and development. These findings suggest that the subjective effects of psychedelics depend on the dysregulation of the association cortices. Evidence from neuroimaging studies also suggests that this cortical dysregulation may result in the disinhibition of “lower”, evolutionarily and developmentally “earlier” systems such as the limbic system. This also throws light on aspects of the role of the DMN, not just in the resting state, or phenomena of ego loss, but in active situations, in which the FPN plays a role in cogitative planning of solutions, while the DMN takes over once these strategies are established and have become familiar. It is also consistent with the phenomena of a sensory flood, as lower level sensory and perceptual networks become more globally interactive with higher abstract networks involving our entire conception of reality.

Barrett et al. (2020) found that psilocybin significantly decreased both the amplitude of low frequency fluctuations as well as the variance of BOLD signal in the left and right claustrum. Psilocybin also significantly decreased functional connectivity of the right claustrum with auditory and default mode networks (DMN), increased right claustrum connectivity with the fronto-parietal task control network (FPTC), and decreased left claustrum connectivity with the FPTC. DMN integrity was associated with right-claustrum connectivity with the DMN, while FPTC integrity and modularity were associated with right claustrum and left claustrum connectivity with the FPTC, respectively. This suggests a major role for altered claustrum signalling in psilocybin's effects.

A theoretical idea advanced to explain salient features of the brain dynamics in psychedelic experiences is the notion of increased entropy. Carhart-Harris et al. (2014) note that “There is an emerging view in cognitive neuroscience that the brain self-organizes under normal conditions into transiently stable spatiotemporal configurations that this instability is maximal at a point where the global system is critically poised in a transition zone between order and chaos”. The paper then goes on to identify “metastability” of a brain network in terms of the variance in the network’s intrinsic synchrony over time and to claim the psychedelic state has higher entropy than the normal waking mental state. While the dynamical details of this have been criticised (Papo 2016), they do serve to have conceptual explanatory power. Papo's critique incorrectly pivots on metastability and the argument is squarely refuted by Toker et al. (2022). Edge-of-chaos dynamics and transitions from chaos to order in critically poised sensitive states are essential to a dynamical model of the brain to avoid the dynamics becoming locked into sub-optimal ordered states, by using the butterfly effect and its “ergodic” ability to fully permeate the space of possibilities.

A second model, extending the entropy idea is that psychedelics may act to “flatten the potential energy landscape” between attracting brain states (Carhart-Harris & Friston 2019), which has received some tentative support in an LSD study (Singleton et al. 2021).  The 2019 paper notes “We call this formulation ‘relaxed beliefs under psychedelics’ (REBUS) and the anarchic brain, founded on the principle that — via their entropic effect on spontaneous cortical activity— psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system.” 

A distinction is then made between two modes of cognition, primary consciousness “a mode of thinking the mind regresses to under certain conditions, e.g., in response to severe stress, psychedelic drugs and in REM sleep”, including magical thinking, “a style of cognition in which supernatural interpretations of phenomena are made”  and secondary consciousness “the consciousness of mature adult humans”. The article then takes the view that “the mind has evolved (via secondary consciousness upheld by the ego) to process the environment as precisely as possible by finessing its representations of the world, so that surprise and uncertainty (i.e., entropy) are minimized.” It then argues “that secondary consciousness actually depends on the human brain having developed/evolved a degree of sub-criticality in its functionality, i.e., an extended ability to suppress entropy and thus organize and constrain cognition. It is argued that this entropy-suppressing function of the human brain serves to promote realism, foresight, careful reflection and an ability to recognize and overcome wishful and paranoid fantasies. Equally however, it could be seen as exerting a limiting or narrowing influence on consciousness”. This leads to the conclusion that “that the underlying neurodynamics of primary states are more “entropic” than secondary states i.e., primary states exhibit more pronounced characteristics of criticality and perhaps supercriticality than normal waking consciousness — implying that the latter is slightly sub-critical, if not perfectly critical.”

Fig 37: Left: REBUS model of lowered potential energy landscapes causing increased upwelling on psychedelics. Right: CTSC model of thalamic filtering. The filter function of the thalamus, under the control of the CSTC feedback loops, is postulated to protect the cortex from exteroceptive sensory information overload, as well as from internal over-arousal. The model predicts that sensory overload of the cortex may result from thalamic gating deficits, which may be caused by ketamine e.g. by blockade of NMDA-mediated glutamatergic (Glu) cortico-striatal  neurotransmission, or excessive stimulation of 5-HT2 receptors—e.g., by psilocybin. James et al. (2022) have also applied Keppler's (2018) zero point field model of consciousness to ayahuasca and DMT.

This leads to a discussion of the role the default mode network is claimed to have maintaining the ego through the internal dialogue, leading to forms of mental illness involving the oppression of over-weaning order, such as depression, where repetitious rounds of internal dialogue occur, reinforcing a pessimistic existential outlook. It is also an ongoing feature of the fear of inevitable death that plagues human society.

As noted, there are some major issues with simply using entropy as a measure of criticality (Papo 2016). Highly entropic systems can be products either of chaotic criticality, or noisy randomness and entropy is itself not a measure of either complexity or criticality. That said, the general theme of balancing novelty with uncertainty is characteristic of brain dynamics, much of which has characteristics of pink, or 1/f noise displayed by edge-of-chaos dynamics, and human creations such as musical compositions, which ideally balance history and novelty.

A third notion is the cortico–striato–thalamo–cortical (CSTC) model which involves circuits between the cortex and the thalamus that mediate control of sensory information flow to the cortex and awareness and attention (Vollenweider and Geyer, 2001). This model highlights 5-HT2a receptor activation on circuits between the thalamus and cortex to explain the subjective effects of psychedelics (Geyer and Vollenweider, 2008). In this view, psychedelics impede sensory gating functions of the thalamus, allowing increased sensory and interoceptive information flow from thalamus to cortical regions. This reduction in sensory gating is proposed to lead to sensory overload of the cortex that results in both the observed perceptual effects and cognitive changes.

McNamara (2022) in discussion each of these three models notes that none provided a full explanation for the intricate all-revealing nature of psychedelic experiences:

The REBUS model (Carhart-Harris & Friston, 2019) largely relies on the Free Energy Principle (Friston, 2010), which claims that brains seek to reduce uncertainty and do this largely via simulation of expected states or processes. As discussed in previous chapters of this book these simulations of expected events occur at all levels of the neural hierarchy with the topmost node in the hierarchy, the PFC, presumably playing a crucial role in enabling these predictive simulations and processing error messages when simulations do not match up with what actually occurs. The REBUS theory proposes psychedelics disrupt these predictive simulations and error processing essentially by down regulating prefrontal and anterior cingulate cortex “top-down” control of the DMN and by disrupting intrinsic DMN circuits themselves. The precision weighting of prior beliefs is disrupted thus allowing prior expectancies and beliefs to undergo reevaluation. The relaxation of top-down priors allows bottom-up information to exert more influence on brain function, and this is what underlies the experiences induced by psychedelics. But can a simple increase in impulses or information coming from the bottom (e.g., distal sensory receptors), or even a reduction in filtering information coming from the distal sensory receptors result in the kinds of experiences people undergo on psychedelics? Would not the information simply be a barrage and blur of inchoate sensory experiences unless some kind of higher cortical cognitive processing was intact at the top of the hierarchy during a psychedelic experience? Instead, people report highly structured sensory experiences and indeed full-blown cognitive apperceptions of intricately structured worlds.

The CSTC model is similar in some respects to the REBUS model in that it implicitly adopts the idea that psychedelic experiences basically involve a removal of top-down inhibitory effects or a removal of the filtering functions of executive control networks in the cortex. This model (Vollenweider & Kometer, 2010) proposes that psychedelics disrupt the gating functions of the thalamus, so all kinds of information gets into the system, flooding the brain/mind and causing ego dissolution and other psychedelic effects. The loss of gating functions of the thalamus allow increased sensory and interoceptive information to flow from thalamus to cortical regions. While LSD, as noted earlier, does appear to increase thalamus to cortex connectivity, we can ask again whether this information overload is enough to account for the structured experiences we see?

The claustro-cortical circuit model argues that the claustrum is key to psychedelic drug effects (Nichols, 2016). The claustrum exhibits a large number of 5HT2A receptors and is intensively interconnected with a large number of cortical regions. Therefore, when you perturb the claustrum you demodulate a very large number of cortical networks. Psilocybin alters connectivity between the claustrum and both the default mode and fronto-parietal attention networks in the human brain, but it is not clear exactly how alteration of claustrum activity then alters other brain networks in such a way as to account for the structured experiences we see in psychedelic states.

Fig 37b: (Top-left) claustrum model of psychedelic effects (Doss et al. 2022). (Lower left) reduction in amygdala activity under enhanced positive mood on psilocybin (Kraehenmann et al. 2015). (Right) increases in cortical and thalamic activation over placebo  induced by psilocybin (red) and decreases (blue) (Gaddis et al. 2022).

A key characteristic of some neural nets using an energy landscape to reach and optimum is to run the simulation at a higher temperature of random fluctuations at first to avoid the system getting stuck in an “alpine lake”, gradually lowering the temperature to reach a quasi-optimal minimum, in a process called annealing. This is a similar process to using a transition from chaos to order to enter a quasi-optimal strange attractor. The idea is that the higher energy landscape is a way the brain filters the doors of perception, by impeding upwelling stimuli using top-down control and that when the landscape is flattened using psychedelics, new information can flood into conscious awareness.

A core basis of this argument is valid – that the brain has evolved to streamline conscious existence for survival, by filtering out uncertainty to enable rapid and decisive decision-making, ensuring organismic survival, consonant with Aldous Huxley’s (1954) notion in “The Doors of Perception “that everyday reality imposes a filter and that psychedelics, by reducing the filter can enable individual consciousness to perceive the “mind at large”.

Summarising the research to date, Drew (2022)  has the following overview:

Studies of functional connectivity have shown that the brain contains various discrete networks. Most scientists think there are about seven or eight discrete networks, including an attention or salience network, with others related to vision, hearing, sensorimotor pro­cessing and executive control. When a person is at ease, activity is seen across a collection of areas called the default mode network (DMN).

In many studies, the researchers have tried to identify specific connectional changes that correlated well with the self-­reported intensity of the trip, or with some particular aspect of it, such as a sense of ego dissolution. These indicate that psy­chedelics lead to “more connections between networks, and less connectivity within net­works,”.  Brain areas that usually have strong functional connec­tions — and operate in a network that has a fairly circumscribed function — become less connected, suggesting that the drugs disrupt those networks’ normal outputs. And brain areas whose activity is normally only weakly correlated become more connected. Most findings are consistent with the brain’s sen­sory areas having more influence on overall brain activity after psychedelics were taken.

Another idea that Carhart-­Harris’s paper on the entropic brain considered was that psychedelics dissolve a person’s sense of self by weakening connections within the DMN — an idea that gained traction far beyond the research community. Both hypotheses have been influential, but they have their critics.

“We don’t know how large the contribution of the default mode network is, because there are ten other brain networks that are also altered,” Katrin Preller says. Similarly, several researchers consider entropy to be too nonspecific.

In 2019, Carhart-­Harris proposed the REBUS model and the anarchic brain (where REBUS stands for ‘relaxed beliefs under psychedelics’), building on Karl Friston;s diea of the brain as a prediction machine that constantly forms models of what it expects to perceive in the world, then tests whether incoming sensory data confirm these models. REBUS proposes that psychedelics weaken the con­straints that a person’s pre­existing beliefs place on their perception of the world and of themselves. Under the influence of psychedelics, sensory inputs and recalled memories are freer to influence the brain and conscious experience.

Girn et al. (2022) found that LSD and psilocybin compress the usual hierarchy of connectivity between sensory and association networks. “These sensory areas — and their bare, concrete processing of the external world — become less separate from the processes conceivably related to our abstract thinking and beliefs,” Girn says. “It doesn’t fully validate the REBUS model, but it’s consistent.”

From research began in the 1990s in humans and animal models, Vollenweider  proposed the CSTC or thalamic gating model. The thalamus is a brain area that processes and filters sensory information en route to the cortex, regulated by the cortex through axons that express the 5­HT2A receptor. Psychedelics seem to inter­fere with the thalamus’s filtering operation, resulting in more sensory signals reaching the cortex. This is proposed to be central to the psychological effects of psychedelics.

In addition to these theories, Doss et al. (2022)  claim that fMRI findings suggest a central role for the claustrum, a small subcortical region rich in 5­HT2A receptors. Like the thalamus, the claus­trum exists in a loop with the cortex.

At its core, the entropic brain hypothesis proposes that the quality of any conscious state depends on the system's entropy measured via key parameters of brain function.

Cieri et al. (2021) note: According to the free energy principle (FEP; Friston et al., 2006) the brain is an open, adaptive, complex system far from equilibrium and as with any adaptive self-organizing biological system in nonequilibrium steady-state with the environment, it must reduce its free energy to resist a natural tendency to disorder (Ashby, 1947; Friston, 2010).  They further explain that the neural complexity and brain entropy (BEN) of spontaneous neural activity decreases during states of reduced consciousness. This evidence has been showed in primary consciousness states, such as psychedelic states, under the name of “the entropic brain hypothesis”, by contrast with physiological and pathological ageing, where BEN is reduced.

However the free energy principle is inadequate because consciousness existence is not just homeostatic, in terms of autopoiesis. Conscious volition is creative and isn't just homeostatic. But the theory is consistent with Huxley’s view of the doors of perception being opened to the “mind at large” through psychedelics, so it does have explanatory value.

Fig 38a: (Left) Psychedelics act on a diverse array of principal binding targets and downstream signalling mechanisms that are not limited to the serotonin 2A receptor or β-arr2. Instead, mechanistic convergence occurs at the level of DNA transcription (Nardou et al. 2023). (Right) signal entropy represented by Lempel-Ziv Complexity eyes closed, with music, eyes open and watching TV.

What feels like enlightenment from the inside looks like disorder from without. The idea here is that the brain processes impose a filter on the cosmic mind so that it can only behave in a way that serves the immediate survival interests of the organism, which makes it virtually impossible for a human to reach moksha. Then psychedelics paradoxically opening the filters causes ultimate reality at large to flood in. But this doesn't mean that the psychedelic experience is just a load of entropic junk – a kind of false vision. It’s not this because the combination of sensory overload and self-annihilation allows the brain dynamic to run free of organismic constraints and respond to the underlying dynamic, closer to a disengaged cosmic phenomenon. From the outside, when we don't know the significance, yes this does look like forms of entropy relative to the organismic constraints.

