Harmaline
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| Dependence liability | N/A |
| Routes of administration | Ingestion |
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| ECHA InfoCard | 100.005.594 |
| Chemical and physical data | |
| Formula | C13H14N2O |
| Molar mass | 214.268 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 232–234 °C (450–453 °F) |
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Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and β-carbolines.[1][2] It is the partly hydrogenated form of harmine. The drug is a monoamine oxidase inhibitor (MAOI) and mild psychedelic with pronounced physical side effects.[1][2]
Use
[edit]Harmaline-containing plants and tryptamine-containing plants are used in ayahuasca brews. The inhibitory effects on monoamine oxidase allows dimethyltryptamine (DMT), the psychoactively prominent chemical in the mixture, to bypass the extensive first-pass metabolism it undergoes upon ingestion, allowing a psychologically active quantity of the chemical to exist in the brain for a perceivable period of time.[3]
Effects
[edit]
The harmala alkaloids are psychoactive in humans.[4] According to Alexander Shulgin, harmaline is the only harmala alkaloid that has a reputation of being hallucinogenic.[1][5] However, other harmala alkaloids and β-carbolines, like harmine, tetrahydroharmine (THH), 6-methoxyharmalan, and 6-methoxytetrahydroharman have also been reported to be hallucinogenic.[6]
Interactions
[edit]Harmaline is a reversible inhibitor of MAO-A (RIMA)".[7] This means that the risk of a hypertensive crisis, a dangerous high blood pressure crisis from eating tyramine-rich foods such as cheese, is likely lower with harmaline than with irreversible MAOIs such as phenelzine. Since harmaline is a RIMA, it could, in theory, induce both serotonin syndrome and hypertensive crises in combination with tyramine, serotonergics, catecholaminergics drugs or prodrugs.
Pharmacology
[edit]Harmaline shows weak but significant affinity for the serotonin 5-HT2A and 5-HT2C receptors (in the low micromolar range).[6][8] Harmaline and the psychedelic DOM partially substitute for each other in rodent drug discrimination tests.[9][6] Harmaline was much more effective in substituting for DOM than harman and harmine, which did not achieve significant generalization and produced behavioral disruption at higher doses.[9] On the other hand, harmaline and 6-methoxyharman were comparable in terms of DOM substitution.[9]
Other actions
[edit]Harmaline is shown to act as an acetylcholinesterase inhibitor.[10] Harmaline also stimulates striatal dopamine release in rats at very high dose levels.[11]
Harmaline is known to act as a histamine N-methyltransferase inhibitor.[12]
A study has reported the antiviral activity of Harmaline against Herpes Simplex Virus 1 and 2 (HSV-1 and HSV-2) by inhibiting immediate early transcription of the virus at noncytotoxic concentration.[13]
Natural occurrence
[edit]Various plants contain harmaline including Peganum harmala (Syrian rue) as well as the hallucinogenic beverage ayahuasca, which is traditionally brewed using Banisteriopsis caapi. Present at 3% by dry weight, the harmala alkaloids may be extracted from the Syrian rue seeds.[4]
History
[edit]Harmaline was first isolated from plants in 1841.[1] The chemical structure of harmaline was not correctly identified until 1919.[1] Harmaline was first synthesized in 1927.[1]
Society and culture
[edit]Legal status
[edit] | The examples and perspective in this article may not represent a worldwide view of the subject. (January 2016) |
Australia
[edit]Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015).[14] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[14]
Canada
[edit]Harmaline and Harmalol are considered Schedule III controlled substances by the Controlled Drugs and Substances Act. Every person found to be in possession of a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding three years; or for a first offence, guilty on summary conviction, to a fine not exceeding one thousand dollars or to imprisonment for a term not exceeding six months, or to both. Every person found to be trafficking a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding ten years, or is guilty on summary conviction (first-time offenders) and liable to imprisonment for a term not exceeding eighteen months.[15]
See also
[edit]- Harmalol
- Ibogamine
- Tetrahydroharmine, a similar harmala alkaloid
References
[edit]- ^ a b c d e f Shulgin AT (1977). "Profiles of Psychedelic Drugs: 4. Harmaline". Journal of Psychedelic Drugs. 9 (1): 79–80. doi:10.1080/02791072.1977.10472029. ISSN 0022-393X. Retrieved 11 April 2025.
