5-MeO-DMT

5-MeO-DMT is used as a recreational drug and as an entheogen. In his book TiHKAL (Tryptamines I Have Known and Loved), Alexander Shulgin lists 5-MeO-DMT's dose as 6 to 20mg smoked or 2 to 3mg by intravenous injection and its duration as 1 to 2hours. It has been described as having a steep dose–response curve. The onset of 5-MeO-DMT smoked is 8seconds to 1minute, with peak effects occurring after 2 to 3minutes, although some report an onset or build-up of as long as 10 to 15minutes. It is described as having a rapid onset of 8 to 15minutes, a short duration of 45 to 60minutes, distinctive subjective effects from other psychedelics, a relative lack of visual effects, strong emotional and bodily experiences, emotional breakthroughs, and personal insights, among other effects. ==Contraindications==

5-MeO-DMT has various possible adverse effects. ==Overdose==

There have been cases of death with 5-MeO-DMT. The estimated lethal dose of 5-MeO-DMT relative to a typical recreational dose in humans is unknown. The median lethal dose (LD50) in animals varies widely, ranging from 1 to 5mg/kg i.v. in sheep to 48mg/kg i.v. in mice. In one case, combination of 5-MeO-DMT with harmala alkaloids, which act as monoamine oxidase inhibitors (MAOIs), as well as with other drugs, resulted in death. However, the exact contribution of 5-MeO-DMT in this case is difficult to determine. ==Interactions==

5-MeO-DMT can be strongly potentiated by combination with monoamine oxidase inhibitors (MAOIs). In addition, it can become orally active with an extended duration in combination with MAOIs. These interactions have the potential to result in serious toxicity and death. ==Pharmacology==

Pharmacodynamics 5-MeO-DMT is a methoxylated derivative of dimethyltryptamine (DMT). While most common psychedelics are believed to primarily elicit psychological effects through agonism of serotonin 5-HT2A receptors, 5-MeO-DMT shows 1,000-fold greater affinity for the serotonin 5-HT1A receptor over the serotonin 5-HT2A receptor. Further, its activity in rats was attenuated with the selective serotonin 5-HT1A receptor antagonist WAY-100635, while selective serotonin 5-HT2A receptor antagonist volinanserin failed to demonstrate any change. Additional mechanisms of action such as inhibition of monoamine reuptake may also be involved in its effects. Similarly to other serotonergic psychedelics, 5-MeO-DMT is a non-selective serotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors, among others. It shows pronounced biased agonism at the serotonin 5-HT2C receptor. The drug is 4- to 10-fold more potent as a hallucinogen than DMT in humans. However, there is partial generalization of 5-MeO-DMT to the selective serotonin 5-HT2 receptor agonist (–)-DOM in animals. there appears to be very little development of tolerance with 5-MeO-DMT. Pharmacokinetics Absorption 5-MeO-DMT is not orally active and must be administered parenterally. Metabolism Bufotenin is an active metabolite of 5-MeO-DMT, formed by O-demethylation by cytochrome P450 CYP2D6. Bufotenin notably has much higher affinity for the serotonin 5-HT2A receptor than 5-MeO-DMT itself. However, bufotenin does not seem to be extensively produced from 5-MeO-DMT in the brain. In addition, peripherally formed bufotenin is less able to exert central effects due to its relative peripheral selectivity in terms of crossing into the brain. Hence, the involvement of bufotenin in the psychoactive effects of 5-MeO-DMT is uncertain. The metabolism of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged by monoamine oxidase inhibitors (MAOIs). In addition, MAOIs allow 5-MeO-DMT to become orally active in humans. Combining 5-MeO-DMT with MAOIs has sometimes resulted in serotonin syndrome and death in humans. Elimination The elimination half-life of 5-MeO-DMT, administered sublingually, was found to be 28minutes. ==Chemistry==

5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, is a substituted tryptamine derivative. Analogues and derivatives Analogues and derivatives of 5-MeO-DMT include dimethyltryptamine (DMT), 5-methoxytryptamine (5-MT or 5-MeO-T), 5-MeO-NMT, 5-MeO-MET, 5-MeO-DET, 5-MeO-MPT, 5-MeO-EPT, 5-MeO-DPT, 5-MeO-MiPT, 5-MeO-EiPT, 5-MeO-PiPT, 5-MeO-DiPT, 5-MeO-MALT, 5-MeO-DALT, 5-MeO-pyr-T, 5-EtO-DMT, 5-MeO-2-TMT (2-methyl-5-MeO-DMT), EMDT (2-ethyl-5-MeO-DMT), psilomethoxin (4-hydroxy-5-MeO-DMT; 5-methoxypsilocin), 5-MeO-AMT, α,N,N,O-TeMS (5-MeO-α,N,N-TMT), 4-MeO-DMT, 6-MeO-DMT, 7-MeO-DMT, and dimemebfe (5-MeO-BFE), among others. ==Natural occurrence==

