Scaline

Mescaline, the most well-known scaline psychedelic.

A scaline, also known as a substituted mescaline analogue and typically but not always a 4-substituted 3,5-dimethoxyphenethylamine, is an analogue of the phenethylamine serotonergic psychedelic mescaline (3,4,5-trimethoxyphenethylamine).

Other related compounds include the 2C (4-substituted 2,5-dimethoxyphenethylamine) and DOx (4-substituted 2,5-dimethoxyamphetamine) compounds as well as 3,4,5-trimethoxyamphetamine (TMA) and other 4-substituted 3,5-dimethoxyamphetamines (3C drugs). They are also mescaline analogues, but the 2C and DOx drugs have a methoxy group at the 2 position instead of the 3 position of the phenyl ring, while TMA is an amphetamine rather than a phenethylamine.

The pharmacology of mescaline analogues has been studied. Mescaline analogues, or 4-substituted 3,5-dimethoxyphenethylamines specifically, tend to be much less potent than the 2C and DOx drugs. This relates to the fact that the 2,4,5-substitution pattern tends to be optimal in terms of receptor affinity and potency. However, mescaline analogues are frequently much more potent than mescaline.

Substituted mescaline analogues have been extensively characterized by Alexander Shulgin and described in his books such as PiHKAL (Phenethylamines I Have Known and Loved) and The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds as well as in his literature reviews. They have also been studied by David E. Nichols and Daniel Trachsel, among other researchers.

A closely related group is thioscalines, which are compounds in which one or more of the methoxy groups of mescaline are replaced with alkylthio groups.

Use and effects

Interactions

Pharmacology

Pharmacodynamics

Society and culture

Canada

Mescaline and 3,4,5-trimethoxyamphetamine (TMA) are the only scalines (and derivatives) that are controlled substances in Canada as of 2025.

List of scalines

4-Substituted

4-Alkoxy-substituted

4-Alkylthio-substituted

Others

3- or 5-Extended

3- or 5-Replaced

2- or 6-Substituted

N-Substituted

α- or β-Substituted

Cyclized

Deuterated

Other compounds

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Retrieved 1 February 2025.
  2. 1 2 3 4 Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT (1978). "Mescaline analogs: substitutions at the 4-position" (PDF). NIDA Res Monogr (22): 27–37. PMID 101882. Archived from the original (PDF) on August 5, 2023.
  3. 1 2 3 4 5 6 7 8 9 Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID 8742795. Archived from the original (PDF) on August 5, 2023.
  4. 1 2 3 4 Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6.
  5. 1 2 Shulgin AT (March 1973). "Mescaline: the chemistry and pharmacology of its analogs". Lloydia. 36 (1): 46–58. PMID 4576313.
  6. 1 2 Alexander T. Shulgin; Ann Shulgin (1991). PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. ISBN 978-0-9630096-0-9. OCLC 25627628.
  7. 1 2 3 4 5 Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley, CA: Transform Press. ISBN 978-0-9630096-3-0. OCLC 709667010.
  8. 1 2 3 Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME (2021). "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Front Pharmacol. 12 794254. doi:10.3389/fphar.2021.794254. PMC 8865417. PMID 35222010.
  9. ↑ Halberstadt AL, Chatha M, Chapman SJ, Brandt SD (March 2019). "Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice". J Psychopharmacol. 33 (3): 406–414. doi:10.1177/0269881119826610. PMC 6848748. PMID 30789291.
  10. 1 2 Stoeckmann OV, Trachsel D, Liechti ME, Rudin D (21 May 2024). "Supplementum 276: Abstracts of the 8th Annual Spring Congress of the Swiss Society of General Internal Medicine: P181. New Mescaline Derivatives: Profiling of Scalines' Potency and Affinity on Different Serotonin Receptor Subtypes". Swiss Medical Weekly. 154 (5): 138S. doi:10.57187/s.3896. ISSN 1424-3997.
  11. ↑ Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA (August 2000). "1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists". Journal of Medicinal Chemistry. 43 (16): 3074–3084. doi:10.1021/jm9906062. PMID 10956215.
  12. ↑ Nichols DE, Dyer DC (February 1977). "Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues". J Med Chem. 20 (2): 299–301. doi:10.1021/jm00212a022. PMID 836502.
  13. ↑ Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, Nichols DE (September 1997). "Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives". J Med Chem. 40 (19): 2997–3008. doi:10.1021/jm970219x. PMID 9301661.
  14. ↑ McLean TH, Chambers JJ, Parrish JC, Braden MR, Marona-Lewicka D, Kurrasch-Orbaugh D, Nichols DE (July 2006). "C-(4,5,6-trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor". J Med Chem. 49 (14): 4269–4274. doi:10.1021/jm060272y. PMID 16821786.
  15. 1 2 3 4 Trachsel, D.; Lehmann, D.; Enzensperger, C. (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. ISBN 978-3-03788-700-4. OCLC 858805226. Retrieved 31 January 2025.
  16. 1 2 3 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628.
  17. ↑ Halberstadt, Adam L.; Chatha, Muhammad; Klein, Adam K.; Wallach, Jason; Brandt, Simon D. (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC 9191653. PMID 31917152. Table 4 Human potency data for selected hallucinogens. [...]
  18. ↑ Trachsel D (2012). "Fluorine in psychedelic phenethylamines". Drug Test Anal. 4 (7–8): 577–590. doi:10.1002/dta.413. PMID 22374819.
  19. ↑ Luethi D, Liechti ME (October 2018). "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". Int J Neuropsychopharmacol. 21 (10): 926–931. doi:10.1093/ijnp/pyy047. PMC 6165951. PMID 29850881.
  20. ↑ Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL (July 2025). "The polypharmacology of psychedelics reveals multiple targets for potential therapeutics" (PDF). Neuron. 113 (19): 3129–3142.e9. doi:10.1016/j.neuron.2025.06.012. PMID 40683247.
  21. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.