What it is
Genetics here means two separate questions, and keeping them apart helps. The first is the genetics of the source. How does a mushroom or a plant build a psychoactive molecule, which genes do the work, and why do two samples of the "same" organism differ? The second is the genetics of the person. Do inherited differences in how a body clears these molecules, or in the receptors they act on, help explain why two people respond differently?
A few terms carry most of the weight. A gene is a stretch of DNA that carries the instructions for one protein, often an enzyme, which speeds up a chemical reaction. In fungi the genes for one compound often sit side by side in a biosynthetic gene cluster, which lets them be switched on together and, as the evidence below shows, handed from one species to another as a unit. An allele is one version of a gene, and a genotype is the pair of versions a person carries. Pharmacogenetics asks how such variants change the way the body handles a drug, either by changing how fast enzymes clear it or by changing the targets it acts on. Epigenetics concerns chemical marks on DNA that can change while the sequence stays the same.
Why does a research organization interested in natural psychedelics for personal growth in healthy adults care? Two claims central to its work can be tested by genetics. One is that a name on a label, such as a species or strain, tells a reader what is in the sample. The other is that a group average describes the individuals inside it.
What is known
How a mushroom builds psilocybin
The psilocybin pathway in Psilocybe mushrooms was worked out in 2017. Fricke and colleagues characterized four enzymes. PsiD is a new class of fungal tryptophan decarboxylase, PsiH adds an oxygen atom, PsiK adds a phosphate, and PsiM adds methyl groups. In a test tube, PsiD, PsiK and PsiM together made psilocybin from 4-hydroxy-L-tryptophan [1].
A second group found the same genes by another route. Reynolds and colleagues sequenced three producing mushrooms and searched for genes found only in producers. Of 37 candidate gene families, only five sat together, all in the producers, and they matched the Fricke genes [2]. No psi genes turned up in Psilocybe fuscofulva, a relative placed at the base of the genus, which fits an ancestor that lacked the ability [2]. The genomes were drafts built from short reads [2].
Where the cluster came from
Psilocybin turns up in scattered branches of the mushroom family tree. Reynolds and colleagues tested whether the cluster had moved between species by horizontal gene transfer, the passing of genes between unrelated organisms instead of from parent to offspring. Tests that forced ordinary inheritance on key lineages were rejected, and a model allowing transfers explained the gene trees in 6 events, against 28 without them.
Bradshaw and colleagues widened the picture in 2024 by sequencing museum specimens. Of 71 specimens labelled Psilocybe, only 52 proved to be true Psilocybe, and the rest belonged to other genera. The team dated the genus's origin and diversification. The cluster showed two gene orders matching the deepest split in the genus, which the authors read as a possible sign of two separate acquisitions, and they inferred four to five possible transfers, to Panaeolus, Gymnopilus, Pluteus and Pholiotina, between 40 and 9 million years ago [3]. Before this work only five of roughly 165 Psilocybe species had genome-level data, though an announcement published online in December 2024 counted eight whole genomes on GenBank before its own five [42]. Species the authors call critical were missing from the sample, the dates rest on secondary calibrations the authors call tentative, and the museum assemblies are fragmentary, with BUSCO completeness between 31 and 95 percent. Although the abstract places the origin in Psilocybe, the discussion allows that a wider sample could push it earlier, into another genus [3].
Mushrooms also arrived at psilocybin twice with different tools. Schäfer and colleagues studied Inocybe corydalina, and found in laboratory tests of four of its five enzymes that none of the reactions known from Psilocybe takes place there. The fifth enzyme, a P450 that would add the oxygen, could not be made soluble for testing and was only modelled by computer. The authors conclude that mushrooms recruited distantly or entirely unrelated enzymes to evolve psilocybin production twice [4]. The work was done in test tubes and has not been shown inside the living fungus.
A 2026 preprint, not yet peer reviewed, adds a warning. Kunik and colleagues report that Galerina indica makes both psilocybin and amatoxins, the toxins of deadly mushrooms. They collected five Galerina specimens, and three were G. indica. The authors suggest the psilocybin genes arrived after the amatoxin genes and that this may have coincided with weaker potency, a guess drawn from chemical structure that was not tested. They write that amatoxins lacking one hydroxyl group, as in the main one they found, remain toxic, and they caution that the blue colour of bruised psilocybin mushrooms can be a useful clue only in well-characterized species with a tradition of use, since it can accompany amatoxins in rare, uncharacterized ones [5]. That caution sits in the preprint's discussion, and the main results do not show its basis. Bluing alone is not enough to identify a mushroom, and this page does not teach identification.
What psilocybin does for the fungus remains unknown, and Meyer and Slot found that no ecological role has been shown by experiment [6].
Cultivated strains: low genetic diversity, very different chemistry
Psilocybe cubensis is the best studied species at population level. McTaggart and colleagues compared 38 isolates from a naturalized Australian population with 86 commercial cultivars. The cultivars had low diversity and signs of self-fertilization and clonal propagation. Across the seven cluster genes, about 60 of the 124 genomes did not differ at any informative site, though the Australian group and three cultivar groups carried several alleles. The authors found no evidence of positive selection on the cluster and say unique variants may change how psilocybin and its analogs are made [7]. Two authors run companies that grow psilocybin mushrooms, and one founded a genomics firm [7]. A study of 89 genomes of a wood-loving group, which the authors treat as one species, found a contrasting pattern in nature. The genomes were 86 Australian haplotypes from at least 28 mushrooms, many of them siblings, plus three from elsewhere. Cluster genes showed 178 amino-acid differences, and the authors write that some genes, notably psiT1, psiT2 and psiH2, may be under balancing selection, a process that keeps variants in a population, though an even spread of variants between sites could instead reflect drift [8].
