Check out the Garden States festival in Victoria if you're keen to engage with the community advocating for responsible use of entheogens.

https://www.instagram.com/p/DPJJSIpkdEE/?igsh=M2hxOWl4cXg3YWtx

Species consist of populations that are connected by gene flow. Populations are often structured by geography, which means that individuals in one area have more DNA in common than in another geographic area. Speciation may occur when barriers prevent gene flow and populations diversify and lose connectivity.

Microorganisms need to maintain species connectivity over evolutionary time to ensure they can exchange DNA and benefit from new alleles and other advantages of recombination. Spatial separation may not equate to speciation in microorganisms that have 'built-in' strategies to control mate recognition. For example, in mushrooms mating is controlled by loci that must differ in potential mating pairs. Some species, like magic mushrooms, must differ at two different parts of the genome (tetrapolar mating compatibility). The outcome is that diversity increases at these parts of the genome among populations and increases chances of sexual reproduction (check out 'negative frequency dependant selection' to understand the dynamics behind these mating compatibility loci). Species connectivity breaks down when these fungi can no longer recognise each other to form a dikaryon.

Mycologists rarely have an opportunity to examine gene flow among populations using whole genomes. Rather, they use short cuts to define species, e.g., a morphological species concept, phylogenetic species concept, or biological species concept. These species concepts are taking one measure of what may constitue a species (similar appearance, similar genes, sexual compatibility and production of viable offspring).

A question was asked whether I was advocating use of a biological species concept for Psilocybe at the end of my AMS talk. I used mating compatibility as one line of evidence for species connectivity of Psilocybe subaeruginosa across Australia. We also showed reticulation in population analyses, shared alleles, and low Fst (high Fst occurs when there is no gene flow). We put forward reasons for why morphological and phylogenetic species concepts were not ideal. I don't think we used a species concept at all, rather, we showed gene flow can and does occur among populations of P. subaeruginosa structured by geography across Australia, the perfect definition of a species.

Gene flow among populations is the ultimate way to test species connectivity. It's not always practical because a researcher must sample widely and it can be expensive to get data. We've set a standard and studies from here must sample new populations to reject that there is gene flow with Australian populations and justify a new species.

Here is a thought experiment for those wondering about Psilocybe cyanescens and other similar taxa. Imagine a scenario where elephants can live for 500 years. 200 years ago, a couple of baby elephants are introduced to Australia. Scientists see a flourishing population of elephants in the outback and decide to describe them as a new species because there is no recent gene exchange with African elephants. Little do they know, the original founding genotypes, taken from Africa, are still alive. What would you do in this scenario as a taxonomist? New species, or still an African elephant?

The scenario holds true for Psilocybe subaeruginosa in the northern hemisphere. We know dikaryotic genotypes of P. subaeruginosa are perennial. If they were originally introduced as dikaryons in the northern hemisphere, their founding genotypes may still exist in Australia. Should the populations in the northern hemisphere be considered different species even if they are identical genotypes to the founding populations in Australia? I think either solution is acceptable, especially in the context of populations. Simplifying communication about mushrooms is my favourite outcome.

I'll share the AMS talk when they make it available online :)

I re-listened to an interview I did with Mel on the Hair Therapist Podcast a couple of weeks ago (available here) and thought I should correct a few things and elaborate on some more. The most important outcome from speaking with Mel is increasing the population who think about safe and equitable use of psilocybin.
 
Astute listeners will have seen that Psymbiotika Lab has received the licence to manufacture and possess psilocybin, and finally, after more than a year, we'll be back on track to determine the tryptamine profiles of mushrooms linked to their genotype at the psilocybin locus.
 
Clarifying statements on how many magic mushrooms have been taken over the last 50-60 years
Humans have used psychoactive mushrooms culturally for at least 7,000–10,000 years (Jack Pettigrew Gwion Gwion link) and 10s to 100s of millions of doses have been used recreationally based on drug-user data in Australia (see here) and the United States (see here). I mentioned a company in the USA who sell more than 400,000 grow kits of magic mushrooms in California per month, which could produce 1 million doses of psilocybin. 
 
The number of times people have used magic mushrooms matters! It is evidence of demand despite their legality, and evidence of safety without supervision from a clinical practitioner.
 