Close biosynthetic relatives of harmaline (harmine and tetrahydroharmine) are known components of plants of several other genera which have medical use but no reputation as hallucinogens [...] The effective dose range of harmaline in man is 70-100 mg i.v., or 300-400 mg orally. The initial effects are noted about one hour following oral administration and persist for about 6 hours [...] The indicators of physical toxicity are common and often severe. Paresthesias of hands, feet, or face are almost always present with the onset of effects, and are usually followed by the sensation of numbness. There can be isolated symptoms such as pressure in the head or chest, nausea and distressful vomiting, dizziness, and general malaise. Mydriasis and pressor effects are never seen. The anxiety and general discomfort encourages a withdrawal from social contact, and a quiet dark environment is preferred by most subjects. The modality most consistently affected by harmaline is the visual sense. There can be vivid images generated, often in the form of meaningful dream-like sequences, and frequently containing subject matter such as wild animals or jungle scenes. Other reported visual syntheses are limited to the generation of geometric patterns which are entertaining but not felt to be of any intrinsic significance.
- ^ a b "Erowid Online Books : "TIHKAL" - #13 HARMALINE". www.erowid.org. Retrieved 11 April 2025.
- ^ 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.
- ^ a b "Peganum Harmala pamphlet: Syrian Rue". Erowid.
- ^ Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID 8742795.
An additional family of compounds should be mentioned here, the β-carbolines. [...] In nature, they usually are found in one of three degrees of hydrogenation: harmine, harmaline, and tetrahydroharmine. [...] Only harmaline, one of the principal components of Ayahuasca, has a reputation for being intrinsically an active hallucinogen. The aromatic analog, harmine, has little if any psychotropic activity.
- ^ a b c Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, Glennon RA (April 1998). "Investigation of hallucinogenic and related beta-carbolines". Drug Alcohol Depend. 50 (2): 99–107. doi:10.1016/s0376-8716(97)00163-4. PMID 9649961.
- ^ Massaro EJ (2002). Handbook of Neurotoxicology. Totowa, NJ: Humana Press. p. 237. ISBN 978-0-89603-796-0.[permanent dead link]
- ^ Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV (August 2000). "Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors". Drug Alcohol Depend. 60 (2): 121–132. doi:10.1016/s0376-8716(99)00148-9. PMID 10940539.
- ^ a b c Glennon RA, Young R, Jacyno JM, Slusher M, Rosecrans JA (January 1983). "DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines". Eur J Pharmacol. 86 (3–4): 453–459. doi:10.1016/0014-2999(83)90196-6. PMID 6572591.
- ^ Zheng XY, Zhang ZJ, Chou GX, Wu T, Cheng XM, Wang CH, Wang ZT (September 2009). "Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of Peganum nigellastrum Bunge by an in vitro TLC- bioautographic assay". Archives of Pharmacal Research. 32 (9): 1245–51. doi:10.1007/s12272-009-1910-x. PMID 19784581. S2CID 1218229.
- ^ Schwarz MJ, Houghton PJ, Rose S, Jenner P, Lees AD (June 2003). "Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism". Pharmacology, Biochemistry, and Behavior. 75 (3): 627–33. doi:10.1016/S0091-3057(03)00129-1. PMID 12895680. S2CID 28243440.
- ^ Cumming P, Vincent SR (September 1992). "Inhibition of histamine-N-methyltransferase (HNMT) by fragments of 9-amino-1,2,3,4-tetrahydroacridine (tacrine) and by beta-carbolines". Biochemical Pharmacology. 44 (5): 989–92. doi:10.1016/0006-2952(92)90133-4. PMID 1530666.
- ^ Bag P, Ojha D, Mukherjee H, Halder UC, Mondal S, Biswas A, Sharon A, Van Kaer L, Chakrabarty S, Das G, Mitra D, Chattopadhyay D (May 2014). "A dihydro-pyrido-indole potently inhibits HSV-1 infection by interfering the viral immediate early transcriptional events". Antiviral Research. 105: 126–134. doi:10.1016/j.antiviral.2014.02.007. PMID 24576908.
- ^ a b "Poisons Standard October 2015". Australian Government. 30 September 2015.
- ^ "Controlled Drugs and Substances Act (S.C 1996, c.19)". Justice Laws Website. 19 September 2019. Retrieved 25 September 2019.
Further reading
[edit]- "Harmaline". TIHKAL. Erowid.org.
- Evans AT, Croft SL (1987). "Antileishmanial Activity of Harmaline and other Tryptamine Derivatives". Phytotherapy Research. 1 (1): 25–27. doi:10.1002/ptr.2650010106. S2CID 85328050.