From ... in Psychedelics — Jun 19, 2020

5-MeO-DMT Guide: Effects, Benefits, Safety, and Legality

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a powerful, short-acting serotonergic psychedelic of the tryptamine class.

Nowadays, it is used in many other parts of the world recreationally and in ceremonial settings for spiritual exploration and its psychotherapeutic effects. Although structurally similar, the effects and potency of 5-MeO-DMT are substantially different than N,N-DMT. Compared to N,N-DMT, 5-MeO-DMT is less of a visual trip and approximately 4 to 6 times as potent. 5-MeO-DMT can be found in synthetic form, in a wide range of South American plant species, and in the venom of a psychoactive toad species, the Colorado River toad. Additionally, researchers have found that it is naturally synthesized in the retina and pineal gland. It has been detected in trace amounts in the human body, including in the cerebrospinal fluid, urine, and blood. The first synthesis of 5-MeO-DMT was in 1936 by the chemists Toshio Hoshino and Kenya Shimodaira. In 1959, it was isolated from the seeds of Anadenanthera peregrina, a South American plant commonly used to create Yopo snuff. Yopo snuff is an entheogen that has been used by various South American tribes for thousands of years. In the West, 5-MeO-DMT is commonly encountered as a synthetic crystalline powder that is smoked or insufflated. Some less common routes of administration include sublingual, intravenous injection, and oral (with an MAO inhibitor). 5-MeO-DMT produces its psychedelic effects by binding to serotonin receptors in the peripheral and central nervous system, particularly 5-HT2 and 5-HT1A receptors. This produces an intense, short-lasting psychedelic experience. When smoked, the effects come on rapidly and last between 5 and 20 minutes. When insufflated, the onset of effects is slower and may last from 30–45 minutes. Regardless of the route of administration, there may be aftereffects for 1–3 hours until the user returns to baseline. 5-MeO-DMT is a structural analog of serotonin and melatonin and a functional analog of other indolealkylamine psychedelics such as N,N-DMT and 5-HO-DMT (bufotenin).

The 5-MeO-DMT molecule’s structure is a methoxylated derivative of DMT. This means it has an methoxy group attached to the DMT compound. It produces its psychedelic effects by binding to various serotonin, or 5-hydroxytryptamine, receptors, primarily the 5-HT2 and 5-HT1A receptors. Other mechanisms of action have not been confirmed, but may include the inhibition of monoamine reuptake.

The CYP2D6 enzyme metabolizes 5-MeO-DMT in the liver, which also metabolizes a wide range of other psychoactive substances. 5-MeO-DMT is known to produce high variability in effects from person to person, even when the same dose is consumed.

The effects may also vary depending on whether the user smokes or insufflates it. Generally, insufflation produces a longer-lasting, more gentle psychedelic experience. When insufflated, a threshold dose is 3–5 mg, a light dose is 5–10 mg, and a common-to-strong dose is 8–15 mg. When 5-MeO-DMT is smoked, which is the most common method of administration, it produces a short-lasting, intense psychedelic experience. Under this route of administration, a threshold dose is 1–2 mg, a light dose is 2–5 mg, and a common-to-strong dose is 5–10 mg. Physical effects of consuming 5-MeO-DMT generally include: 5-MeO-DMT’s cognitive effects produce a similar experience to that of N,N-DMT, although with fewer visual effects.

These effects generally include (varying based on dosage, the individual, and set and setting): Preliminary research is increasingly uncovering that 5-MeO-DMT may hold psychotherapeutic potential similar to ayahuasca and psilocybin. According to a 2018 web-based survey published in the Journal of Psychopharmacology, survey respondents who have used 5-MeO-DMT and who have psychiatric disorders noted sustained improvements in PTSD, depression, and anxiety, as well as alcoholism and drug use disorder. A preliminary study from 2019 published in Psychopharmacology investigated the psychological and cognitive effects in 42 individuals who smoked Colorado River toad venom.

The researchers administered psychological tests prior to consumption, the day after, and at a four-week follow-up.

They found that a single inhalation of the 5-MeO-DMT-containing toad venom enhanced life satisfaction, increased mindfulness, and reduced depression, anxiety, and stress.

These positive effects were found to be significantly sustained at the four-week follow-up. Interestingly, the participants who reported profound mystical experiences such as ego dissolution showed the highest ratings of life satisfaction and the lowest ratings of depression and stress. Ego dissolution experiences have been found to be effective in dissolving the fear of death, dismantling negative habitual thought patterns, and relinquishing the grip of past traumas.