Illegality of psilocybin increases risk for people who are afraid/ashamed/apprehensive to ask for help about best practice but will try magic mushrooms anyway. Is there a future model to protect people who will take psilocybin regardless of the legality but who may experience side effects? 
 
What is better, discouraging use of psilocybin by keeping it illegal (which we already know is an ineffective deterrent), or developing a safe-use model for psilocybin? Many organisations have provided resources for people who want to explore psilocybin, but even with this shared knowledge by the community, many potential users are confused. I am contacted with relative frequency asking for assistance in dosing psilocybin (despite not having anything to do with ingestion of psilocybin in my research). In my opinion, the most unsafe use of psilocybin will happen because it is illegal.
 
In the podcast I compare the number of clinical doses (100s to 1000s) to recreational doses (10s to 100s of millions). We can reject a narrative that safe use requires supervision from a trained psychiatrist. The sheer numbers of safe, unassisted psychedelic experiences overwhelms an agenda that psilocybin only benefits those supervised by a trained psychiatrist. Is there a model for people that want supervision but that don't want the high costs associated with psychedelic therapy (estimated at AU$15–25K)? I very much dislike a clinical-use-only model because it deprives healthy people an opportunity to experience benefits of psilocybin. The consistent themes that develop from user accounts is that psilocybin causes breakthroughs, transcendence, creativity, mysticism and bliss.
 
If policy makers are genuinely concerned about safety, a conversation is needed about how psilocybin can be managed to reduce risks around counter-indications or inexperienced users causing themselves harm by eating poisonous mushrooms. 
 
Innovation of psilocybin beyond mental health and neurogenesis
A preprint under review determined that psilocybin improved neurological tissue damage in rodents (available here), and this is an underexplored field of study. Psychedelics in general are neuritogenic, in that they promote dendritic growth in neuronal models and are neuroplastic in that they increase activation and communication between neurones (see here, here, and here). The neuritogenic properties of psychedelics are primarily explored in psychiatric disorders and it is unknown whether psilocybin and related compounds will benefit neurodegenerative disorders or neural tissue damage. Our research network will test a hypothesis using our mushrooms that psilocybin has potential innovations for therapeutics in neurodegeneration and rehabilitation of nerve damage and applications in neurological disorders.
 
Clarifying whether Aboriginal people used magic mushrooms
Psilocybe subaeruginosa has a centre of origin in Australia. It was here before people arrived. It potentially had a more widespread distribution than now, given that there were more available habitats, and it was colder.
 
Aboriginal people had at least 50,000 years to learn whether Psilocybe subaeruginosa was edible. It would have appeared annually, in the same area given that it is perennial. As mentioned in the podcast, Aboriginal people tested all flora, fauna and funga for their edibility or innovation. It is less plausible that they ignored P. subaeruginosa than that they determined whether it was edible. The links between Aboriginal culture and psilocybin are my opinions and they are i) connection to country, and ii) connection to ancestors through time and space. Connectedness and mystical visions are well-known psychoactive properties of magic mushrooms.
 
Does it matter whether the knowledge is lost or not shared? Probably not, I think it is easy enough to make the case that Aboriginal people tested Psilocybe subaeruginosa (probably multiple times over 50,000 years). The biggest impact is that the Therapeutic Goods Administration has different powers in regulating foods and medicines that were used traditionally. I believe this space is ripe for exploration.
 
Clarifying the licence issued by QHealth for Psymbiotika Lab
Shortly after the interview, we were issued our permit to continue our research on magic mushrooms. It took 14 months and I gained valuable experience navigating bureaucracy. I ended up talking to local members in government (my local member, Dr Barbara O'Shea, is just brilliant) to try and fan the bureaucratic flames, but in the end, understanding the legislation and knowing how to appeal a decision is how we advanced the application.