The chemistry tells another story. Sharchaton and colleagues grew 14 P. cubensis strains from two commercial suppliers under one protocol and measured tryptamines. Total content ranged from 2.62 to 20.65 mg per gram of dried mushroom, a 7.8-fold spread. Single fruiting bodies of one strain also varied [11]. Strain identity rested on appearance, and the DNA barcode region (ITS) placed each sample only at species level. The comparison between strains used repeated measurements of one powdered sample per strain, with no repeated growing runs. The study had no genomic reference for the strains and did not sequence the psilocybin cluster [11].
Put the two together and a puzzle appears. If the cluster varies so little across cultivars, something else may account for a 7.8-fold difference, though no strain has been both sequenced and measured. Candidates include how the genes are switched on, other genes outside the cluster, the residual cluster variants McTaggart flagged, and growth differences nobody has measured. One lead is a 4.6-kilobase insertion at the end of the PsiM gene in a 2021 draft reference genome of a strain labelled P.envy, by authors at commercial testing firms, which earlier cultivar surveys had not shown. The authors say its significance is unknown, and no paper has linked it to chemistry [10]. Seibold and colleagues found that in P. mexicana genes that build tryptophan switch on when psilocybin production starts, but public P. cubensis data, re-analysed by the same authors and not tested in a parallel experiment, showed only marginal changes, so the two species may regulate supply differently [12]. Whether the 14 strains overlap with the 86 sequenced cultivars is not established. Only Penis Envy appears under the same name in both sets, and McTaggart's paper notes that cultivars sharing a name across suppliers are not genetically alike [7] [11]. The full cultivar list, in a supplementary table, was not read. A survey of five Psilocybe genomes also predicted much more metabolic capacity than chemistry has revealed, and aeruginascin was detected only in very minor amounts, under 0.1 percent of the psilocybin signal. One author holds rights in a psychedelic company [13].
The plant side
Plant work is younger. In iboga, Farrow and colleagues built the first transcriptome, the catalogue of active genes, and identified the last two enzymes of ibogaine biosynthesis, shown in yeast, bacteria and test tubes and not in the living plant. The methylating enzyme worked on noribogaine at only 3 percent of its activity on a related compound, which points to a branched route, and the authors could not rule out another methyltransferase [14]. A 2024 commentary reports that a study had worked out the full mescaline pathway in peyote [15]. A forensic transcriptome of peyote turned up specimens that contain no mescaline, [16]. So plants also show a gap between the species name and the chemistry in the sample, and the genetic reasons are only beginning to be mapped.
The pathway moved into microbes
The pathway has been rebuilt in other organisms as laboratory science. Hoefgen and colleagues expressed the cluster in a mould [17], and Adams and colleagues reported 1.16 grams per litre of psilocybin from engineered E. coli, a route Milne and colleagues describe as relying on added precursors [18]. Milne and colleagues made it in baker's yeast from glucose, using a decarboxylase from the plant Catharanthus roseus in place of PsiD. Hydroxylation was the early bottleneck, and a partner enzyme from P. cubensis raised combined psilocybin and psilocin about 29-fold in small cultures, after which methylation by PsiM became the limiting step. The authors declared a patent application [19]. Meng and colleagues solved crystal structures of PsiD, PsiK and PsiM, though the PsiK structure was captured with tryptamine instead of its natural substrate and so shows an inactive state [20]. The known genes are enough to make the molecule in a microbe, and a single defined molecule can come from a source with no mushroom-to-mushroom variation. What that changes for whole natural preparations these papers do not address.
The person: how bodies handle these compounds
Some human genetic data exist, though they are narrow. The best evidence concerns CYP2D6, the gene for a liver enzyme that clears many drugs. Its variants sort people into poor, intermediate, normal and ultrarapid metabolizers. Vizeli and colleagues in Basel pooled four placebo-controlled crossover studies of LSD in 81 healthy volunteers, all of European descent. People with no working CYP2D6 had a longer LSD half-life and about 75 percent more total exposure to the drug and its main metabolite. Only 7 of the 81 had no working CYP2D6, against 74 who did, so that figure rests on seven people. Their peak concentration did not differ significantly. They also rated their altered state higher, especially anxious ego dissolution, and the effects lasted longer, a difference that held in the parametric test only. Ratings of drug effect at the peak did not differ. Variants in four other enzymes made no detectable difference, and neither did sex or body weight. The authors list limits: a modest sample, a hypothesis set in advance but not corrected for multiple tests, and rare variants in CYP3A4 [21].
A larger pooled analysis of nine studies and 213 healthy volunteers found that the amount given was the strongest predictor of LSD's effects and that CYP2D6 activity was the only other predictor of blood concentration. Lower activity went with more anxious ego dissolution. Mood, openness and earlier experience also predicted the response, and results were corrected for multiple tests [22]. That analysis contains the four studies behind the 81-person result, so it extends that result and is not an independent confirmation. In 23 healthy volunteers, six weeks of paroxetine, which blocks CYP2D6, raised LSD peak and total exposure by factors of about 1.4 and 1.5. In the three poor metabolizers, whose enzyme was already inactive, paroxetine did not change exposure, which rests on three people. Blood expression of HTR2A, SLC6A4 and BDNF did not change [23].