Mediano et al. (2024) note that the strongest increases in brain entropy which measures (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes accentuated in the closed eye condition of sensory withdrawal. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing a video—potentially due to a "competition" between external stimuli and endogenous LSD-induced imagery.

The emerging picture is that, despite using wide varieties of techniques which are often not directly comparable, there is some support for all of these models, which illustrates how pervasive the psychedelic state is on the generation of conscious experience and serves to underline what a comprehensive transformation of our world view the psychedelic state actually entails, based on the wide distribution of 5HT2a receptors.

As novel studies continue to emerge further findings continue to emerge. Kraehenmann et al. (2015) demonstrate reduction of amygdala activity during enhanced positive mood on psilocybin emphasising the positive aspects of the experience. Gaddis et al. (2022) showing significant psilocybin-induced alterations in spatial organisation of intra-thalamic components. Increased auditory-sensorimotor–thalamic connectivity is also shared between LSD, MDMA and stimulants (Avram et al. 2022). Barnett et al. (2020) have noted decreased directed functional connectivity in the psychedelic state, while Jobst et al. (2021) noted increased sensitivity to strong perturbations in a whole-brain model of LSD and Olsen et al. (2022 noted) time-varying functional connectivity, associated with plasma psilocin and subjective effects. Moliner et al. (2023) show that LSD and psilocin directly bind to TrkB the BDNF receptor promoting neural plasticity, with affinities 1,000-fold higher than those for other antidepressants. Nardou et al. (2023) have also found that in young mice, psychedelics reopen the social reward learning critical period leading to long-term pro-social behaviour noting that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening.

There are also scientific hints that psychedelics, such as DMT, which it is also believed occurs naturally in the brain has neurogenerative effects. Ly et al. (2018) report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo Calder & Hasler (2023) reinforce this with details of dendritogenesis and neural plasticity.

Fig 38: (1) Changes in neuronal structure, spinogenesis and the involvement of the 5-HT2a receptor in neural plasticity. (2) The involvement of DMT in neurogenesis. Neurospheres were cultured for 7 days in the presence of DMT. (3) Live-cell images of rat embryonic cortical neurons (DIV6) expressing Myc–5-HT2AR–CFP, b2AR-ECFP, or ECFP. Signals from the fluorescent protein and fluorescent plasma membrane marker in cyan and white (Vargas et al. 2023). Widefield images of rat embryonic cortical neurons (DIV6) that were administered compounds DMT, psilocin and psilocybin with (+) and without (−) electroporation, which creates temporary openings in the plasma membrane, which enables highly charged molecules to pass through and access the intracellular space. The membrane-permeable 5HT2a agonists DMT and psilocin were able to promote dendritogenesis regardless (Lower) Timeline showing the earliest and latest observations of various changes in neuroplasticity following treatment with a single dose of the serotonergic psychedelics LSD, psilocybin/psilocin, DMT, or DOI. One dot represents one study and time point. Human studies are shown in yellow; animal and in vitro studies are shown in purple. BDNF = brain-derived neurotrophic factor, IEGs = immediate early genes. Based on data for synaptic density, it is assumed that rates of dendritogenesis and synaptogenesis also increase at 6 h post-treatment (Calder & Hasler 2023).

These changes are accompanied by increased synapse number and function. DMT treatment has also been found to activate the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks (Morales-Garcia et al. 2020). Increased hippocampal neurogenesis also occured in mice treated with 0.1 mg/Kg, who also extinguished cued fear conditioning significantly more rapidly (Catlow et al. 2013). Similar plas1city changes have been aaributed to all classic psychedelics (Ly e al. 2018, 2021, Sotille et al. 2022). Vargas et al. (2023) further show fig 38(3) that this is common to classic psychedelics and involves intra-neuronal 5HT2a receptors also consistent with the metabotropic findings of fig 34 (b, c, d and u).

6 Therapy and Quantum Change: The Results from Scientific Studies

The theme of ego-dissolution and the DMN is also discussed with Robin Carhart-Harris at length in Michael Pollen’s (2018) work. It provides a general perspective in which to understand the basis of some of the outstanding claims about the mental states psychedelics induce. As noted, psychedelics have been found to share characteristics both with meditative states and religious contemplation, in which experimenters have found a reduction in the activity of the DFM. Silencing of the internal dialogue in ego dissolution also involves extensive sensory-existential changes in which the boundary between self and other/world becomes blurred. It is important to understand that dissolving of the DMN in the acute psilocybin phase is naturally followed by a reintegration to an active and more functional DMN than in depressive illness. Carhart-Harris extends this blurring to explaining the magical thinking that frequently leads people experiencing deep insights under psychedelics to describe them as veridically true – revealed truths rather than just a personal opinion. He suggests that one explanation of this is that relative judgment that something is just a personal opinion requires separation of subjectivity to carry weight, but in the state of union no such distinction exists.

This raises a fundamental question. Are the insights real or illusory? This is the same question that plagues the status volitional will. Reductionistic materialists attempt to finesse this position by claiming we are simply the product of our circumstances and the causality of brain processes and that the notion of ‘free-will” is just an illusion resulting from evolution requiring us to invest in the notion as a rationale to proceed on the basis of an organismic personal autonomy that doesn’t actually exist. Subjective consciousness then becomes an epiphenomenon, having no causal effect on the material world.

However, most people and the law act on the conviction that we are intentional beings who have consequences on the world around us and that we are accountable for our actions. Premeditation is in criminal law the defining foundation of conscious intent that determines the severity of a crime. We thus need to assess deep psychedelic experiences by the same token. Reports from very astute and trustworthy individuals consistently declare that a genuine veridical experience has taken place, having the nature of truth of the same status as both swearing legal evidence and a replicable observation of the physical world.

Aldous Huxley ^[31] wrote in The Doors of Perception: “Each person is at each moment capable of remembering all that has ever happened to him and of perceiving everything that is happening everywhere in the universe. The function of the brain and nervous system is to protect us from being overwhelmed and confused by this mass of largely useless and irrelevant knowledge, by shutting out most of what we should otherwise perceive or remember at any moment, and leaving only that very small and special selection which is likely to be practically useful. According to such a theory, each one of us is potentially Mind at Large” …  “In the final stage of egolessness there is an 'obscure knowledge' that All is in all — that All is actually each. This is as near, I take it, as a finite mind can ever come to 'perceiving everything that is happening everywhere in the universe.”

Fig 38b: Huxley’s reducing valve (Swanson 2018). The word psychedelic means “psyche revealing”, where psyche means the human mind, soul, or spirit and dēlos means ‘clear, manifest’.  Thus, Osmond’s (1957) proposed name-change— psychedelic—was intended to capture the spirit of filtration theory, by inhibiting certain brain processes which normally maintain their own inhibitory constraints on our perceptions, emotions, thoughts, and sense of self.

Huxley is highly critical of the limiting nature of the doors of perception’s usual filter: “To make biological survival possible, Mind at Large has to be funnelled through the reducing valve of the brain and nervous system. What comes out at the other end is a measly trickle of the kind of consciousness which will help us to stay alive on the surface of this particular planet. To formulate and express the contents of this reduced awareness, man has invented and endlessly elaborated those symbol-systems and implicit philosophies which we call languages. Every individual is at once the beneficiary and the victim of the linguistic tradition into which he or she has been born — the beneficiary inasmuch as language gives access to he accumulated records of other people's experience, the victim in so far as it confirms him in the belief that reduced awareness is the only awareness and as it be-devils his sense of reality, so that he is all too apt to take his concepts for data, his words for actual things.”

This criticism has become even more urgent and critical in a time of planetary climate and ecocrisis, when this reduced tribal awareness driven by ego-consciousness is causing dire risk of a mass extinction of the diversity of life and potentially the extinction of the human species.  To a reader not familiar with these states, it is hard to give credibility to the notion that a person under the influence of an agent originally labelled as an “hallucinogen” that is known to have both transcendent and potentially diabolically dysphoric dimensions as Huxley emphasised in “Heaven and Hell” (1956) can also have experiences with the long-lasting therapeutic relief or mystical insight, let alone be literally and veridically true.

However this is precisely what a number of studies, where precisely these insights under psychedelics have been repeatedly shown to have long lasting insights and benefits, both in severe depression and in people suffering a terminal condition and in normal people experiencing mystical states  (Carhart-Harris t al. 2016b, Griffiths et al. 2006, 2008, 2011, 2016, 2021). Studies are also exploring psilocybin use in bipolar disorder (Aaronson et al 2023, Gard et al. 2021, Monaco K 2023, Morton et al. 2023, Yaden et al. 2023). 

Fig 39: (a) Assessments of improvement in depression, anxiety and quality of life up to 6 months after psilocybin study in subjects facing life-threatening cancer (Griffiths  et al. 2016) (b) Improvements in subjects with treatment-resistant depression after psilocybin study (Carhart-Harris et al. 2016b), compared with Ketamine (Zarate et al. 2012).  (c) Assessments 2 & 14 months after the psilocybin study Griffiths et al. (2006, 2008). The largest study of its kind (Goodwin et al. 2022) has confirmed these findings for a one-dose treatment for a treatment-resistant episode of major depression.

The titles of these research papers “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance”, “Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later”, and “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” indelibly attest to the genuine long-term effects that these experiences induced.

The most striking finding from this 14-month follow-up evaluation of the effects of psilocybin ... administered to hallucinogen-naïve volunteers is that a large proportion of volunteers rate their "psilocybin experience" as among the most personally meaningful and spiritually significant of their lives. Fifty-eight percent and 67% of volunteers, respectively, rated the experience as being among the five most personally meaningful experiences of their lives, and the five most spiritually significant experiences of their lives; 11% and 17%, respectively, indicated that it was the single most meaningful experience, and the single most spiritually significant experience. Furthermore, 64% of the volunteers also indicated that the psilocybin experience increased their sense of well-being or life satisfaction moderately or very much, and no volunteer rated the experience as having decreased well-being or life satisfaction.

McNamara (2022) who has become prominent as a researcher into the neurological basis of religious experience strongly confirms the significance of these findings for mystical and religious experience:

It is now very well established that psychedelics reliably produce mystical-like experiences. The first well-documented experimental study to investigate the effects of a serotoninergic psychedelic on mystical experience was the so-called Good Friday experiment conducted by Walter Pahnke at Boston University’s Marsh Chapel in 1962. The study involved administration of either 30 mg psilocybin (n = 10) or 200 mg nicotinic acid (n = 10) to seminary students during the Good Friday religious service (Pahnke, 1967). After the experience, and at a six-month follow-up, participants were assessed for mystical experiences based on the model of mystical experience developed by Stace (1960). The Stace dimensions of mystical experience include sense of unity, sacredness, positive mood, transcendence of time and space, noetic quality, ineffability, paradoxicality, transiency and persisting positive changes in attitudes and behaviors. Four of the participants in the psilocybin conditions reported most or all of these dimensions while none in the control group did. Doblin (1991) tracked down sixteen of the original twenty participants twenty-five years later and confirmed that many of the positive benefits linked to the psychedelic experience remained!

In a now landmark psychedelic study (Griffiths et al., 2006) using the MEQ, the mean percentage of endorsed items was 78 percent immediately after psilocybin and 33 percent after the control substance methylphenidate. Follow-up some fourteen months later did not substantially change these numbers. In addition, the appearance and intensity of mystical experiences appears to be dose dependent (Barrett et al., 2015; Griffiths et al., 2011): volunteers received 5, 10, 20 and 30 mg/70 kg of psilocybin in separate sessions with at least one month between each session and a placebo session randomly placed within the sequence. The mean percentage of maximum total possible score on the MEQ30 on session days was 23 percent, 47 percent, 52 percent, 70 percent and 77 percent after placebo and 5, 10, 20 and 30 mg/70 kg psilocybin. This score for 30 mg/70 kg at fourteen months was 81 percent. Hierarchical regression analysis demonstrated that MEQ30 scores significantly predicted various clinical, health and spiritual well-being outcomes.

When the people who have them (1) describe the experiences as mystical, religious and spiritual, (2) when these experiences are associated with benign to excellent clinical outcomes, (3) when the phenomenology of the experiences are substantially similar and (4) when the mystical experiences are dose-dependent, I think we can conclude that these experiences are psychedelically induced and genuine religious mystical experiences.

Ketamine has similarly shown promise in treatment-resistant depression, though effects do not last as long as those observed with psilocybin. A possible mechanism has been found in the disassembly of perineuronal nets restraining new synapse formation in established learned memories (Venturino  et al. 2021). Other evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner (Kadriu et al. 2021). The notion Craddock that ketamine and psychedelics share an interaction with microtubules affecting consciousness does not at this point have evidential support.

Fig 40: Selected results from Griffiths et al. (2018). All at 6-months after, except for the top-left rating of psilocybin effect.

A later study (Griffiths et al. 2018) combined the use of psilocybin with meditation and other spiritual practices, echoing the way in which movements such as the Native American Church and the Union Vegetale provide a spiritually conducive context to engender positive outcomes, designed to tap into quantum change experiences – sudden, distinctive, benevolent, and often profoundly meaningful experiences that are said to result in personal transformations that affect a broad range of personal emotions, cognitions and behaviours (Miller, 2004; Miller and C’de Baca, 2001). The discussion notes that: “The study showed robust interactive positive effects of psilocybin dose and added support for spiritual practices on a wide range of longitudinal measures at 6 months including interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and rating of participants by community observers. Analyses suggest that the determinants of these effects were the intensity of the psilocybin occasioned mystical experience and the rates of engagement with meditation and other spiritual practices. Most broadly, as a model system for studying so-called quantum change experiences, which have been described for centuries but which have eluded rigorous prospective experimental analysis, further investigation of psilocybin-occasioned experiences may have broad implications for the development of drug and non-drug interventions in both therapeutic and nontherapeutic applications in order to engender enduring positive trait-level changes in attitudes and behavior and in healthy psychological functioning”.