Some additional details for under-explained topics and questions that I couldn't answer on the spot for Mel
- There are more than 150 clinical trials underway testing psilocybin across a variety of mental health issues (ClinicalTrials.gov).
- I did not mention psilocybin can be produced biosynthetically in bacteria or yeast cells. I'm unsure of the cost of this method and whether it must happen under patent. I liken synthetic and biosynthetic psilocybin to candy bananas in Australia. Candy bananas are based on the flavour of gros michel bananas, which is no longer a commercial cultivar thanks to a soil-borne plant disease. If you are craving the flavour of a banana, the synthetic, replicated flavour of a candy banana might hit the spot. For those who enjoy the texture of bananas chopped on cereal or pancakes, or covered in peanut butter or whatever, a real banana may be preferred. Same with magic mushrooms and synthetic psilocybin. If all you care about is the compound, synthetic will do the trick. If you're interested in exploring the versatility of the tryptamine profile, or how your experience may be impacted by MAO inhibitors in a natural mushroom, maybe you would prefer magic mushrooms. I look forward to trials that directly compare experiences on synthetic, biosynthetic and natural psilocybin.
- Here's a list curated by Mind Medicine Australia on the clinical trials underway in Australia
- And another MMA link to the Authorised Prescribers of psilocybin in Australia

This post is inspired by an overlapping blog post on the Psymbiotika Lab website here and a journalist bud, Pat, who writes for Double Blind magazine. 

​Do either of these dogmas sound familiar:

• Psilocin binding to 5HT2A receptors dictates the trip. Dose, set, and setting are the variables that cause differences in user experiences.
• A cube is a cube.

To some extent they go hand-in-hand, although the former is more extreme. 

To what degree do we understand serotonin pathways in humans? Are the brain and neural networks simple or complex? Are biological systems simple or complex? Do we understand the full pathways and mechanisms of prescribed serotonin agonists like SSRIs? Do we understand how non-psychoactive receptor agonists impact binding of hallucinogens, and do we even understand agonism of psilocin at 5HT2A?

I would argue we have a long way to go before we set dogmas on psychoactive substances and their actions to humans. We have a piece, currently in preparation, discussing how psilocybin skipped preclinical research and that we need to get basic knowledge to help advance all research on psilocybin.

Here’s a little figure I whipped up on LucidChart to illustrate where you land with how open you are to hypotheses beyond the two dogmas above.

We are testing a hypothesis that differences in the ratios of psilocybin and its analogs will impact the psychoactive experience. These ratios vary among different genotypes of P. cubensis when bred for allelic differences at the psilocybin locus. Ultimately we will either support or reject that allelic diversity at the genes that produce psilocybin impacts an experience.

Until there is clear evidence that supports or rejects whether a cube is a cube, it could be fun to keep an open mind. Cubes under cultivation have low founding diversity and have been highly inbred. There are some easy comparisons to make if you want to test for yourself if a cube is a cube. We have shown (figures in a couple of places below) that the following populations of cultivars differ in their alleles at the genes that produce psilocybin: Penis Envy, Golden Teacher, Treasure Coast, and Luminous. Compare different members of those populations to make up your own mind on whether a cube is a cube in the meantime… but hopefully genuine data coming to you soon.
​
Links to references in the figure (and a couple of others)
Psychoactive effects cannot be differentiated by users (ref here)
Analogs of psilocybin bind to serotonin receptors just as well as (if not better than) psilocin (refs here and here)
Analogs of psilocybin are non-hallucinogenic but norpsilocin may have antidepressant activity (ref here)
Naturally derived psilocybin outperforms synthetic psilocybin in terms of longevity of neural plasticity in mice (ref here)
And here’s a link to the piece on diversity at psilocybin alleles in cubes (here)

I’ve pondered the evolutionary origins of psilocybin for longer than I’ve researched magic mushrooms. Framing the case for designer shrooms landed me with a satisfactory answer, and I can stop thinking about it. I recently shared these thoughts in a talk to the Queensland Mycological Society (available here, but the sound could be better) and thought I should put them on the blog. These ideas are not new; some are explored by Meyer and Slot (available here) and by Walton (available here), who writes about amatoxins.

​Evolutionary Timeline: Psilocybin has been around for a long time, at least as long as Psilocybe, which is 20–90 million years old according to a clock-like rate of evolution. The most recent common ancestor of Psilocybe has a mean age of 66 million years (estimated by Bradshaw et al., 2024). Magic mushrooms have diversified into similar niches worldwide, each with different symbionts in their ecosystems. As mentioned for designer shrooms, the genetic pathways to produce psilocybin have been refined over 20+ million years to suit particular niches, and this may lead to variations in user experiences between different species of magic mushrooms, but this hypothesis requires testing.

