Chemistry:5-Chloro-DMT

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5-Chloro-DMT, or 5-Cl-DMT, also known as 5-chloro-N,N-dimethyltryptamine, is a psychedelic drug of the tryptamine family related to dimethyltryptamine (DMT) and other psychedelic tryptamines such as 5-bromo-DMT and 5-fluoro-DMT.[1] It has been encountered as a novel designer drug.[2][3][4]

Use and effects

5-Chloro-DMT was not included nor mentioned in Alexander Shulgin's book TiHKAL (Tryptamines I Have Known and Loved).[5] No experience reports existed for the drug as of 2020.[2] In addition, its routes of administration and doses were unavailable as of 2020.[4] In any case, it is known that the closely structurally related psychedelics DMT, 5-bromo-DMT, and 5-MeO-DMT are all inactive orally.[6][5]

Interactions

Pharmacology

Pharmacodynamics

5-Chloro-DMT activities
Target Affinity (Ki, nM)
5-HT1A 33 (Ki)
41 (EC50)
94% (Emax)
5-HT2A 134 (Ki)
310a (EC50)
45%a (Emax)
5-HT2C 55 (Ki)
22a (EC50)
81%a (Emax)
SERT 830 (Ki)
394 (IC50)
Notes: The smaller the value, the more avidly the drug interacts with the site. Footnotes: a = Stimulation of IP1 formation. Sources: [7]

5-Chloro-DMT acts as a serotonin receptor agonist.[1][8][9][10] It is known to have affinity for and act as an agonist of the serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors.[1][7][11][12] The drug shows higher affinity for the serotonin 5-HT1A receptor compared to unsubstituted dimethyltryptamine (DMT), with around 10-fold higher selectivity for this receptor over the serotonin 5-HT2A receptor.[1] It exhibits lower efficacy in terms of serotonin 5-HT2A receptor calcium mobilization relative to the parent compound DMT.[1]

The drug produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with intermediate potency among halogenated derivatives.[1][10][13] In addition, it produces hypolocomotion and hypothermia, effects that appear to be mediated through serotonin 5-HT1A receptor activation.[1]

5-Chloro-DMT demonstrates similar biased agonism patterns at the serotonin 5-HT2A receptor compared to other halogenated derivatives, showing higher potency and efficacy for β-arrestin2 recruitment relative to miniGαq recruitment, with bias factors comparable to serotonin.[1]

Chemistry

Analogues

Analogues of 5-chloro-DMT include dimethyltryptamine (DMT), 5-fluoro-DMT, 5-bromo-DMT, 5-TFM-DMT, 6-fluoro-DMT, bretisilocin (5-fluoro-MET), 5-chloro-AMT, 6-fluoro-AMT, 7-chloro-AMT, and 5,N,N-TMT, among others.[1]

History

5-Chloro-DMT was first described in the scientific literature by Benington and colleagues by 1960.[14] It was encountered as a novel designer drug by 2020.[2][3][4]

Society and culture

Canada

5-Chloro-DMT is not a controlled substance in Canada as of 2025.[15]

United States

5-Chloro-DMT is not an explicitly controlled substance in the United States.[16] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Neuropharmacology of halogenated DMT analogs: psychoplastogenic and antidepressant properties of 5-Br-DMT, a psychedelic derivative with low hallucinogenic potential". Molecular Psychiatry. October 2025. doi:10.1038/s41380-025-03308-2. PMID 41120735. 
  2. ↑ 2.0 2.1 2.2 "Identifying New/Emerging Psychoactive Substances at the Time of COVID-19; A Web-Based Approach". Front Psychiatry 11. 2020. doi:10.3389/fpsyt.2020.632405. PMID 33633599. 
  3. ↑ 3.0 3.1 "Analytical Report: 5-Cl-DMT.". Slovenia: Nacionalni Forenzični Laboratorij. July 2020. https://www.policija.si/apps/nfl_response_web/0_Analytical_Reports_final/5-Cl-DMT-ID-2175-20_report.pdf. 
  4. ↑ 4.0 4.1 4.2 "5-Cl-DMT" (in ru). АИПСИН. https://aipsin.com/newsubstance/498/. 
  5. ↑ 5.0 5.1 Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. http://www.erowid.org/library/books_online/tihkal/tihkal.shtml. 
  6. ↑ "Sea DMT: God Molecule or Barnacle Repellent?". Vice. 26 March 2013. https://www.vice.com/en/article/sea-dmt-000481-v20n3/. 
  7. ↑ 7.0 7.1 "Pharmacologic Activity of Substituted Tryptamines at 5-Hydroxytryptamine (5-HT)2A Receptor (5-HT2AR), 5-HT2CR, 5-HT1AR, and Serotonin Transporter". The Journal of Pharmacology and Experimental Therapeutics 385 (1): 62–75. April 2023. doi:10.1124/jpet.122.001454. PMID 36669875. 
  8. ↑ "Synthesis of some 5- and 6-chloro, 5-methyl, and 5,6,7-trimethyl derivatives of tryptamine". Journal of Organic Chemistry 25 (9): 1542–1547. September 1960. doi:10.1021/jo01079a020. 
  9. ↑ "Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space". Marine Drugs 15 (8): 248. August 2017. doi:10.3390/md15080248. PMID 28792478. 
  10. ↑ 10.0 10.1 "Psychedelic-inspired drug discovery using an engineered biosensor". Cell 184 (10): 2779–2792.e18. May 2021. doi:10.1016/j.cell.2021.03.043. PMID 33915107. 
  11. ↑ "A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines". The Journal of Biological Chemistry 299 (10). October 2023. doi:10.1016/j.jbc.2023.105231. PMID 37690691. 
  12. ↑ Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery, 10 March 2023, doi:10.21203/rs.3.rs-2667175/v1, https://www.researchsquare.com/article/rs-2667175/latest.pdf, retrieved 18 March 2025 
  13. ↑ "5-halo-substituted DMT derivatives. Hallucinogenic response and early gene expression in mice". Neuroscience Applied 3. 2024. doi:10.1016/j.nsa.2024.104390. 
  14. ↑ "Synthesis of Some 5- and 6-Chloro, 5-Methyl, and 5,6,7-Trimethyl Derivatives of Tryptamine". The Journal of Organic Chemistry 25 (9): 1542–1547. 1960. doi:10.1021/jo01079a020. ISSN 0022-3263. https://pubs.acs.org/doi/abs/10.1021/jo01079a020. Retrieved 29 October 2025. 
  15. ↑ "Controlled Drugs and Substances Act". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 
  16. ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf 



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