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5-MeO-DMT

A substance page: what the research shows, where it is thin, and what Metanoia asks

Research page · fullLast reviewed 5 October 2026

Read this first. This page is education, not instructions to use. Metanoia does not supply any substance. In the United States, most of the substances discussed here are Schedule I under federal law (21 CFR 1308.11), their legal status differs between countries and between US states, and none of this is legal advice. Nothing here is medical advice, and nothing here describes or recommends a dose. "Healthy adults" means people with no diagnosed psychiatric or major medical condition, the population Metanoia studies. Most of what is known about 5-MeO-DMT in people comes from ceremony attendees, online surveys, small studies of screened volunteers and trials in people with a diagnosis, so the text names the group each study used, because that changes what the result can mean for everyone else.

What it is

5-MeO-DMT is a tryptamine, built on the same skeleton as serotonin and closely related to DMT. Its full name is 5-methoxy-N,N-dimethyltryptamine, and in the clinical literature it also appears as mebufotenin. It was first synthesized in 1936 [6], and it occurs in nature by two quite different routes.

The first is plants: small amounts have been found in several Amazonian plants, including the seeds used to make the snuffs known as yopo [1]. The second is an animal. The Colorado River toad (Incilius alvarius, formerly Bufo alvarius) releases a milky secretion from skin glands, and 5-MeO-DMT is its main psychoactive ingredient. It is the only animal known to secrete the molecule [2]. In five samples of dried secretion from ceremony facilitators, about a fifth to a third of the weight was 5-MeO-DMT [5].

A 2025 study of wild toads found 5-MeO-DMT in all 26 I. alvarius tested and in none of two other toad species sampled alongside them, by a method that was not quantitative. The authors list three possibilities: the toad makes it, a microbe living on or in the toad does, or the toad takes it up from a plant or fungal source. They see production by the toad itself, by converting bufotenine, as plausible, but the enzyme involved has not been confirmed in the toad's glands [2]. The 2022 review presents that conversion as established [1].

The secretion also holds bufagins, a group of heart-active steroids [1]. In the one quantitative analysis read for this page, one such steroid was present in four of five dried samples at 0.005 to 0.013 milligrams per gram and the other was below the limit of quantification in all five, against 204 to 307 milligrams of 5-MeO-DMT per gram [5]. A review of toad toxins lists these steroids for this species but takes the entry from other reviews, and the heart toxicity it describes concerns toad venoms in general [30]. No source read measured effects on the heart from this secretion in people, and whether trace amounts matter when it is smoked has not been studied.

What is known

The short version. Controlled research on 5-MeO-DMT in people is young, small, mostly company-sponsored, and almost all of it was done in people with a diagnosis. For healthy adults the evidence is thin: small uncontrolled field studies, online surveys, and short safety studies in volunteers describe an intense, very brief experience, often rated as mystical, with modest gains on mood and mindfulness questionnaires, no placebo comparison, and all on self-report. The results in depression carried formulations into phase 2 and phase 2b trials, but say little about personal growth in healthy people.

How it acts in the body

Most classic psychedelics act mainly on the serotonin 5-HT2A receptor. 5-MeO-DMT binds that receptor too, but binds 5-HT1A far more tightly, by roughly 300 to 1,000 fold in two binding studies on cloned human receptors. How the two receptors divide the human experience is not settled, and these figures reach this page through a narrative review (grade 1), not from the original binding papers [1].

Swallowed, the molecule is inactivated by monoamine oxidase A in the gut and liver, so it is usually inhaled, injected, or given nasally or under the tongue, and the enzyme CYP2D6 converts part of it into bufotenine, which binds 5-HT2A more tightly than the parent molecule does [1]. In the intranasal phase 1 trial (44 psychedelic-naive volunteers), the median time to peak blood concentration was about 4 to 15 minutes depending on the step, the mean terminal half-life was 15 to 27 minutes, and bufotenine was almost always below the limit of quantification [13]. Interviews with 32 volunteers in that trial, funded by Beckley Psytech with company staff among the authors, found mostly elementary visual effects [14].

Field studies of ceremonies and retreats

The earliest human data come from researchers who visited places where people already used the material, and none of these studies had a control group.

A prospective study at four ceremony sites in three European countries followed people who inhaled vapor from dried toad secretion. Of 75 who agreed to take part, 42 completed the baseline and next-day questionnaires and only 24 the four-week follow-up. Life satisfaction rose and stayed up at four weeks, and depression, anxiety and stress ratings fell but reached significance only at four weeks, while divergent thinking did not change. The authors name the weaknesses: no comparison group, 33 of the 75 who consented giving no data after the ceremony, and 18 of the remaining 42 missing at follow-up, which they say may reflect bad experiences. About three quarters reported no psychiatric condition, 93 percent had used other psychedelics before, and the ceremony leaders were not clinicians, so this is not a screened healthy-adult sample [5].

A smaller study followed 11 people who inhaled synthetic 5-MeO-DMT in one-to-one sessions in Prague. None reported a clinician's diagnosis, though four mentioned past depression, anxiety or trauma-related problems, and screening was done from self-report by a facilitator without clinical training. Depression improved right after the session, but by day seven the change was no longer significant (p = 0.073). Five of the 11 reported adverse effects during the session and three in the following days [6].

