5-MeO-DMT
5-MeO-DMT.svg
5-MeO-DMT-3d-sticks.png
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
  • 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 Edit this at Wikidata
Chemical and physical data
FormulaC13H18N2O
Molar mass218.300 g·mol−1
3D model (JSmol)
  • COc2ccc1[nH]cc(CCN(C)C)c1c2
  • 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 checkY
  • Key:ZSTKHSQDNIGFLM-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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]

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, it's 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]

Research

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 Ireland Limited has sponsored a completed study in healthy volunteers and an ongoing study in TRD patients.[17]

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.[18] 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."[19]

Sources

This section is missing information about popularity of toad source; specific synthetic routes. Please expand the section to include this information. Further details may exist on the talk page. (February 2021)

5-MeO-DMT can be produced synthetically.[20][21]

Plant sources
Family Plants
Rutaceae Dictyoloma incanescens,[22] Limonia acidissima,[23] Melicope leptococca[24]
Fabaceae Anadenanthera peregrina,[25] Acacia auriculiformis,[25] Acacia victoriae,[25] Desmodium gangeticum,[25] Lespedeza bicolor,[24][23] Mimosa pudica,[25] Mucuna pruriens,[23][24] Phyllodium pulchellum[23][24]
Poaceae Phalaris tuberosa[25]
Malpighiaceae Diplopterys cabrerana[26]
Cactaceae Echinocereus salm-dyckianus,[23] Echinocereus triglochidiatus[23]
Myristicaceae Horsfieldia superba,[23] Iryanthera macrophylla,[23] Osteophloeum platyspermum,[26] Virola theiodora,[23] V. calophylla,[26] V. multinervia,[26] V. peruviana,[26] V. rufula,[26] V. venosa[26]
Animal Sources
Family Animals
Bufonidae Colorado River toad (Bufo alvarius)[27][13][24]
Fungal Sources
Family Fungi
Amanitaceae Amanita citrina,[26] Amanita porphyria[26]

Legal status

China

As of October 2015, 5-MeO-DMT is a controlled substance in China.[28]

Australia

As a structural analog of N,N-dimethyltryptamine (DMT), 5-MeO-DMT is a Schedule 9 prohibited substance under the Poisons Standard.[29]

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.[30]

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.[31]

United States

5-MeO-DMT was made a Schedule I controlled substance in January 2011.[32]

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.[33] 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