These positive findings corroborate a previous survey of 362 adults published in the American Journal of Drug and Alcohol Abuse. In this survey, nearly 80% of respondents reported lasting improvements in anxiety and depression after using 5-MeO-DMT in a group setting. Similar to the aforementioned study, the greatest improvements in depression and anxiety were seen in respondents who experienced intense types of mystical experiences. Anecdotally, users who consume 5-MeO-DMT generally report similar benefits to users who consume pure DMT. One user reports his worries and fears fading away after smoking an undetermined amount of the substance. He kept the substance for three months before trying it. This could provide some insight into the extent to which users worry about things, only to realize it was an entirely positive experience for themselves. Another user with a similar experience goes as far as stating, “It was a cleansing experience to the highest degree.” He felt after consuming 5-MeO-DMT for the second time that he was reconnected with himself, allowing him to finally be the person he truly desired to become. Being neither psychologically nor physically addictive, 5-MeO-DMT is known for its low abuse potential and relative safety profile when consumed in normal dose ranges and under proper set and setting. While 5-MeO-DMT is active orally when taken with a monoamine oxidase inhibitor (MAOI), this dangerous combination can cause serotonin syndrome, severe hypertensive symptoms, seizures, and lethal intoxications. In addition, 5-MeO-DMT is dangerous to take with stimulants as well as some antidepressants, including RIMAs (reversible monoamine oxidase inhibitors) and SSRIs (selective serotonin reuptake inhibitors). It is strongly advised to follow harm reduction practices when using 5-MeO-DMT. A sober sitter or active facilitator can ensure an environment of physical and psychological safety when using this substance.

The overwhelming effects of 5-MeO-DMT, especially at high doses, may include loss of consensus reality, respiratory depression, temporary unconsciousness, and motor impairment. In some users, 5-MeO-DMT can bring on psychological difficulties after the experience, such as paranoia, anxiety, panic attacks, difficulty sleeping, and preoccupation with the experience.

The latter may be a result of difficulty integrating the experience, which is often compounded by “white-outs,” or memory suppression of the experience. For this reason, users should be accompanied by a sitter during the experience and start with a low, precisely-measured dose to gauge effects. As with other psychedelics, taking 5-MeO-DMT can lead to the development of HPPD, PTSD, or psychosis. HPPD, or hallucinogen persisting perception disorder, involves a user experiencing hallucinations well after a trip has ended.

These hallucinations vary from minor to severe. Some individuals suffering from this disorder experience light visual snow while others experience full-blown hallucinations. A particularly difficult or negative trip can cause HPPD or PTSD. Psychosis particularly affects individuals with a history of schizophrenia or psychotic breaks. Most users never experience any of these disorders, but they can occur. In the United States, the Controlled Substances Act has listed 5-MeO-DMT as a Schedule I controlled substance since 2011. This makes it illegal to possess, consume, and distribute for any reason. In the United Kingdom, 5-MeO-DMT is a class A drug, the same as ecstasy and LSD. China listed 5-MeO-DMT as a controlled substance in 2015. Australia lists it as a structural analog of DMT, making it a schedule 9 prohibited substance under the Poisons Standard. Sweden made it illegal to sell or possess in 2004. Turkey listed it as a controlled substance in 2013. In Canada, 5-MeO-DMT is currently not controlled. 5-MeO-DMT and 4-AcO-DMT (4-Acetoxy-N,N-dimethyltryptamine) are both DMT derivatives that act on 5-HT receptors, but they substantially differ in their history, effects, route of consumption, and duration of action. While 5-MeO-DMT has a long history of use from natural sources such as Yopo snuff, 4-AcO-DMT was first synthesized in 1963 by Albert Hofmann and Franz Troxler at Sandoz Laboratories. 4-AcO-DMT is a semisynthetic tryptamine that is believed to be a prodrug of psilocin. That is to say, it is metabolized by the body into psilocin, similar to psilocybin. For this reason, the effects of 4-AcO-DMT closely resemble the effects of psilocybin mushrooms. 5-MeO-DMT is commonly smoked or insufflated, while 4-AcO-DMT is either ingested orally or insufflated.

The primary effects of 4-AcO-DMT last 4 to 6 hours, whereas 5-MeO-DMT’s short-lived trip lasts from 5–45 minutes depending on whether it is smoked or insufflated. Deaths from 5-MeO-DMT are rare.

The reported deaths from 5-MeO-DMT have been from dangerous combinations with MAOIs such as harmaline (found in ayahuasca). Harmaline profoundly potentiates the serotonergic effects of 5-MeO-DMT, which can result in fatal serotonin toxicity. Orally ingesting Colorado River toad venom is potentially fatal, as the venom contains cardiotoxic compounds such as bufotoxin and bufogenin (which are rendered inactive by smoking). Although its use in shamanic settings extends millennia beyond its scientific discovery, 5-MeO-DMT was first synthesized in 1936. In 1959, it was initially isolated from the bark of the plant Dictyoloma incanescens. On a weight basis, LSD is the strongest psychedelic, being psychoactive at doses on the order of millionths of a gram (microgram). In terms of subjective effects, 5-MeO-DMT, commonly referred to as the God Molecule, is widely regarded as the strongest psychedelic. 5-MeO-DMT is roughly 4 to 6 times as potent as N,N-DMT.

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