5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

class. It is found in a wide variety of plant species, and also is secreted by the glands of at least one toad species, the

Colorado River toad The Colorado River toad (''Incilius alvarius''), formerly known as the Sonoran Desert toad, is found in northern Mexico and the southwestern United States. It exudes toxins from glands within its skin that have psychoactive properties. Descript ...

. Like its close relatives DMT and

bufotenin Bufotenin (5-HO-DMT, bufotenine) is a tryptamine derivative - more specifically, a DMT derivative - related to the neurotransmitter serotonin. It is an alkaloid found in some species of toads (especially the skin), mushrooms and plants. ...

(5-HO-DMT), it has been used as an

entheogen Entheogens are psychoactive substances that induce alterations in perception, mood, consciousness, cognition, or behavior for the purposes of engendering spiritual development or otherwiseRätsch, Christian, ''The Encyclopedia of Psychoac ...

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the sout ...

. Slang terms include Five-methoxy, The power, and Toad venom.

Chemistry

5-MeO-DMT was first synthesized in 1936, and in 1959 it was isolated as one of the psychoactive ingredients of '' Anadenanthera peregrina''

seed A seed is an embryonic plant enclosed in a protective outer covering, along with a food reserve. The formation of the seed is a part of the process of reproduction in seed plants, the spermatophytes, including the gymnosperm and angiospe ...

s used in preparing

Yopo ''Anadenanthera peregrina'', also known as yopo, jopo, cohoba, parica or calcium tree, is a perennial tree of the genus ''Anadenanthera'' native to the Caribbean and South America. It grows up to tall, and has a horny bark. Its flowers grow ...

snuff. It was once believed to be a major component of the psychoactive effects of the snuff, although this has recently been shown to be unlikely, due to the limited or sometimes even non-existent quantity contained within the seeds, which instead achieve their psychoactivity from the ''O''-

demethylated Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen ato ...

metabolite of 5-MeO-DMT,

. It is

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

mainly by

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

Effects

Depending on whether smoked or insufflated, total duration of experience can last between 10 minutes for the former, or up to 2 hours for the latter. Effects vary and can range from radical perspective shifting and perception of new insights, euphoria, immersive experiences,

dissociation Dissociation, in the wide sense of the word, is an act of disuniting or separating a complex object into parts. Dissociation may also refer to: * Dissociation (chemistry), general process in which molecules or ionic compounds (complexes, or salts ...

and non-responsiveness, sensual/erotic enhancement, to dysphoria, fear, terror, and panic.

Uses

It has anti-anxiety and anti-depressant effects.

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 Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in a substance through the mouth into the gastrointestinal tract, such as through eating or drinking. In single-celled organisms in ...

in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

Pharmacology

5-MeO-DMT is a

methoxylated In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula . On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position as ...

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

of DMT. While most common psychedelics are believed to primarily elicit psychological effects through agonism of serotonin 5-HT_2A receptors, 5-MeO-DMT shows 1000-fold greater

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for 5-HT_1A over 5-HT_2A; further, its activity in rats was attenuated with the 5-HT_1A selective antagonist

WAY-100635 WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at ...

while 5-HT_2A selective antagonist volinanserin failed to demonstrate any change. Additional

mechanisms of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

such as

inhibition Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ar ...

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...

may be involved. A 2019 European study with 42 volunteers showed that a single inhalation produced sustained enhancement of satisfaction with life, and easing of

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, depression, and

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats o ...

(PTSD). In 2018, researchers also discovered that 5-MeO-DMT is a psychoplastogen, which refers to a compound capable of promoting rapid and sustained

neural plasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...

Research

Neurogenesis

A 2018 study demonstrated that a single dose of 5-MeO-DMT induced neurogenesis in mice.

Clinical Development

5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients with

Treatment-Resistant Depression Treatment-resistant depression is a term used in psychiatry to describe people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time. Definitions of treatment- ...

(TRD).

Biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...

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. Beckley Psytech in collaboration with King's College London research 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."

Sources

5-MeO-DMT can be produced synthetically.

Legal status

China

As of October 2015, 5-MeO-DMT is a

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...

in China.

Australia

As a

structural analog A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a c ...

of ''N'',''N''-dimethyltryptamine (DMT), 5-MeO-DMT is a Schedule 9 prohibited substance under the Poisons Standard.

Sweden

''Sveriges riksdags'' health ministry ''Statens folkhälsoinstitut'' 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 act ''Lagen om förbud mot vissa hälsofarliga varor'' (translated ''Act on the Prohibition of Certain Goods Dangerous to Health'') in October 2004, making it illegal to sell or possess.

Germany

As of 2001 5-MeO-DMT is listed as a controlled substance. Attachement I BtMG. BGBl. I 2001, 1180 - 1186;

Turkey

5-MeO-DMT has been controlled in

Turkey Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a transcontinental country located mainly on the Anatolian Peninsula in Western Asia, with a small portion on the Balkan Peninsula in ...

since December 2013.

United States

5-MeO-DMT was made a Schedule I

in January 2011.

Possibility of Unknown Active Species

Alexander Shulgin in his book

TiHKAL ''TIHKAL: The Continuation'' is a 1997 book written by Alexander Shulgin and Ann Shulgin about a family of psychoactive drugs known as tryptamines. A sequel to '' PIHKAL: A Chemical Love Story'', ''TIHKAL'' is an acronym that stands for "Trypt ...

experimented with different dosing regiments and forms of delivery for 5-MeO-DMT including: smoking, oral, and even IV injection. In his commentary on the bottom of the entry for 5-MeO-DMT he noted that the very potent effects attributed to this drug only seemed to exist when smoking it. Moreover, this curious feature was not found among most of the other related drugs including the parent compound DMT itself which can produce roughly equivalent experiences across all means of administration. The non-effect of Shulgin's oral dosing of 5-MeO-DMT can be dismissed as the result of monoamine oxidases degrading the drug in the digestive tract. This, however, does not explain why his IV dosing produced both much milder and rather different effects then his smoking regimen did. As a result, Shulgin speculates that there is a possibility that the active species actually responsible for the intense experience attributed to 5MeO-DMT may actually be an as-of-yet unknown compound that forms in the smoke of 5-MeO-DMT. A related possibility is that smoking 5MeO-DMT produces some unknown key enhancer compound whose co-administration with 5MeO-DMT mixed in the smoke is critical for the "traditional" 5MeO-DMT experience.

References

External links

TiHKAL #38 on Erowid
an
Erowid's 5-MeO-DMT Vault

5-MeO-DMT Entry in TiHKAL • info

Free Harm Reduction Courses

5-MeO-DMT Harm Reduction Forums
{{DEFAULTSORT:MeO-DMT, 5- Ayahuasca Entheogens Psychedelic tryptamines Tryptamine alkaloids Indole ethers at the benzene ring Serotonin receptor agonists Psychedelic drugs Designer drugs Dimethylamino compounds