5-MeO-DMT

5-methoxy-N,N-dimethyltryptamine1, bufotenine methyl ether1, O-methylbufotenine1, OMB1

Both the plant and animal worlds are sources of the psychoactive tryptamine compound 5-MeO-DMT. It was first described in plants in a member of the family Rutaceae called Dictyoloma incanescens.1 It is also found in high concentrations in the parotid gland secretions of the Colorado River toad Bufo alvarius.2 Historically, synthetic, toad- and plant-based sources of 5-MeO-DMT have been used for recreational and spiritual purposes. 5-MeO-DMT is one of the main active ingredients in ayahuasca, a hallucinogenic decoction used by the indigenous people of the Amazon river basin.3

A 2010 review article cites several references indicating 5-MeO-DMT has been detected in human urine, blood, and cerebrospinal fluid and may also be synthesized in the retina and pineal gland.2 Furthermore, elevated levels of 5-MeO-DMT and its analogs have been detected in the body of fluids of people suffering from psychiatric disorders such as schizophrenia.

The Chemistry of 5-MeO-DMT

5-MeO-DMT is a tryptamine alkaloid that is substituted by a methoxy group at position 5. It was first synthesized by Hoshino and Shimodaira in 1936.4 5-MeO-DMT is a derivative of DMT (N,N-dimethyltryptamine), and the neurotransmitter serotonin (Figure 1).

Figure 1: The chemical structures of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), N,N,-dimethyltryptamine (DMT), and 5-hydroxytryptamine (serotonin).

The Pharmacology of 5-MeO-DMT

The psychedelic effects of oral ingestion of 5-MeO-DMT are fast-acting, short-lived. This is because it is quickly rendered inactive due to deamination by the enzyme monoamine oxidase A (MAO-A). 5-MeO-DMT also undergoes O-demethylation by the cytochrome P450 2D6 enzyme.5,6 The O-demethylation of 5-MeO-DMT creates the compound 5-HO-DMT (bufotenine). Studies have shown that 5-HO-DMT has a greater affinity for the serotonin 5-HT2A receptor than 5-MeO-DMT.7–9 Because of the fast oral metabolism, users often inhale the vapor (insufflation) of 5-MeO-DMT.10

Substantial research indicates that the 5-HT1A receptor is important for the effects of 5-MeO-DMT.7,11–15 There is also some experimental evidence indicating agonism at 5-HT1B may also be involved.16–20

The Applications and Potential of 5-MeO-DMT

In humans, research suggests that 5-MeO-DMT improves symptoms of anxiety and depression.21,22 A 2018 study in mice found that a single dose of 5-MeO-DMT stimulates neurogenesis.23 The authors theorize that this effect may help explain the observed antidepressant properties of DMT derivatives. An in vitro study done in 2014 indicates that DMT and 5-MeO-DMT may regulate inflammation and immune homeostasis via the sigma-1 receptor.24

Two recent human studies found beneficial effects from the inhalation of vaporized toad secretions containing 5-MeO-DMT.21,25 However, due to the presence of other compounds in the secretions (the entourage effect), it is difficult to evaluate the effects of 5-MeO-DMT alone.

    References
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  3. Rivier L, Lindgren J-E. “Ayahuasca,” the South American Hallucinogenic Drink: An Ethnobotanical and Chemical Investigation. Economic Botany. 1972;26(2):101-129. http://www.jstor.org/stable/4253328.
  4. Hoshino T, Shimodaira K. Synthesis of bufotenin and 3-methyl-3-β-oxyethyl-indolenine. Syntheses in the indole group. XIV. Justus Liebigs Annalen der Chemie. 1935;520(1):19-30. doi:10.1002/jlac.19355200104
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  20. Tricklebank MD, Forler C, Middlemiss DN, Fozard JR. Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat. European Journal of Pharmacology. 1985;117(1):15-24. doi:10.1016/0014-2999(85)90467-4
  21. Uthaug MV, Lancelotta R, van Oorsouw K, et al. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology. April 2019. doi:10.1007/s00213-019-05236-w
  22. Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. The American Journal of Drug and Alcohol Abuse. 2019;0(0):1-9. doi:10.1080/00952990.2018.1545024
  23. Lima da Cruz RV, Moulin TC, Petiz LL, Leão RN. A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus. Front Mol Neurosci. 2018;11. doi:10.3389/fnmol.2018.00312
  24. Szabo A, Kovacs A, Frecska E, Rajnavolgyi E. Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells. Langmann T, ed. PLoS ONE. 2014;9(8):e106533. doi:10.1371/journal.pone.0106533
  25. Barsuglia JP, Davis AK, Palmer R, et al. Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Front Psychol. 2018;9. doi:10.3389/fpsyg.2018.02459