If you're like me, you might be thinking about how 66 million years ago is a perfect match to when the dinosaurs were wiped out by a meteor strike. Poor T-rexes and those giant grazers like Brontosaurus may never have accidentally experienced the effects of psilocybin. Or, for those of you who think psilocybin came from outer space, what a coincidence... right. As someone who has done a bunch of molecular dating, it's a good idea to look at the whole time estimate rather than the mean age. Here's a cool site to visualise the Earth 66 million years ago.

​Innovation of psilocybin in evolution: I end up on the hypothesis that psilocybin was innovated to either protect, attract, or control metazoans that ate mushrooms (nematodes, insects, gastropods) across different niches. The exact reason psilocybin evolved in the common ancestor remains unclear and can never be truly known. Instead, let’s examine its current potential evolutionary innovations.

Protection: Psilocybin likely was/is used as a deterrent over evolutionary time. Serotonin controls appetite in all metazoans that eat fungi (see here). Magic mushrooms might trick their predators into early satiation, thus saving their fruiting bodies from grisly mastication. Meyer and Slot discuss this hypothesis. Psilocybin could also protect through disorientation, which overlaps with control. To support a hypothesis of protection in extant species of magic mushroom, metazoans would need to be observed rejecting more after an original taste, and it would be beneficial to know which serotonin pathway was triggered.

Attraction: One of my co-authors, Jan T, has photographed slugs and insects consuming spores inside lamellae of Psilocybe subaeruginosa, likely aiding in dispersal. Animals that provide dung niches, like cows dropping a substrate for P. cubensis, might help spread spores in ideal environments. Walton (link in paragraph one) discusses similar symbioses in relation to amatoxins. Walton makes the case of an evolutionary dead end if an organism harms the provider of their niche. Cows likely eat P. cubensis, whether accidentally in deep grass or possibly intentionally if mushrooms are palatable. Cubes could cut out the middle man (grass) by having their spores directly eaten by their primary niche provider. In some niches (particularly for taxa in dung), Psilocybe may well have benefitted from attracting spore dispersers. To support a hypothesis of attraction, metazoans would need to preferentially choose Psilocybe over comparable food, further, it would be necessary to determine whether spores remain viable after digestion (which we know is true for P. cubensis), and whether attraction is linked to any serotonin-based reward.

Control and manipulation: Psilocybin might play a role in controlling its predators with an example I liken to 3D-chess. Amateur mycologist and absolute legend, Dave Bennett, contacted me when I was working at UQ and described an experiment in which they fed slugs magic mushrooms. Slugs with a magic mushroom diet switched from nocturnal to diurnal feeding. Psilocybin may affect photoreception, which is controlled by serotonin in arthropods (and made famous by the parasites that manipulate amphipods, read about it here). In this case, is psilocybin manipulating its predators to be active during the day to increase their chances of predation by birds or bigger animals? 3D-chess indeed. To support a hypothesis of manipulation, a behavioural change must be observed that can be linked to benefit the mushroom.

Conclusion: Psilocybin was/is likely innovated by magic mushrooms as a protectant, attractant, and manipulator, all in the name of sexual reproduction and spore dispersal. We will never know with certainty why the common ancestor of Psilocybe produced this secondary metabolite. Instead, we should consider psilocybin as a compound continuously innovated by magic mushrooms in various niches. Mammals likely had no symbiosis with the common ancestor of psilocybin-producing mushrooms, but evolutionary innovation allows old compounds to take on new roles over time and space, and magic mushrooms formed new symbioses based on a dung niche and serotonin receptors of mammals. The profound and life-changing effects of psilocybin on humans is an evolutionary stroke of good fortune, but I’ve come around to the idea that selection may have innovated it closer to our mammalian home.

Clear Statement: The evolutionary origin of psilocybin had nothing to do with mammals. However, if we treat psilocybin as a dynamic compound innovated by fungi to exploit different niches, then mammals certainly provided new opportunities for niche exploration, spore distribution, and protection, attraction, or control through their serotonin receptors. The difficulty is testing these hypotheses ethically and legally, I’m just glad we’re part of a community that does the science despite the hurdles in place to develop new knowledge.