MDMA is not a classic psychedelic, so it counts only as indirect evidence. In a pooled analysis of eight trials and 139 healthy people, 7 of them poor metabolizers, those poor metabolizers had a 15 percent higher peak of MDMA and a 50 percent higher peak of its active metabolite MDA, with blood pressure and subjective effects rising faster. The effects were small, because MDMA blocks CYP2D6 itself [24].
For psilocin, the active form of psilocybin, the picture splits. In test tubes, recombinant CYP2D6 cleared nearly all of it and CYP3A4 about 40 percent, with a small contribution from MAO-A, while a recombinant UGT1A10 did not process it. Yet CYP2D6 genotype did not influence psilocin blood levels in the volunteers studied, a small sample the authors call preliminary. Response was not measured, so this says nothing directly about how a person feels. The paper's main text gives no genotype group sizes [25], though a later review reports 3 poor, 25 intermediate, 58 normal and 2 ultrarapid metabolizers, a count not confirmed in the original [31]. Two reviews repeat the enzyme claim without adding independent evidence. A systematic review of 14 studies names CYP2D6, CYP3A4 and MAO-A as the main routes, yet the only included study that assigns enzymes to psilocin is the one above, and the review's own table says CYP2D6 contributes minimally and the role of CYP3A4 is uncertain [26]. A review of sex hormones says in its text that human data confirm both routes and in its table calls their role minimal in vivo [33]. A test-tube pathway and a genotype effect in people are separate questions, and so far the second has returned a null.
For DMT, MAO-A is the main clearing enzyme, but in laboratory tests CYP2D6 also cleared DMT rapidly [27]. A small descriptive report of 14 experienced members of a religious group that drinks ayahuasca described fast and slow metabolizers of harmine, an ayahuasca alkaloid that CYP2D6 metabolizes. It is a sample of unusual users and was not a controlled trial [28]. A 2026 computer model built on six volunteers predicted that CYP2D6-blocking antidepressants would raise harmine exposure by about 1.2 to 1.3 times and DMT exposure by about 2.1 times, but it includes no genotype data and belongs with drug interactions more than with inherited variation [29].
Receptors, candidate genes and hormones
The main target of classic psychedelics is the serotonin 2A receptor, encoded by HTR2A. In healthy volunteers, blocking it with ketanserin blocked the psychosis-like effects of psilocybin [30]. No human study was found that tests whether ordinary variants of HTR2A change a person's response. A cell study of seven HTR2A variants reported statistically significant but modest changes in how four psychedelics signal through the receptor, with effects that differed by compound [43]. PubMed searches run for this page on 1 and 2 October 2026 returned no records pairing HTR2A and genetic polymorphism under the hallucinogens heading, or BDNF Val66Met with that heading or with psilocybin. Those are search results and cannot show that nothing exists, and the newest papers may not be indexed yet. A review of pharmacogenomics in psychedelic therapy says evidence is limited, particularly for pharmacodynamics, and its authors hold shares in a psychedelic company [31]. The Basel authors note they did not examine receptor-gene variants [22].
Border and colleagues tested 18 candidate genes for depression each studied ten or more times, in samples of 62,138 to 443,264 people, and found no clear association for any of them, apart from one very small COMT effect on current depression severity and one DRD2 gene-level signal that appeared in one sample and not the other. They concluded that the earlier positive reports were probably false positives [32]. That study concerned depression, not psychedelic response.
A 2026 review reports that estradiol and progesterone generally raise CYP3A4 activity, while findings for CYP2D6 are, in its words, scarce and mixed, with a hint from transgenic mice. It adds that platelet, PET and SPECT studies in women indicate higher 5-HT2A availability when progesterone is low, though the platelet studies differ on the exact phase of the cycle and their relevance to the brain is uncertain. It states that direct human data on psychedelic exposure across hormonal states remain absent [33]. A systematic review of 32 trials in healthy adults reports large differences between people in how these compounds are handled and calls for work on genetic, physiological and demographic factors. It did not assess genotype itself [34].
Epigenetic marks
The one human epigenetic study found was in a clinical group. Urban and colleagues measured blood DNA methylation in 37 detoxified patients with alcohol use disorder, randomized to psilocybin or placebo,. The trial's primary outcomes did not differ between groups (p = 0.095). The authors accepted a lenient significance threshold because the study was underpowered. The candidate-gene results did not survive correction for multiple testing, and two methylation changes near the serotonin 2A receptor gene were nominal only, meaning significant before that adjustment and not after it. One site linked to the gene TLE4 looked strong in a cross-sectional test, but the two groups already differed at baseline and the difference reversed. A test found no sign that methylation explained the fall in depression scores, and blood is not brain. Twenty-one of the 37 patients smoked, and no genetic variants were analysed. The authors call the work hypothesis-generating [35].
