Harmala alkaloid

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Peganum harmala, commonly known as Syrian rue Peganum harmala1.jpg
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 beta-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.

Contents

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]

Uses

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

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 [ citation needed ]. 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.

Anticancer

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." [15]

Australia

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015). [16] 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. [16]

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. [16]

Chemical forms

7-Methoxy-1-methyl-9H-pyrido[3,4-b]indole
Harmine structure.svg
Harmine is a reversible inhibitor of monoamine oxidase A (RIMA). [17]
4,9-Dihydro-7-methoxy-1-methyl-3H-pyrido[3,4-b]indole
Harmaline structure.svg
Harmaline is also a RIMA. [18]
1-Methyl-4,9-dihydro-3H-pyrido[3,4-b]indol-7-ol
Harmalol.svg
1,2,3,4-tetrahydro-harmine
Tetrahydroharmine structure.svg
1-Methyl-3,4-dihydro-beta-carboline. Harmalan occurs in foodstuffs. [19]
Harmalane.svg
Isoharmine.svg
Methyl 7-methoxy-beta-carboline-1-carboxylate
Methyl 7-methoxy-beta-carboline-1-carboxylate.svg
7-Methoxy-3,4-dihydro-beta-carboline-1-carboxylic acid
Harmalinic acid.svg
1-Carbamoyl-7-methoxy-beta-carboline
Harmanamide.svg
1-Acetyl-7-methoxy-beta-carboline
Acetylnorharmine.svg

See also


Related Research Articles

<span class="mw-page-title-main">Ayahuasca</span> South American psychoactive brew

Ayahuasca is a South American psychoactive beverage, traditionally used by Indigenous cultures and folk healers in the Amazon and Orinoco basins for spiritual ceremonies, divination, and healing a variety of psychosomatic complaints.

<i>N</i>,<i>N</i>-Dimethyltryptamine Chemical compound

N,N-Dimethyltryptamine is a substituted tryptamine that occurs in many plants and animals, including humans, and which is both a derivative and a structural analog of tryptamine. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.

<span class="mw-page-title-main">Monoamine oxidase inhibitor</span> Type of medication

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

<i>Banisteriopsis caapi</i> Species of plant

Banisteriopsis caapi, also known as, caapi, soul vine, yagé (yage), or ayahuasca, the latter of which also refers to the psychedelic decoction made with the vine and a plant source of dimethyltryptamine, is a South American liana of the family Malpighiaceae. It is commonly used as an ingredient of ayahuasca, a decoction with a long history of its entheogenic use and holds status as a "plant teacher" among the Indigenous peoples of the Amazon rainforest.

β-Carboline Chemical compound also known as norharmane

β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.

<i>Peganum harmala</i> Species of plant

Peganum harmala, commonly called wild rue, Syrian rue, African rue, esfand or espand, or harmel, is a perennial, herbaceous plant, with a woody underground rootstock, of the family Nitrariaceae, usually growing in saline soils in temperate desert and Mediterranean regions. Its common English-language name came about because of a resemblance to rue. Because eating it would sicken or kill livestock, it is considered a noxious weed in a number of countries. It has become an invasive species in some regions of the western United States. The plant is popular in Middle Eastern and north African folk medicine. The alkaloids contained in the plant, including the seeds, are monoamine oxidase inhibitors.

Harmine is a beta-carboline and a harmala alkaloid. It occurs in a number of different plants, most notably the Syrian rue and Banisteriopsis caapi. Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamines, making it a Reversible inhibitor of monoamine oxidase A (RIMA). Harmine does not inhibit MAO-B. Harmine is also known as banisterin, banisterine, telopathin, telepathine, leucoharmine and yagin, yageine.

<span class="mw-page-title-main">Harmaline</span> Chemical compound

Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine.

<span class="mw-page-title-main">Tetrahydroharmine</span> Chemical compound

Tetrahydroharmine (THH) is a fluorescent indole alkaloid that occurs in the tropical liana species Banisteriopsis caapi.