When the TGA down-scheduled psilocybin, I felt hopeful. I envisioned Australia leading the charge to alleviate a global mental health crisis. Some psychiatrists have expressed concerns that the TGA announcement may have been premature. Importantly, the announcement has advanced the discussion and helped to further erode a stigma that psilocybin is a dangerous drug without potential.

Strict clinical use is not a solution
Psilocybin shows potential to treat mental health disorders affecting up to 40% of the population, however, clinical trials face significant challenges. One key issue is to demonstrate meaningful performance over placebos — participants often discern whether they have received the treatment or a control. This is a challenge for all psychedelics, and outperforming a placebo applies to all medications. Current research does not conclusively support psilocybin as a prescribed treatment and there is ongoing debate within the psychiatric community on how to accurately measure its benefits for mental health (discussed in a review here).

The population interpreted the TGA decision as tacit approval that psilocybin is a promising treatment for depression. I know first-hand because I was contacted by many to be included in trials, even though I work on the evolution of fungi. The TGA announcement swelled demand from desperate people who cannot be treated in a short time frame. This highlights a need to evaluate legislation and operational procedures for psilocybin. Under the current trajectory, even those who fit the criteria for clinical use may be financially excluded given the estimated prices of treatment (at $15–25,000).

The second problem is that benefits of psilocybin are not limited to those with mental health disorders, and a therapeutic-only model unfairly excludes many. People seeking profound and life-changing experiences from psilocybin, which are agreed clinical outcomes, are still penalised harshly for possession of a compound that can only be prescribed if they meet conditions of a mental health disorder.

What about safety?
Harm from psilocybin use typically stems from impaired function during an experience, contraindications with serotonin receptor medications, discomfort or unpleasant thoughts, and it should be avoided by those with a predisposition to schizophrenia (some reviews on the dangers exist here, and here). Legal penalties for possession are perhaps the strongest deterrent for people not on antidepressants or without a genetic link to schizophrenia.

While acknowledging the potential risks of impairment during a psilocybin experience, we must recognise that safety concerns alone should not dictate legality. Many legal activities carry inherent risks, from extreme sports to alcohol consumption, yet society manages these risks through education, regulation, and responsible use guidelines. Similarly, promoting safe usage practices and informed decision-making around psilocybin can mitigate potential harms and allow individuals to responsibly explore its therapeutic potential.

Psilocybin is arguably safer than many substances we encounter daily. It is non-addictive, has no known lethal dose, and has been used tens to hundreds of millions of times without incident (based on grey-market data, there are more than 1 million doses taken in California per month). The impairment lasts up to four hours and is best experienced privately and in a stress-free environment, hence an emphasis on set and setting in the clinical space. Human culture has found ways to mitigate risks in many activities considered risky, and we can surely solve responsible use of psilocybin through education and restricted access.

What Safe Use Might Look Like
Given that psilocybin is non-addictive, has not caused any direct deaths in its countless uses, and we know how to mitigate the primary risks, is it time to reconsider legislation around psilocybin? These authors consider psilocybin as a drug with low potential for abuse and low risk of addiction, equivalent of a schedule 4 medicine. What would be the outcome if it was not considered a medicine at all (similar to a restricted substance, alcohol)?

Changing psychedelic legislation is complex and requires creative solutions. If someone has done their research, believes they might benefit, and wishes to use psilocybin responsibly, should they be penalised under laws created when psilocybin was misunderstood and stigmatised?

Under a model where people are not prosecuted for psilocybin use, they could operate under a social contract of responsible use, whether for self-improvement or therapeutic benefit. This approach would reduce legal penalties, allow use beyond mental health conditions, eliminate clinical expenses for users, and still be applicable for clinical use for those in need. This could happen if psilocybin was not treated as a medicine but as a restricted compound, similar to addictive and carcinogenic compounds such as alcohol and nicotine.

Conflicts of interest and bias
Conflicts of interest can bias this conversation. Psychiatrists advocate for controlled, clinical use and their training and expertise is the requirement to assess and prescribe psilocybin to those who fit their criteria. Psilocybin is still available in psychedelic assisted therapy if it is a restricted rather than controlled compound.