Miller (2004) notes: “The person typically experiences mystical quantum change passively, not a product of personal will or control, and has a difficult time expressing the experience in words. They usually are intensely positive, joyful experiences, and often the person senses the presence of an awe-inspiring transcendent Other. Often there is a noetic element of revelation, a sudden knowing of a new truth. An experience of unity is common; for example, an ineffable oneness with all of humankind, with nature, or the universe. In these respects, the mystical type of quantum change is similar to common reports of near-death experiences (Lorimer 1990). At the most mystical level, quantum changers seemed to become more alike, as if they had in some way glimpsed the same truth. They often voiced the experience of being interconnected with and part of all of humanity and creation. Those who had experienced themselves in the presence of a transcendent Other gave strikingly similar descriptions. They felt awe but rarely fear, for in its presence they had experienced unspeakable love and acceptance. The insightful type of quantum change lacks most of the mystical components save one: the noetic element of sudden realization or knowing with great and sudden force, and in the moment of seeing, the person recognizes them for authentic truth (or Truth). Their effect tends to be a reorganization of one’s perceptions of self and reality and a cathartic, ecstatic, sense of relief and release. They knew instantly they had passed through a one-way door through which there was no return. They were changed, freed right then, and knew it immediately. Often, characteristics that had been valued least became most important [spirituality and generosity] , and those that had ranked as highest priorities [such as status and possessions]  fell to the bottom”.

A further study (Griffiths et al. 2019) compared “God-encounter experiences” under classic psychedelics and naturally.  While “the Non-Drug Group was most likely to choose "God" as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose "Ultimate Reality." Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. … These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences.  A long-term increase in mindfulness is also noted (Madsen et al. 2020).

Having these mystical experiences, the patient is able to overcome their depression or reframe that depression and return to a more baseline mental being. It really seems to restore … the wellness and balance in the life of the patient. It's quite magical. We don't know yet, but I strongly suspect that you cannot separate the two [effects therapeutic and psychedelic]. Hallucinating is an essential part of the way these drugs work. Chris Koch chief scientist of the Allen Institute's MindScope Program.”

Bill Richards ^[32] notes that mystical experience isn’t something vague, but a specific form of human consciousness. ‘When it’s expressed through questionnaires you can find evidence of  six categories, which [are]: unity; transcendence of time and space; intuitive knowledge (what William James called the noetic quality); a sense of sacredness or awesomeness; deeply felt positive mood, such as joy, peace, love, purity; and claims of ineffability and what we call paradoxicality — that it’s very hard to put these experiences into words and when people try to express it they keep contradicting themselves, that’s the paradoxicality: 'I died but I’ve never been so alive, the ultimate reality was one but it was many, it was beyond time but it included time’ — ultimately the Buddhist claim of the nothingness that contains all reality. And it seems contradictory, but mystics would say the problem isn’t in the experience; it’s in our ability to express the experience within language, at this point in the development of language. And that the answer, the truth is always "both and" rather than "either or”.’

As a warning to unsupported experiences in a bad setting, a survey by Griffiths’ group of extreme, challenging experiences (Barrett et al. 2016, Carbonaro et al. 2016), 1993 individuals (mean age 30 yrs; 78% male) completed an online survey about their single most psychologically difficult, or challenging experience (worst “bad trip”) after consuming psilocybin mushrooms. 39% rated it among the top five most challenging experiences of his/her lifetime. 11% put self or others at risk of physical harm; factors increasing the likelihood of risk included estimated dose, duration and difficulty of the experience, and absence of physical comfort and social support. 2.6% behaved in a physically aggressive or violent manner and 2.7% received medical help. Of those whose experience occurred >1 year before, 7.6% sought treatment for enduring psychological symptoms. Three cases appeared associated with onset of enduring psychotic symptoms and three cases with attempted suicide. Intriguingly, the degree of difficulty was positively associated with enduring increases in well-being. Despite difficulties, 84% endorsed benefiting from the experience and the researchers noted that the incidence of risky behaviour or enduring psychological distress is extremely low when psilocybin is given in laboratory studies to screened, prepared, and supported participants.

It is extremely significant that facing the fear of immanent death, possibly in pain and debilitation, which is the most real and terrifying crisis any conscious mortal being can face, can be redeemed on an ongoing, not just a transient basis, by a psychedelic experience. This attests to these experiences not being illusory but evidential to the conscious mind as the antidote to the mortal dilemma. This is precisely what “moksha”, the primary goal of all Eastern spirituality, seeks to attain through a lifetime of renunciation and devoted meditation. It also stands as highly evidential that in their signature work “The Psychedelic Experience”, Leary, Alpert and Metzner  (1964) presented a guide for readers to navigate the psychedelic state, framed as a modern representation of the Bardo Thodol or Tibetan Book of the Dead – “The Great Liberation upon Hearing in the Intermediate State” – (Lāma Kazi Dawa-Samdup Eng trans 1927), the Tibetan Buddhist manual for successfully negotiating death and rebirth.

Michael Pollen notes a conversation with Roland Griffiths, in which, despite being a world renowned academic researcher leading the field, he has to pick his words very carefully: "The first time I raised [Bob] Jesse’s idea of the betterment of well people with Roland Griffiths, he seemed to squirm a bit in his chair and then chose his words with care 'Culturally right now that is a dangerous idea to promote’ ". However Roland later commented "We're all dealing with death – this is far too valuable to limit to sick people", afterwards carefully amending it to "This will be far too valuable to limit to sick people".

A Psychedelics Pioneer Takes the Ultimate Trip

Marchese (2023) NYT

As the founding director of the Johns Hopkins Center for Psychedelic and Consciousness Research, Dr. Roland Griffiths has been a pioneer in investigating the ways in which psychedelics can help treat depression, addiction and, in patients with a life-threatening cancer diagnosis, psychological distress. He has also looked at how the use of psychedelics can produce transformative and long-lasting feelings of human interconnectedness and unity.  Griffiths, who is 76, has been diagnosed with Stage 4 metastatic colon cancer, in all likelihood terminal, that has brought forth transcendently positive feelings about existence that he calls the great mystery of consciousness. “We all know that we’re terminal,” says Griffiths, “So I believe that in principle we shouldn’t need this cancer diagnosis to awaken. I’m excited to communicate, to shake the bars and tell people, ‘Come on, let’s wake up!’ ”

In spite of the diagnosis, life has been more beautiful, more wonderful than ever. When I first got that diagnosis, because I work out regularly, I watch my diet, I sleep well, this came out of left field. There was this period in which it felt like I was going to wake up and say, “Boy, that was a bummer, a bad dream.” But soon I started to contemplate the different psychological states that would be naturally forthcoming: depression, anxiety, denial, anger, or adopting some belief system of religious outcomes, which as a scientist I was not cut out to do. I went through those, exploring what life would be like if I inhabited those reactions, and I quickly concluded that that was not a wise way to live. I have a long-term Vipassana meditation practice and the focus there is on the nature of mind, of consciousness, and one comes to see that thoughts, emotions, are transient. That practice — and some experience with psychedelics — was incredibly useful because what I recognized is that the best way to be with this diagnosis was to practice gratitude for the preciousness of our lives. Grasping for the cure wasn’t useful.

After getting the diagnosis, I had no immediate interest in psychedelics. I felt in many respects that I was having a very psychedelic-like experience. There was this awakening, this aliveness, and I hesitated to take a psychedelic because I wondered whether it was going to disrupt that. Then a question arose: Is there something I’m avoiding by not taking a psychedelic? Am I defending against some dark, fearful thing I’m in denial about? Am I papering it over with this story of how great I’m doing and actually I’m scared to death? I thought, Well, this would be an interesting stress test. So I did a session with LSD. First, asking myself, “Is there something I am not dealing with?” The answer came back: “No, the joy you’re experiencing is great. This is how it should be.” Then I asked a question directly of the cancer: “What are you doing here? I got nothing back. Then I wanted to humanize it, and I said: “I really respect you. I talk about you as a blessing. I have had this astonishing sense of well-being and gratitude, despite everything that’s happening, and so I want to thank you. This process, is it going to kill me?” The answer was, “Yes, you will die, but everything is absolutely perfect; there’s meaning and purpose to this that goes beyond your understanding, but how you’re managing that is exactly how you should manage it.” So then I said: “OK, there’s purpose and meaning. I’m not ungrateful for the opportunity, but how about giving me more time?” [Laughs.] I got no response to that. But that’s OK.

Our first study was in cancer patients. Ironically enough, these were cancer patients who were depressed and anxious because of a life-threatening diagnosis. The findings of that study were profound: A single treatment of psilocybin produced large and enduring decreases in depression and anxiety. I’ve had some limited experience with psychedelics since then. We’ve now treated hundreds of participants with psychedelics and before sessions, one of the key things that we teach them is that upon taking a psychedelic, there’s going to be an explosion of interior experiences. What we ask them to do is be with those experiences — be interested and curious. You don’t have to figure anything out. You’re going to have guides, and we’re going to create this safety container around you. But here’s the trick: These are not necessarily feel-good experiences. People can have experiences in which they feel like they come to this beautiful understanding of who they are and what the world is, but people can also have frightening experiences. The preparation we give for these experiences is to stay with them, be curious and recognize the ephemeral nature of them. If you do that, you’re going to find that they change. The metaphor we use is, imagine that you’re confronted with the most frightening demon you can imagine. It’s made by you, for you, to scare you. I’ll say: “There’s nothing in consciousness that can hurt you. So what you want to do is be deeply curious and, if anything, approach it.” If your natural tendency is to run, it can chase you for the entire session. But if you can see it as an appearance of mind, then you go, “Oh, that’s scary, but yeah, I’m going to investigate that.”

Griffiths in one of the psilocybin treatment rooms. 

The approach that you’re describing is pretty far from the typical mind-set of many doctors, who are working within a framework of curing, fixing, prevention. So if the ultimate goal is to help more otherwise healthy people get safe access to the potential benefits of using psychedelics, which of course would need to be used in a safe setting and supervised by trained experts, wouldn’t that require a radical rethinking by medical practitioners about what helping people even means? 

Yes, it will. One of the inspirations for the endowment is that it’s not aimed at patient populations. Right now, there’s money pouring into this area, but that’s all going to be patient-related — there’s a pathway to medical approval. I do have concerns that we don’t replicate the mistakes that occurred in the 1960s, which over-promoted psychedelics’ use culturewide. They’re so powerful that if misaligned with cultural institutions, they can result in cultural kickback. In the 1960s they became aligned with the antiwar movement and radicalized-youth movement that was terrifying to existing political structures and institutions, and as a consequence, legislation was put up against them, funding dried up. We need to proceed cautiously. It’s going to be critically important not to threaten existing cultural institutions. So I’ve been a proponent of medicalization, because with medicalization, we already have regulatory structures in place. It goes through F.D.A. approval; they’re going to set standards to maximize safety by specifying who should be eligible to receive, who is authorized to prescribe, and under what conditions treatment should occur. So I’m cautious, but that’s why I’ll have the endowment in perpetuity. If we look at the long range, this could be critical to the survival of our species.

It is Griffiths’s belief that humanity has developed — and is developing — technologies that could threaten its ongoing survival. He also believes that psychedelic experiences can provide the basis for moral and ethical principles that would lessen the likelihood that humanity will drive itself off a cliff. Because there’s something about the nature of these experiences under these certain conditions that produce remarkable experiences of interconnectedness of all things. At the deepest level, if we recognize we’re all in this together, then we have the kernel of what I suspect is most religious traditions and impulses and that is realizing that the Golden Rule makes a lot of sense. After we spoke, Griffiths mailed me a medallion embossed with an image of mushrooms and inscribed with the phrase “May you remain aware of awareness.”

I’ve noticed that often when you discuss human consciousness and our awareness of the preciousness of life, you talk about those things as an awe-inspiring “mystery.” What do you get out of putting it in those terms? Because consciousness may be a mystery now, but I’ve read theories that are convincing, to a layperson like me, that thoughts come from emotions and our emotions are one of the body’s mechanisms of maintaining homeostasis. Or as far as the awareness that life is precious, I could easily imagine that biophilia has evolutionary advantages. So I don’t see why these states of being have to be understood as mysteries. Does it diminish them to see them as explainable? 

I can easily inhabit an evolutionary account that explains how we have come to be who we are — with the exception of the question of interiority! Why would evolution waste its precious energy on our having interior experiences at all? I don’t get that. To me, it’s a very precious mystery, and that mystery, if you want to put it in religious terms, is God. It’s the unknowable. It’s unfathomable. I don’t believe in God as conceptualized within different religious traditions, but the mystery thing is something that strikes me as undeniable. I want everyone to appreciate the joy and wonder of every single moment of their lives. We should be astonished that we are here when we look around at the exquisite wonder and beauty of everything. I think everyone has a sense of that already. It’s leaning into that more fully. There is a reason every day to celebrate that we’re alive, that we have another day to explore whatever this gift is of being conscious, of being aware, of being aware that we are aware. That’s the deep mystery that I keep talking about. That’s to be celebrated!

On the question of authenticity of the psychedelic experience, opinions vary.  David Nichols (2011), the Perdue pharmacologist who founded the Hefter Institute to support psychedelic research (Nichols, Roseman & Timmermann 2018) and synthesised the psilocybin for Griffith's experiments said "If it gives them peace, if it helps people to die peacefully with their friends and their family at their side, I don't care if it's real or illusion". But Roland Griffiths acknowledges "authenticity is a scientific question not yet answered – all we have to go by is the phenomenology” – i.e. the quality of personal reports. In response to Michael's "staunchly materialist" world view Roland replied "Okay then, but what about the miracle that we are conscious? Just think about that for a second, that we are aware and that we are aware that we are aware! How unlikely is that?”

Primary consciousness associated with reduction of the internal dialogue and ego-dissolution is not just a question of flawed magical thinking that the mind regresses to, but is shared by psychedelics, meditation and deep religious contemplation, all of which in varying ways seek to calm the internal dialogue, attributed to inhibition of the DMN.

Michael  Pollen cites a number of themes relating to this, including the undifferentiated inclusive mentality of the child mind advanced by Alison Gopnik  who co-hosted a talk with Robin Carhart-Harris (2016), echoing sayings of Yeshua and Don Jose Matsuwa. Gopnik refers to a wider nuanced “lantern awareness” which becomes a starker “spotlight awareness” of the Cartesian theatre in adulthood, which as we age, becomes more and more locked into habitual routines that have been found successful in the past. It also applies to releasing the inability of the ordered mind to think outside the box and to be creative, as opposed to conservative and analytic consciousness, which is strongly history-based, rather than novelty-based.