Where the evidence is thin
The human samples are small. The CYP2D6 analyses above enrolled 81, 139 and 213 people, far fewer than in the depression gene study cited earlier, and they are not three independent results, since the 213-person LSD analysis contains the four studies of the 81-person one and the MDMA analysis concerns a different drug. Nearly all the human data pairing genotype with response came from one research group in Basel using similar designs. The raw data are not public, and the group declares ties to a psychedelic drug developer, Definium Therapeutics (formerly Mind Medicine Inc.). One author consults for it, knowledge from the studies is licensed to it, and it co-funded the paroxetine trial [22] [23]. A second group, in Auckland, tried to test genotype in 40 healthy men given LSD under double-blind conditions and found no poor or ultrarapid metabolizers among those who could be classified, so it left genotype out of its model and neither replicated nor contradicted the Basel result [41]. The LSD cohort was of European ancestry, screened for little earlier drug use, tested in a quiet hospital room, with self-rated outcomes. Variant frequencies differ across populations. In the Basel sample 7 of 81 volunteers, about 9 percent, had no working enzyme. A summary of 177 reports covering about 60,000 people puts the predicted share of poor metabolizers at 5.4 percent in Europeans and 0.4 percent in East Asians, and the reduced-function allele CYP2D6*10 at about 45 percent in East Asians against 2.6 percent in Europeans [36]. Findings from one ancestry cannot be assumed for another.
Several results are nulls or weak, and on the source side cultivar genetics and chemistry have not been tied to the same strains, while the Galerina result rests on a preprint with three specimens.
Ethics, access and ownership
Sequencing a fungus or a plant is "utilization of genetic resources" in the language of the Nagoya Protocol [37]. It calls for benefits to be shared fairly with the country of origin and, where indigenous and local communities hold the resources or the knowledge, with those communities, on mutually agreed terms and with prior informed consent [37]. It also asks Parties to consider simplified access measures for non-commercial research, taking into account a possible change of intent [37]. As of 4 October 2026 the Convention's secretariat lists 143 Parties to the Protocol, and the United States is not one of them [38]. The Convention's parties agreed in 2022 on a multilateral mechanism for sharing benefits from digital sequence information, and decision 16/2 adopted its operating terms, including a fund called the Cali Fund, though the official page gives no year for that decision [39]. This page describes these texts and does not interpret them. How the Protocol and national access laws apply to a particular specimen, including historical museum specimens or cultivars descended from Mesoamerican material, is a question for the Protocol text and the country concerned. Ownership is a live question too, since the yeast work declared a patent application [19].
For people, access and fairness run through the same variants. If the evidence on who clears a compound slowly is built in one ancestry, any later use of genotype information will serve that group best. The United States genetic nondiscrimination law covers health insurance and employment, and the National Human Genome Research Institute states, on a page last updated in January 2022, that it does not cover life, disability or long-term-care insurance, while some states add their own protections [40]. Because relatives share DNA, one person's consent does not fully cover the people who share it.
What is not known
Do common variants of HTR2A or other receptor and signalling genes change the response of healthy adults? No human study found here tested it. Does CYP2D6 genotype matter for psilocybin in people, given the test-tube evidence and a single small, preliminary null? Does it matter for DMT-containing preparations? How much of any difference between people is genetic, compared with the amount taken, mood, setting, hormones and earlier use? For LSD there is a partial answer, and for other compounds there is none. Do the findings hold in people of other ancestries?
On the source side, what explains the 7.8-fold spread among cultivars whose cluster genes vary little? Do any of the 14 strains that were measured match the 86 that were sequenced? What does psilocybin do for the fungus? How common are mushrooms that carry both psilocybin and amatoxins, and does bruising colour mean anything reliable across species? Why do some peyote specimens contain no mescaline?
What Metanoia asks
Do inherited differences in CYP2D6 or CYP3A4 change how a healthy person responds? Where do differences between cultivars come from, beyond the psilocybin genes themselves? Do hormonal states change response in people, and by how much? And how much does the name of a species or strain tell a reader about what is in the sample?
Metanoia's long-term goal is a comprehensive research center: an institution that keeps monitoring and reporting the field's evidence, convenes researchers, registries and regulators around shared reporting standards, and also conducts its own research, beginning with a validated measure of flourishing and a naturalistic observational cohort studied under those standards, and growing toward laboratory work in cultivation, chemistry and genetics under full legal authorization. The center is planned, not built, and its location has not been decided. Whether human genetic data could be collected at all, under what ethics review and with what protection for genomic data, is itself one of the questions this discipline asks.
Genetics is the reason a single average can mislead. For an outcome measure, which Metanoia is still developing, the question is which factors that might explain individual differences should be recorded, instead of assuming everyone responds alike. For the material standard, two reports that name the same mushroom may describe different chemistry, so how much a name can say is a question too. No study read for this page linked a genetic variant to a change on any of the twelve dimensions in healthy adults.
History in brief
Psilocybin was structurally described and synthesized in 1958, and a biosynthetic route was proposed later from labelled precursors [2]. The authors of the genomics papers note that prohibition limited research on its genetics for decades [2] [3]. Traditional and ethnographic use is graded 4 and is not described here beyond the statement in Bradshaw's introduction, because no ethnographic source was read for this page. Tradition validates neither a safety claim nor a benefit claim.
Sources
Reliability levels: 1 is a primary source or any peer-reviewed publication, including reviews, meta-analyses and commentary. 2 is a reliable secondary source that is not peer-reviewed. 3 is a grey or community source, including company statements and preprints. 4 is a traditional or ethnographic source. Levels 3 and 4 describe the type of source and say nothing about quality. Every entry is level 1 except the one preprint (level 3). Official treaty and agency pages are level 1 as primary sources. Identifiers were checked against PubMed on 1, 2 and 4 October 2026. Each entry says how much was read.