Those outside the clinical model argue that psilocybin has been safely used for decades without therapeutic oversight. The psychedelic community has developed guidelines and knowledge for responsible use, available to anyone at minimal expense and outside clinical settings.

There are concerns about biases in the production and distribution of psilocybin. Those who have developed doses would benefit from keeping psilocybin as a scheduled substance, as it keeps competitors out and prevents access to market by mushroom growers who can produce psilocybin very cheaply (and who would benefit from an open supply chain).

If you’ve made it this deep, you may know my opinion already: I think psilocybin should equitably be available to those who have done independent research and believe they would benefit (giving them the same standing as tens to hundreds of millions of people who have tried psilocybin illegally). Our new company researches the phenotypic outcomes of genetic diversity and provides psilocybin for research use. We benefit if psilocybin is heavily legislated and excludes others from competing. However, the humanitarian outcomes of changing legislation around psilocybin and my personal beliefs are contrary to my commercial interest at this point in time.

Where we need research
We need foundational knowledge on psilocybin and other tryptamines found in magic mushrooms. This knowledge should come from cellular models and invertebrate animal models (the original targets of psilocybin). Human clinical trials seem premature without a thorough understanding at the cellular level.

There seems to be a trend in clinical literature that psilocybin is only safe with therapy. The non-clinical community would posit that the psilocybin experience itself is therapeutic. It would be insightful to see a controlled experiment comparing outcomes with and without psychotherapy following psilocybin use. The psychedelic assisted therapy model has adopted therapy without meaningful comparison to a control (see section on conflicts of interest).
​
Areas we must discuss as a community
Clinical use has helped reduce the stigma around magic mushrooms, but it cannot be the only safe avenue for psilocybin use. We need a conversation about the safe and legal use of magic mushrooms outside clinical settings to meet the growing demand. Psilocybin will be used by people no matter how it is scheduled, and given its availability in magic mushrooms that are ubiquitous in Australia, and its ease of production, the black market demand will remain and be met. A discussion should address therapeutic access and public safety concerns without exacerbating black market activity and aim to:

1. Increase safety (through set and setting, mushroom identification, purity).
2. Promote responsible use.
3. Decrease disproportionate legal penalties.

People should not be prosecuted as criminals if they are aware of the risks and choose to use psilocybin to improve their mental health or for recreational benefits. The risks and safety of psilocybin have been demonstrated by its extensive use over the past 50 years. Even though these data are not peer-reviewed, they are meaningful and have advanced knowledge on psilocybin more than a scientific community that must operate under ethical rules and within the legislation of scheduled compounds.

Taxonomy is the bedrock of communication about life. If other facets of communication changed, it'd be pretty frustrating, e.g., "from here on, hello will mean mustard". 

I witnessed the saltiness of taxonomic change first hand in South Africa. Africans had spent their lives calling their iconic, thorny trees Acacia. Acacia even means thorny. That didn't suit taxonomists and all the African acacia were renamed to Vachellia. The non-thorny Aussie trees, of which there were >1,000 species compared to 100-ish in Africa, took the name. Ja, I can see why they'd be salty.

In other areas of science, we support or reject hypotheses and move on. Taxonomy is descriptive, hypotheses can be loosely applied (we hypothesise this is a monophyletic group of taxa), but it's a stretch. When two people describe the same piece of art or music, they may differ in their opinion. The same is true for taxonomy. Applying taxonomic ranks to organisms is arbitrary and cases can be made to split or lump any rank at a shared common ancestor. Ultimately, determining gene flow among populations paints a clear picture of species boundaries, but who has the time to do this for millions of fungi.

I find it interesting that we become attached to taxonomic names, even when there is evidence to support that they should be called something else. I think we are more emotional because of the vagueness in species/taxon delimitation. In the smut and rust section of this blog, you can read about the taxonomic name for corn smut and why it should be called something other than Ustilago (but jeeze, you'd have to be bored). Clearly even I become emotional about taxonomy.

Taxonomic names, as long as they were validly described, are always there for communication and can be used eternally (as long as people know what organism you mean). Just 'cause some fella is saying all the northern hemisphere wood-loving shrooms are Psilocybe subaeruginosa doesn't mean you have to forgo these names. Keep on using them... what do you think African people call acacia (hint: not Vachellia)? The only change here is that we know Australia is the centre of origin of P. subaeruginosa and it has spread to the northern hemisphere where multiple new names have been applied to one taxon.