McNamara (2022) notes the significance of “entity” experiences under psychedelics, particularly DMT which involve the perceived relationship with other visionary agents, which may take diverse forms from fairies, through monsters, thieranthropes (human-animal sprits), aliens, angels, deities and demons and serpents and their parallel with other forms of religious and mystical visionary experience, several of which are illustrated in figs: 168, 195, 203, 246 & 247:

Supernatural agent (SA) encounters are often a part of religious experiences. Existing reviews (Davis et al., 2020, Griffiths et al., 2019) report that on average greater than 80 percent of people who have taken a psychedelic at moderate to high dosage report encounters with nonnatural or supernatural entities. Survey results from the Davis et al. and Griffiths et al. studies revealed that people who had taken an agent with DMT described the SA encounters they experienced as being just as real as encounters with people when off psychedelics.  The most commonly endorsed labels for the SAs they encountered when on DMT were “being” (60 percent), “guide” (43 percent), “spirit” (39 percent), “alien” (39 percent) and “helper” (34 percent). Virtually all respondents reported having had an emotional response to the experience including joy (65 percent), trust (63 percent), surprise (61 percent), love (59 percent), kindness (56 percent), friendship (48 percent) and fear (41 percent). The SA was considered to be a conscious being (96 percent), intelligent (96 percent), benevolent (78 percent), sacred (70 percent) and had agency in the world (54 percent). Most respondents believed that the SA was absolutely real, not hallucinated, with 72 percent believing that the entity continued to exist after their encounter.

These experiences can vary from ecstatic to stressful encounters such as with the “angel of death” but the encounter can result in beneficial experience:

In the Davis et al. (2020) survey study more than two-thirds of respondents (69 percent) endorsed receiving a message, task, mission, purpose or insight into personal issues from the entity encounter. All this speaks to the potential therapeutic benefits of such insights. The individual is receiving highly meaningful information from an awe inspiring source, so the information is taken to heart in a way that could impact therapeutic potential.

These can take the form of a near-death like experience as in my encounter with “Brahman” both as ultimate reality and as an ever-compassionate “entity” in the experience which precipitated this cosmology.

Shannon (2002 p13) notes the multi-modal nature of psychedelic experience extending beyond the superficial senses:

Ayahuasca induces powerful visions as well as hallucinations in all other perceptual modalities. Pronounced non-perceptual cognitive effects are also manifest. These include personal insights, intellectual ideations, affective reactions, and profound spiritual and mystical experiences. Moreover, Ayahuasca introduces those who partake of it to what are experienced as other realities. Those who consume the brew may feel that they are gaining access to new sources of knowledge and that the mysteries and ultimate truths of the universe are being revealed to them. All this is often coupled with what drinkers describe as an encounter with the Divine.

But there are also outstanding differences between psychedelic experiences and meditative and contemplative ones, which are essential to understand and are pivotal to the central enigma of existential cosmology. Mediation seeks to achieve enlightenment by careful top down control, mediated by equanimity, rejection of grasping desires, one-pointed concentration and compassionate emotion. Religious contemplation seeks repose in prayer and devotion. Thus the person involved finds a degree subjective fulfilment, amid acceptance of a spiritual or religious doctrine they are already committed to.  Although these experiences of ego dissolution may induce positive outcomes for the individual, they also tend to confirm established beliefs, rather than open the floodgates to new ideas challenging one’s preconceived assumptions. By contrast, psychedelics are liable to induce insights of a novel and existentially challenging nature, such as the somewhat baffling notion of “the mind at large” as a spontaneous discovery.

Psychedelics provide a complex cyclonic perturbation of existential and sentient consciousness, not a simple “enlightenment pill”.  Bill Richards notes: ’The relation of the drug to the experience is not like taking an aspirin to get rid of your headache. What the psychedelic substance … they all seem to be skeleton keys that open up the mind, that give you an opportunity to explore, but where you go and what happens depends on who you are, kind of who you are, your maturity, your life history, your capacity to be able to choose to trust unconditionally, your feeling of safety, your courage. So much more is involved than just taking the drug.’

What we are dealing with in psychedelics is a whole constellation of mental states, depending on the circumstances and mind set of the person involved. They can take on visionary aspects of traditional notions such as soul theft and sorcery and invoke complex detailed visions from which the word ‘trip’ arises, including specific socio-cultural motifs such as snakes and animistic visionary deities. Some of these can be hilarious, others frightening. Some can be profound, others frivolous or meaningless. Some can lead to messianic delusions and others to creative art, musical composition and scientific discoveries. Albert Hoffman has stated that Karry Mullis, who invented the polymerase chain reaction that is now identified to be the core of molecular biology techniques and essential for Covid-19 testing, told him he credited its discovery to his use of LSD in his student days where he synthesised LSD. It was reported that he was actually coming down from a trip when the idea struck him. We are dealing with an agent invoking as many diverse features as existence can provide. The critical issue underlying this retinal carnival of experiences is how it can reveal underlying experiential knowledge difficult or impossible to gain through any other route.

Their political liberalism and nature-relatedness dimensions have been confirmed (Nour et al. 2017, Lyons & Carhart-Harris 2018).  Nearly nine hundred participants provided information about their naturalistic psychedelic, cocaine, and alcohol use, and answered questions relating to personality traits of openness and conscientiousness, nature relatedness, – “I am not separate from nature but part of nature” – and political attitudes. Participants also rated the degree of ego dissolution experienced during their “most intense” recalled psychedelic experience. Analysis revealed that lifetime psychedelic use (but not lifetime cocaine use or weekly alcohol consumption) positively predicted liberal political views, openness and nature relatedness, and negatively predicted authoritarian political views, after accounting for potential confounding variables. Ego dissolution correlated significantly with these effects.

Psychedelics clearly have political and revolutionary implications that can lay siege to traditional cultural values. It is admitted that the initial wave of repression of psychedelics was political in nature in response to a social movement rejecting the core tenets of a consumer society polarised between materialistic exploitation and religious and sexual conservatism. Fifty three years later, we find ourselves only moderately emerging from a period of repression lasting half a century, still tightly regulated, so as to be applicable only to scientific studies, largely on pathological conditions of depression and terminal illness, or direct scientific inquiry but not for the betterment of sane and healthy people.

There is a deep parallel between the Catholic repression of gnostic elements in the Inquisition that arose ultimately from cross fertilisation of ideas during the Crusades, and of the witch hunts against older spiritual beliefs centred around the ancient European Goddess whose practices Christianity replaced and the reaction to the social values emerging from psychedelics in the 1960s.

The same repressive end result as the middle ages Christian repressions of dissent occurred when LSD become popularised and suddenly, because it had not yet become illegal, huge quantities of very pure acid flooded into rock culture, by devoted underground chemists not seeking financial rewards but for the “common good”, celebrated by the Beatles’ “Tomorrow Never Knows” citing Leary’s Bardo Thodol, and “Lucy in the Sky with Diamonds”, while on the East Coast of the US, Timothy Leary was pronouncing “turn on, tune in and drop out” and on the West Coast, the Grateful Dead, playing “Dark Star” on acid, the Electric Kool-aid Acid tests and the Merry Pranksters, were blowing young peoples minds, while the infectious ethic of free love was shredding conventional sexual morality.  This blew the cover on just how seriously the political and revolutionary implications of psychedelics were laying siege to traditional cultural and particularly commercialistic political and religious values.

In a commentary confluent with Symbiotic Existential Cosmology's gradations of primal subjectivity, Leary said:

There are as many levels of consciousness as there are anatomical structures in your body for receiving and decoding energy. The five most important levels of consciousness are sleep, symbol, sense, cellular awareness, and molecular consciousness (Timothy Leary 1966 Turn on, Tune in and Drop Out)

Despite the fact that many of these events passed safely without incident, that LSD didn’t split peoples chromosomes, that groups of people hadn’t stared at the sun until they went blind, by the mid-1960s the backlash against the use of LSD and its perceived corrosive effects on the values of the Western middle class resulted in governmental action to restrict the availability of psychedelics by making any use of them illegal. Both LSD and psilocybin were declared "Schedule One" substances. The governors of Nevada and California signed bills into law on May 30, 1966 and the rest of the world followed shortly after, fulfilling the dark ending of Huxley’s (1962) allegory in “Island”, in which the people of Pala consume yellow mushrooms which they call “moksha” to induce visionary states, but are in the end subjected to a military takeover by a neighbouring conservative religious culture. The picture hardened with the case of Charles Manson. The prosecution contended that, while Manson never directly ordered the murders, his ideology constituted an overt act of conspiracy.

However that didn’t stop consumption of psychedelics, which have remained an underground transformative staple at music festivals, forming the entheogenic ^[33] counterpoint to MDMA’s entactogenic love-in experience in the rave party scene. Entheogen (see Ott 1993) is a term that, by its own meaning infers that deity emerges from the sacrament rather than vice versa, confirming the overwhelming impression from this class of agents that they have transcendent dimensions. Stanislav Groff coined the term “holotropic” ^[34], to cover wholeness seeking in all its forms from experiencing the totality as in the mind at large to peri-natal experiences of a physical rebirth struggle.

But repressive legislation of the war on drugs has still had a mind-numbingly counter-productive effect. People are incarcerated for long periods for simple possession of psychedelics. For four decades they were effectively eliminated from scientific knowledge, or assessment. Society as a whole has had almost no opportunity to figure out what role these profoundly transformative agents have in world culture, despite the fact that the natural entheogens have been used for millennia for spiritual and therapeutic purposes in every culture that has consumed them. This means that the role of entheogens has until subtly in the 21st century, been suppressed entirely by the very world societies that have claimed to be the pillar of scientific enlightenment. At the same time, while psychedelics continue to be used devotedly by an underground network of devoted psychonauts, they tend to be trivialised as mere entertainment. Their potential impact on society’s, and the planet’s future, remains occluded as an illegal recreational playground of no confirmed value, or significance.

Currently natural psychedelics are used scientifically in research, and particularly into therapy for pathological conditions of depression and terminal illness. They also continue to be used in some settings for religious and spiritual purposes such as Santo Daime, the Union Vegetale and the Native American Church, much as they have for centuries. Finally they are used  recreationally as an illegal but sometimes tolerated fringe activity, partly because they are easy to cultivate and almost impossible to eradicate. All of these uses create a gloss on the phenomenon which clouds its full potential. Recreational use tends to trivialise it and reduce it to the pursuit of pleasure. Spiritual and religious use tends to reinforce existing attitudes, from Christian doctrine to tribal sorcery and witchcraft.

Demonstrating just how complex the discourse on sacred mushrooms are, Andy Letcher in “Mad Thoughts on Mushrooms” (2007) cites three dominant discourses in a Foucauldian sense: (1) Psychotic where hallucinogens are perceived to induce psychosis, (2) Therapeutic, where they are seen to have therapeutic value when confined to the clinic, and (3) Prohibitionary when they escape the clinic and should be suppressed by the full force of the law. In this view the pendulum swung firstly from (1) –> (2) –> (3) and is now swinging back towards (2) while still remaining a discourse of containment and marginalisation on the part of academics, out of realistic fear of a regulatory backlash.

Running counter to these three dominant discourses are four resistive discourses: (4) Recreational ,in which breaking the bounds is advocated both for the pleasure these experiences brain and for the pleasure of transgression against the imposed restrictive order;  (5) Psychedelic, for their ability to reveal or make manifest the hidden dimensions of the self; (6) Entheogenic, stemming ultimately from Gordon Wasson's religious experiences on mushrooms in a group conference in which Carl Ruck coined the term, meaning  “generating God within,” or “becoming God within”, and finally; (7) Panpsychic / Animistic, that is, they evoke, not theophany but animaphany. Here, mushrooms are not regarded as altering, consciousness but as adjusting what it is possible to perceive, and therefore the spirits and beings occasioned by mushrooms are neither hallucinations nor some aspect of the self, but beneficent discarnate entities with whom the practitioner attempts to forge relationships. They thus tend to evoke states of consciousness in which the consciousness of animals and plants, to other, e.g. spirit entities, or the mind at large, are experienced.

David Luke (2020) also lists a diverse collection of anomalous experiences spanning the transpersonal and psychedelic including (a) synesthesia, (b) extra-dimensional percepts, (c) out-of-body experiences, (d) near death experiences, (e) entity encounters including (mythological beings, chimeras, extraterrestrials, angels and celestial beings, semi-divine beings such as Jesus or Buddha, demons, monsters and beings of death), (f) interspecies communication, (g) possession, and (h) telepathy, precognition, clairvoyance and psychokinesis. DMT is particularly prone to spirit images, as illustrated in “Ayahuasca Visions” (Luna & Amaringo 1991). Shaun Smith (2015) notes the contrasting neurotheological view of theistic phenomena being explained through neurobiology with the theoneurological view of Robert Strassman (2001,2014) in which God or deity is able to alter neurobiology through "the spirit molecule" DMT. Not all of the examples cited by Luke are psychedelic induced and several of the psychedelic examples  echo in greater intensity and embellishment those in dreaming and hypnagogic imagery, in which the subject finds themselves immersed in perceived situations and encounters with entities that evaporate with arousal. These can be considered as visions at the periphery of the nierika portal.

At an extreme, we have Terrence McKenna's far-fetched statement identifying mushroom spores, rather than the cosmological consciousness and visions they evoke, as galactic entities of enlightenment spread across the universe:

“I am old, older than thought in your species, which is itself fifty times older than your history. Though I have been on earth for ages, I am from the stars. My home is no one planet, for many worlds scattered through the shining disc of the galaxy have conditions which allow my spores an opportunity for life.” (McKenna 1993 210).

There is a fine line between this kind of statement, which most people will find unbelievable fantasy, and a much more widely held, meaningful and validating discourse that the mushroom experience can evoke a universal consciousness that may inform in meaningful, or even urgent ways, the ensuing direction a person’s life needs to take.

Yaden et al. (2021) call for epistemic humility ^[35] regarding psychedelics and the hard problem: “We conclude by calling for epistemic humility regarding the potential for psychedelic research to aid in explaining the hard problem of consciousness while pointing to ways in which psychedelics may advance the study of many specific aspects of consciousness.” Epistemic humility is applying a rule that we can’t assess reality in itself – the very core of the psychedelic experience of “ultimate reality” unless we do so with the filters of the doors of perception slammed shut!

How they can say this, while holding the purse strings of the dominant therapeutic discourse, is extremely  troubling.

Their reasoning is not really about psychedelics but about the confounding nature of the hard problem: “The hard problem of consciousness is currently not scientifically answered, and it is not clear that a scientific answer is even possible, which is why it is called “a hard problem.” They then note that the hard problem is often described in terms of the “explanatory gap” (Levine, 1983), noting: “This phrase may be an understatement – there is far more than a gap, but rather a yawning chasm between our current scientific understanding and the prospect of explaining the hard problem of consciousness.” This is the chasm of the psychedelic experience in which materialistic science fails the test because it can’t explain conscious volitional will either. To use the term scientific in this way is a contradiction to the meaning of science ^[36] as a word which embraces knowledge more generally than physical investigation.