A third study analysed exit surveys from 20 participants in a paid four-day retreat in Baja California, Mexico, who had passed a medical screen, though psychiatric history was not collected in depth. The response rate was 26 percent (20 of 76), and the first author was employed by the retreat center. After vaporized toad secretion, 75 percent met the study's definition of a complete mystical experience. The retreat also gave ibogaine two days earlier, and the study was neither prospective nor placebo-controlled [9].

Large online surveys

The first, in 2017, drew 515 respondents through internet advertising, with a donation to a nonprofit for each completed survey. The results are averages over items: about 90 percent endorsed each mystical-experience item at a moderate or strong level on average, 57 percent met the complete-mystical-experience criterion, and challenging-experience items were endorsed by 37 percent on average with very slight mean intensity, though single items ran higher, such as 52 percent for a profound experience of their own death and 48 percent for feeling as if dead or dying. Among respondents with a lifetime diagnosis most reported improvement, but between 2 percent (depression) and 10 percent (obsessive-compulsive disorder) said symptoms got worse, and no validated symptom measure was used. The material was mixed, 55 percent synthetic by report and none verified [7].

The second surveyed 362 members of one US group who had used synthetic 5-MeO-DMT in its structured sessions, reached through the group's newsletter. Of those reporting a diagnosis of depression or anxiety, about 80 percent said the condition had improved and 3 percent and 2 percent said it had worsened, but the diagnoses were self-reported and unverified, only seven had used it specifically for depression or anxiety [1] [8], and the design was cross-sectional and retrospective, with no standardized scales [8]. Both include many people with diagnoses, and they and the reactivation analysis below come from the same 2017 survey effort, so they are not independent samples [7] [8] [10].

Controlled studies in healthy volunteers

Controlled work in healthy people has mostly addressed safety and pharmacology, with synthetic material. An early phase 1 study gave 22 healthy volunteers inhaled single steps at four levels, and four others an individualized escalation, all of whom had taken at least two classic psychedelics before. Mystical-experience ratings rose with every step, though ego-dissolution ratings differed only for the individualized escalation (oceanic boundlessness p = 0.053). Cognition, mood and well-being measures did not change in a step-dependent way. Blood pressure was taken by hand half an hour before and one and three hours after the session, not at the peak. Adverse events were mostly mild and no serious event occurred [12]. That is a useful null, with no placebo arm and one week of follow-up.

The phase 1 trial of the intranasal formulation BPL-003 was double-blind and placebo-controlled, with 44 psychedelic-naive volunteers, 31 on the active material and 13 on placebo. It was exploratory, with no sample size calculation, and the authors say participants could tell what they had received, so blinding failed in practice. It reported no serious adverse events, no rise in suicidal thinking and no persisting perceptual disturbance in the week of follow-up. At each of the two highest steps 3 of 5 participants had a complete mystical experience, 6 of 10 together. Blood pressure and heart rate rose briefly and settled within 90 minutes without treatment: systolic pressure went above 140 in 15 of 31 against 3 of 13 on placebo, diastolic above 90 in 17 of 31 against none, and heart rate above 100 in 7 against none, with a peak of 181 systolic. The investigator did not classify these rises as clinically significant, and the authors note that body movement can affect such readings [13].

Registry records list further healthy-volunteer studies, none with posted results, among them a randomized, blinded intravenous trial at the University of Basel in 40 healthy adults that lists resilience and life satisfaction as secondary outcomes and runs from March 2026 to March 2028 [21]. A sublingual study enrolled adults with symptoms of depression or anxiety, so it is not a healthy-adult study here [34].

Trials in people with a diagnosis

This section covers clinical populations. The results do not transfer to healthy adults.

GH001, an inhaled synthetic formulation made by GH Research, was first tested in 16 people with treatment-resistant depression, open-label: 7 of 8 were in remission at day seven in the group with escalating steps within a single day, against 2 of 4 and 1 of 4 in the two single-step groups, and flashbacks were reported by 4 of the 16 [15]. A phase 2b trial randomized 81 people, 40 to GH001 and 41 to placebo, and depression scores fell 15.5 points more with GH001 by day eight, with 23 of 40 in remission against none of 41. No severe or serious adverse events were reported in the placebo-controlled week, though adverse events overall were common on the active material (29 of 40), and the authors say the effect cannot be hidden from participants and blinding was not assessed. In the six-month open-label extension, only 3 of the 23 who reached remission stayed in remission without further treatment, the other 20 were treated again after a median of 6 weeks, 15 of them three or four more times, with 20 of 23 in remission at six months. The company funded both trials. It took part in the design and analysis of the first, and its employees took part in the design, data collection and analysis of the second, and many authors report ties to it [15] [16].

Beckley Psytech's intranasal formulation BPL-003 reported a phase 2 dose-finding trial of 196 people, with results posted to the registry on 10 September 2026. The comparator was a sub-therapeutic low strength, not an inert placebo. At day 29 the highest strength improved the depression score by 11.2 points and the lowest by 5.8, a difference of 5.3 points (p = 0.0033), and the low-strength group improved a good deal on its own. The randomization ratio was changed partway through, from 1:1:1 to 3:1:3, and the target size fell from 225 to 203. Five serious adverse events were recorded, one of them, suicidal ideation, judged related to the treatment, and a rise in blood pressure was among the common adverse events, in 12 of 73 on the highest strength against 3 of 74 on the lowest. The agreement with the sponsor allows a 60-day review and a publication delay of up to 6 months, and no peer-reviewed paper was found [17]. Earlier open-label BPL-003 studies in depression and alcohol use disorder were positive on their own terms [18] [19], but the alcohol study ran inside a 10-week cognitive behavioral therapy program, so the effect of the compound cannot be separated from the therapy [19].

