5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine), also known as ''O''-methylbufotenin or mebufotenin (), is a

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

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 firs ...

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

Colorado River toad The Colorado River toad (''Incilius alvarius''), also known as the Sonoran Desert toad, is a toad species found in northwestern Mexico and the southwestern United States. It is well known for its ability to exude toxins from glands within its sk ...

. It may occur naturally in humans as well. Like its close relatives

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT) and

bufotenin Bufotenin, also known as dimethylserotonin or as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine (DMT) and of the neurotransmi ...

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

entheogen Entheogens are psychoactive substances used in spiritual and religious contexts to induce altered states of consciousness. Hallucinogens such as the psilocybin found in so-called "magic" mushrooms have been used in sacred contexts since ancie ...

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a considerably smaller portion in the Northern Hemisphere. It can also be described as the southern Subregion#Americas, subregion o ...

. 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 Michael Kevin Pollan (; born February 6, 1955) is an American journalist who is a professor and the first Lewis K. Chan Arts Lecturer at Harvard University. Concurrently, he is the Knight Professor of Science and Environmental Journalism and the ...

, as the "Mount Everest of psychedelics".

Adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s of 5-MeO-DMT include sickness,

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

chest pressure Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with na ...

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

fear Fear is an unpleasant emotion that arises in response to perception, perceived dangers or threats. Fear causes physiological and psychological changes. It may produce behavioral reactions such as mounting an aggressive response or fleeing the ...

, terror,

confusion In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"

paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety, suspicion, or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of co ...

crying Crying is the dropping of tears (or welling of tears in the eyes) in response to an emotional state or physical pain. Emotions that can lead to crying include sadness, anger, joy, and fear. Crying can also be caused by relief from a period ...

, loss of

awareness In philosophy and psychology, awareness is the perception or knowledge of something. The concept is often synonymous with consciousness. However, one can be aware of something without being explicitly conscious of it, such as in the case of bli ...

and

motor control Motor control is the regulation of movements in organisms that possess a nervous system. Motor control includes conscious voluntary movements, subconscious muscle memory and involuntary reflexes, as well as instinctual taxes. To control ...

, and reactivations. The drug acts as a non-selective

serotonin receptor agonist A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...

, including of the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_1A and 5-HT_2A receptors, among others. However, 5-MeO-DMT differs from most other serotonergic psychedelics in having 100- to 1,000-fold higher

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 Pa ...

for the serotonin 5-HT_1A receptor over 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 experience A religious experience (sometimes known as a spiritual experience, sacred experience, mystical experience) is a subjective experience which is interpreted within a religious framework. The concept originated in the 19th century, as a defense ag ...

s in most people who take it. Like DMT, 5-MeO-DMT is only active non-orally and has a very rapid

onset of action Onset of action is the duration of time it takes for a drug's effects to come to prominence upon administration. With oral administration, it typically ranges anywhere from 20 minutes to over an hour, depending on the drug in question. Other meth ...

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 Isolation is the near or complete lack of social contact by an individual. Isolation or isolated may also refer to: Sociology and psychology *Social isolation *Isolation (psychology), a defense mechanism in psychoanalytic theory *Emotional iso ...

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 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 Sing ...

in some countries, for instance the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Northwestern Europe, off the coast of European mainland, the continental mainland. It comprises England, Scotlan ...

Australia Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...

, and

New Zealand New Zealand () is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and List of islands of New Zealand, over 600 smaller islands. It is the List of isla ...

. 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 Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

). 5-MeO-DMT is being developed for potential use in medicine in the treatment of

neuropsychiatric disorder A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

s such as depression.

Uses

Recreational

5-MeO-DMT is used as a

recreational drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

Medical

Preliminary clinical findings suggest that 5-MeO-DMT might have

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

effects.

Religious

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 A sacrament is a Christian rite which is recognized as being particularly important and significant. There are various views on the existence, number and meaning of such rites. Many Christians consider the sacraments to be a visible symbol ...

. 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 Parsley, or garden parsley (''Petroselinum crispum''), is a species of flowering plant in the family Apiaceae that is native to Greece, Morocco and the former Yugoslavia. It has been introduced and naturalisation (biology), naturalized in Eur ...

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, inge ...

in the

Dosage

5-MeO-DMT has been described as having a steep dose–response curve.