Although psychedelics may not of themselves automatically solve the hard problem, the psychedelic experience cited in this article has led to the cosmological description in this article, which does provide a concise solution to the hard problem. The problem is not with psychedelics, but the assumptions of materialism and physicalism of the current dominant fashion in scientific exploration of brain states. This is confirmed by their statement that: “it is not clear that a scientific answer is even possible”. This highlights what the author sees as a dangerous development in psychedelic research, where the agent most startlingly evoking subjective changes to experience is being filtered through a materialistic filter by the very academics acting as the mediators of therapeutic use and research into these agents. This looks to be an example of the dominant discourse in therapeutic use being applied by the mediators of the research to undermine both the psychedelic and entheogenic resistive discourses and the validity of psychedelics outside the laboratory as agents of cosmological investigation.

At the opposite extreme, Bernardo Kastrup (2013), proposes analytical idealism as an alternative, the notion that reality is essentially mental and inseparable from mind:

The scientific method allows us to study and model the observable patterns and regularities of nature … But our ability to model the patterns and regularities of reality tells us little about the underlying nature of things.

Mind is the medium of everything that you have ever known, seen, or felt; everything that has ever meant anything to you. Whatever has never fallen within the embrace of your mind, might as well have never existed as far as you are concerned. Your entire life and universe – your parents and the people you love, your first day at school, your first kiss, every time you were sick, the obnoxious boss at work, your dreams and aspirations, your successes, your disappointments, your worldview, etc. – are and have always been phenomena of your mind, existing within its boundaries.

Kastrup (2016, Kastrup & Kelley 2018), has  taken the position that  psychedelics are precisely what the term indicates –  mind manifesting, and sought to contend that psychedelics manifest the  idealist principle and that the commentary on the emerging psychedelic research, even by the papers' authors is biased to justify  a materialist interpretation of the results. Kastrup cites the research of Carhart-Harris and others showing reductions in activity to be evidence for the basis of "mind-expansion" not being physical in origin, particularly when accompanied by mystical peak experiences and that accompanying research such as the homological scaffolds indicating are of marginal value added to ensure a physicalist interpretation of psychedelic brain states, when the reality of reduced activity indicates they are mind states per se. David Nutt (2023) argues that we don’t need to adopt an untestable metaphysical worldview to explain the subjective richness of psychedelic experiences.

The position of Symbiotic Existential Cosmology agrees that conscious experience is primary, but acknowledges that psychedelics are chemical neurotransmitter analogues means that the brain is critically involved in the psychedelic state and that the universe is necessary for the psychedelic state to occur and for our biological survival as well, and that a reduction in default mode activity is consistent with peak experiences, and increasing decoherence of activity correlates both with a reduction in coherent power and with increasing inter-connectivity between brain regions.

Symbiotic cosmology does not conform to the philosophical classification in Yaden et al. (2021) into 3 broad categories: materialist, dualistic, and monistic. Symbiotic Existential Cosmology is a form of interactive complementary aspect monism with is implicitly panpsychic so it is not materialist, but neither is it simple dualism or monism. It is a description based on complementarity extending the  wave-particle complementarity of quantum physics to a cosmological subject-object complementarity in which the two complements cannot be separated in a dualism, just as wave and particle aspects are alternate manifestations of a single quantum identity which cannot be separated, yet it is not monistic because it is a complementarity, not simply a monistic theory of a cosmic mind alone.

Yaden et al. (2021) attempt to justify their conclusion by citing four authors, (Blackmore, 2013; Letheby, 2015; Bayne and Carter, 2018; Johnson, 2020). A viewing of Susan Blackmore’s 2020 Tucson talk however makes clear that she considers the debate whether psychedelics reveal new discoveries or merely cause distortions of the psyche will only be revealed by the new wave of psychedelic research which I support. Bayne and Carter do not treat the hard problem as such, but critique the idea of layers of consciousness and the simplistic notion that psychedelics per se invoke a "higher" form of consciousness, or even that what psychedelics do reveal can be classified in terms of one-dimensional layers, with which this article again agrees. In fact the notion of the nierika advanced in this article is more like a cyclonic vortex having a multitude of divergent experiential features, some illusory and some informative, with the centre of the cyclone providing a portal to deeper forms of experience which may have abstract or cosmological value. This is not a linear indexed description and the subjective process of entering such states requires going “deeper into the abyss” of unconstrained consciousness rather than any simplistic view of “higher" conscious states.

Link Swanson (2018) provides a comprehensive review of theories of the psychedelic state, from the first discovery of mescalin, through the psychotomimetic era of researchers experiencing its effects, but using their experiences to treat the experience as a form of reduced control shared by psychopathic states, to  filter theories of Huxley and others and then on to more recent theories as outlined above, as well as ones we shall explore in the brain consciousness section such as integrated information theory and  Friston's free energy principle:

He notes that Friston's theory can also be interpreted in terms of psychedelics:

In one model of global brain function based on the free-energy principle (Friston, 2010), activity in deep-layer projection neurons encodes top-down inferences about the world. Speculatively, if deep-layer pyramidal cells were to become hyperexcitable during the psychedelic state, information processing would be biased in the direction of inference—such that implicit models of the world become spontaneously manifest—intruding into consciousness without prior invitation from sensory data. This could explain many of the subjective effects of psychedelics (Muthukumaraswamy et al., 2013).

Summing up he sees common threads in these perspectives, in a view that's sees psychedelic research as an "acid test" of grand unified theories of brain function:

The four key features identified in filtration and psychoanalytic accounts from the late 19th and early 20th century continue to operate in 21st-century cognitive neuroscience: (1) psychedelic drugs produce their characteristic diversity of effects because they perturb adaptive mechanisms which normally constrain perception, emotion, cognition, and self-reference, (2) these adaptive mechanisms can develop pathologies rooted in either too much or too little constraint (3) psychedelic effects appear to share elements with psychotic symptoms because both involve weakened constraints (4) psychedelic drugs are therapeutically useful precisely because they offer a way to temporarily inhibit these adaptive constraints.

Psychedelic drugs offer a unique way to iteratively develop and test such big-picture explanatory frameworks: these molecules can be used to probe the links between neurochemistry and neural computation across multiple layers of neuroanatomy and phenomenology. Meeting the challenge of predicting and explaining psychedelic drug effects is the ultimate acid test for any unified theory of brain function.

Letheby invokes three descriptions of psychedelic experience: (1) Yes – by inducing mystical states of consciousness, psychedelics afford direct knowledge of supernatural, transcendent dimensions of reality (the entheogenic resistive discourse). (2) No – since materialism or physicalism is true, there are no transcendent realities, and psychedelics just cause compelling hallucinations or delusions (the dominant hallucinogenic and psychotomimetic discourse). (3) Neither – a third view that psychedelics can afford genuine epistemic benefits, even if materialism is true and there is no transcendent reality. Rather than helping us learn new factual information, psychedelics then allow us to understand or appreciate already-known (or otherwise knowable) facts in deep, vivid, affectively and motivationally significant ways. This is again taking a position with implicit dependence on a materialistic viewpoint, while conceding psychedelics may reveal epistemic benefits, so it is confining its own conclusion by its founding assumption of materialism. The symbiotic cosmology is again neither simply an old view, nor is it materialistic. It has resemblances to Upanishadic thought dating back to 700 BC, but it is not a monist theory and is based extensively on detailed investigation of quantum reality, chaotic systems, evolutionary origins of membrane excitability and neuroscience in a novel cosmological description induced by a mushroom experience.

Matt Johnson (2020) , who is both a cited reference and also a co-author of Yaden et al., takes issue with the very concept of consciousness itself as “sloppy”, noting that “one might question whether the different concepts associated with consciousness should even be identified under a singular construct.” This has some validity, for example the subjectivity of consciousness is distinct from its features of coherent attentiveness and from the distinct nature of specific qualia and with notions of self-consciousness and the cognitive mind of thoughts and verbal processes. But consciousness is all these things in a coherent concept, integral to our existential condition, so sloppy is derogatory and unscientific. Consciousness is our most enduring and all-encompassing arena of experience. It is not sloppy! It is fundamental and essential!

In dealing with the hard problem, Matt says "Explaining the existence of experience itself, which is the “hard problem” of consciousness, is at present something that appears outside of the realm of empirical science. Some philosophers and scientists have disputed the existence of this hard problem, but I do not think the problem should be dismissed”.

But empiric ^[37] means “experience”, as does experiment, and there is abundant evidence coming also out of the Johns Hopkins team attesting to experiments confirming experiential observations of quantum change involving “ultimate reality” (Griffiths et al. 2018, 2019). These represent statistical evidence, just as the moksha epiphany does. The claims about consciousness and the experiments on mystical states are thus presenting mutually-contradictory academic reasoning. A critique is made of psychedelic states as having no evidential value based on a preamble assessment that the hard problem is empirically unscientific. This contradicts the definition of empirical, whose root lies in subjective accounts, by invalidating veridical reporting. The legal system depends centrally on veridical evidence.  It is integral to interrogating the subjective condition sine qua non. So the materialist assumption is empirically counterproductive.

In summing up Johnson states: “I suggest that psychedelic science has, to date, not provided substantial advancement in our understanding of any of these concepts [easy or hard] purported to relate to consciousness”.  This is a very pessimistic and confounding view for research in psychedelic science that is showing real promise of cultural benefit. Given a priori assumption of the hard problem’s quasi-unscientific status, it is hard to see how substantial advancement could ever occur on either the role of psychedelics as an informant of the nature of reality, or the status of the hard problem itself. This again underlines the fallacy of academic reasoning that is subservient to the materialistic hypothesis to the extent that no other type of cosmology can be entertained and no empirical result can be gained except by objective means. But biogenic/panpsychic cosmology is biologically precise and seamlessly consistent with multiple steps of the evolutionary pathway so it is a meticulous natural description, consistent with quantum and dynamical physics and with neuroscience. Therefore such reasoning is integral to the scientific discourse.

This error of empiricism applies critically to analysis of the symbiotic cosmology because the principal evidence for it has to come veridically from first person reports. We can’t directly see the consciousness of others, so it is impossible to see the consciousness in simpler life forms or physical processes directly. One can rightly conclude that panpsychic cosmology is the only class of cosmology in which conscious volitional intent is real, so by the veridical test of validity Occam's razor cuts for panpsychism as a necessity.  This is because volitional will implies the conscious mind affect the physical brain and hence the physics of the universe. Therefore mind is a complementary aspect of the physical universe. To a materialist this appears to be adding something that is unnecessary but from the veridical perspective it is essential, because materialist cosmology does not admit conscious volitional will. The inescapable solution is quantum panpsychism.

The problem for mechanists is that intervening states of consciousness are largely inaccessible. But organismic consciousness is evident in humans and mammals generally and is accessible also in other forms in deeply unbounded mental states of meditation or psychedelic transcendence, in which organismic consciousness is asymptotically convergent to an unbounded abstract state identifiable to the subject with the mind at large. Thus the two accessible avenues for scientific discovery are the organismic state and the mind at large. This is why the role of psychedelics becomes sine qua non optimal. If you take them out of the equation, you really have only sparse states of meditative vigil and the dreaming state. Thus to discount the importance of psychedelics is futile and counterproductive.

Yaden et al. nevertheless do concede the potentiality of psychedelics to address the hard problem: “The scientific study of psychedelics and consciousness, in all of its meanings, is still nascent. While we cannot, at present, see any clear scientific traction resulting from the intersection of psychedelics and the hard problem of consciousness, we are open to the possibility of being proven wrong.” This article now of full book length monograph articulates a strategic response.

Moreover several researchers state that the subjective experience of psychedelics, not just their physiological or neurochemical attributes are potentially pivotal in their beneficial effects. Yaden and Griffiths (2020) conclude that:

Based on the results from experimental studies of moderate to high dose psychedelics we believe that the case for subjective effects playing a major role in enduring beneficial effects is compelling. Across a number of studies, when the intensity of the subjective psychedelic effect is controlled, certain subjective effects predict desirable outcomes. Underlying neurobiological mechanisms are likely necessary but not sufficient to confer full and enduring beneficial effects.

Johnson (2022) in reviewing Chris Letheby’s “Philosophy of Psychedelics” (2021) concurs with both this viewpoint and the central role of a “natrualism” that leads to a more supernatural worldview that is not just a comforting delusion:

Letheby argues based on the evidence that subjective experience does play a causal role in long-term benefit. This is supported by studies showing that the mystical-type nature of the experience can predict how therapeutic or otherwise positive the sessions will be in the long term, providing information in some cases that is above and beyond the predictive value of the dose itself or the participants’ ratings of drug intensity. Letheby posits that the subjective experience causes lasting therapeutic benefit independent of whether the session involved or left patients with supernatural ideation.

Letheby argues, successfully in my opinion, that the core mechanism of psychedelic therapy benefit is not the provision of a comforting delusion, for example, one in which people shift to a more supernatural worldview. He argues instead that “naturalism” is the lens through which the key mechanisms of psychedelic therapy can be understood by combining empirical evidence across multiple disciplines through scientific reasoning. … Letheby believes that changes in self-representation are the missing link connecting mystical experiences to therapeutic outcomes

Safron & Johnson (2022) examining both present trends and future possibilities, note the relationship between psychedelics and natural dreaming states:

While we agree that some psychedelic experiences may be understood as a transient form of psychosis, we would add that the same thing can be said about dreaming.  … Intriguingly, while the mechanisms of action for both classic and non-classic psychedelics vary, there appear to be multiple pathways for inducing states in involving greater tendencies for imagining novel scenarios under states of more vivid and intense conscious experience, potentially contributing to the phenomenology of a “waking dream.” While a detailed exploration is beyond the scope of the present discussion, partially overlapping effects from classic psychedelics, anticholinergic drugs (e.g. tropanes), kappa- receptor agonists (e.g. Salvia divinorum), and NMDA-receptor antagonists (e.g. dextromethorphan, or ketamine) suggest that anything that disrupts global integration processes while maintaining (potentially elevated) consciousness has the potential to induce profoundly altered states, and potentially altered traits.

They conclude the following about the future of psychedelics as a discovery process in the context of formative quantum change experiences:

While we must continue to seek the most powerful and encompassing models we can find, we must also avoid the temptation of assuming that a single account will be adequate for explaining the diverse range of effects associated with different psychedelics under different sets and settings. Some may suggest that the mystic nature of psychedelic experiences reveal the truth of a perennial religion, and perhaps even the veracity of metaphysical principles that some would consider to be supernatural (Timmermann et al., 2021). Others might conclude that egoless experiences reveal that selves were illusions all along (Millière et al., 2018; Milliere and Metzinger, 2020), so pointing to the veracity of some schools of Buddhist thought.