GH001 trials in bipolar II disorder (6 people) and postpartum depression (10 people) were terminated early, and the registry gives difficult recruitment as the reason [21]. The open-label postpartum trial had no control group, enrolled 10 of the 15 planned, and reported all ten in remission at day eight, and the company that funded it employs many of the authors, who hold stock options [20]. All these trials are small or sponsor-run, and none involved healthy adults.

Null and cautionary findings

In the healthy-volunteer study, cognition, mood and well-being measures did not move in a step-dependent way [12]. In the Prague study the cortisol and IL-6 changes were unrelated to any mental-health rating [6], and in the toad ceremony study divergent thinking did not change [5]. People with the most intense experiences reported the biggest changes, although in the toad study that link held on the first day and was absent at four weeks [5] [8]. That fits a drug effect. It also fits people who expected a profound change and found one.

Safety in healthy adults

What follows describes findings, the groups they come from and the conditions. It does not assess risk for any individual.

Acute effects

Commonly listed reactions across surveys and trials include fear, anxiety, confusion, paranoia, nausea and vomiting, headache, and pressure in the chest or abdomen [1]. Blood pressure and heart rate rose briefly in healthy volunteers given the intranasal material [13], and similar brief rises were recorded in patients in the alcohol trial (4 of 13), the postpartum trial and the dose-finding depression trial [17] [19] [20]. One severe event, a blood pressure rise, occurred among 12 patients in an open-label depression study and resolved [18]. Stimulating 5-HT1A tends to lower blood pressure and heart rate while stimulating 5-HT2A raises them [1], and what the trials observed was a transient rise.

Short duration and risk

Cognition and movement return to baseline quickly [1] [12], but that is a statement about duration. The sources do not offer a short experience as evidence of low risk, and none of them assessed the vulnerability of individuals.

Reactivations

A distinctive after-effect is the "reactivation", a short return of some of the experience, or of sensory disturbances such as flashes of light, in the week or two afterward [1] [10]. The literature does not use the terms consistently, and the 2022 review itself moves between "reactivation" and "flashback" [1]. In a survey of 513 people, 73 percent of those who used synthetic material in a structured group reported one, against 27 percent in the general sample, and most rated theirs as positive or neutral, with 4 percent and 7 percent rating theirs negative [10]. The authors point to selection bias and note that the structured group had been told in advance that reactivations can happen, so the gap cannot be read as structured use causing them, and a small group may have a negative reactivation that needs urgent care [10]. Among 90 Spanish-speaking respondents, 69 percent reported reactivations and 97 percent called them positive or neutral [11]. Trials record flashbacks as adverse events in 1 of 22 healthy volunteers [12], 4 of 16 patients with treatment-resistant depression [15], and 2 of 13 in the alcohol trial [19], whose registry record counted no reactivations on its own questionnaire while listing two flashbacks, identity confusion, panic and one episode of suicidal thinking as adverse events [32]. The phase 2b trial reported no flashbacks [16]. Rare psychosis has also been reported in the literature, sometimes with other tryptamines [1].

Interactions

The review expects exposure to rise and last longer when an MAO-inhibiting drug or plant is present, because monoamine oxidase is what breaks the molecule down, and it names a risk of serotonin-excess effects [1]. One published case describes a 25-year-old man found dead after taking herbal extracts that contained beta-carbolines (a class that includes MAO inhibitors), DMT and 5-MeO-DMT. The medical examiner called the cause hallucinogenic amine intoxication and the manner of death undetermined [23]. A letter from several pharmacologists asked for clarity about that report, and a review of drug interactions describes a dispute over whether the high 5-MeO-DMT level came from an ayahuasca drink or from a synthetic source [24] [31]. The letter itself was not read. The same review lists a non-fatal case: a 17-year-old who combined Peganum harmala seed extract, which contains beta-carbolines, with 5-MeO-DMT and developed severe poisoning, with a body temperature of 40.7 degrees Celsius, a heart rate of 186 and muscle breakdown. It advises caution with MAO inhibitors and says the evidence rests on these two cases and on preclinical work [31]. One case with several compounds cannot show what any single one contributed, and the searches for this page found no other published fatality naming 5-MeO-DMT, though they were not exhaustive.

The toad secretion is a different exposure

Controlled safety data exist for synthetic material, and none exist for the toad secretion in people. A review of 208 dogs with known or suspected I. alvarius exposure in Arizona clinics found neurologic signs in 87.5 percent, respiratory signs in 76.9 percent and cardiac signs in 74.5 percent. The abstract does not identify which compound caused the cardiac signs, and the full text could not be read [22]. A 1994 paper reported that the secretion, known to be toxic when eaten, appeared safe to smoke in the authors' own experiments, but those were self-experiments and only the abstract was available, so this is the authors' account and not safety data [4]. Neither finding says how the secretion would perform in a controlled human trial.