Effects

When smoked, the duration of the effects of 5-MeO-DMT can be as little as ten minutes; when insufflated, up to two hours, although the peak effects are usually in the range of 10–40 minutes. Effects vary and can range from radical perspective shifting and perception of new insights, euphoria, immersive experiences, dissociation and non-responsiveness, sensual/erotic enhancement, to dysphoria, fear, terror, panic, and

ego death Ego death is a "complete loss of subjective self-identity". The term is used in various intertwined contexts, with related meanings. The 19th-century philosopher and psychologist William James uses the synonymous term "self-surrender", and Jung ...

. The subjective effects of 5-MeO-DMT are described as distinct from those of DMT and other psychedelics. Whereas DMT is described as producing more "information-rich" experiences, with "rich sensory phenomenology", visuals, and experiences of encountering entities and visiting other worlds, 5-MeO-DMT is described as having a relative lack of visual effects, producing a sense of "nothingness", and causing experiences that are said to be "content-free" and sometimes known as "whiteouts". These experiences have been described as "beyond ordinary human comprehension", with a subjective impression of a void or

amnesia Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...

of the experience. In spite of this however, some have described the experiences as

orgasm Orgasm (from Greek , ; "excitement, swelling"), sexual climax, or simply climax, is the sudden release of accumulated sexual excitement during the sexual response cycle, characterized by intense sexual pleasure resulting in rhythmic, involu ...

ic,

ecstatic Ecstasy () is a subjective experience of total involvement of the subject with an object of their awareness. In classical Greek literature, it refers to removal of the mind or body "from its normal place of function." Total involvement with a ...

, and blissful, whereas others have described them as terror or "information overwhelm". As with DMT and other psychedelics, the experiences with 5-MeO-DMT are often described as overwhelming, profound, spiritual, religious, and/or mystical. The experiences of 5-MeO-DMT have been related to the experience of ecstatic seizures.

Interactions

Pharmacology

Pharmacodynamics

5-MeO-DMT is a methoxylated

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

(DMT). While most common psychedelics are believed to primarily elicit psychological effects through

agonism Agonism (from Greek 'struggle') is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks to show how indivi ...

5-HT_2A receptors, 5-MeO-DMT shows 1,000-fold greater

for the serotonin 5-HT_1A receptor over the serotonin 5-HT_2A receptor. In line with its affinity for serotonin 5-HT_1A receptors, 5-MeO-DMT is extremely potent at suppressing the firing of

dorsal raphe nucleus The dorsal raphe nucleus is one of the raphe nuclei. It is situated in the brainstem at the midline. It has rostral and caudal subdivisions: * The rostral aspect of the ''dorsal'' raphe is further divided into interfascicular, ventral, ventrolater ...

serotonin

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s. Further, its activity in rats was attenuated with the selective serotonin 5-HT_1A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.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 the ...

, while selective serotonin 5-HT_2A receptor antagonist volinanserin failed to demonstrate any change. Additional mechanisms of action such as

inhibition Inhibitor or inhibition may refer to: 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 neurotransm ...

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 are ...

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

may also be involved in its effects. Similarly to other serotonergic psychedelics, 5-MeO-DMT is a non-selective

, including of the serotonin 5-HT_1A, 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors, among others. It is 4- to 10-fold more potent as a hallucinogen than DMT in humans. In contrast to most serotonergic psychedelics however, it has been said that it is unclear that the hallucinogenic effects of 5-MeO-DMT are principally mediated by activation of the

5-HT_2A receptor. In any case, 5-MeO-DMT does still activate the serotonin 5-HT_2A receptor and does still produce psychedelic effects. It has been proposed that 5-MeO-DMT be considered an "atypical" psychedelic. This relates to the fact that 5-MeO-DMT has 100- to 1,000-fold

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

for the serotonin 5-HT_1A receptor over the serotonin 5-HT_2A receptor and that the actions of 5-MeO-DMT appear to be primarily mediated by serotonin 5-HT_1A receptor activation. For example, the potencies of drugs substituting for 5-MeO-DMT in

drug discrimination Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...

assays is well-correlated with their serotonin 5-HT_1A receptor affinities, and the discriminative stimulus effects of 5-MeO-DMT are attenuated by serotonin 5-HT_1A receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. However, there is partial

generalization A generalization is a form of abstraction whereby common properties of specific instances are formulated as general concepts or claims. Generalizations posit the existence of a domain or set of elements, as well as one or more common characteri ...