  1. ^ Araújo AM, Carvalho F, Bastos M, Guedes de Pinho P, Carvalho M (August 2015). "The hallucinogenic world of tryptamines: an updated review". Archives of Toxicology. 89 (8): 1151–73. doi:10.1007/s00204-015-1513-x. PMID 25877327. S2CID 4825078.
  2. ^ "Ultimate Guide to 5-MeO-DMT - Experience, Benefits, & Side Effects". 29 June 2020.
  3. ^ Ott J (July–September 2001). "Pharmañopo-psychonautics: human intranasal, sublingual, intrarectal, pulmonary and oral pharmacology of bufotenine". Journal of Psychoactive Drugs. 33 (3): 273–81. doi:10.1080/02791072.2001.10400574. PMID 11718320. S2CID 5877023.
  4. ^ a b Shen HW, Jiang XL, Winter JC, Yu AM (October 2010). "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Current Drug Metabolism. 11 (8): 659–66. doi:10.2174/138920010794233495. PMC 3028383. PMID 20942780.
  5. ^ "5-MeO-DMT Effects by Erowid". Erowid.org. Retrieved 2021-07-30.
  6. ^ Davis, Alan K.; So, Sara; Lancelotta, Rafael; Barsuglia, Joseph P.; Griffiths, Roland R. (March 2019). "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. 45 (2): 161–169. doi:10.1080/00952990.2018.1545024. PMC 6430661. PMID 30822141.
  7. ^ Davis, Alan K; Barsuglia, Joseph P; Lancelotta, Rafael; Grant, Robert M; Renn, Elise (30 April 2018). "The epidemiology of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption". Journal of Psychopharmacology. 32 (7): 779–792. doi:10.1177/0269881118769063. PMC 6248886. PMID 29708042.
  8. ^ John Mann; Adam Gottlieb (2015) [First published 1970]. "back cover". The Book of Sacraments: Ritual Use of Magical Plants. Ronin Publishing. ISBN 978-1-57951-210-1.
  9. ^ a b "5-MeO-DMT Timeline". Erowid.
  10. ^ Ray, Thomas S (2010). "Psychedelics and the Human Receptorome". PLOS ONE. 5 (2): e9019. Bibcode:2010PLoSO...5.9019R. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
  11. ^ Krebs-Thomson K, Ruiz EM, Masten V, Buell M, Geyer MA (December 2006). "The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats". Psychopharmacology. 189 (3): 319–29. doi:10.1007/s00213-006-0566-1. PMID 17013638. S2CID 23396616.
  12. ^ Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–7. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101.
  13. ^ a b Uthaug MV, Lancelotta R, van Oorsouw K, Kuypers KP, Mason N, Rak J, Šuláková A, Jurok R, Maryška M, Kuchař M, Páleníček T, Riba J, Ramaekers JG (September 2019). "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. 236 (9): 2653–2666. doi:10.1007/s00213-019-05236-w. PMC 6695371. PMID 30982127.
  14. ^ Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE (2018). "Psychedelics promote structural and functional neural plasticity". Cell Reports. 23 (11): 3170–3182. doi:10.1016/j.celrep.2018.05.022. PMC 6082376. PMID 29898390.
  15. ^ Lima da Cruz, RV; Moulin, TC; Petiz, LL; Leão, RN (2018). "A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus". Frontiers in Molecular Neuroscience. 11: 312. doi:10.3389/fnmol.2018.00312. PMC 6131656. PMID 30233313.
  16. ^ "Home | GH Research". GH Research Limited.
  17. ^ "Pipeline | GH Research". GH Research Limited.
  18. ^ Carpenter, David E. (2022-02-16). "More Companies Embrace 5-MeO-DMT to Create Therapies". Lucid News. Retrieved 2022-03-06.
  19. ^ Siebert, Amanda. "Could 5-MeO-DMT Allow For More Affordable Psychedelic-Assisted Therapy? Beckley Psytech Thinks So". Forbes. Retrieved 2022-03-06.
  20. ^ Sherwood, Alexander M.; Claveau, Romain; Lancelotta, Rafael; Kaylo, Kristi W.; Lenoch, Kelsey (2020-12-02). "Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use". ACS Omega. 5 (49): 32067–32075. doi:10.1021/acsomega.0c05099. ISSN 2470-1343. PMC 7745443. PMID 33344861.
  21. ^ Carpenter, David E. (2021-02-02). "Psychedelic Toads Pushed To The Limit, Conservationists Urge Synthetic 5-MeO-DMT Option". Forbes. Retrieved 2021-02-04.
  22. ^ Uthaug MV, Lancelotta R, Szabo A, Davis AK, Riba J, Ramaekers JG (March 2020). "Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment". Psychopharmacology. 237 (3): 773–785. doi:10.1007/s00213-019-05414-w. PMC 7036074. PMID 31822925.
  23. ^ a b c d e f g h i "tryptamines: fungi". bluezoo.org.
  24. ^ a b c d e "Erowid Psychoactive Vaults: Tryptamine FAQ". www.erowid.org.
  25. ^ a b c d e f "Some simple tryptomines" (PDF). troutsnotes.com. Retrieved 2020-07-04.
  26. ^ a b c d e f g h i Khan, JaVed I.; Kennedy, Thomas J.; Christian Jr, Donnell R. (2011). Basic Principles of Forensic Chemistry. Springer Science & Business Media. p. 196. ISBN 978-1-934115-06-0.
  27. ^ Carpenter DE. "5-MeO-DMT: The 20-Minute Psychoactive Toad Experience That's Transforming Lives". Forbes.
  28. ^ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
  29. ^ "Poisons Standard July 2016". Federal Register of Legislation.
  30. ^ "Förordning om ändring i förordningen (1999:58) om förbud mot vissa hälsofarliga varor" (PDF). Svensk författningssamling (in Swedish). 7 September 2004.
  31. ^ "Turkish Law" (PDF). Resmi Gazete. 16 December 2013.
  32. ^ Drug Enforcement Administration (DEA), Department of Justice (December 2010). "Schedules of controlled substances: placement of 5-methoxy-N,N-dimethyltryptamine into Schedule I of the Controlled Substances Act. Final rule" (PDF). Federal Register. 75 (243): 79296–300. PMID 21171485.
  33. ^ "Shulgin's TiHKAL entry for 5-MeO-DMT via Erowid".