Plants There are various known plant sources of 5-MeO-DMT. The smoking of I. alvarius secretions should not be confused with the urban legend of toad licking. Since 1983, the animal has become a popular source of 5-MeO-DMT for recreational or spiritual purposes. Unfortunately, this increased demand and use of the toads as a source of 5-MeO-DMT has put strain on their populations. Concerned with the ecological impacts of the growing use of I. alvarius secretions as a source of 5-MeO-DMT, Ken Nelson would later advocate for the use of synthetic 5-MeO-DMT and conservation of the Colorado River Toad. Fungi Fungal sources of 5-MeO-DMT include Amanita citrina and Amanita porphyria. ==History==

5-MeO-DMT was first synthesized by Toshio Hoshino in 1935. It was isolated from the flowering plant Dictyoloma incanescens in 1959. The drug was subsequently isolated from numerous other plant, fungal, and animal sources over time. In 1965, 5-MeO-DMT was reported to be the main component of the hallucinogenic snuff known variously as parica, epena, or yakee that is prepared and used from the resin of the Virola theiodora tree by indigenous people in Northern South America. It was isolated from the toad Incilius alvarius (formerly Bufo alvarius and also known as the Sonoran Desert toad, Colorado River toad, or simply bufo) by Vittorio Erspamer by 1965. Alexander Shulgin briefly reported that 5-MeO-DMT was hallucinogenic in humans, via parenteral but not oral routes, in 1970, with additional details published later on. In addition, they described the finding as the first instance of a psychedelic from an animal source to be discovered. 5-MeO-DMT became a controlled substance in the United States in 2009. ==Society and culture==

Names 5-MeO-DMT is the common informal name of the drug and an acronym of one of its chemical names. Mebufotenin is the generic name of the drug and its . Other names can include O-methylbufotenin, O-methyl-5-HO-DMT, and O,N,N-trimethylserotonin. Religious use The Church of the Tree of Life, founded in California in 1971 by John Mann but now defunct, declared the use of 5-MeO-DMT to be a sacrament. From approximately 1971 to the late 1980s, 5-MeO-DMT was discreetly available to its members. Between 1970 and 1990, smoking of 5-MeO-DMT on parsley was probably one of the two most common forms of ingestion in the United States. Canada 5-MeO-DMT is not an explicitly nor implicitly controlled substance in Canada as of 2025. China As of October 2015, 5-MeO-DMT is a controlled substance in China. Germany As of 2001 5-MeO-DMT is listed as a controlled substance. Attachement I BtMG. BGBl. I 2001, 1180 - 1186; Sweden The Swedish government classified 5-MeO-DMT, listed as 5-metoxi-N,N-dimetyltryptamin (5-MeO-DMT) in their regulation SFS 2004:696, as "health hazard" under the Lagen om förbud mot vissa hälsofarliga varor (Act on the Prohibition of Certain Goods Dangerous to Health) in October 2004, making it illegal to sell or possess. Turkey 5-MeO-DMT has been controlled in Turkey since December 2013. United States 5-MeO-DMT was made a Schedule I controlled substance in January 2011. ==Research==

Preliminary clinical findings suggest that 5-MeO-DMT might have antidepressant and anxiolytic effects. A 2019 European study with 42 volunteers showed that a single inhalation of 5-MeO-DMT produced sustained enhancement of satisfaction with life, and easing of anxiety, depression, and post-traumatic stress disorder (PTSD). A 2018 study found that a single dose of 5-MeO-DMT induced neurogenesis in mice. Depression 5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients with treatment-resistant depression (TRD). Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers and phase 1/2 study in TRD patients where 87.5% of patients with TRD were brought into remission on day 7 in the phase 2 part of the study. GH Research is currently planning a phase 2b study in TRD patients and have received approval for studies in patients with bipolar II disorder and a current depressive episode and patients with postpartum depression. In February 2025, GH Research announced that their Phase 2b clinical trial of GH001, met its primary endpoint in patients with TRD. In 2026, the FDA allowed advanced trials for GH001. Beckley Psytech in collaboration with King's College London evaluated the safety and tolerability of intranasal 5-MeO-DMT in healthy subjects, in a phase 1 study. Beckley Psytech CEO Cosmo Feilding-Mellen sees a potential in the short-acting nature of 5-MeO-DMT compared to psilocybin: "Requiring one or two therapists to sit in a room with a single patient for the entire duration of an MDMA or psilocybin experience, which is essentially a whole working day, is probably going to be very resource-intensive and expensive. There is already a global shortage of psychotherapists, and this poses a potential bottleneck to patient access in the future." The research initiative by ataiBeckley, received a Breakthrough Therapy designation by the FDA for BPL-003, an intranasal spray containing 5-MeO-DMT, for Treatment-Resistant Depression. Concerns have been raised about the potential use of 5-MeO-DMT in medicine due to the extreme and frequently challenging natures of the experiences. ==See also==