of 5-MeO-DMT to the selective serotonin 5-HT₂ receptor agonist (–)-DOM in animals. In accordance with the preceding findings, 5-MeO-DMT is reported to produce notably distinct subjective effects compared DMT and other psychedelics in humans. Although 5-MeO-DMT shows dramatically higher affinity for the serotonin 5-HT_1A receptor than for the serotonin 5-HT_2A receptor, the situation appears to be very different in terms of its actual activational potencies at these receptors. Its values have been found to be 1.80 to 3.87nM at the serotonin 5-HT_2A receptor and 3.92 to 1,060nM at the serotonin 5-HT_1A receptor. For comparison, the values of DMT were found to be 38.3nM at the serotonin 5-HT_2A receptor and >10,000nM at the serotonin 5-HT_1A receptor in one of the same studies. Hence, 5-MeO-DMT appears to be similarly potent or as much as 200-fold more potent as an agonist of the serotonin 5-HT_2A receptor than of the serotonin 5-HT_1A receptor. In addition, 5-MeO-DMT is 10-fold more potent than DMT as an agonist of the serotonin 5-HT_2A receptor. Besides the serotonin receptors, 5-MeO-DMT is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

MT₁ and MT₂ receptors. Unlike DMT, 5-MeO-DMT is not a

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

or agonist of the

sigma receptor Sigma receptors (σ-receptors) are protein receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, sigma-1 rec ...

s. In contrast to certain other tryptamines, 5-MeO-DMT is inactive as a

monoamine releasing agent A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrati ...

, including of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

, and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

. However, it is a weak

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...

, with an value of 2,184nM. Conversely, it is inactive as a

and

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinep ...

( = >10,000nM). Similarly to DMT, but in contrast to most other psychedelics, like LSD and psilocybin, there appears to be very little development of tolerance with 5-MeO-DMT. In fact, there may even be

sensitization Sensitization is a non-associative learning process in which repeated administration of a stimulation, stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole ...

to the effects of 5-MeO-DMT. The lack of tolerance development with 5-MeO-DMT may be due to biased agonism of the serotonin 5-HT_2A receptor. More specifically, 5-MeO-DMT activates the G_q

signaling pathway In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...

of the serotonin 5-HT_2A receptor with much less

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

in recruiting

β-arrestin2 Beta-arrestin-2, or β-arrestin2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ''ARRB2'' gene. Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desens ...

. Activation of β-arrestin2 is linked to receptor downregulation and

tachyphylaxis Tachyphylaxis (Greek ταχύς, ''tachys'', "rapid", and φύλαξις, ''phylaxis'', "protection") is a medical term describing an acute, sudden decrease in response to a drug after its administration (i.e., a rapid and short-term onset of drug ...

. 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

, depression, and

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(PTSD). A 2018 study found that a single dose of 5-MeO-DMT induced

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

in mice.

Pharmacokinetics

5-MeO-DMT is

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

and is thought to easily cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. Accordingly, 5-MeO-DMT readily accumulates in the brain in animals with levels higher than in blood. This is in notable contrast to

(5-HO-DMT or ''N'',''N''-dimethylserotonin) and

(5-HT), which are

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

and have varying degrees of peripherally selectivity. Bufotenin is an

active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

of 5-MeO-DMT, formed by ''O''-

demethylation 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 at ...

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

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. CYP2 ...

. Bufotenin notably has much higher

for the serotonin 5-HT_2A 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 Metabolism (, from ''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 cellular processes; the co ...

of 5-MeO-DMT can be dramatically reduced and its levels markedly augmented and prolonged by

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

s (MAOIs). In addition, MAOIs allow 5-MeO-DMT to become orally active in humans. Combination of 5-MeO-DMT with MAOIs has sometimes resulted in

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

and death in humans.

Chemistry

5-MeO-DMT, also known as 5-methoxy-''N'',''N''-dimethyltryptamine, is a

substituted tryptamine Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all trypt ...

. It is the 5- methoxylated derivative of ''N'',''N''-dimethyltryptamine (DMT), the ''N'',''N''- dimethylated derivative of

5-methoxytryptamine 5-Methoxytryptamine (5-MT, 5-MeO-T, or 5-OMe-T), also known as serotonin methyl ether or ''O''-methylserotonin and as mexamine, is a tryptamine derivative closely related to the neurotransmitters serotonin and melatonin. It has been shown to oc ...

(5-MT; mexamine), and the ''O''-methylated derivative of

(5-HO-DMT). It has a relatively high experimental log P of 3.30.