Dependence and long-term effects

Few survey respondents reported craving (8 percent) [7], though the US scheduling decision records a high abuse potential [25]. Follow-up in healthy adults runs to about a week under control [12] [13] and four weeks without a control group [5]. Repeated use over years is unstudied.

The toad: conservation and ethics

The 2025 field team notes that illegal collection of I. alvarius to harvest 5-MeO-DMT may present a significant threat to the species. Their introduction also says demand has led to widespread illegal hunting, but as a claim taken from elsewhere, and the paper reports no collection figures or population trend [2]. None of the sources read for this page gives a count or a trend for wild populations. A 2022 review adds that the toad was judged not endangered on the international red list, but that listing dates from an assessment in 2004, and the authors consider it plausible that the rising popularity of toad ceremonies could affect the population over time [1]. The current red-list entry and state-level protections were not checked.

A research group grew a cell line from a small gland biopsy taken under anesthesia from two toads, which stayed alive. Mass spectrometry of the culture medium gave a signal consistent with 5-MeO-DMT, far weaker than natural secretion, and the authors could determine neither a concentration nor a yield and say further work is needed to confirm that the cells make the molecule from scratch. The first author reports equity in a company. The paper also says the toad is under severe ecological pressure, but it cites a general paper on amphibian declines, so that statement is not counted here [3]. No study has compared plant-derived, cell-derived, toad-derived and synthetic material in people.

Legal status

Each entry names the jurisdiction and the official text it rests on, and was checked on 2 October 2026. This describes the law and grants no permission.

United States (federal). 5-MeO-DMT is a Schedule I hallucinogenic substance, listed at 21 CFR 1308.11(d)(15) with DEA code 7431, and bufotenine is listed nearby at (d)(17) with code 7433, in the Electronic Code of Federal Regulations, where the latest amendment of this section is dated 21 September 2026 [26]. Paragraph (d) applies to any preparation containing a listed substance, so by its wording the entry is not limited to the synthetic form. The Drug Enforcement Administration placed 5-MeO-DMT in Schedule I by a final rule published on 20 December 2010 at 75 FR 79296, effective 19 January 2011, recording high abuse potential, no accepted medical use and a lack of accepted safety under medical supervision. Its reasoning leaned on pharmacological similarity to DMT, LSD and mescaline, on anecdotal reports, and on reports that included one death. Research is permitted with a Schedule I registration [25]. State law varies and is not surveyed here.

United Kingdom. The Misuse of Drugs Act 1971 names N,N-dimethyltryptamine and bufotenine in Schedule 2, Part I (Class A). It does not name 5-MeO-DMT, but the same part covers compounds structurally derived from tryptamine by listed modifications, and on a plain reading 5-MeO-DMT matches that description. That is this page's own interpretation, not a quotation of a listing, and it is not verified against any official guidance. The text read was the latest revised version on legislation.gov.uk [27].

Canada, federal. In the Justice Laws consolidation of the Controlled Drugs and Substances Act, Schedule III names N,N-dimethyltryptamine (item 7), psilocin and psilocybin. No entry naming 5-MeO-DMT was found in the schedules or anywhere else in the text of the Act, searched in full. Whether another provision or a regulation reaches it was not assessed, so this page draws no conclusion about its status in Canada. The Act was last amended 18 July 2026 [28].

International treaty status and the law of other countries were not examined.

What is not known

Open scientific questions

The largest gap is the simplest. No published randomized, placebo-controlled study has asked what 5-MeO-DMT does for well-being, mindfulness, creativity, relationships or resilience in healthy adults, and none has followed such people beyond weeks. Blinding is a second problem: an experience this brief and this intense is hard to hide, as the authors of the intranasal and phase 2b trials say, and the comparator in the biggest trial, a low strength, still produced marked improvement [13] [16] [17].

Context is a third. The reactivation survey found large differences between structured group use and general use [10], and no study has separated the effect of the molecule from that of the preparation, the facilitator and the group. Nothing is known about how toad secretion, plant preparations, cell-derived and synthetic material compare in people, or which other compounds in the secretion matter, if any, and why the toad makes the molecule is unsettled [2]. Genetic and medication-related differences in CYP2D6 and monoamine oxidase could change exposure [1], but this has not been studied in healthy adults, and a 2026 pharmacokinetic review calls their clinical relevance unclear [29]. Reactivations have no explanation yet, and the studies use different scales with no shared set of growth outcomes.

What Metanoia asks

Metanoia is a California 501(c)(3) public charity advancing the science of natural psychedelics for personal growth and human flourishing in healthy adults. Not treating illness. Expanding potential. Metanoia has not run a study on 5-MeO-DMT, does not provide or direct anyone toward it, and does not treat any condition with it. It has a set of questions and a measurement approach that is still being built.

The questions are these:

  • What does the molecule do, alone, in someone with no diagnosis, when growth-type outcomes are measured over months against a control condition?
  • How much of what people report comes from the substance, and how much from the setting and the meaning they bring?
  • Do variation in CYP2D6 and monoamine oxidase, or ordinary medications, predict who has which kind of experience, and what would a careful research screening need to check?
  • What, if anything, does the toad secretion contain that the purified molecule does not, and do synthetic, plant-derived and cell-derived material behave alike, without harming wild animals?
  • How could preparation and integration around an experience that is over in minutes be studied?
  • What predicts a hard reactivation?