In particular Timmermann et al. (2021) cite a move away from physical materialism:

Results revealed signifcant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. With the exception of fatalism, these changes endured for at least 6 months, and were positively correlated with the extent of past psychedelic-use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience.

On the other hand, Millière et al. (2018) cite a diversity of selfless states in both psychedelic and meditative experiences:

We suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-related thoughts and mental time travel, and embodied aspects rooted in multisensory processes, may be differently affected by psychedelics and meditation practices.

Milliere and Metzinger, (2020) go further and address the foundational question of the link between subjective consciousness and self-awareness in states of ego-dissolution:

Let us call the general claim that some basic form of self-consciousness or sense of self is ubiquitous to all conscious experiences, the Ubiquity Thesis.

For example, the subjective effects of certain psychoactive drugs, and particularly those of classic psychedelic drugs such as LSD, psilocybin, or 5-MeO-DMT, present a special interest for the assessment of the Ubiquity Claim. Indeed, these drugs are known to have dramatic effects on self-consciousness, and some reports even suggest that they might temporarily suppress any form of self-consciousness – a phenomenon known as ‘drug-induced ego dissolution’ in the scientific literature (Nour & Carhart-Harris, 2017).

In his article “Being for no-one: psychedelic experience and minimal subjectivity”, Chris Letheby (2020) asks whether reports of drug-induced ego dissolution provide us with solid evidence against so-called “subjectivity theories of consciousness”, according to which phenomenal consciousness constitutively involves a minimal form of self-awareness or “subjectivity”. Letheby argues that the alternative notion that putatively selfless states of consciousness associated with depersonalization might not in fact be phenomenally conscious at all, does not work well for reports of selfless states of consciousness induced by classic psychedelic drugs, particularly potent and fast-acting psychedelics such as DMT and 5-MeO-DMT, because there is little doubt that the relevant states are phenomenally conscious.

Miguel Sebastián (2020) argues that given a proper understanding of a minimal form of self-awareness that he labels “Perspectival First-Person Awareness” (or PFP-awareness), it becomes apparent that even putatively selfless states of consciousness do not entirely lack self-awareness. PFP-awareness is anchored in a non-conceptual, identification-free self-attribution that defines the ultimate origin of the first-person perspective of conscious experience. … He concentrates on the phenomenology of states induced by psychedelic drugs, meditation and dreams, as they have been claimed to present the biggest threat to the Ubiquity Thesis. First, he argues that although there are good reasons to think that some forms of self-awareness that typically accompany our ordinary experience can be compromised in altered states of consciousness, this does not mean PFP-awareness is absent in these states.

Fig 40b: The PEMM Tristinction (Sjöstedt-Hughes 2023).

Sjöstedt-Hughes (2023) sees psychedelic states as trisecting with both metaphysics and mystical states, noting that psychedelic-induced metaphysical experiences should be integrated and evaluated with recourse to metaphysics in which one sees the potential bridge between reason-based philosophy and practical therapy — with psychedelic-assisted psychotherapy there is the potential and mutually beneficial fusion of philosophy with practical science.

Thus we see overall that paradoxically, the psychedelic experience, although being regarded as a highly exotic mental state, also has foundational insights about the universality of both subjective consciousness and self-consciousness.

The thesis in this monograph takes a form of a scientific investigation that sets up a verifiable framework to present a cosmology, consisting of interlocking biogenic, panpsychic and symbiotic aspects, scientifically accounting for the flowering of conscious life in the universe, that has components of discourse (2) that they are therapeutic, (5) that they reveal the self, (6) that they induce moksha and (7) in that this is not a theistic description of reality, but one in which consciousness as we know it is widespread in all eucaryote organisms, and in the mind at large through them, so that the animistic actually has a valid cosmological basis.

The Indigenous Psychedelic Dimension

Kerowen Cornelius (2023) reviewing the ethical implications of the scientific explosion of interest in psychedelics as therapeutic tools, for indigenous communities, who have a long history of sacred and medicinal use, cites Yulia Celidwen’s efforts to form a consortium to address these concerns:

Over thousands of years, Indigenous communities have cultivated relationships with and accumulated knowledge on psychedelics such as psilocybin mushrooms, the Amazonian botanical brew ayahuasca, and the West African shrub iboga. More recently, psychedelics have exploded onto the stage of Western science. Clinical trials of these substances in the past 15 years have produced remarkable results in the treatment of depression, addiction, post-traumatic stress disorder, and end-of-life anxiety. Media buzz has generated a rush to legalize their therapeutic use, catapulting the global psychedelic drugs market from $3.8 billion in 2020 to an estimated $11.82 billion by 2029. But both Native and non-Native critics say the industry is ignoring the emotional, cultural, and ecological harms it is causing the Indigenous peoples who originated psychedelic medicine.

Fig 40c: Indigenous models of consciousness exemplified by animistic individual consciousness as the embodiment of global consciousness and its nested types (Lorencova & Trnka 2023).

Many Indigenous Nations are concerned they are being excluded from psychedelic spaces that extract their knowledge, threaten what they see as their intellectual property, and detach their medicines from their spiritual contexts, the paper finds. In addition, international demand is driving people to unsustainably harvest iboga, the plants used to make ayahuasca, and the hallucinogenic cactus peyote. Meanwhile, burgeoning retreat centers that offer psychedelic therapy often charge thousands of dollars for experiences that culturally appropriate Indigenous traditions yet share few benefits with these often impoverished communities.

Celidwen et al. (2023) in Lancet notes:

The resurgence of Western psychedelic research and practice has led to increasing concerns from many Indigenous Nations regarding cultural appropriation, lack of recognition of the sacred cultural positioning of these medicines, exclusionary practices in research and praxis, and patenting of traditional medicines. Indigenous voices and lead- ership have been notably absent from the Western psychedelic field currently widely represented by Westerners. An Indigenous-led globally represented group of practitioners, activists, scholars, lawyers, and human rights defenders came together with the purpose of formulating a set of ethical guidelines concerning traditional Indigenous medicines current use in Western psychedelic research and practice.

A global Indigenous consensus process of knowledge-gathering was engaged which identified eight interconnected ethical principles, including: Reverence, Respect, Responsibility, Relevance, Regulation, Reparation, Restoration, and Reconciliation. A summary of the work is presented here with suggested ethical actions for moving forward within Western psychedelic research and practice spaces.

The first and foremost of these is reverence for nature and the diversity of life.

Reverence for Mother Nature

Traditional Indigenous medicine is an ethical, ecosystem-protective, and holistic system of medicine that interconnects humans and the environment. A sense of reverence for the planet guides all relationships, as well as a commitment to preserve all life. Traditional Indigenous medicine from a systems and relational perspective prompts insight for compassionate living and awareness of collective care to sustain the well-being of the medicines themselves as well as all future generations.

Concrete problem

Western psychedelic research and practice has its roots within traditional Indigenous medicines systems yet have turned ‘kincentric’ approaches (treating all relationships, including medicines, as kin) to anthropocentric approaches (human-centric). This anthropocentric approach fails to adequately reference or acknowledge Indigenous paradigms in Western procedures, thus expropriating Indigenous knowledges while separating the medicines from the context of their original environments.

Reverence-governed actions

The explicit acknowledgement of Indigenous Peoples and their traditional medicines and practice as the root of Western psychedelic research and practice; Western psychedelic research and practice references Indigenous concepts of reverence as guided by local Indigenous scholars and communities; the Western psychedelic research and practice community takes action to support Indigenous Nations protection of the at-risk land and natural environments where these traditional Indigenous medicines originate; support Indigenous Peoples in their fulfillment of the right to life and of the right to live in peace on ancestral lands.

Four later sections in this work – Psychedelic Agents in Indigenous American Cultures , Shipibo: Split Creations and World Trees, Meso-American Animism and the Huichol and Redemption of Soma and Sangre in the Sap and the Dew, deal in detail with indigenous use as a pivotal heritage of psychedelic knowledge.

The Devil’s Keyboard: Sanity, Hallucinations and Visions in the Sappy, Conscious Human Brain

The mammalian brain is not just a seething storm of electrical excitations reverberating through neural networks, but is driven at all stages through the intervening sappy connections that neurotransmitters, neuromodulators and receptors provide between one neuron and the next in the passage of such excitations as they develop strange attractors and other dynamic phenomena of cerebral processing. Neuromodulators do not just affect our moods but are key players in major life decisions. We can better understand these by examining the way psychoactive agents act on many receptors at once, like chords, sequential melodies, or extreme dissonances, enhancing some receptors and depressing the activity of many of others, leading to unpredictable and sometimes uncontrolled consequences and the ways human society, for better or worse, chooses to use these substances to ensure “sanity” or achieve insight.

Fig 41: The Devil’s Keyboard Plot of receptor binding in pKi of major classes of psychoactive drugs, from antipsychotics through antidepressants and antihistamines to entactogens and entheogens, generated using the PDSP database (http://pdsp.med.unc.edu/dataMining/pdspConfigGraph.php and PLoS ONE 5/2 e9019 1-17). Five key classes of modulatory neurotransmitters, serotonin, acetyl-choline, dopamine, histamine and nor-epinephrine, cross indexed against key classes of psychoactive agents – typical and atypical antipsychotics, antihistamines, tricyclic and SSRI , SNRI antidepressants, entactogens, and psychedelics for receptor activity as inverse agonist, antagonist, agonist and super-agonist.  An inverse agonist binds to the same receptor-binding site as an agonist and not only antagonises the effects of an agonist but, moreover, exerts the opposite effect by suppressing spontaneous receptor signalling (when present). If we look across receptors and the various molecules used to alter the flow of these pathways, we begin to gain an understanding of how psychoactive molecules in the sappy biochemical brain activate positively and negatively  the “Devil’s keyboard”  of receptors bound to by these molecules, many of which act on several receptors at once.

Two key primary agents are the amino acid glutamate and the closely related gamma-amino-butryic acid (GABA) which form the excitatory and inhibitory components driving the oscillations of the central pathways for information processing. Both these two are primal amino acids found in the Murchison chondrite and scattered in cosmic gas clouds, so they are not just a quirk of biology. These have both ionopore receptors, which can excite or inhibit electrical oscillations and slower longer-acting metabotropic receptors which modulate overall activity on a contextual basis by signalling to protein pathways interacting with the nucleus and adjacent receptors.

Along with these two, there are several additional simple molecules, many amines, such as dopamine, nor-epinephrine, serotonin (5OH-tryptamine) and complementing them, acetyl choline that, like glutamate and GABA, have an ancient origin as social signalling molecules in single-celled eucaryotes and which also have both ionotropic and metabotropic receptor versions. The amine and choline pathways also form the complementary components of the bodily adrenergic and cholinergic autonomic nervous system. Other receptors have more complex substrates such as the polypeptide endorphins of the opioid receptor.

Antipsychotics – Agents of Darkness

At the negative extreme a dark, diabolical side of psychotherapeutic agents, is presented in the form of antipsychotics. Although an affront to human autonomy, these are admittedly less damaging than a long line of previous diabolical and devastating treatments for key psychotic conditions, from schizophrenia to mania and depression.

The treatment of mental illness has a long tortured history. Lobotomy was one of a series of radical invasive physical therapies that signalled a break with a psychiatric culture of therapeutic nihilism that had prevailed since the late nineteenth-century. The new "heroic" physical therapies devised during this experimental era, including malarial therapy for general paresis of the insane, deep sleep therapy, in which the patients were put into long deep coma, insulin shock therapy, in which patients were repeatedly injected with large doses of insulin in order to produce daily comas over several weeks, cardiazol shock therapy and electroconvulsive therapy, both of which induced seizures, and finally prefrontal lobotomy helped to imbue the then therapeutically moribund and demoralised psychiatric profession with a renewed sense of optimism in the curability of insanity and the potency of their craft at the cost of a complete loss of autonomy and identity by the vulnerable afflicted.

Patients of lobotomy were, immediately following surgery, often stuporous, confused, and incontinent. Some developed an enormous appetite and gained considerable weight. Seizures were another common complication. Emphasis was put on the training of patients. Following the operation, spontaneity, responsiveness, self-awareness, and self-control were reduced. The activity was replaced by inertia, and people were mostly left emotionally blunted and restricted in their intellectual range. Walter Freeman ( the father of the Walter Freeman who proposed strange attractors in brain states) described one 29-year-old woman as being, following lobotomy, a "smiling, lazy and satisfactory patient with the personality of an oyster" who could not remember his name and endlessly poured coffee from an empty pot. The originator of the procedure, Portuguese neurologist António Moniz, shared the Nobel Prize for Physiology or Medicine of 1949 for the "discovery of the therapeutic value of leucotomy in certain psychoses", which has been the subject of continuing controversy. Lobotomy has become a disparaged procedure, a byword for medical barbarism and an exemplary instance of the medical trampling of patients' rights.

Fig 42: (Left) Freeman stated that this woman was schizophrenic and all that could be done was to turn her into a 'veritable household pet’. (Centre) Lobotomy procedure and deep brain stimulaion.  (Right) Electroconvulsive therapy.

Katie Serena (2022) notes: Rosemary Kennedy JFK’s sister suffered oxygen deprivation during birth. As a child, she was unable to keep up with her siblings. Her lack of inclusion often caused her to experience “fits,” which were later discovered to have been seizures or episodes relating to her mental illness. She was also reportedly causing trouble for the nuns in the American convent. According to them, Rosemary was caught sneaking out at night to go to bars, where she met strange men and went home with them. .Joe Kennedy was grooming his two oldest boys for careers in politics. Because of this, Rose and Joe worried that Rosemary’s behavior could create a bad reputation not just for herself but for the whole family in the future, and eagerly searched for something that would help her. Despite the ominous stories about the lobotomy, Joe needed no convincing to sign Rosemary up for the procedure, as it seemed like this was the Kennedy family’s last hope for her to be “cured.” Years later, Rose would claim that she had no knowledge of the procedure until it had already happened. No one thought to ask if Rosemary had any thoughts of her own. In 1941, when she was 23 years old, Rosemary Kennedy received a lobotomy. During the procedure, two holes were drilled in her skull, through which small metal spatulas were inserted. The spatulas were used to sever the link between the pre-frontal cortex and the rest of the brain. Though it is not known whether he did so on Rosemary, Dr. Freeman would often insert an icepick through the patient’s eye to sever the link, as well as the spatula. Throughout the entire operation, Rosemary was awake, actively speaking with her doctors and even reciting poems to her nurses. The medical staff all knew that the procedure was over when she stopped speaking to them. Immediately after the procedure, the Kennedys realized that something was wrong with their daughter. Not only had the operation failed to cure her intellectual challenges, but it had also left her extremely disabled. Rosemary Kennedy could no longer speak or walk properly. She was moved to an institution and spent months in physical therapy before she regained normal movement, and even then it was only partially in one arm. Her family did not visit her for 20 years while she was shuttered away in the institution. It wasn’t until after Joe suffered a massive stroke that Rose went to go see her daughter again. In a panicked rage, Rosemary attacked her mother during their reunion, unable to express herself any other way.