Synthesis

In addition to naturally-occurring sources, 5-MeO-DMT can be produced synthetically.

Analogues and derivatives

Analogues of 5-MeO-DMT include 4-MeO-DMT,

5-MeO-AMT 5-MeO-αMT, also known as 5-methoxy-α-methyltryptamine or as α,''O''-dimethylserotonin (α,''O''-DMS or Alpha-O), is a serotonergic psychedelic of the tryptamine, α-alkyltryptamine, and 5-methoxytryptamine families. It is a derivative of α ...

, 5-MeO-DET, 5-MeO-DPT,

5-MeO-DIPT 5-MeO-DiPT, also known as 5-methoxy-''N'',''N''-diisopropyltryptamine and sometimes as foxy methoxy or simply foxy, is a psychedelic drug of the tryptamine and 5-methoxytryptamine families. It is the 5-methoxy derivative of diisopropyltryptami ...

5-MeO-MiPT 5-MeO-MiPT is a psychedelic and hallucinogen of the tryptamine family. It used by some as an entheogen. It has structural and pharmacodynamic properties similar to the drugs 5-MeO-DiPT, DiPT, and MiPT. It is commonly used as a "substitute" for ...

5-EtO-DMT 5-Ethoxy-DMT (5-ethoxy-''N'',''N''-dimethyltryptamine, 5-EtO-DMT, ''O''-ethylbufotenine) is a tryptamine chemical derivative, derivative which has been previously synthesized as a chemical intermediate, but has not been studied to determine its p ...

, 5-MeO-MET, and 5-MeO-pyr-T. Other analogues include

dimemebfe Dimemebfe (5-MeO-BFE) is a recreational drug and research chemical. It acts as an agonist for the 5-HT1A and 5-HT2 family of serotonin receptors. It is related in structure to the psychedelic tryptamine derivative 5-MeO-DMT, but with the indo ...

and EMDT.

Natural occurrence

Plants

Toads

The

is a noted animal source of 5-MeO-DMT. First described in '' Bufo Alvarius: the Psychedelic Toad of the Sonoran Desert'' in 1984 by Ken Nelson (writing under the pseudonym of Albert Most), smoking the parotoid secretions of the animal produces a powerful and short-lived

psychedelic experience A psychedelic experience (known colloquially as a trip) is a temporary altered state of consciousness induced by the consumption of a psychedelic substance (most commonly Lysergic acid diethylamide, LSD, mescaline, psilocybin mushrooms, or N,N- ...

. The smoking of ''I. alvarius'' secretions should not be confused with the urban legend of toad licking. Since 1983, the animal has since became 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

History

5-MeO-DMT was first synthesized by Toshio Hoshino in 1935. It was

from the

flowering plant Flowering plants are plants that bear flowers and fruits, and form the clade Angiospermae (). The term angiosperm is derived from the Ancient Greek, Greek words (; 'container, vessel') and (; 'seed'), meaning that the seeds are enclosed with ...

'' Dictyoloma incanescens'' in 1959. The drug was subsequently isolated from numerous other

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

fungal A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...

, and

animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

source Source may refer to: Research * Historical document * Historical source * Source (intelligence) or sub source, typically a confidential provider of non open-source intelligence * Source (journalism), a person, publication, publishing institute ...

s over time. The behavioral effects of 5-MeO-DMT in animals were first reported by 1961. In 1965, 5-MeO-DMT was reported to be the main component of the

hallucinogenic snuff A hallucinogenic snuff, or psychedelic snuff, is a powder prepared from plants containing psychedelic alkaloids and insufflated (snorted) to produce hallucinogenic effects. Hallucinogenic snuffs have been used as entheogens by indigenous peop ...

known variously as parica, epena, or yakee that is prepared and used from the

resin A resin is a solid or highly viscous liquid that can be converted into a polymer. Resins may be biological or synthetic in origin, but are typically harvested from plants. Resins are mixtures of organic compounds, predominantly terpenes. Commo ...

of the '' Virola theiodora'' tree by indigenous people in Northern

. It was isolated from the

toad Toad (also known as a hoptoad) is a common name for certain frogs, especially of the family Bufonidae, that are characterized by dry, leathery skin, short legs, and large bumps covering the parotoid glands. In popular culture (folk taxonomy ...