​The figure illustrates genomic relationships based on core and accessory genes between sister species. For magic mushrooms, the sisters are cubes and subs. Note they are highly separated by core genes and there is almost no overlap of accessory (non-core) genes. Colletotrichum is the other example, and it has been split like a banana in a dessert bar. Note that the core and accessory don't clearly separate species. Likely these are all the same taxon and taxonomists have described clones as different species (which could be acceptable in some instances).

After this explanation, if you still prefer species complexes and lots of names for the same taxon, why not spend your time and resources examining the boundaries of recombination to demonstrate speciation in process?

Set and setting, and psilocin binding to 5HT2A receptors are the two domgas of how magic mushrooms work. To the point it feels that's all we think matters to dictate a psilocybin experience from magic mushrooms.

Let's think back a couple of million years to before mammals were on the scene.

Under a clock-like rate of speciation, species are between 500K to 5 million years old. Genera are somewhat older, and Basidiomycota are an anomaly compared to other organisms. Genera of Basidiomycota are usually 20–100 million years old. (Check out this paper if you want to read more: ​https://academic.oup.com/mbe/article/32/4/835/1078218).

Psilocybe could be anywhere from 20 to 100 million years old. We assume that the most recent common ancestor of all species of Psilocybe could produce psilocybin (because all except one produce it), and likely psilocybin is the same age as Psilocybe.

All species of Psilocybe, extant and extinct, have forged their way in niches of leaf litter, wood, grass, moss, and dung. We don't know the exact purpose of psilocybin, whether to repel, control, or attract, but we can be certain it targets metazoans with serotonin receptors. Whatever metazoans dominate the different niches of Psilocybe, we can be sure over an evolutionary time scale the genes that produce psilocybin in 200 or so species are refined to best target species of slug, arthropod, nematode, or whatever was eating it for whatever reason in whatever niche. This has happened time and again with co-evolved relationships, especially those with metabolites governing the symbiosis.

If you accept that there are different predators across 200 species of Psilocybe, you may be on the way to understanding why I think different magic mushrooms give different psychedelic experiences. Different effects from different species given an evolutionary time scale is hopefully palatable, but to say that allelic variation in one species changes an experience is more difficult to swallow, especially with the dogmas of how trips work.

We showed that populations of P. subaeruginosa maintain genetic diversity in the alleles that produce psilocybin rather than just one becoming dominant (balancing selection to be fancy). This is probably why WLP can be in some, but not all genotypes and is maintained in populations. What the blazes is the benefit of all this diversity? Diversity to the extent that psilocybin alleles are barely shared by closely related populations and there is reason to suspect recombination within the locus itself that would ensure that the same alleles in the pathway are not linked (or not always inherited together).

Long story short, our work on subs shows an evolutionary process of maintaining allelic diversity in the psilocybin pathway (or balancing selection).

Cubes have a solid 5–6 alleles at the psilocybin locus in the entire population of cultivated mushrooms and a bunch more in naturalised populations. I've grown most of these and am in the process of testing the tryptamine landscape in homozygous genotypes. I've crossed different alleles to see what happens when the psilocybin locus is heterozygous.

I've never been more convinced that there are phenotypic impacts from genotypic diversity, and I hope to hold hard evidence soon. Rest assured, if the time comes, the people will be able to decide if there are differences themselves. In the meantime, do me a favour next sub season: don't combine harvests from different patches. Experience them separately and share whether there is a difference (given a consistent set and setting). Expect there to be different psilocybin alleles at different mushroom sites, unless the mushrooms are harvested from mulch/woodchips that have been spread artificially (wild harvests will guaranteed be different alleles).

More on all this soon.

Full piece at Current Biology here:
https://www.sciencedirect.com/science/article/pii/S0960982223014604?dgcid=author.
​And just in case you hadn't seen that our sub work is publicly available, just not peer reviewed right here: https://www.authorea.com/users/700719/articles/687526-wood-loving-magic-mushrooms-from-australia-are-saprotrophic-invaders-in-the-northern-hemisphere.