Proscaline

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved) and other publications, Alexander Shulgin reports that a dose of 30 to 60mg orally produces effects lasting 8 to 12hours. The onset was not described, but peak effects occurred after about 2hours. A typical dose estimate is 45mg. Doses as high as 80mg have also been explored. The drug has approximately 6 or 7times the potency of mescaline, which itself has a listed dose range of 200 to 400mg.

The effects of proscaline have been reported to include insignificant closed-eye visuals, sharpening of the senses, hyperawareness, relaxation and feeling at ease, deep feelings of peace and contentment, euphoria, no enhanced clarity or deep realizations, feelings of uninhibited eroticism, pain relief, drowsiness, intoxication and feeling drunk, irritability, restlessness, tremors, insomnia, difficulty with dreams, long-lasting residual effects, and no next-day hangover.

Interactions

Pharmacology

Pharmacodynamics

Proscaline is a serotonin 5-HT2 receptor agonist, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. Activation of the serotonin 5-HT2A receptor is thought to be responsible for its psychedelic effects. The drug is much more potent as an agonist of the serotonin 5-HT2C receptor than as an agonist of the serotonin 5-HT2A or 5-HT2B receptors.

It produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.

Chemistry

Proscaline, also known as 4-propoxy-3,5-dimethoxyphenethylamine, is a substituted phenethylamine and scaline (4-substituted 3,5-dimethoxyphenethylamine) derivative related to mescaline (3,4,5-trimethoxyphenethylamine). It is the 4-propoxy homologue of mescaline.

Properties

Proscaline is much more lipophilic than mescaline or escaline (log P = 1.70, 0.78, and 1.11, respectively), which is expected to be more optimal and advantageous in terms of drug-like properties such as blood–brain barrier permeability.

Synthesis

The chemical synthesis of proscaline has been described.

Analogues

Analogues of proscaline include mescaline, escaline, isoproscaline, allylescaline, methallylescaline, cyclopropylmescaline, cycloproscaline, fluoroproscaline, and 3C-P, among others.

History

Proscaline was first synthesized and studied by Otakar Leminger in 1972. The drug was later synthesized by Alexander Shulgin and further described in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). It was encountered as a novel designer drug in Europe in 2013.

Society and culture

Legal status

Canada

Proscaline is not a controlled substance in Canada as of 2025.

United Kingdom

Proscaline is a Class A controlled substance in the United Kingdom.

United States

Proscaline is not an explicitly controlled substance in the United States. However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

References

References

1. [http://www.erowid.org/library/books_online/pihkal/pihkal140.shtml Proscaline entry in PiHKAL]
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3. (2003). "Hallucinogens: A Forensic Drug Handbook". Elsevier Science.
4. (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology.
5. Alexander T. Shulgin. (1980). "Burger's Medicinal Chemistry". Wiley.
6. (1982). "Psychotropic Agents, Part III: Alcohol and Psychotomimetics, Psychotropic Effects of Central Acting Drugs". Springer Berlin Heidelberg.
7. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun.
8. (16 January 2013). "Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics". Purdue University.
9. (2012). "Fluorine in psychedelic phenethylamines". Drug Test Anal.
10. (2021). "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Front Pharmacol.
11. Leminger, Otakar. (1972). "The Chemistry of Alkoxylated Phenethylamines – Part 2". Chemický Průmysl.
12. (2014). "New phenethylamines in Europe". Drug Test Anal.
13. https://isomerdesign.com/bitnest/external/EMCDDA/New-Drugs-In-Europe-2013
14. (March 2019). "Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice". J Psychopharmacol.
15. "Controlled Drugs and Substances Act".
16. (January 2026). "Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026)". U.S. [[Department of Justice]]: [[Drug Enforcement Administration]] (DEA): Diversion Control Division.