These are questions and not a program of work.

Any future human work by Metanoia would start from four record-keeping standards (what the material was, what exposure occurred, the surrounding context, and the outcome) and an outcome measure, still in development, addressed to the twelve dimensions of human potential the research asks about. None of that infrastructure has been built for this substance yet.

History and tradition

The sources read mention tradition only in passing. No traditional or ethnographic source (grade 4) was read, and what follows comes from peer-reviewed papers (grade 1) that report the history secondhand, told from outside the communities concerned.

For plants, a survey paper states that plant extracts and preparations such as yopo snuff were reportedly used among Indigenous peoples of the Americas back to pre-Columbian times, resting on earlier papers and not on first-hand records [7]. For the toad, the same survey paper says little evidence supports the idea that Indigenous cultures used the secretion and that its use may be a recent development, taking that from a media report and not from a study [7]. The 2019 field study says historical use by Indigenous peoples in the southwestern United States and northern Mexico may have occurred, but the purpose is unclear and a recent origin of current use cannot be ruled out [5]. No ethnographic record of Indigenous use of the toad secretion was found in the literature read for this page. The review dates the modern practice to a chemical analysis in the 1960s and an underground pamphlet in 1984 [1], and a 2023 paper on the toad's biocultural history, read as an abstract only, says that unrestrained use for spiritual and adventure purposes produced mistaken and exploitative narratives of ancient Indigenous use [33]. A further paper from 2026 could not be accessed, so this page does not use it [35].

An ancient toad ritual is a claim this page cannot support from what was read. The sources describe plant snuffs as the older practice, but only as reported history and not from first-hand documentation.

Sources

Grade key: 1 = primary source or any peer-reviewed publication (including narrative and systematic reviews and meta-analyses), and official primary records such as law, registries and agency documents. 2 = reliable secondary source that is not peer reviewed. 3 = grey or community source, including preprints, company announcements and organizational statements. 4 = traditional or ethnographic source. Grades 3 and 4 are source types, not lower quality. Grade describes the type of source, not the strength of the design, which is given in the text and in each entry. "Read in full" means the whole text was read, though supplementary files were not. "Read in part" means the passages cited were read and the document was searched, but it was not read end to end. "Abstract only. Full text not accessible." means only the abstract and indexing record could be read. Everything was accessed on 1 or 2 October 2026.

