5-MeO-DMT

5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) or O-methyl-bufotenin is a psychedelic of the tryptamine 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. Like its close relatives DMT and bufotenin (5-HO-DMT), it has been used as an entheogen in South America.[1] Slang terms include Five-methoxy, The power, and Toad venom.[2]

5-MeO-DMT
Clinical data
Routes of
administration		Smoked, Insufflated, Oral
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • DE: Anlage I (Authorized scientific use only)
  • UK: Class A
  • US: Schedule I
  • Illegal in China, Sweden, Turkey
Identifiers
IUPAC name
  • 2-(5-Methoxy-1H-indol-3-yl)-N,N-dimethylethanamine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.012.558
Chemical and physical data
FormulaC13H18N2O
Molar mass218.300 g·mol−1
3D model (JSmol)
SMILES
  • COc2ccc1[nH]cc(CCN(C)C)c1c2
InChI
  • InChI=1S/C13H18N2O/c1-15(2)7-6-10-9-14-13-5-4-11(16-3)8-12(10)13/h4-5,8-9,14H,6-7H2,1-3H3 Y
  • Key:ZSTKHSQDNIGFLM-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Chemistry

5-MeO-DMT was first synthesized in 1936, and in 1959 it was isolated as one of the psychoactive ingredients of Anadenanthera peregrina seeds used in preparing Yopo 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 metabolite of 5-MeO-DMT, bufotenin.[3][4] It is metabolized mainly by CYP2D6.[4]

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 and non-responsiveness, sensual/erotic enhancement, to dysphoria, fear, terror, and panic.[5]

Uses

It has anti-anxiety and anti-depressant effects.[6][7]

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.[8][9] Between 1970 and 1990, smoking of 5-MeO-DMT on parsley was probably one of the two most common forms of ingestion in the United States.[9]

Pharmacology

5-MeO-DMT is a methoxylated derivative of DMT. While most common psychedelics are believed to primarily elicit psychological effects through agonism of serotonin 5-HT2A receptors, 5-MeO-DMT shows 1000-fold greater affinity for 5-HT1A over 5-HT2A;[10] further, its activity in rats was attenuated with the 5-HT1A selective antagonist WAY-100635 while 5-HT2A selective antagonist volinanserin failed to demonstrate any change.[11] Additional mechanisms of action such as inhibition of monoamine reuptake may be involved.[12] A 2019 European study with 42 volunteers showed that a single inhalation produced sustained enhancement of satisfaction with life, and easing of anxiety, depression, and post-traumatic stress disorder (PTSD).[13]

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.[14]

Neurogenesis
See also: Ayahuasca § Neurogenesis; Banisteriopsis caapi § Neurogenesis; and N,N-Dimethyltryptamine § Neurogenesis

A 2018 study demonstrated that a single dose of 5-MeO-DMT induced neurogenesis in mice.[15]

Clinical Development

5-MeO-DMT is being developed and evaluated for potential therapeutic effects in patients with Treatment-Resistant Depression (TRD).[16] Biopharmaceutical company GH Research has sponsored a completed phase 1 study in healthy volunteers[17] 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.[18] 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.[19]

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.[20] 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."[21]

Sources

5-MeO-DMT can be produced synthetically.[22][23]

Plant sources
FamilyPlants
RutaceaeDictyoloma incanescens,[24] Limonia acidissima,[25] Melicope leptococca[26]
FabaceaeAnadenanthera peregrina,[27] Acacia auriculiformis,[27] Acacia victoriae,[27] Desmodium gangeticum,[27] Lespedeza bicolor,[26][25] Mimosa pudica,[27] Mucuna pruriens,[25][26] Phyllodium pulchellum[25][26]
PoaceaePhalaris tuberosa[27]
MalpighiaceaeDiplopterys cabrerana[28]
CactaceaeEchinocereus salm-dyckianus,[25] Echinocereus triglochidiatus[25]
MyristicaceaeHorsfieldia superba,[25] Iryanthera macrophylla,[25] Osteophloeum platyspermum,[28] Virola theiodora,[25] V. calophylla,[28] V. multinervia,[28] V. peruviana,[28] V. rufula,[28] V. venosa[28]
Animal Sources
FamilyAnimals
BufonidaeColorado River toad (Bufo alvarius)[29][13][26]
Fungal Sources
FamilyFungi
AmanitaceaeAmanita citrina,[28] Amanita porphyria[28]

China

As of October 2015, 5-MeO-DMT is a controlled substance in China.[30]

Australia

As a structural analog of N,N-dimethyltryptamine (DMT), 5-MeO-DMT is a Schedule 9 prohibited substance under the Poisons Standard.[31]

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.[32]

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 since December 2013.[33]

United States

5-MeO-DMT was made a Schedule I controlled substance in January 2011.[34]

Possibility of Unknown Active Species

Alexander Shulgin in his book TiHKAL 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.[35] 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 track. 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.

See also

References
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