- Fricke J, Blei F, Hoffmeister D. Enzymatic synthesis of psilocybin. Angew Chem Int Ed 2017, 56(40):12352-12355. DOI 10.1002/anie.201705489 PMID 28763571. Grade 1. Enzyme characterization in vitro. Abstract only. Full text not accessible.
- Reynolds HT, Vijayakumar V, Gluck-Thaler E, Korotkin HB, Matheny PB, Slot JC. Horizontal gene cluster transfer increased hallucinogenic mushroom diversity. Evol Lett 2018, 2(2):88-101. DOI 10.1002/evl3.42 PMID 30283667. Grade 1. Comparative genomics and enzyme assays. Read in full (PMC6121855), re-read on 4 October 2026 with its tables. Supplementary data not read. Italic species names were lost in the text conversion, so names were taken from its Table 1. Note: the cluster's PsiD turned tryptophan into tryptamine in a test tube and left phenylalanine, tyrosine and 5-hydroxytryptophan alone. The three producers were compared with relatives that do not make psilocybin. The genomes were drafts built from short reads at 16 to 45 times coverage, and regulations on the substrates prevented further enzyme tests. The tests that rejected ordinary inheritance gave p = 0.004 and 0.036, and the authors call it the first reported transfer of a secondary-metabolite gene cluster between mushroom-forming fungi. Older labelling experiments had suggested the methyl groups go on first, so the order of steps found by Fricke et al. was a surprise.
- Bradshaw AJ, Ramírez-Cruz V, Awan AR, Furci G, Guzmán-Dávalos L, Dentinger BTM. Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster. PNAS 2024, 121(3):e2311245121. DOI 10.1073/pnas.2311245121 PMID 38194448. Grade 1. Phylogenomics of museum specimens. Read in full (PMC10801892), re-read on 4 October 2026 with the genus names restored. Supplementary appendix not read. Note: of the 71 labelled specimens, 23 were type specimens that anchor species names. Using 2,983 single-copy genes, the stem lineage is placed at about 67 million years ago and the diversification at about 56 million years ago. The cluster showed one gene order in 17 specimens and another in 35. The critical species missing from the sample include P. fuscofulva. The authors also note that Mesoamerican peoples used these mushrooms for centuries and that colonial persecution followed.
- Schäfer T, Haun F, Rupp B, Hoffmeister D. Dissimilar reactions and enzymes for psilocybin biosynthesis in Inocybe and Psilocybe mushrooms. Angew Chem Int Ed 2025, 64(46):e202512017. DOI 10.1002/anie.202512017 PMID 40977073. Grade 1. Enzyme characterization in vitro. Read in full (PMC12603985), 4 October 2026. Supporting information not read. Note: the Inocybe tryptophan decarboxylase needs the cofactor pyridoxal phosphate, and the pathway branches, ending in baeocystin as a second product.
- Kunik AR, Christopher MW, Lemmond B, Dentinger BTM, Slot J, Garrett TJ, Smith ME. The "dark magic mushroom" co-produces amatoxins and psilocybin. bioRxiv 2026 (posted 22 July 2026). DOI 10.64898/2026.07.17.739257 PMID 42539197. Grade 3. Preprint, not peer reviewed. Read in full (PMC13419790), 4 October 2026, including the discussion passage on bluing, which is paraphrased and not quoted. Supplements not read. Note: the main amatoxin was alpha-proamanitin, which lacks one hydroxyl group found in the classic toxin. The five Galerina specimens were collected in the southeastern United States.
- Meyer M, Slot J. The evolution and ecology of psilocybin in nature. Fungal Genet Biol 2023, 167:103812. DOI 10.1016/j.fgb.2023.103812 PMID 37210028. Grade 1. Review. Abstract only. Full text not accessible.
- McTaggart AR, McLaughlin S, Slot JC, McKernan K, Appleyard C, Bartlett TL, et al. Domestication through clandestine cultivation constrained genetic diversity in magic mushrooms relative to naturalized populations. Curr Biol 2023, 33(23):5147-5159. DOI 10.1016/j.cub.2023.10.059 PMID 38052161. Grade 1. Population genomics, 38 isolates and 86 cultivars. Read in full (author's copy from a university laboratory website), 4 October 2026. Supplementary tables, including the cultivar list, not read. Two authors run psilocybin-mushroom companies and one founded a genomics firm. Note: the three cultivar groups with several alleles were Blue Magnolia, Luminous and P-envy. The authors tie the low diversity and the signs of self-fertilization and clonal propagation to domestication through cultivation.
- McTaggart AR, Scarlett K, Slot JC, Barlow C, Appleyard C, Gardiner DM, et al. Wood-loving magic mushrooms from Australia are saprotrophic invaders in the Northern Hemisphere. Fungal Syst Evol 2024, 14:209-217. DOI 10.3114/fuse.2024.14.14 PMID 39830294. Grade 1. Population genomics, 89 genomes. Read in full (PMC11736257), 4 October 2026. Supplementary tables not read. One author owns a psilocybin-mushroom company.
- McTaggart AR, James TY, Slot JC, Barlow C, Fechner N, Shuey LS, Drenth A. Genome sequencing progenies of magic mushrooms (Psilocybe subaeruginosa) identifies tetrapolar mating and gene duplications in the psilocybin pathway. Fungal Genet Biol 2023, 165:103769 (online 29 December 2022). DOI 10.1016/j.fgb.2022.103769 PMID 36587787. Grade 1. Genome sequencing of five siblings. Abstract only. Full text not accessible (the repository record holds metadata only). Note: five siblings carried identical cluster alleles and three copies of PsiH.
