Written by Sally Turner MSc
What is 5-MeO-DMT?
5-methoxy-N,N-dimethyltryptamine, or ‘toad venom’ as it’s better known, is a tryptamine psychedelic that occurs naturally in multiple species of plants and shrubs, is present endogenously in some humans (1, 2), and is excreted by the Colorado river toad (hence the nickname). 5-MeO-DMT has been consumed by indigenous populations in South America for centuries (3, 4). More recently, Californian churchgoers, revolutionary drug scientist Alexander Shulgin, and even legendary boxer Mike Tyson, have discovered the power of 5-MeO-DMT.
What does 5-MeO-DMT do and how does it do it?
As the “Godfather of Ecstasy”, Alexander Shulgin described (5), 5-MeO-DMT is a seriously potent psychedelic. Like other classic serotonergic psychedelics (e.g., Psilocybin, LSD, mescaline), 5-MeO-DMT causes profound changes in consciousness (i.e., ‘trips’) which can manifest as new insights, hallucinations, time-perception distortions, and mystical experiences. 5-MeO-DMT also sometimes causes such intense ego dissolution that consumers think they have died, as Mike Tyson can attest to. Unlike other psychedelics though, the psychedelic experience on 5-MeO-DMT happens almost instantly after administration, and the effects last just ~45 minutes.
Like other tryptamines, 5-MeO-DMT mainly binds to serotonin receptors in the brain. One of these receptors (5-HT1A), is a target of many psychiatric treatments. 5-MeO-DMT heavily binds with this receptor, which might be why some consumers experience euphoria or panic/fear, or both during a trip. It’s likely that 5-MeO-DMT exerts its influence through a combination of activating these receptors as well as binding to dopamine and noradrenergic transporters in the brain (6)
“This is a very strong hallucinogen. It was like adding
the MDMA experience to DMT. I’ve never been hit this hard”
(Alexander Shulgin, TIKHAL)
Recreational uses of 5-MeO-DMT
Monitoring recreational use of 5-MeO-DMT is difficult, as it is usually grouped with other tryptamines, or less-specifically within the ‘psychedelic’ category of large-scale questionnaires. Despite that, we know that only 1.2% of US adults report ever using any tryptamine psychedelic (7). Those who do try 5-MeO-DMT use it infrequently (~ once a year) and mainly for spiritual reasons (3).
Despite its potency and associated feelings of fear, less than 40% of consumers report any challenging experiences from it, and just 1% of those who do, later experience psychiatric problems (3 ). Less than 40% might sound like a lot of people, but most people reported their experience to be ‘mild’ or ‘moderate’, so this may not be as alarming as it first sounds. Regardless, 5-MeO-DMT, like other psychedelics, is unlikely to become a popular party drug due to its potent, intense, and short-lived characteristics
Medicinal uses of 5-MeO-DMT
Despite its lack of popularity, the medicinal uses of 5-MeO-DMT are surprisingly well-documented, for mental health at least. Before we get into the studies, remember 5-MeO-DMT’s fast-acting characteristic. Well, this could be what popularises 5-MeO-DMT in future psychiatric care, placing it above psilocybin as the least costly psychedelic treatment. But currently, there isn’t enough research to determine the efficacy of 5-MeO-DMT for patients with different psychiatric presentations, so for now, at least, psilocybin seems to be the best-evidenced option for psychedelic therapy.
How does 5-MeO-DMT affect mental health, and are there any benefits?
We’ve all heard about the medicinal potential of psilocybin, but when it comes to 5-MeO-DMT, most of us are none the wiser. One study found that 5-MeO-DMT improves mental health, life satisfaction scores, and reduces depression, anxiety, and stress for at least 4 weeks post-consumption(8). These effects were present in 100% of the sample (42 participants) and were corroborated in a follow-up study (9).
Research (10, 22) has shown that nearly 80% of patients with post-traumatic stress disorder (PTSD), 77% of patients with depression, and nearly 90% of ‘treatment-resistant’ patients with depression experienced significantly marked improvements in their conditions following 5-MeO-DMT consumption. Not only is this positive news for those living with these often debilitating conditions, but similar results were found in healthy individuals too.(8-10) So far, we haven’t seen any published systematic randomised-control-trials (RCTs) of the therapeutic efficacy and safety of 5-MeO-DMT (12), which limits the inferences that can be made about the safety of 5-MeO-DMT. More evidence is needed before 5-MeO-DMT’s potential to treat psychiatric conditions can be concluded.
What about physical health?
