5-MeO-DMT

5-MeO-DMT, also known as 5-methoxy-N,N-dimethyltryptamine, as well as O-methylbufotenin or mebufotenin, is an atypical psychedelic drug, entheogen, and alkaloid of the tryptamine and 5-methoxytryptamine families. It is found naturally in a wide variety of plant species, and is also secreted by the glands of at least one toad species, the Colorado River toad (Incilius alvarius, formerly Bufo alvarius). It may occur naturally in humans as well. Like its close relatives dimethyltryptamine (DMT) and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Slang terms include five-methoxy, the power, bufo, and toad venom. The drug has been described as the most powerful psychedelic and, by journalist Michael Pollan, as the "Mount Everest of psychedelics".

Adverse effects of 5-MeO-DMT include sickness, vomiting, headache, chest pressure, fatigue, anxiety, fear, terror, confusion, paranoia, crying, loss of awareness and motor control, and reactivations. The drug acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT_1A and 5-HT_2A receptors, among others. However, 5-MeO-DMT differs from most other serotonergic psychedelics in having much greater activity at the serotonin 5-HT_1A receptor in addition to the serotonin 5-HT_2A receptor. In relation to this, 5-MeO-DMT has been described as an "atypical" psychedelic and as producing subjective effects notably distinct from those of DMT and other psychedelics, for instance having a relative lack of visual effects. Nonetheless, 5-MeO-DMT reliably produces mystical experiences in most people who take it. Like DMT, 5-MeO-DMT is only active non-orally and has a very rapid onset and short duration. However, 5-MeO-DMT is 4- to 20-fold more potent than DMT in humans.

5-MeO-DMT was first described by 1936, was first isolated from natural sources by 1959, and was first reported to be hallucinogenic by 1970. The use of 5-MeO-DMT-containing toad venom was first described in 1984. It is a controlled substance in some countries, for instance the United States, United Kingdom, Australia, and New Zealand. The drug is used recreationally and several deaths have been reported in association with its use. Use of 5-MeO-DMT is rare compared with other psychedelics, with only 0.003% of the United States general population having reported taking it in 2019 (compared to 8.5% for psilocybin). 5-MeO-DMT is being developed for potential use in medicine in the treatment of neuropsychiatric disorders such as depression.

5-MeO-DMT is used as a recreational drug and as an entheogen. It is not orally active, requiring a parenteral route such as smoking to produce effects. Other non-oral routes such as intravenous injection, intramuscular injection, rectal administration, sublingual administration, or intranasal administration have also less commonly been used. In addition to non-oral administration, 5-MeO-DMT can be combined with a monoamine oxidase inhibitor (MAOI) such as the reversible inhibitor of monoamine oxidase A (RIMA) harmaline to allow for oral activity and a much longer duration than it would have otherwise. However, combination of 5-MeO-DMT with MAOIs can also result in accidental overdose, including instances of serotonin syndrome and death. In addition to pure synthetic 5-MeO-DMT, it is often used by smoking in the form of the venom taken from the Colorado River toad (Incilius alvarius, formerly Bufo alvarius and also known as the Sonoran Desert toad).

In his book TiHKAL (Tryptamines I Have Known and Loved), Alexander Shulgin lists 5-MeO-DMT's dose as 6 to 20 mg smoked or 2 to 3 mg by intravenous injection and its duration as 1 to 2 hours. Other sources state the dose of 5-MeO-DMT to be 2 to 15 mg smoked and its duration as 5 to 20 minutes or 12 minutes typically. It has been described as having a steep dose–response curve. 5-MeO-DMT is not orally active at doses of up to at least 35 mg and is almost always used via smoking. The onset of 5-MeO-DMT smoked is 8 seconds to 1 minute, with peak effects occurring after 2 to 3 minutes, although some report an onset or build-up of as long as 10 to 15 minutes. The main effects when smoked last about 10 minutes, with a total duration of 20 to 60 minutes. Taken by intravenous injection, the onset of 5-MeO-DMT is within 1 minute and the duration was 10 minutes in one instance. With harmaline doses of 70 to 150 mg orally, 5-MeO-DMT becomes orally active at doses of 10 to 25 mg, the onset is 15 to 18 minutes, peak effects occur after 1.5 hours, and the duration is at least 3 or 4 hours. In addition, harmaline at sufficient doses such as 150 mg or more can add its own hallucinogenic effects to the experience.

The effects of 5-MeO-DMT have been reported by Shulgin. The perceptual effects included no noticeable visual effects or sensory involvement, not seeing anything whilst eyes shut except a bright white light, inability to see in general, multi-color phosphene visuals filling entire visual field, a certain resonance of auditory perception or electrical buzzing that synchronized with visual perception, slightly diminished hearing, ear ringing, feeling barraged by stimuli, rush, and a tremendous and intense sense of speed and acceleration. Other effects included a "white-out" or "singularity" experience (as opposed to a "black-out"), mental activity almost absent, mind completely referenceless, cosmic consciousness type of experience, feelings of and longing for connection and transcendence, feeling like one is experiencing all possible thoughts and realities simultaneously, feeling like one is experiencing a very large number of objects, situations, and emotions all at once instead of only one at a time, feeling like one is an ocean, intense depersonalization, impressive recall of early memories and emotional significance of these memories, time constriction (such as experiencing 40 minutes as mere seconds), and insights.

Effects related to spatial and bodily awareness included altered body perception, normal physical perceptions dissolving away from awareness, loss of contact with one's body and surroundings, feeling like one was not there in one's body or in time, feeling like all the blood in one's body had turned to concrete, and not being able to tell if eyes were closed or open. Emotional effects included a sense of excitement, feelings of awe and wonder, feeling amazed or "blown away", feelings of love and energy, feelings of ecstasy, emotions synchronized with visuals, strong feelings of gratitude for the experience, feeling overwhelmed, feeling "scared the hell out", feeling the "energy of terror", screaming in one's head, fear of death, feeling like one had died or killed themselves, feeling at risk of psychic damage, and relief upon coming down. Further effects included an intensity greater than anything one has experienced before, simply the most intense experience possible, feeling like the entire universe had exploded through one's consciousness, feeling like there is no possibility of examining the experience, an inability to judge by any method of the mind, feeling conked on the head, little or no memory of the experience, and loss of continuity of consciousness like a black-out from too much alcohol.

Behavioral effects included falling over while sitting, curling up in a fetal position, squirming and writhing around, making frightening noises, and alarming other people. Physical side effects included physical weakness, shakiness, tremors, shivers emanating from the head, center, or heart, and slight nausea. The taste when smoking was described as mild, with none of the plastic taste of dimethyltryptamine (DMT). In the case of an unspecified large overdose smoked, the person lapsed into a coma-like state, their face turned purple, they stopped breathing and had to be resuscitated multiple times, and they experienced a several-day psychosis necessitating antipsychotics.