After 2,500 operations, Freeman performed his final ice-pick lobotomy on a housewife named Helen Mortenson in February 1967. She died of a brain haemorrhage, and Freeman's career was finally over. Freeman sold his home and spent the rest of his days traveling the country in a camper, visiting old patients, trying desperately to prove that his procedure had transformed thousands of lives for the better. Freeman died of cancer in 1972.

Deep brain stimulation is an invasive process which surgically inserts a stimulating electrode into deep brain regions such as the striatum, nucleus accumbens, subcallosal cingulate and thalamus (Delaloye & Holtzheimer 2014), using an implanted device to marginally help patients with intractable depression, where no other treatment works: "Things got a little bit easier". Participating neurologist Helen Mayberg (Byrne 2023) notes: "In this process, we are using crude devices, we're sticking a wire into the brain. I hope I live long enough to see that people won't require a hole in their brain and a device implanted in this way. I often have a nightmare with my tombstone that kind of reads like, what did she think she was doing?" 150,000 people in the US have such operations for intractable Parkinsons. Metzger et al. (2023) have designed a functioning brain-computer interface (BCI) to enable a paralysed person to "speak" using an electrode grid over motor areas. Elon Musk (2019) has gained FDA approval for human studies of a BCI, implanted on the cortex (Paul & Singh 2023), which could detect motor signals to help people with paralysis, and also be used for patterned neuronal stimulation, but casual use carries surgical risks of irreversible brain tissue damage, infection, and scarring and acute ethical risks, with cyborg implications about the technologisation of human consciousness, as his design for $2000 entirely robotic brain surgery shows:

Musk has claimed Neuralink's device could be used for a range of therapeutic uses, to treat conditions like blindness, paralysis, depression. But he has also said that the eventual aim is to create a "general population device" that could connect a user's mind directly to supercomputers and help humans keep up with artificial intelligence. He has also suggested that the device could eventually extract and store thoughts, as "a backup drive for your non-physical being, your "digital soul." A video released in 2021 shows a monkey using the device to play the video game Pong with his mind and another from 2022 appeared to show a monkey typing on a computer "telepathically". In a current statement, a spokesperson for the FDA would only confirm that Neuralink was approved for an investigational device exemption (IDE) – the FDA process that allows a device to be used for clinical studies. The company would need to assemble an institutional review board to approve and monitor the research. The FDA's approval last week comes after the regulator initially rejected Neuralink's previous bid for clinical trials in 2022, citing "dozens of deficiencies" the company had to address before human testing, according to a report from Reuters. The company has killed more than 1,500 animals since it began experimenting on them in 2018. Employees told the news service the mortality rate has been higher than necessary due to Musk's gruelling development timeline.

By contrast with removing key and essential parts of the brain, electroconvulsive therapy is a psychiatric treatment where a generalised seizure is electrically induced to manage refractory mental disorders. Typically, 70 to 120 volts are applied externally to the patient's head. ECT is used, where possible with informed consent, as an intervention for resistant major depressive disorder, schizophrenia, treatment-resistant catatonia, prolonged or severe mania. A course involves multiple administrations, two or three times a week until the patient no longer has symptoms. Although it is claimed to be an effective treatment for depression, cognitive impairment is noticed after ECT. The American Psychiatric Association acknowledges: "In some patients the recovery from retrograde amnesia will be incomplete, and evidence has shown that ECT can result in persistent or permanent memory loss”, although it is disputed whether it causes permanent brain damage.

Antipsychotics are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of other psychotic disorders, including bipolar disorder, encompassing mania and depression. First-generation (typical) antipsychotics were introduced in the 1950s following on from the discovery of promethazine in the 1940s, which also has antipsychotic properties but is used as a first generation sedative antihistamine. Chlorpromazine, derived from promethazine originally as a sedative, was found to have neuroleptic properties in the early 1950s, and was the first typical antipsychotic. Second-generation (atypical) antipsychotics, were sought in the 1970s to address some of the side effects including mortality risk.

Fig 43: Thorazine (chlorpromazine) advertised both for aggressive mania (in men) “When the patient ashes out against ‘them’ Thorazine quickly puts and end to his violent outburst” and menopausal depression (in women). “To help you relieve the severe emotional upset of the menopausal patient – Thorazine”.  Centre Right: “Hallucinating and delusional? – Consider starting her on Haloperidol”. Right: Quetiapine advert 2009 .“Bipolar depression doesn’t just affect you – IT CAN CONSUME YOU”. Marketed as both an atypical antipsychotic and as an adjunct treatment for bipolar, or just persistent, depression, complete with five pages of legal disclaimers, including: High blood sugar and diabetes, Weight gain, potentially fatal neuroleptic malignant syndrome (fever, rigid muscles, confusion), “tardive dyskinesia (TD) uncontrollable movement of the face, tongue, or other parts of the body” which can become permanent, Cataracts, Suicidal thoughts, increased risk of death, ”Priapism"  2011 Seroquel TV Advert

Research has shown that use of any antipsychotic is associated with smaller brain tissue volumes, including white matter reduction and that this brain shrinkage is dose dependent and time dependent. The use of antipsychotics may result in many unwanted side effects such as involuntary movement disorders, such as tardive dyskinesia, gynecomastia, impotence, weight gain and metabolic syndrome increasing the risk of heart disease, stroke and type 2 diabetes.

To understand how antipsychotics affect receptors in the brain, it is highly informative to examine in detail their receptor binding properties to the major classes of psychoactive receptors.  A key core of antipsychotics involves antagonism at dopamine receptors, believed to be driving psychosis. As shown in detail in fig 41, the prototypical antipsychotic chlorpromazine is an antagonist at all five dopamine receptors D1-5. However, it also antagonises multiple serotonin receptors, all muscarinic acetyl-choline receptors M1-5, histamine H1, and all the α-adrenergic receptors for nor-epinephrine. This is an effect like an elephant sitting on the devil’s keyboard, flattening (a) mood (serotonin) (b) alertness (acetyl choline) (c) motivation (dopamine) (d) wakefulness (histamine) and (e) vigilance (nor-epinephrine). Its introduction has been ironically labeled as one of the great advances in the history of psychiatry.

Other typical antipsychotics are tuned to enhance the focus on antagonising dopamine receptors. Fluphenazine does this strongly with less anticholinergic effects. It is less prone to causing sedation, or low blood pressure but is associated with a higher frequency of movement disorders. Haloperidol does it  even more aggressively, by being an inverse agonist, particularly at D2 as well as D3, D4 (orange squares in fig 41).  However this extreme dopamine suppression causes Haloperidol to be the most prone to the rare neuroleptic malignant syndrome, a life-threatening reaction that can occur in response to antipsychotic medication, due to a sudden drop in dopamine levels, paradoxically causing glutamate over-stimulation. Neuroleptic, originating from Greek: νεῦρον (neuron) and λαμβάνω (take hold of)—thus meaning "which takes the nerve"—refers to both common neurological effects and side effects. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications include rhabdomyolysis, when damaged muscle tissue releases its proteins into the bloodstream, leading to heart and kidney damage or failure. All antipsychotics cause a significant increase in death rates when used for elderly dementia. In comparison with atypical risperidone, haloperidol was associated with a mortality ratio of 2.14 in one study and in another both typical and atypical (risperidone, olanzapine, quetiapine, and aripiprazole) had ratios of 1.6 against placebo, implying a death rate for haloperidol against placebo of over 3 times higher.

The atypical  antipsychotics, perhaps with the exception of risperidone, fare little better, although they were intended to reduce negative side-effects, and display the same warnings about the same spectrum of outcomes. Quetiapine suppresses  the same receptors as chlorpromazine and olanzapine is in addition an aggressive inverse agonist for serotonin receptors 5HT2a, b, & c blanking out emotional mood.

Antidepressants – Brave New World

The history of antidepressants is equally chequered. Monoamine oxidase inhibitors (MAOIs) were the first type of antidepressant developed. Monoamine oxidase is a generalised enzyme which clears the brain of any superfluous monoamine transmitters. Use of MAOIs typically requires diet restrictions and avoiding certain other medications because MAOIs can cause dangerously high blood pressure when taken with certain foods or medications, as noted in serotonin syndrome. MAOIs also affect other neurotransmitters in the brain and digestive system, causing additional side effects.

The next generation of anti-depressants were tricyclics. Imipramine, originally investigated as an antipsychotic, was discovered in the early 1950s, and was the first tricyclic antidepressant, along with amitriptyline. As shown in fig 41, they  inhibit serotonin uptake, although antagonising 5HT2a and c, and although not suppressing dopamine, are still strongly anticholinergic, sedative antihistamines that suppress α-adrenergic receptors. Common side effects include sleepiness, sudden weight gain, dry mouth, constipation, nausea, and blurry vision, increased risk of suicide in those under the age of 25, mania, and urinary retention. A withdrawal syndrome may occur if the dose is rapidly decreased.

Tricyclic antipsychotics, antidepressants and antihistamines all have anticholinergic action which has been associated with increases in dementia and mortality (Gray et al. 2015, McMichael et al. 2020) with high use contributing to an approximately 50% increase in both.

Fig 44: Targeting women: (Left) Mother's little helper": Before the current fashion in SSRI antidepressants, benzodiazepines such as valium (diazepam) and serax (oxazepam) were massively marketed to vulnerable women trapped in domestic incarceration until their recreational popularity and withdrawal symptoms became apparent. (Right) Doxepin – sine qua non! "Sinequan helped her save her family life". The Prozac Promise – Confidence, Convenience, Compliance. Zoloft used for the same purpose as serax. Effexor "I got my playfulness back". In another "I got my mummy back"! Petition: Effexor withdrawal Can bring you to your knees!

Subsequent drug development has focussed closely on the serotonin transporter SERT as a way of enhancing mood in a modulated manner. The current round of SSRI and SNRI antidepressants are head and shoulders above the previous ones, although their efficacy and the basis of their action is still debated (Moncrieff et al. 2022, Erritzoe et al. 2022).  Serotonin reuptake inhibition of the serotonin transporter SERT is believed to be responsible for their anti-depressant activity, although longer term neurogenesis has also been reported. The SSRI fluoxetine (prozac) and the SNRI venlafaxine (effexor) thus increase serotonin by reducing the reuptake of serotonin by the serotonin SERT transporter. Common side effects are agitation, nausea, digestive upset, loss of appetite and weight loss dizziness, blurred vision, dry mouth, excessive sweating, insomnia or drowsiness, loss of libido (Cox 2024), anorgasmia, erectile dysfunction, dependence and withdrawal symptoms. Severe side effects include increased risk of suicide, mania, and serotonin syndrome. Antidepressant withdrawal syndrome may occur if stopped. Fluoxetine has a less  problematic tendency to antidepressant withdrawal syndrome than venlafaxine and can be used as a stepping stone out.

The effectiveness of antidepressants is still only marginal against placebo, or effective psychological support and they come with problems of long-term dependence potentially as serious as with previous use of benzodiazepines such as “mother’s little helper” valium was. By comparison psychedelic therapy holds great promise because it doesn’t require daily dosing on an indeterminate basis and the transformative nature of the experience can enable the person to reevaluate their life and meaning in the psychedelic context, giving them a new more wholesome accepting perspective on existence, even for people facing terminal conditions. In 2020 around 4000 death in the US were associated with antidepressants.

Reversing the effect of SERT is also believed to be responsible for the serotonin flooding causing the prosocial entactogenic effect of the amphetamine analogue ecstasy or MDMA (3,4-Methylenedioxy-methamphetamine). The insights of MDMA experiences have proved effective in dealing with intractable conditions such as post-traumatic stress syndrome (PTSD) through a refreshed world view again without having to have daily medication. However MDMA can cause neurological oxidative damage and medium term depletion of SERT transporters, and deaths have been recorded. In Australia 62% of deaths were attributed to drug toxicity (48% multiple drug toxicity and 14% MDMA toxicity alone), and 38% to other causes (predominantly motor vehicle accidents) with MDMA recorded as a contributory factor (Roxburgh & Lappin 2020). The more serious adverse effects include hypertension, hyperthermia, serotonin syndrome, seizures, stroke, hyponatremia and cardiac arrest, involving multiple factors such as dancing in high temperatures in crowded spaces.

Serotonin Super-Agonists – Agents of Illumination and Annihilation

The most positive tolerable therapeutic agents are in the serotonin receptor class, the 5HT2a receptor fig 43, is widely distributed across the cortex, receiving inputs from 5HT1a neurons sending ascending pathways from the basal Raphe nucleus widely across cortical areas, where they couple e.g. to 5HT2a receptors on vertically-aligned pyramidal neurons and affect mood. Serotonin receptors are diverse with types 1 - 7, both excitatory and inhibitory, with 5HT1 having five subtypes, 5HT2 three and 5HT3 being ionotropic.

The super-agonist effect of psychedelics differs from that of  both antidepressants and MDMA because it leads instead to the psychedelic state, putatively via exciting a second subcellular G-protein linked pathway modulating the adjacent metabotropic glutamate receptor mGluR2 as illustrated in fig 34(d). It acts primarily as a super-agonist of 5HT2a and 5HT2c but is also a partial agonist of dopamine and nor-epinephrine receptors (green squares) adding motivational drive and vigilance to the experience. LSD has an even broader distribution of activations, giving it the rich quality of experience appreciatively noted by the research chemist Dave Nicholls.

Fig 45: Timothy Leary, Alexander and Anne Shulgin (Alex Gray) and Albert Hofmann (Robert Venosa).

Note however there is also a dark side – overdosing on SSRIs or SNRIs (serotonin norepinephrine reuptake inhibitors), or combining two agents, including a variety of drug combinations from pethidine which is also serotogenic with SSRIs and some psychedelics (mescalin) and monoamine oxidase inhibitors, can cause the potentially fatal condition, serotonin syndrome, involving high body temperature and blood-pressure , agitation, seizures and muscle breakdown.

