Biology:Harmala alkaloid

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Short description: Group of chemical compounds

Peganum harmala, commonly known as Syrian rue

Harmala alkaloids are several alkaloids that act as monoamine oxidase inhibitors (MAOIs). These alkaloids are found in the seeds of Peganum harmala (also known as harmal or Syrian rue), as well as Banisteriopsis caapi (ayahuasca), leaves of tobacco[1] and coffee beans.[2]

The alkaloids include harmine, harmaline, harmalol, and their derivatives, which have similar chemical structures, hence the name "harmala alkaloids". These alkaloids are of interest for their use in Amazonian shamanism, where they are derived from other plants. Harmine, once known as telepathine and banisterine, is a naturally occurring β-carboline alkaloid that is structurally related to harmaline, and also found in the vine Banisteriopsis caapi. Tetrahydroharmine is also found in B. caapi and P. harmala. Dr. Alexander Shulgin has suggested that harmine may be a breakdown product of harmaline.[3] Harmine and harmaline are reversible inhibitors of monoamine oxidase A (RIMAs). They can stimulate the central nervous system by inhibiting the metabolism of monoamine compounds such as serotonin and norepinephrine.

The harmala alkaloids occur in Peganum harmala in concentrations of roughly 3%, though tests have documented anywhere from 2–7% or even higher,[4] as natural sources tend to vary widely in chemical makeup. Harmala alkaloids are also found in the Banisteriopsis caapi vine, the key plant ingredient in the sacramental beverage ayahuasca, in concentrations that range between 0.31 and 8.43% for harmine, 0.03–0.83% for harmaline and 0.05–2.94% for tetrahydroharmine.[5] Although other psychoactive plants are occasionally added to ayahuasca to achieve visionary states of consciousness, the recipes vary greatly and no single combination is common. Peganum harmala, normally consumed as a tea or used as an incense, is mentioned in classical Persian literature both as a sacred sacrament and as a medicine. The harmala alkaloids are not especially psychedelic, even at higher dosages, when hypnagogic visions, alongside vomiting and diarrhea, become the main effect.

Harmala alkaloids are also found in many other plants, such as Passiflora. The leaves of P. incarnata have been reported variously to give 0.005%, 0.12%, and 0% harmala alkaloids.[6]

Telepathine

Telepathine was originally thought to be the active chemical constituent of Banisteriopsis caapi, a key plant ingredient in the preparation of ayahuasca; a sacramental beverage from the Amazon.[7] This isolated chemical was so named because of the reported effects of ayahuasca among the indigenous users, including: collective contact with and/or visions of jaguars, snakes, and jeweled birds, and ancestral spirits; the ability to see future events; and as the name suggests, telepathic communication among tribal members.[8] It was assumed to be a newly discovered chemical at the time, however, it was soon realized that telepathine was already more widely known as "harmine" from its previous discovery in Peganum harmala (Syrian rue).[9]

Use and effects

Harmaline and harmine fluorescence under ultraviolet light. These three extractions indicate that the middle one has a higher concentration of the two compounds.

Various harmala alkaloids such as harmaline have hallucinogenic effects and have been referred to as oneirogens.

As mentioned above, some harmala alkaloids can be used as a monoamine oxidase inhibitor (MAOI) to facilitate the ingestion of dimethyltryptamine (DMT) and other tryptamines; while not generally used as a hallucinogen alone, there are reports of such use.[10] In high doses, it acts as purgative. Harmala alkaloids from Banisteriopsis caapi have been used to treat Parkinson's disease . As a benzodiazepine site inverse agonist, harmala alkaloids are used as a model for essential tremor (ET) when injected to animals. Rats being treated with harmaline exhibit severe tremors after 5–7 minutes. Individuals diagnosed with essential tremor have been found to have elevated blood levels of harmala alkaloids.[11]

Harmala alkaloids interact with smoked cannabis[12][13] when either smoked/vaporized, or taken orally as an extract or as a tea. Reports are scarce, but generally users experience more intense cannabis-like effects, as well as mild psychedelic effects such as hallucinations, ego dissolution, and increased emotions, especially in large doses.

Unlike MAOIs such as phenelzine, harmine and harmaline are reversible and selective meaning they do not have nearly as high a risk for "cheese syndrome" caused by consuming tyramine-containing foods, which is a risk associated with monoamine oxidase A inhibitors, but not monoamine oxidase B inhibitors.[14] Both MAO-A and MAO-B break down tyramine, but large doses of harmala alkaloids begin to affect MAO-B as well.