Some in-vivo research in the 1970s and 80s found that 5-MeO-DMT can regulate the neuroendocrine system in mice by promoting and regulating prolactin (13-15). 5-MeO-DMT also helps regulate BDNF(16) (brain-derived neurotrophic factor), which helps the brain to maintain homeostasis, plays a crucial role in neuroplasticity, and its dysregulation is involved in multiple psychiatric conditions(17). Additionally, 5-MeO-DMT can reduce cortisol levels: a hormone involved in the body’s stress response. Chronic exposure to cortisol can cause several physical health conditions including high blood pressure and diabetes (type II). Speculatively, 5-MeO-DMT may prove useful for treating these conditions, although this is yet to be researched.
Is 5-MeO-DMT harmful?
Most countries have designated 5-MeO-DMT as Schedule I, indicating it has ‘no medicinal value’ and a ‘lack of safety information’. This means research into the harms, medicinal potential, and recreational attributes of 5-MeO-DMT, is limited.
Some reports have described deaths related to 5-MeO-DMT. However, when we look more closely, these deaths were in fact attributed to substances within the 5-MeO-DMT family, and not 5-MeO-DMT itself. As with all psychedelics though, consumers need to understand and respect set and setting. That is, consumers need to be properly informed, engage when in an appropriate mindset, and be in a comfortable environment when taking psychedelics.
Although preliminary evidence has pointed to 5-MeO-DMT’s potential to reduce mental health symptoms, it can also induce panic, fear, terrifying experiences, although rarely has been associated with psychosis (5). These experiences seem to be limited to those with a history of, or predisposition to, psychotic illness, and appear more likely to occur in people who take more than one tryptamine in the same session (18). Even rarer, 5-MeO-DMT has been associated with a heightened risk of serotonin syndrome in people taking MAOI inhibitors (19 ). These results suggest that long-lasting mental health harms of 5-MeO-DMT are quite unlikely for the majority of us, but extra care should be taken by those predisposed to psychotic illness and/or those using anti-depressant medications.(11, 19)
Is 5-MeO-DMT harmful?
The medicinal potential of 5-MeO-DMT is only just being understood by researchers. We are yet to fully understand what 5-MeO-DMT can do. It seems to have significant potential for treating neuropsychiatric symptoms, even for those categorised as “treatment-resistant” by traditional standards. But 5-MeO-DMT use is not without its risks, anyone thinking of consuming it should carefully consider whether they are capable of coping with its effects on their consciousness. Proceed with caution when it comes to 5-MeO-DMT, as even Alexander Shulgin himself struggled with the resulting come-down.
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- Ermacova, A. O., Dunbar, F., Rucker, J., & Johnson, M. W. (2021). A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology, 36(3), 273-294. https://doi.org/10.1177/02698811211050543
- Davis, A. K., Barsuglia, J. P., Lancelotta, R., et al. (2018). The epidemiology of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) use: benefits, consequences, patterns of use, subjective effects, and reasons for consumption. Journal of psychopharmacology, 32(7), 779-792. DOI: 1177/0269881118769063
- Weil, A. T., & Davis, W. (1994). Bufo Alvarius: a potent hallucinogen of animal origin. Journal of ethnopharmacology, 41(1-2), 1-8. https://doi.org/10.1016/0378-8741(94)90051-5
- Shulgin, A., & Shulgin, A. (1997). TiKHAL: the continuation. Berkeley: Transform Press. https://erowid.org/library/books_online/tihkal/tihkal.shtml
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- Uthang, M. V., Lancelotta, R., & van Oorsouw, K. (2019). A single inhalation of vapor from dried toad secretion containing 5-methoxy-N, N-dimethyltryptamine (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, 235(9), 2653-2666. DOI: 1007/s00213-019-05236-w
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- Davis, A. K., Lancelotta, R., Barsuglia, J. P., et al. (2019). 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American Journal of Drug and Alcohol Abuse, 45(2), 161-169. DOI: 1080/00952990.2018.1545024
- Reckweg, J. T., Uthang, M. W., Szabo, A., et al. (2022). The clinical pharmacology and potential therapeutic applications of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT). Journal of Neurochemistry, 162(1), 128-146. DOI: 1111/jnc.15587
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- Lima da Cruz, R. V., Moulin, T. C., Petiz, L. L., & Leāo, R., N. (2018). A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mic ventral dentate gyrus. Frontiers in Molecular Neuroscience, 11(312), 1-11. DOI: 3389/fnmol.2018.00312
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