The natural entheogens, psilocin, DMT and mescaline, are safe and can be highly illuminating, when used in a safe context, as is LSD although extremely potent. Deaths from overdose are unknown and the few deaths to which natural entheogens are attributed are due to accidental misadventure. Maria Sabina, the mushroom benefactress lived to 93 and last time I took peyote with the road man Tellus Goodmorning he was also 93.  Mescaline was first isolated and identified in 1897 by Arthur Heffter and first synthesised in 1919 by Ernst Späth. LSD was first synthesised Nov 16, 1938, by Albert Hofmann, but it wasn’t until 1963 that Hofmann and Troxler reported the synthesis of psilocybin. Starting from mescaline, which although not a serotonin analogue binds to the 5HT2a receptor in the same way as psilocin and DMT, a series of more potent mescaline analogs has been created (Shulgin  1991), such as 2CB, 2CB-Fly and the super-potent  25I-NBOMe. Psilocin also has several psychedelic analogues (Shulgin 1997).

But there are plain bad psychedelics too. Bromo-DragonFLY (BrDF) is a very potent hallucinogen, having around one third the potency of LSD and it has an extremely long duration of action, up to several days and is relatively toxic. It can easily be confused with related less potent agents e.g. 2CB-FLY, which is 20x less potent, 2CB or 2CE which is 100 times less potent. Two young adults died after overdosing on BrDF, which they thought was 2C-E, and several others were hospitalised during the same incident. Because they took a dosage appropriate for 2C-E, those who took the drug received, in some cases, 100x the normal dose. Both deaths followed seizures, vomiting blood, and terrifying hallucinations. A 35-year-old male required amputation of the front part of his feet and several fingers on one hand after taking a massive overdose. The compound acted as a long-acting vasoconstrictor, leading to necrosis and gangrene which became apparent several weeks after the overdose occurred. A 22-year-old male from Copenhagen died after ingesting BrDF. His friend described the trip saying, "It was like being dragged to hell and back again. Many times. It is the most evil [thing] I've ever tried. It lasted an eternity.”

The lesson for me is to trust natural entheogens. Sacred mushroom species such as Psilocybe cubensis have evolved to provide a genetically pure psychedelic experience with no dangerous contaminants. Magic mushrooms are some of the safest recreational drugs around. Out of a survey of more than 12,000 people who did shrooms in 2016, just 0.2 percent said they needed emergency medical care—a rate that was five to six times lower than LSD, cocaine, MDMA, and alcohol, and three times lower than weed. However some wood-loving species Psilocybe azurescens, cyanescens, and subaeruginosa can cause temporary muscle weakness or paralysis.

Cannabinoids

Cannabis plants have a great variety of psychoactive molecules. In particular cannabidiol moderates the effects of the principal psychoactive agent 9-THC to give a more health promoting effect. 11-hydroxy-THC can be formed after consumption of THC from inhalation and oral use, although levels of 11-hydroxy-THC are typically higher when eaten compared to inhalation. The pharmacokinetic equivalency ratio comparing Delta-9-THC with 11-Hydroxy-Δ9-THC means that one milligram of THC in edible form, is equivalent to 5.71 milligrams of THC in smokable form.

Fig 46: (Left) Sadhu attending the Maha Shivaratri festival Nepal marking a remembrance of "overcoming darkness and ignorance" in life and the world on the night before the new moon. (Lower) Some key natural and synthetic cannabinoids. (Upper-left) Scythians used cannabis ritually by heating whole plants in braziers in an enclosed space (Rudgley 1993). The black residue inside the gold vessels dating from the fourth century BC contained opium and cannabis (Curry 2015). (Upper-right). Vessels for heating cannabis resin of the Sogdians, a people of western China and Tajikistan who were Zoroastrians (Ren 2019). A 700-900 BC Israelite temple with active cannabis is shown in fig 140.

Cannabinoid metabotropic receptors have a variety of functions. CB1 occurs widely in the brain and CB2 is expressed on cells of the immune system where it has an immunomodulatory effect, reducing inflammatory response where it plays a role in processes including implantation of the fertilised embryo. CB1 receptors are thought to be one of the most widely expressed G protein-coupled receptors in the brain. This is due to endocannabinoid-mediated depolarization-induced suppression of inhibition, a very common form of short-term plasticity in which the depolarization of a single neuron induces a reduction in GABA-mediated neurotransmission. Interference with working memory, displayed by cannabinoids is believed to result from secondary action of glial astrocytes, which have CB1 receptors, on hippocampal pyramidal, cells. The actions of 9-THC result from partial agonist activity at the cannabinoid receptor CB1 (Ki = 40.7 nM), located mainly in the central nervous system, and the CB2 receptor (Ki = 36 nM), mainly expressed in cells of the immune system, meaning it binds similarly to both.

Anandamide, the principal enodcannabinoid, along with 2-arachidonyl-glycerol, both derived from the prominent fatty acid arachidonic acid which occupies 20% of the fatty component of the brain, was first described (and named) in 1992 by Raphael Mechoulam and co-workers. The group went on to devise far more potent synthetic cannabinoids. HU-210, HU for Hebrew University, synthesised by Mechoulam has 100-800 times the potency of THC which itself is active in quantities of around 1-5 mg.

While natural cannabis is a safe herbal product used for up to five thousand years as a psychoactive substance, and the only deaths attributed to natural cannabis use are associated with other factors such as injuries from vehicle accidents where cannabis is detected, synthetic cannabinoids have exploded on the recreational market, some with serious damaging side effects and deaths. 

A series of potent naphthoylindole cannabinoids, the JWH family named after John W. Huffman, of Clemson University introduced a wide array of new cannabinoids with new structural arrangements ad some with disquieting side effects. JWH-018 is a full agonist of both the CB1 and CB2 cannabinoid receptors and has been associated with unpleasant effects, including seizures, possibly associated with GABA inhibition and dissociative and anxiety episodes. JWH-073 acts as a partial agonist at both the CB1 and CB2 cannabinoid receptors. It is five times more selective for the CB2 subtype. JWH-015 has an affinity for CB2 receptors of 13.8 nM, while its affinity for CB1 is 383 nM, meaning that it binds almost 28 times more strongly to CB2 than to CB1. JWH-081 by contrast is ten times more selective for CB1. Two fluorinated compounds XLR-11 and AM-2201 have recently been associated with acute kidney damage (Murphy et al).

AB-Fubinaca was originally developed by Pfizer in 2009 as an analgesic medication but was never pursued for human use. In 2012, it was discovered as an ingredient in synthetic cannabinoid blends in Japan. In 2016, a "mass casualty event" in Brooklyn, New York, where 33 people ranging in age from 25 to 59 years old were adversely affected by the drug. 18 were hospitalized. All of the victims were described by-standers as “zombielike” and the cause was attributed to closely-related AMB-Fubinaca with a methoxy group instead of an amine. A sudden spate of around 60 deaths in New Zealand, which had never experienced deaths from natural cannabis, accompanied by zombie incidents, were also attributed to the drug, with tested products containing between 32 mg/g and 400 mg/g of the active ingredient, between 2x to 25x stronger than the product involved in the mass casualty event in New York a year earlier.

Deleriants – Devil’s Breath and Witches Brew

There is a long diverse history of use of solanaceous plants from belladonna (deadly nightshade) and mandrakes to Datura and Brugmansia species to induce states of delirious hallucination in which the subject is unable to differentiate their sometimes mundane hallucinations from reality, becoming unable to look after their own affairs, often slumping into unconsciousness and awakening with little memory of what has happened. This is the basis of the witches’ flight on a broom stick, reputedly after rubbing the ointment on their skin and vaginal membranes. It is caused by toxic quantities of scopolamine, which is an undiscriminating muscarinic acetyl-choline antagonist, although also an essential medicine.

Fig 47: Datura stramonium, or devil's trumpet, renowned for the Jimson weed incident named after Jamestown, Virginia, where English soldiers consumed it for food while attempting to suppress Bacon's Rebellion. They spent 11 days in altered mental states of hallucinatory delirium incarcerated for their own protection. Guambioano drawing of a woman under a borachero tree of the evil eagle of toxic flight Brugmansia volcanicola, or angel's trumpet tree Colombian Andes. The Dance of the Sabbath (Gustav Doré). A young Basque witch applying her flying ointment José de la Pena. Atropa belladonna and Henbane Hyoscyamus niger. Ceremonial scopolamine use goes back to the beginning of the first millennium BC (Guerra‐Doce et al. 2023).

Its use in psychoactive quantities, like that of other anticholinergic agents leads, to accumulating brain atrophy. In smaller doses it is used for motion sickness and postoperative nausea and vomiting. Originally used as an anaesthetic and amnesiac in childbirth, it is frequently used to drug victims to induce docility, persuading the victim to release their bank accounts, after which they awaken not remembering what happened. In South America it is sometimes added to hallucinogenic ayahuasca potions containing DMT.

Then Rachel said to Leah, Give me, I pray thee, of thy son’s mandrakes. And she said unto her, Is it a small matter that thou hast taken my husband? and wouldest thou take away my son’s mandrakes also? And Rachel said, Therefore he shall lie with thee tonight for thy son’s mandrakes (Gen 30:14).

NMDA Dissociatives

Ketamine is a dissociative anaesthetic which induces a trance-like state providing pain relief, sedation, and amnesia. At sub-anaesthetic doses it is a recreational drug which induces a profound dissociative trance like experience entirely different from psychedelics and is a promising agent for pain and treatment-resistant depression. It is one of the safest anaesthetics, in contrast with opiates, ether, and propofol, it suppresses neither respiration nor heart rate. Ketamine is an NMDA receptor antagonist which putatively acts by blocking the passage of ions in the ion channel. Related agents are PCP, N₂O, Xenon and dextromethorphan. The psychotropic effects of ketamine range from dissociation and depersonalization. Depending on the setting they can be pleasant or distressing and include a sensation of feeling light, body distortion, absence of time sense, novel experiences of cosmic oneness and out-of-body experiences. PCP has gained notoriety for uncontrolled behaviour, because it stimulates other receptors including D2, notably alleviated in an overdose by Haloperidol’s D2 suppression. By contrast, overdosing Ketamine results in falling into the anaesthetic K-hole.

μ-Opioid Analgesics and κ-Opioid Dissociatives

Opioid receptors are a group of inhibitory G protein-coupled receptors with opioid polypeptides as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. Opioid receptors are distributed widely in the brain, in the spinal cord, on peripheral neurons, and digestive tract. The opioid receptor class consists of four types δ, κ, μ, ζ and nociceptin – DOR, KOR, MOR, ZOR & NOR. Opiate drugs, such as morphine, act as MOR agonists setting off inhibitory effects, building up tolerance and causing withdrawal symptoms, possibly via NOR. NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates. NOP and KOP do not react with MOP agonists such as α-endorphin, the 16 unit polypeptide Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr, but dynorphins such as 13 unit dynorphin A – Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys. The opioid receptors appear to maintain a dynamic equilibrium of pain perception, with opiates effect being due to MOP with NOP contributing to tolerance and withdrawal symptoms, with KOP having an alleviating role.

Fig 48: Top row: Poppy Goddess with slit pods (1400–1100 BC Gazi, Crete), Juglet with traces of papaverine unique to the opium poppy Papaver somniferum (Daley 2018), The sacred mushroom benefactress Maria Sabina holding Salvia divinorum.

Opium has been revered as a sacred potion since the dawn of urban culture, with sacred use manifest in the slit poppy pods on the crown of the Minoan Goddess and the presence of opium along with cannabis in the Scythian rituals. Opiates remain core essential medicines playing a key role in the management of pain, but they are also prime targets of dependence, addiction and mortality because of their seductive ability to escape the pain of the mortal coil. This leads to opiates and the ensuing synthetic opioids being primary agents of drug-induced mortality.

As can be seen in the figure above, opioids have beed developed in two ways, firstly by modification of morphine to heroin (diamorphine) , oxycodone and others, and secondly after the discovery of pethidine to arrive at fentanyl and carfentanyl, having exponentiating potencies and risks. The strength of sample opioids relative to morphine is: Codeine 1/10, Pethidine 1/3, Morphine 1, Oxycodone 3/2, Methadone 3, Heroin 3, Fentanyl 100, Carfentanyl 10,000.  Correspondingly the overdose death rates in the US for opioids in 2020 are very high and skewed towards the most potent: Heroin 13,000, Prescription opioids 16,000, Fentanyl 57,000. A significant share of these deaths can be directly attributed to the criminal mass marketing of opioids by the US drug industry.

Similarly to μ-opioid receptor agonists, such as morphine, κ-opioid agonists are potently analgesic, and have been employed clinically in the treatment of pain, however they also produce side effects such as dysphoria, hallucinations, and dissociation, which has limited their clinical usefulness. κ-opioid receptors are extremely widely distributed in the brain, spinal cord, and in peripheral tissues, including high levels in the prefrontal cortex, raphe nuclei (dorsal), ventral tegmental area, substantia nigra, dorsal striatum (putamen, caudate), ventral striatum, amygdala, claustrum, hippocampus, hypothalamus, midline thalamic nuclei, locus coeruleus, spinal trigeminal nucleus, parabrachial nucleus, and solitary nucleus.

They may provide a natural addiction control mechanism, and therefore, drugs that target this receptor may have therapeutic potential in the treatment of addiction. Ibogaine a natural hallucinogen from Africa has seen a wave of popularity as a means to escape addiction and alcohol dependence. There is evidence that distribution and/or function of κ-opioid receptors may differ between sexes. The effects of the κ-opioid agonist salvinorin-A include baffling dysphoric visual spatial experiences quite different from psychedelics, and loss, or inversion of one’s body image to become an external part of the environment, like the walls of the room, or crushed between giant wheels in a huge aircraft hangar. As can be seen in fig 34(h), ibogaine’s unique receptor binding profile involves super-agonism of 5HT2a providing a psychedelic effect, agonism of κ-opioid receptors providing both alleviation of dependence and a salvinorin-like dissociative effect and antagonism of NMDA receptors, akin to Ketamine’s dissociative effect.

Uppers and Downers

Two central drugs of key medical use and recreational and addictive misuse second only to opioids are stimulants, providing euphoriant stimulus and emotional drive, and sedatives, providing obliterating relaxation and somnolence.

Fig 49: Left: Erythroxylum coca providing cocaine. Right: Catha edulis (Khat) providing the stimulant cathinone.