- McKernan K, Kane LT, Crawford S, Chin CS, Trippe A, McLaughlin S. A draft reference assembly of the Psilocybe cubensis genome. F1000Res 2021, 10:281. DOI 10.12688/f1000research.51613.2 PMID 34322225. Grade 1. Genome assembly. Read in full (PMC8220353), 4 October 2026. The species name is italic in the original and was lost in the PubMed record, so the title is reconstructed from the keywords. The authors are affiliated with commercial testing companies. One strain, named anecdotally. Note: the draft reference genome is 46.6 million bases in 32 pieces, with the whole cluster on one of them.
- Sharchaton A, et al. Surprising variability in tryptamine profiles of Psilocybe cubensis fruiting bodies: inter- and intra-strain differences across 14 strains cultivated under controlled conditions. J Fungi 2026, 12(7):486. DOI 10.3390/jof12070486 PMID 42506248. Grade 1. Chemical analysis of 14 strains from two commercial suppliers. Read in full (PMC13412672), 4 October 2026. The first author's name was checked against the PubMed record. Supplementary tables not read. Note: six tryptamines were measured. Psilocybin alone ranged from 2.03 to 19.60 mg per gram. Coefficients of variation (spread relative to the average) for psilocybin across single fruiting bodies were 12.8 to 23.4 percent, in six strains of five fruiting bodies each.
- Seibold PS, Dörner S, Fricke J, Schäfer T, Beemelmanns C, Hoffmeister D. Genetic regulation of L-tryptophan metabolism in Psilocybe mexicana supports psilocybin biosynthesis. Fungal Biol Biotechnol 2024, 11(1):4. DOI 10.1186/s40694-024-00173-6 PMID 38664850. Grade 1. Comparative transcriptomics. Read in full (PMC11046786), 4 October 2026. The P. cubensis comparison is a re-analysis of public data. Supplementary file not read. Note: in P. mexicana the genes that consume tryptophan switch off as psilocybin production starts.
- Dörner S, Rogge K, Fricke J, Schäfer T, Wurlitzer JM, Gressler M, et al. Genetic survey of Psilocybe natural products. ChemBioChem 2022, 23(14):e202200249. DOI 10.1002/cbic.202200249 PMID 35583969. Grade 1. Genome mining of five species. Read in full (PMC9400892), 4 October 2026. Supporting information not read. One author holds rights in a psychedelic company. Note: aeruginascin was detected in P. cyanescens and P. mexicana.
- Farrow SC, Kamileen MO, Meades J, Ameyaw B, Xiao Y, O'Connor SE. Cytochrome P450 and O-methyltransferase catalyze the final steps in the biosynthesis of the anti-addictive alkaloid ibogaine from Tabernanthe iboga. J Biol Chem 2018, 293(36):13821-13833. DOI 10.1074/jbc.RA118.004060 PMID 30030374. Grade 1. Transcriptomics and enzyme assays in plants. Read in full (PMC6130943), 4 October 2026. Supplementary tables and figures not read.
- Courdavault V, Papon N. Plant drugs: transcending the mescaline biosynthesis. Curr Biol 2024, 34(16):R791-R793. DOI 10.1016/j.cub.2024.06.061 PMID 39163844. Grade 1. Peer-reviewed commentary on other work. The studies it appears to concern, Watkins et al. 2023 (Plant J) and Berman et al. 2024 (Mol Plant), were located, but their full text was not accessible. Abstract only. Full text not accessible.
- Hwang EM, Jeong KS, Yoo SY, Kim J, Choe S, Kim JY. Comparative transcriptomic analysis provides novel insights into mescaline biosynthesis by Lophophora williamsii. J Forensic Sci 2025, 70(2):490-503 (online 26 November 2024). DOI 10.1111/1556-4029.15679 PMID 39592450. Grade 1. Transcriptome sequencing. Abstract only. Full text not accessible. Note: the specimens also yielded large pools of candidate genes, 215 O-methyltransferases among them.
- Hoefgen S, Lin J, Fricke J, Stroe MC, Mattern DJ, Kufs JE, et al. Facile assembly and fluorescence-based screening method for heterologous expression of biosynthetic pathways in fungi. Metab Eng 2018, 48:44-51. DOI 10.1016/j.ymben.2018.05.014 PMID 29842926. Grade 1. Metabolic engineering. Abstract only. Full text not accessible. Note: the cluster was expressed in the mould Aspergillus nidulans.
- Adams AM, Kaplan NA, Wei Z, Brinton JD, Monnier CS, Enacopol AL, et al. In vivo production of psilocybin in E. coli. Metab Eng 2019, 56:111-119. DOI 10.1016/j.ymben.2019.09.009 PMID 31550507. Grade 1. Metabolic engineering. Abstract only. Full text not accessible. The note about added precursors comes from the description in Milne et al.
- Milne N, Thomsen P, Mølgaard Knudsen N, Rubaszka P, Kristensen M, Borodina I. Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives. Metab Eng 2020, 60:25-36. DOI 10.1016/j.ymben.2019.12.007 PMID 32224264. Grade 1. Metabolic engineering. Read in full (PMC7232020), 4 October 2026. Two authors declare a patent application related to the work. Note: the yeast titres were 627 mg per litre of psilocybin with 580 mg per litre of psilocin in the same cultures.