  1. Reckweg JT, Uthaug MV, Szabo A, Davis AK, Lancelotta R, Mason NL, Ramaekers JG. The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). J Neurochem 2022, 162:128-146. PMID 35149998. DOI 10.1111/jnc.15587 Grade 1. Peer-reviewed narrative review with no stated search method. Several authors report consulting for companies developing 5-MeO-DMT. Read in full. Detail moved from the text: inhaled effects peak within minutes and last about 15 to 20 minutes, and intramuscular injection is reported to be slower and gentler, lasting up to an hour. The review lists bufotenine, other indole compounds, catecholamines and sterols in the secretion, citing chemical work from the 1960s, and notes plant sources in seeds, bark and leaves, usually together with DMT and other indole alkaloids. Two binding studies put the affinity for 5-HT1A at 1.9 to 3 nanomolar. The review says Indigenous use for shamanic purposes in South America and the Caribbean has been suggested but strong evidence is lacking, dates the modern toad practice to a chemical analysis in the 1960s and an underground pamphlet in 1984 with the first guide to collecting, drying and smoking it, and cites ethical and ecological arguments against clinical development of toad venom.
  2. Luccioni MD, Wyman JT, Espinoza EO, O'Connell LA. Diet and chemical defenses of the Sonoran Desert toad. PLoS One 2025, 20(11):e0335661. PMID 41212884. DOI 10.1371/journal.pone.0335661 Grade 1. Field study, 29 I. alvarius sampled, secretions analysed from 26 by a qualitative method. Read in full. Detail moved from the text: the study sampled wild toads around Tucson, Arizona, the toad's diet looked much like its neighbours' diet, which argues against specialized prey as the source, the secretion comes from glands behind the eyes and from the skin, and the team kept its site locations approximate.
  3. Lerer L, Reynolds E, Varia J, Blakolmer K, Lerer B. Cell-based synthesis of 5-methoxy-N,N-dimethyltryptamine. Psychedelic Med 2023, 1(1):38-42. PMID 40047010. DOI 10.1089/psymed.2022.0001 Grade 1. Laboratory report, two toads, qualitative mass spectrometry. The first author reports equity in a company. Read in full. Detail moved from the text: the authors propose the approach as a route that would avoid harvesting wild toads.
  4. Weil AT, Davis W. Bufo alvarius: a potent hallucinogen of animal origin. J Ethnopharmacol 1994, 41(1-2):1-8. PMID 8170151. DOI 10.1016/0378-8741(94)90051-5 Grade 1. Self-experiment and ethnopharmacological argument. Abstract only. Full text not accessible. Detail moved from the text: a 1994 article argued that the toad was a more likely candidate than the cane toad for early ritual use in Mesoamerica and reported the secretion to be psychoactive when smoked, but framed Precolumbian use as something that could have happened.
  5. Uthaug MV, Lancelotta R, van Oorsouw K, et al. A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology 2019, 236:2653-2666. PMID 30982127. DOI 10.1007/s00213-019-05236-w Grade 1. Prospective observational study, no control group, 75 consented, 42 analysed at 24 hours, 24 at four weeks. Read in full. Detail moved from the text: a convergent-thinking score also rose and stayed up at four weeks, on the mindfulness questionnaire only two facets changed at four weeks (non-judging and awareness, the second by a very small amount), stronger ego dissolution went with higher life satisfaction and lower depression and stress on the first day but not at four weeks, and convergent thinking was negatively correlated with ego dissolution the next day, so the cognitive gain and the central experience pulled in opposite directions. The dried samples held small amounts of bufotenine and DMT.
  6. Uthaug MV, Lancelotta R, Szabo A, Davis AK, Riba J, Ramaekers JG. Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology 2020, 237(3):773-785. PMID 31822925. DOI 10.1007/s00213-019-05414-w Grade 1. Prospective observational study, no control group, n = 11. Read in full. A correction published on 19 May 2026 (Psychopharmacology 2026, 243(6):1553-1554, PMID 42151447, DOI 10.1007/s00213-026-07086-9) restores an omitted appendix on the setting and the screening and changes no data. The correction was also read in full. Detail moved from the text: saliva taken soon after the session showed higher cortisol and lower IL-6, unrelated to the mental-health ratings. The mindfulness facet of non-judgment improved right after the session and was the only one of five facets to change significantly, anxiety and stress had fallen by day seven, effect sizes were 0.31 to 0.67, all participants had used psychedelics before, and the amount given was unrelated to the strength of the experience.
  7. Davis AK, Barsuglia JP, Lancelotta R, Grant RM, Renn E. The epidemiology of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) use: benefits, consequences, patterns of use, subjective effects, and reasons for consumption. J Psychopharmacol 2018, 32(7):779-792. PMID 29708042. DOI 10.1177/0269881118769063 Grade 1. Online cross-sectional survey, n = 515, internet-recruited in 2017. Read in full, from the author manuscript. Detail moved from the text: 79 percent of respondents were men and 86 percent white, most had used it fewer than four times, mainly for spiritual exploration, 1 percent each named legal, medical or psychiatric problems, and among respondents with a lifetime diagnosis 79 percent of those with post-traumatic stress and 77 percent of those with depression said symptoms improved. Note: the 52 and 48 percent in the survey chapter are two separate items in the paper's table of challenging experiences (a profound experience of their own death, and feeling as if dead or dying), not two readings of one item.
  8. Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Am J Drug Alcohol Abuse 2019, 45(2):161-169. PMID 30822141. DOI 10.1080/00952990.2018.1545024 Grade 1. Online cross-sectional survey, n = 362, one US group, same 2017 survey effort as item 7. Read in full, from the author manuscript. Detail moved from the text: the group's sessions last six to seven hours, 41 percent of the sample reported a diagnosis of depression and 48 percent of anxiety, improvement was linked to a more intense mystical experience and unrelated to how challenging the experience was, older respondents were less likely to report improvement, and the sample was English-speaking and mostly white college graduates.