'' 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 Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American biochemist, broad researcher of synthetic psychoactive compounds, and author of works regarding these, who independently explored the organic chemistry and ph ...

briefly reported that 5-MeO-DMT was hallucinogenic in humans, via

parenteral In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

but not

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

route Route or routes may refer to: * Air route, route structure or airway * GPS route, a series of one or more GPS waypoints * Route (gridiron football), a path run by a wide receiver * Route (command), a program used to configure the routing table * ...

s, in 1970, with additional details published later on. Albert Most, real name Ken Nelson, was the first to describe the use of ''Incilius alvarius'' toad

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...

as a psychedelic in his published pamphlet '' Bufo Alvarius: the Psychedelic Toad of the Sonoran Desert'' in 1984. Subsequently,

Andrew Weil Andrew Thomas Weil (, born June 8, 1942) is an American celebrity doctor who advocates for integrative medicine. Early life and education Weil was born in Philadelphia, on June 8, 1942,The editors of EB (2015). "Andrew Weil, American Physici ...

and Wade Davis, in part citing the pamphlet, described the psychoactive effects of the toad in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

in 1992. In addition, they described the finding as the first instance of a psychedelic from an animal source to be discovered.

Recreational use Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

of the toads, beyond the pamphlet, was encountered by the late 1980s and became a media sensation. 5-MeO-DMT became a

in the

in 2009.

Society and culture

Legal status

Australia

As a

structural analog A structural analog, also known as a chemical analog or simply an analog, is a chemical compound, compound having a chemical structure, structure similar to that of another compound, but differing from it in respect to a certain component. It can ...

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

Canada

5-MeO-DMT is legal for personal use and possession in Canada, though sale, distribution, and other activities involving the substance are illegal under Canadian federal law.

China

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

China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...

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 in October 2004, making it illegal to sell or possess.

Turkey

5-MeO-DMT has been controlled in

Turkey Turkey, officially the Republic of Türkiye, is a country mainly located in Anatolia in West Asia, with a relatively small part called East Thrace in Southeast Europe. It borders the Black Sea to the north; Georgia (country), Georgia, Armen ...

since December 2013.

United States

5-MeO-DMT was made a Schedule I

in January 2011.

Research

Depression

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

treatment-resistant depression Treatment-resistant depression (TRD) is often defined as major depressive disorder in which an affected person does not respond adequately to at least two different antidepressant medications at an adequate dose and for an adequate duration. Inad ...

(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. In February 2025, GH Research announced that their Phase 2b clinical trial of GH001, met its primary endpoint in patients with treatment-resistant depression (TRD). The trial demonstrated a placebo-adjusted reduction of 15.5 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 8, with 57.7% of patients achieving remission compared to 0% in the placebo group. The trial also met all secondary endpoints, and the treatment was well-tolerated with no serious adverse events reported. Beckley Psytech in collaboration with King's College London is evaluating 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." Ultra-short-acting psychedelics like

DMT Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a serotonergic hallucinogen and investigational drug of the tryptamine family that occurs naturally in many plants and animals, including humans. D ...

and 5-MeO-DMT may be advantageous to longer-acting psychedelics like

in terms of practicality for use as therapeutic interventions in clinical settings. 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.

References

External links

5-MeO-DMT - Isomer Design

5-MeO-DMT - PsychonautWiki

5-MeO-DMT - Erowid

5-MeO-DMT - TiHKAL - Erowid

5-MeO-DMT - TiHKAL - Isomer Design

5-MeO-DMT: Unpacking The Mysteries of This Powerful Psychedelic - Tripsitter
{{DEFAULTSORT:MeO-DMT, 5- 5-HT1A agonists 5-HT1B agonists 5-HT1D agonists 5-HT1E agonists 5-HT1F agonists 5-HT2A agonists 5-HT2B agonists 5-HT2C agonists 5-HT5A agonists 5-HT6 agonists 5-HT7 agonists Ayahuasca Biased ligands Designer drugs N,N-Dialkyltryptamines Dimethylamino compounds Entheogens Experimental hallucinogens Melatonin receptor agonists 5-Methoxytryptamines Psychedelic tryptamines Serotonin receptor agonists Tryptamine alkaloids

Uses

Recreational

Medical

Religious

Dosage

Effects

Interactions

Pharmacology

Pharmacodynamics

Pharmacokinetics

Chemistry

Synthesis

Analogues and derivatives

Natural occurrence

Plants

Toads

Fungi

History

Society and culture

Legal status

Australia

Canada

China

Germany

Sweden

Turkey

United States

Research

Depression

See also

References

External links