- Meng C, Guo W, Xiao C, Wen Y, Zhu X, Zhang Q, et al. Structural basis for psilocybin biosynthesis. Nat Commun 2025, 16(1):2827. DOI 10.1038/s41467-025-58239-x PMID 40121242. Grade 1. Structural biology with a mouse experiment. Read in full (PMC11929908), 4 October 2026. Supplementary information not read.
- Vizeli P, Straumann I, Holze F, Schmid Y, Dolder PC, Liechti ME. Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis. Sci Rep 2021, 11(1):10851. DOI 10.1038/s41598-021-90343-y PMID 34035391. Grade 1. Pooled analysis of four randomized, placebo-controlled, double-blind crossover studies, 81 healthy volunteers. Read in full (PMC8149637), 4 October 2026, including Table 1. Supplementary tables not read. Group sizes: 7 without working CYP2D6, 74 with. One author consults for Definium Therapeutics (formerly Mind Medicine Inc.). Note: the volunteers were aged 25 to 60. No working CYP2D6 is about 5 to 10 percent of the European population by the authors' account. The higher ratings included visionary restructuralization as well as anxious ego dissolution.
- Vizeli P, et al. Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants. Transl Psychiatry 2024. DOI 10.1038/s41398-024-03074-9 PMID 39231959. Grade 1. Pooled analysis of nine double-blind crossover studies, 213 healthy volunteers. Read in full (PMC11374807), 4 October 2026. Supplementary table not read. Includes the four studies of source 21. Data owned by the university hospital and licensed to Definium Therapeutics (formerly Mind Medicine Inc.).
- Becker AM, Humbert-Droz M, Mueller L, Jelušić A, Tolev A, Straumann I, et al. Acute effects and pharmacokinetics of LSD after paroxetine or placebo pre-administration in a randomized, double-blind, cross-over phase I trial. Clin Pharmacol Ther 2025, 117(6):1784-1792. DOI 10.1002/cpt.3618 PMID 40022427. Grade 1. Randomized crossover trial, 23 healthy volunteers. Read in full (PMC12087691), 4 October 2026. Data S1 not read. Funded by the university hospital and Definium Therapeutics (formerly Mind Medicine Inc.).
- Schmid Y, Vizeli P, Hysek CM, Prestin K, Meyer zu Schwabedissen HE, Liechti ME. CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4-methylene-dioxymethamphetamine in a controlled study in healthy individuals. Pharmacogenet Genomics 2016, 26(8):397-401. DOI 10.1097/FPC.0000000000000231 PMID 27253829. Grade 1. Pooled analysis of eight double-blind placebo-controlled crossover studies, 139 healthy volunteers. Read in full (PMC4949007), 4 October 2026. Supplemental content not read.
- Thomann J, Kolaczynska KE, Stoeckmann OV, Rudin D, Vizeli P, Hoener MC, et al. In vitro and in vivo metabolism of psilocybin's active metabolite psilocin. Front Pharmacol 2024, 15:1391689. DOI 10.3389/fphar.2024.1391689 PMID 38741590. Grade 1. Laboratory metabolism study with human plasma samples. Read in full (PMC11089204), 4 October 2026. The main text gives no genotype group sizes. Supplementary material not read.
- Meshkat S, Al-Shamali H, Perivolaris A, Tullu T, Zeifman RJ, Zhang Y, et al. Pharmacokinetics of psilocybin: a systematic review. Pharmaceutics 2025, 17(4):411. DOI 10.3390/pharmaceutics17040411 PMID 40284409. Grade 1. Systematic review. Read in full (PMC12030428), 4 October 2026. Supplementary tables not read. Several authors declare industry ties. Note: six of the 14 studies were clinical, with 112 healthy volunteers.
- Eckernäs E, Macan-Schönleben A, Andresen-Bergström M, Birgersson S, Hoffmann KJ, Ashton M. N,N-dimethyltryptamine forms oxygenated metabolites via CYP2D6: an in vitro investigation. Xenobiotica 2023, 53(8-9):515-522. DOI 10.1080/00498254.2023.2278488 PMID 37916667. Grade 1. Laboratory metabolism study. Abstract only. Full text not accessible.
- Callaway JC. Fast and slow metabolizers of Hoasca. J Psychoactive Drugs 2005, 37(2):157-161. DOI 10.1080/02791072.2005.10399797 PMID 16149329. Grade 1. Small descriptive report, 14 experienced members of a religious group. Abstract only. Full text not accessible. Note: the 14 members were of the União do Vegetal.
- Ribeiro GSG, Paranhos BAPB, Dörr F, Yonamine M, Villanova B, Guerra LTL, et al. Predicting drug-drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling. Front Mol Biosci 2026, 13:1768402. DOI 10.3389/fmolb.2026.1768402 PMID 41788629. Grade 1. Computer modelling calibrated on six volunteers. Read in full (PMC12957174), 4 October 2026. Supplementary material not read.
- Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport 1998, 9(17):3897-3902. DOI 10.1097/00001756-199812010-00024 PMID 9875725. Grade 1. Controlled study in healthy volunteers. Abstract only. Full text not accessible.
- Halman A, Conyers R, Moore C, Khatri D, Sarris J, Perkins D. Harnessing pharmacogenomics in clinical research on psychedelic-assisted therapy. Clin Pharmacol Ther 2025, 117(1):106-115 (online 30 September 2024). DOI 10.1002/cpt.3459 PMID 39345195. Grade 1. Review. Read in full (PMC11652822), 4 October 2026. Three authors hold shares in Psychae Therapeutics.