  9. Barsuglia J, Davis AK, Palmer R, et al. Intensity of mystical experiences occasioned by 5-MeO-DMT and comparison with a prior psilocybin study. Front Psychol 2018, 9:2459. PMID 30574112. DOI 10.3389/fpsyg.2018.02459 Grade 1. Single-group observational study, n = 20, no placebo, ibogaine given earlier in the program, first author employed by the retreat center. Read in full. Detail moved from the text: participants had also passed an ECG and a urine drug test, the mean total Mystical Experience Questionnaire score was 4.17 out of 5, the authors found no difference from the higher group in an earlier laboratory psilocybin study though that was a different sample and not a head-to-head trial, the retreat gave ibogaine two days before the 5-MeO-DMT session, and the authors asked readers to consider the species' ecological stability and other sources of the molecule.
  10. Ortiz Bernal AM, Raison CL, Lancelotta RL, Davis AK. Reactivations after 5-methoxy-N,N-dimethyltryptamine use in naturalistic settings: an initial exploratory analysis of the phenomenon's predictors and its emotional valence. Front Psychiatry 2022, 13:1049643. PMID 36523876. DOI 10.3389/fpsyt.2022.1049643 Grade 1. Secondary analysis of the 2017 surveys, n = 513, shares its data with items 7 and 8. Read in full.
  11. Ortiz Bernal AM, Raison CL, Lancelotta RL, Timmermann C, Sepeda ND, Davis AK. Reactivations associated with the use of 5-MeO-DMT among Spanish-speaking individuals: prevalence, predictors, and emotional valence. J Psychoactive Drugs 2025. PMID 41129673. DOI 10.1080/02791072.2025.2577305 Grade 1. Online cross-sectional survey, n = 90. Abstract only. Full text not accessible.
  12. Reckweg J, Mason NL, van Leeuwen C, Toennes SW, Terwey TH, Ramaekers JG. A phase 1, dose-ranging study to assess safety and psychoactive effects of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in healthy volunteers. Front Pharmacol 2021, 12:760671. PMID 34912222. DOI 10.3389/fphar.2021.760671 Grade 1. Phase 1, n = 22 healthy volunteers, all with prior psychedelic experience, no placebo arm. Read in full. Detail moved from the text: challenging-experience ratings were low, and because vital signs were not taken at the peak the study says nothing about the minutes of the experience itself. Detail moved from the text (continued): the authors had not expected the null on cognition, mood and well-being, since the volunteers were healthy with minimal symptoms at baseline.
  13. Rucker JJ, Roberts C, Seynaeve M, et al. Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. J Psychopharmacol 2024, 38(8):712-723. PMID 38616411. DOI 10.1177/02698811241246857 Grade 1. Double-blind placebo-controlled phase 1, n = 44, exploratory. Read in full. Detail moved from the text: systolic pressure above 140 in 48 percent of the active group and 23 percent of placebo, diastolic above 90 in 55 percent and none, heart rate above 100 in 23 percent and none, five participants above 160 systolic. Nasal discomfort, nausea, headache and vomiting were the most common events.
  14. Ermakova AO, Dunbar F, Seynaeve M, Millière R. Mapping the phenomenology of intranasal 5-MeO-DMT in psychedelic-naive healthy adults. Sci Rep 2025, 15:38874. PMID 41198731. DOI 10.1038/s41598-025-22620-z Grade 1. Qualitative interviews within a phase 1 trial, 40 interviewed, 32 of them on active material, funded by Beckley Psytech. Read in full. This paper counts the trial's participants differently from item 13 (45 randomized plus 5 in an open cohort, against 44), and the difference is not explained. Detail moved from the text: onset within two minutes, a peak at about 8 to 15 minutes, and a return toward baseline over 45 to 60 minutes.
  15. Reckweg JT, van Leeuwen CJ, Henquet C, et al. A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression. Front Psychiatry 2023, 14:1133414. PMID 37409159. DOI 10.3389/fpsyt.2023.1133414 Grade 1. Open-label, n = 16, patients, company-funded. Read in full.
  16. Cubala WJ, Bajbouj M, Bauer M, et al. GH001 vs placebo in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry 2026, 83(6):561-569. PMID 41879760. DOI 10.1001/jamapsychiatry.2026.0096 Grade 1. Randomized double-blind placebo-controlled phase 2b, n = 81, patients, company-funded. Read in full. Detail moved from the text: the trial ran at 16 European sites, the effect size was -2.0, and 57.5 percent were in remission.
  17. ClinicalTrials.gov record NCT05870540 (BPL-003 phase 2 dose-finding in treatment-resistant depression, sponsor listed as AtaiBeckley Inc.), results posted 10 September 2026, read through the registry's public API. https://clinicaltrials.gov/study/NCT05870540. Grade 1 as an official registry record. The posted results are sponsor-reported and not peer reviewed. 196 enrolled, 193 started the core period, patients. Read in full. Detail moved from the text: 95 percent interval 1.8 to 8.9, and the low-strength group's improvement is a reminder that expectation, support and natural recovery matter in these trials.
  18. Roberts C, Seynaeve M, Ermakova AO, et al. A phase 2 uncontrolled, open-label study of intranasal BPL-003 in patients with treatment-resistant depression. J Psychopharmacol 2026, 40(8):1247-1260. PMID 41761045. DOI 10.1177/02698811261420087 Grade 1. Open-label, n = 12, patients. Abstract only. Full text not accessible. Detail moved from the text: the open-label depression study enrolled 12 people.
  19. Marsden J, Kelleher M, Dunbar F, et al. 5-MeO-DMT for alcohol use disorder: an open-label, phase 2, proof-of-concept clinical trial. Addiction 2025. PMID 41368982. DOI 10.1111/add.70260 Grade 1. Open-label, n = 13, patients, within a cognitive behavioral therapy program. Abstract only. Full text not accessible. The trial's registry record was read (item 32). Detail moved from the text: the alcohol study enrolled 13 people.
  20. Johnson M, Aceves Baldo P, Arbe E, et al. Inhaled mebufotenin (GH001) for adult patients with postpartum depression: a phase 2a open-label clinical trial. J Clin Psychiatry 2026, 87(3). PMID 42247279. DOI 10.4088/JCP.25m16284 Grade 1. Open-label, n = 10, patients, company-funded. Read in full. Detail moved from the text: seven of the 10 had a peak experience on the scale used, and blood pressure and heart rate rose briefly after dosing and returned to baseline within 20 to 60 minutes.