Template:Oral doses and durations of β-carbolines or harmala alkaloids

Pharmacology

Harmala alkaloids act as reversible monoamine oxidase inhibitors (MAOIs), specifically of monoamine oxidase A (MAO-A). They also have other activities, such as interactions with serotonin 5-HT2 receptors.[15][16] Harmaline and the serotonergic psychedelic DOM substitute for one another in rodent drug discrimination tests.[17][15]

Anticancer activity

Isolated harmine was found to exhibit a cytotoxic effect on HL60 and K562 leukemic cell lines. This action might explain the previously observed cytotoxic effect of P. harmala on these cancer cells."[18]

Society and culture

Australia

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015).[19] 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.[19]

Exceptions are made when in herbs, or preparations, for therapeutic use such as: (a) containing 0.1 per cent or less of harmala alkaloids; or (b) in divided preparations containing 2 mg or less of harmala alkaloids per recommended daily dose.[19]

List of harmala alkaloids

Name Chemical Formula Chemical Name Structure
Harmine C13H12N2O 7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole
Harmaline C13H14N2O 4,9-Dihydro-7-methoxy-1-methyl-3H-pyrido[3,4-b]indole
Harmalol C12H12N2O 1-Methyl-4,9-dihydro-3H-pyrido[3,4-b]indol-7-ol
Tetrahydroharmine C13H16N2O 1,2,3,4-Tetrahydroharmine
Harmalan C12H10N2 1-Methyl-3,4-dihydro-β-carboline
6-Methoxyharman (isoharmine) C13H12N2O 6-Methoxy-1-methyl-β-carboline
Harmine acid methyl ester C15H18N2O3 Methyl 7-methoxy-β-carboline-1-carboxylate
Harmilinic acid ? 7-Methoxy-3,4-dihydro-β-carboline-1-carboxylic acid
Harmanamide ? 1-Carbamoyl-7-methoxy-β-carboline
Acetylnorharmine ? 1-Acetyl-7-methoxy-β-carboline

See also

References

  1. ↑ Kivell, Bronwyn M; Danielson, Kirsty (2016). Neuropathology of Drug Addictions and Substance Misuse. Elsevier. 
  2. ↑ Herraiz, Tomas; Chaparro, Carolina (18 January 2006). "Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee". Life Sciences 78 (8): 795–802. doi:10.1016/j.lfs.2005.05.074. PMID 16139309. 
  3. ↑ Shulgin, Alexander; Shulgin, Ann. "#13. HARMALINE". Tryptamines i Have Known And Loved: The Chemistry Continues. Erowid. http://www.erowid.org/library/books_online/tihkal/tihkal13.shtml. 
  4. ↑ "beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO)". Food and Chemical Toxicology 48 (3): 839–45. March 2010. doi:10.1016/j.fct.2009.12.019. PMID 20036304. 
  5. ↑ Callaway JC, Brito GS & Neves ES (2005). Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis Journal of Psychoactive Drugs 37(2): 145-150.
  6. ↑ "Passiflora: a review update". Journal of Ethnopharmacology 94 (1): 1–23. September 2004. doi:10.1016/j.jep.2004.02.023. PMID 15261959. 
  7. ↑ Djamshidian, Atbin; Bernschneider-Reif, Sabine; Poewe, Werner; Lees, Andrew J. (January 2016). "Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?". Movement Disorders Clinical Practice 3 (1): 19–26. doi:10.1002/mdc3.12242. ISSN 2330-1619. PMID 30713897. 
  8. ↑ "Telepathine (ayahuasca) and psychic ability: field research in South America" (in en-GB). British Psychological Society (Scarborough, UK). 2009-09-20. https://gala.gre.ac.uk/id/eprint/3908/. 
  9. ↑ "NCATS Inxight: Drugs" (in en). https://drugs.ncats.io/substances?q=%22TELEPATHINE%22. 
  10. ↑ Shulgin, Alexander. "#13 Harmaline", Erowid Online Texts: TiHKAL #13 HARMALINE, retrieved November 26, 2006.
  11. ↑ "Elevation of blood beta-carboline alkaloids in essential tremor". Neurology 59 (12): 1940–4. December 2002. doi:10.1212/01.wnl.0000038385.60538.19. PMID 12499487. 
  12. ↑ "Syrian Rue & Cannabis - Erowid Exp - 'Intense, Terrifying and Unconcerning'". https://erowid.org/experiences/exp.php?ID=1113. 
  13. ↑ "Syrian Rue & Cannabis - Erowid Exp - 'Testing Its Power'". https://erowid.org/experiences/exp.php?ID=38821. 
  14. ↑ "The scientific investigation of Ayahuasca: a review of past and current research.". The Heffter Review of Psychedelic Research 1 (65–77): 195–223. 1998. http://psychoactiveherbs.com/catalog/article_info.php?articles_id=9. Retrieved 2007-06-04. 
  15. ↑ 15.0 15.1 "Investigation of hallucinogenic and related beta-carbolines". Drug Alcohol Depend 50 (2): 99–107. April 1998. doi:10.1016/s0376-8716(97)00163-4. PMID 9649961. 
  16. ↑ "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. August 2000. doi:10.1016/s0376-8716(99)00148-9. PMID 10940539. 
  17. ↑ "Arylalkylamine drugs of abuse: an overview of drug discrimination studies". Pharmacol Biochem Behav 64 (2): 251–256. October 1999. doi:10.1016/s0091-3057(99)00045-3. PMID 10515299. https://www.designer-drug.com/pte/12.162.180.114/dcd/pdf/glennon.arylalkylamine.drugs.of.abuse.pdf. 
  18. ↑ "Xanthomicrol is the main cytotoxic component of Dracocephalum kotschyii and a potential anti-cancer agent". Phytochemistry 66 (13): 1581–92. July 2005. doi:10.1016/j.phytochem.2005.04.035. PMID 15949825. Bibcode: 2005PChem..66.1581J. 
  19. ↑ 19.0 19.1 19.2 Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534



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