- Border R, Johnson EC, Evans LM, Smolen A, Berley N, Sullivan PF, et al. No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. Am J Psychiatry 2019, 176(5):376-387. DOI 10.1176/appi.ajp.2018.18070881 PMID 30845820. Grade 1. Preregistered analyses in large population and case-control samples. Read in full (PMC6548317), 4 October 2026. The supplement, which lists the 18 genes, was not read.
- Kuypers KPC, Mason NL, Carlier A, Totomanova I, Haijen-Bongers ECHM. Psychedelics and women's mental health: the effects of female sex hormones on psychedelics' efficacy and tolerability. Mol Psychiatry 2026 (online 4 August 2026). DOI 10.1038/s41380-026-03801-2 PMID 42552418. Grade 1. Narrative review. Read in full (publisher's open-access PDF), 4 October 2026. Reference list and figures not read.
- Hampsey E, Martin K, Kalfas M, Benson L, Wihlborg S, Jelen L, et al. A systematic review of the pharmacokinetics of classical serotonergic psychedelic compounds in healthy adult subjects. J Psychopharmacol 2026, 40(8):1213-1223. DOI 10.1177/02698811261453938 PMID 42212869. Grade 1. Systematic review, 32 trials. Read in full (PMC13415903), 4 October 2026. Supplemental material not read.
- Urban MM, Zillich L, Rieser NM, Herdener M, Spanagel R, Vollenweider FX, et al. Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder. Transl Psychiatry 2026, 16(1). DOI 10.1038/s41398-026-03961-3 PMID 42192100. Grade 1. Exploratory analysis within a randomized, placebo-controlled trial, 37 patients with alcohol use disorder (clinical population). Read in full (PMC13212986), re-read on 4 October 2026. Supplementary figures not read. Note: methylation was measured at baseline, one day later and four weeks later. Mean days abstinent were 11.2 after placebo and 17.8 after psilocybin.
- Gaedigk A, Sangkuhl K, Whirl-Carrillo M, Klein T, Leeder JS. Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med 2017, 19(1):69-76. DOI 10.1038/gim.2016.80 PMID 27388693. Grade 1. Summary of 177 reports covering about 60,000 people. Read in full (PMC5292679), 4 October 2026. Supplementary frequency tables not read. Used for allele and phenotype frequencies.
- Secretariat of the Convention on Biological Diversity. Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity. Official text, https://www.cbd.int/abs/doc/protocol/nagoya-protocol-en.pdf. Grade 1. Treaty text. Articles 1 to 10 and the preamble read directly on 4 October 2026. Articles 11 to 36 and the annex not read. Note: the Protocol defines utilization of genetic resources as research and development on their genetic or biochemical composition.
- Convention on Biological Diversity. Parties to the Nagoya Protocol, https://www.cbd.int/abs/nagoya-protocol/signatories/. Grade 1. Official list. Read directly on 4 October 2026: 143 Parties, and the United States listed with no signature or ratification date. The page shows no update date.
- Convention on Biological Diversity. Digital sequence information on genetic resources and the Cali Fund, https://www.cbd.int/dsi-gr. Grade 1. Official page. Read directly on 4 October 2026 (page updated 10 March 2025). It names decision 16/2 and the Cali Fund and gives no year for the decision. The decision text and contribution rules were not read.
- National Human Genome Research Institute. Genetic discrimination, https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination. Grade 1. Official page. Read directly on 4 October 2026. The page states it was last updated on 6 January 2022 and that the health insurance protections do not cover long-term-care, life or disability insurance.
- Morse JD, Jeong SH, Murphy RJ, Muthukumaraswamy SD, Sumner RL. Pharmacokinetics and pharmacodynamics of sublingual microdosed lysergic acid diethylamide in healthy adult volunteers. J Psychopharmacol 2025, 39(9):976-989. DOI 10.1177/02698811251330747 PMID 40251818. Grade 1. Randomized, double-blind, placebo-controlled parallel trial, 80 healthy men, 40 in the LSD arm. Read in full (PMC12371133), 4 October 2026. Supplementary material not read. Some authors received funding from MindBio Therapeutics.
- Bollinger IM, Singer H, Jacobs J, Tyler M, Scott K, Pauli CS, Miller DR, Barlow C, Rockefeller A, Slot JC, Angel-Mosti V. High-quality draft genomes of ecologically and geographically diverse Psilocybe species. Microbiol Resour Announc 2025, 14(2):e00250-24. Published online 27 December 2024 (PubMed), in the February 2025 issue (volume 14, issue 2). DOI 10.1128/mra.00250-24 PMID 39727395. Grade 1. Genome assemblies of five species. Read in full (PMC11812301), 4 October 2026. Most authors are affiliated with a nonprofit foundation, some also with companies, and the funding includes company sources.
- Schmitz GP, Jain MK, Slocum ST, Roth BL. 5-HT2A SNPs alter the pharmacological signaling of potentially therapeutic psychedelics. ACS Chem Neurosci 2022, 13(16):2386-2398. DOI 10.1021/acschemneuro.1c00815 PMID 35894503. Grade 1. Cell-based study of seven HTR2A variants. Abstract only. Full text not accessible. A seven-fold change that a review attributes to related work was not verified and is not used.
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