  21. ClinicalTrials.gov, search for 5-MeO-DMT, GH001, BPL-003, mebufotenin and related terms, run through the public API on 2 October 2026. 23 records, including NCT05698095, NCT06816667, NCT07444788, NCT05839509 and NCT05804708 and the two device trials NCT06511947 and NCT07540494. https://clinicaltrials.gov/. Grade 1 as registry records. Records about ibogaine, two surveys and an observational study of people enrolled in another trial were screened out by hand. Status, enrollment and termination reasons read. Results sections absent for most. Detail moved from the text: a sublingual study enrolled adults aged 40 to 80, and two trials of a new inhaler device labeled healthy volunteers are open-label pharmacokinetic and safety studies in which "healthy" meant good mental health in the investigator's judgment. The literature was not searched for each record.
  22. Wilkins A, Cagle L, Wells R, Granfone M. Clinical review of Colorado river toad (Incilius alvarius) intoxication in dogs in Arizona: clinical signs, treatments, and outcomes. J Am Vet Med Assoc 2026, 264(6). PMID 41564560. DOI 10.2460/javma.25.10.0676 Grade 1. Retrospective review, 208 dogs. Abstract only. Full text not accessible. Detail moved from the text: the review covered Arizona clinics from 2007 to 2010, 99 percent of the dogs survived to discharge, and the picture resembled poisoning by the cane toad.
  23. Sklerov J, Levine B, Moore KA, King T, Fowler D. A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. J Anal Toxicol 2005, 29(8):838-841. PMID 16356341. DOI 10.1093/jat/29.8.838 Grade 1. Single case report. Abstract only. Full text not accessible.
  24. Callaway JC, Grob CS, McKenna DJ, Nichols DE, Shulgin A, Tupper KW. A demand for clarity regarding a case report on the ingestion of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in an ayahuasca preparation. J Anal Toxicol 2006, 30(6):406-407. PMID 16872575. DOI 10.1093/jat/30.6.406 Grade 2. Published letter, peer-review status not verified. Not read. Full text not accessible. Title and indexing record only, with a description in item 31.
  25. Drug Enforcement Administration. Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule, 75 FR 79296, 20 December 2010, effective 19 January 2011. Federal Register document 2010-31854. https://www.govinfo.gov/content/pkg/FR-2010-12-20/html/2010-31854.htm. Grade 1. Official legal text. Read in full through text extraction, 2 October 2026. Detail moved from the text: the rule notes that the substance occurs naturally in humans, some toads and some plants.
  26. 21 CFR 1308.11, Schedule I, paragraphs (d)(15) and (d)(17). Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/chapter-II/part-1308/section-1308.11. Grade 1. Official legal text. The latest amendment of the section is dated 21 September 2026 and no later version existed on 2 October 2026. Read in part: the introduction to paragraph (d) and entries (15) and (17).
  27. Misuse of Drugs Act 1971, Schedule 2, Part I. https://www.legislation.gov.uk/ukpga/1971/38/schedule/2. Grade 1. Official legal text, latest available revised version. Read in part: paragraphs 1(a) and 1(b), with a search of the whole Schedule for the compound's name, 2 October 2026. Detail moved from the text: the matching wording covers ring substitution with alkoxy groups and alkyl substitution on the side-chain nitrogen.
  28. Controlled Drugs and Substances Act, S.C. 1996, c. 19, Schedule III. Justice Laws Website, Government of Canada. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/. Grade 1. Official legal text. Read in part: the opening of Schedule III, with a search of the whole Act. Last amended 18 July 2026 (accessed 4 October 2026). The search of the whole Act was run on 2 October 2026.
  29. Hampsey E, Martin K, Kalfas M, Benson L, Wihlborg S, Jelen L, Young AH, Rucker J. A systematic review of the pharmacokinetics of classical serotonergic psychedelic compounds in healthy adult subjects. J Psychopharmacol 2026, 40(8):1213-1223. PMID 42212869. DOI 10.1177/02698811261453938 Grade 1. Systematic review, 32 trials included. Read in full. Detail moved from the text: only two of the 32 included trials were 5-MeO-DMT trials, so the review adds no evidence beyond them.
  30. Qi J, Zulfiker AHM, Li C, Good D, Wei MQ. The development of toad toxins as potential therapeutic agents. Toxins (Basel) 2018, 10(8):336. PMID 30127299. DOI 10.3390/toxins10080336 Grade 1. Peer-reviewed review. Read in full.
  31. Halman A, Kong G, Sarris J, Perkins D. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol 2024, 38(1):3-18. PMID 37982394. DOI 10.1177/02698811231211219 Grade 1. Systematic review. Read in part: abstract, methods, the 5-MeO-DMT section, the discussion of the two case reports and the limitations.
  32. ClinicalTrials.gov record NCT05674929 (BPL-003 in alcohol use disorder, the registry record of item 19), results posted 22 May 2026, read through the registry's public API. https://clinicaltrials.gov/study/NCT05674929. Grade 1 as an official registry record. The posted results are sponsor-reported and not peer reviewed. Read in full.
  33. Villa RA. Toad in the road: biocultural history and conservation challenges of the Sonoran Desert Toad. J Psychedelic Stud 2023, 7(S1):68-79. DOI 10.1556/2054.2023.00269 Grade 1. Abstract only. Full text not accessible.
  34. Bistué Millón MB, et al. Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study. Neuropsychopharmacology 2025. PMID 40659913. DOI 10.1038/s41386-025-02167-3 Grade 1. Phase 1, adults with symptoms of depression or anxiety. Abstract only. Full text not accessible. Detail moved from the text: the abstract reports that repeated low sublingual amounts were well tolerated.
  35. Ortiz Bernal AM, Raison CL, Vargas Prieto AM, Davis AK. Fabricated ancestrality: the Sonoran Desert toad, psychedelic globalization, and the ecological politics of 5-MeO-DMT. Psychedelics 2026, 3:100012. DOI 10.1016/j.psyche.2026.100012 Grade 1. Not read. Full text not accessible. Not used for any claim on this page.

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