Pharmahuasca is a pharmaceutical version of the entheogenic brew ayahuasca. Traditional ayahuasca is made by brewing the MAOI-containing Banisteriopsis caapi vine with a DMT-containing plant, such as Psychotria viridis. Pharmahuasca refers to a similar combination that uses a pharmaceutical MAOI instead of a plant.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

<span class="mw-page-title-main">Tetrahydroharmol</span> Chemical compound

Tetrahydroharmol is a bioactive beta-carboline harmala alkaloid. It acts as a reversible inhibitor of monoamine oxidase A.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<span class="mw-page-title-main">Tryptoline</span> Chemical compound

Tryptoline, also known as tetrahydro-β-carboline and tetrahydronorharmane, is a natural organic derivative of beta-carboline. It is an alkaloid chemically related to tryptamines. Derivatives of tryptoline have a variety of pharmacological properties and are known collectively as tryptolines.

<span class="mw-page-title-main">3,4-Dimethoxyphenethylamine</span> Chemical compound

3,4-Dimethoxyphenethylamine (DMPEA) is a chemical compound of the phenethylamine class. It is an analogue of the major human neurotransmitter dopamine where the 3- and 4-position hydroxy groups have been replaced with methoxy groups. It is also closely related to mescaline which is 3,4,5-trimethoxyphenethylamine.

<span class="mw-page-title-main">6-MeO-THH</span> Chemical compound

6-MeO-THH, or 6-methoxy-1,2,3,4-tetrahydroharman, is a β-carboline derivative and a structural isomer of tetrahydroharmine (7-MeO-THH). 6-MeO-THH is mentioned in Alexander Shulgin's book TiHKAL, stating that 6-MeO-THH is very similar to the other carbolines. Limited testing suggests that it possesses mild psychoactive effects at 1.5 mg/kg and is said to be about one-third as potent as 6-methoxyharmalan. It has been isolated from certain plants of the Virola family.

<span class="mw-page-title-main">Tetrahydroharman</span> Chemical compound

Tetrahydroharman(e), also known as 1-methyl-1,2,3,4-tetrahydro-β-carboline, is a general name for one of two isomers:

  1. (1S)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
  2. Calligonine ((1R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole)
<span class="mw-page-title-main">Harmane</span> Chemical compound

Harmane (harman) is a heterocyclic amine found in a variety of foods including coffee, sauces, and cooked meat. It is also present in tobacco smoke.

<span class="mw-page-title-main">Changa (drug)</span> DMT-infused smoking blend

Changa is a blend of N,N-Dimethyltryptamine (DMT) mixed with a monoamine oxidase inhibitor (MAOI). The addition of MAOIs extends the DMT experience in duration and intensity when compared with smoking DMT freebase alone. Typically, extracts from DMT-containing plants are combined with a blend of different MAOI-containing herbs, such as the ayahuasca vine, and/or leaf or harmala alkaloids from Peganum harmala to create a mix that is 25 to 50% DMT.

References

  1. ↑ Kivell BM, Danielson K (2016). Neuropathology of Drug Addictions and Substance Misuse. Elsevier.
  2. ↑ Herraiz T, Chaparro C (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 . Retrieved 21 November 2023.
  3. ↑ Shulgin A, Shulgin A. "#13. HARMALINE". Tryptamines i Have Known And Loved: The Chemistry Continues. Erowid.
  4. ↑ Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H (March 2010). "beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO)". Food and Chemical Toxicology. 48 (3): 839–45. doi:10.1016/j.fct.2009.12.019. hdl:10261/77694. 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. ↑ Dhawan K, Dhawan S, Sharma A (September 2004). "Passiflora: a review update". Journal of Ethnopharmacology. 94 (1): 1–23. doi:10.1016/j.jep.2004.02.023. PMID   15261959.
  7. ↑ Djamshidian A, Bernschneider-Reif S, Poewe W, Lees AJ (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. PMC   6353393 . PMID   30713897.
  8. ↑ "Telepathine (ayahuasca) and psychic ability: field research in South America". British Psychological Society. Scarborough, UK. 20 September 2009.
  9. ↑ "NCATS Inxight: Drugs". drugs.ncats.io. Retrieved 28 January 2020.
  10. ↑ Shulgin, Alexander. "#13 Harmaline", Erowid Online Texts: TiHKAL #13 HARMALINE, retrieved November 26, 2006.
  11. ↑ Louis ED, Zheng W, Jurewicz EC, Watner D, Chen J, Factor-Litvak P, Parides M (December 2002). "Elevation of blood beta-carboline alkaloids in essential tremor". Neurology. 59 (12): 1940–4. doi:10.1212/01.wnl.0000038385.60538.19. PMC   4992345 . PMID   12499487.
  12. ↑ "Syrian Rue & Cannabis - Erowid Exp - 'Intense, Terrifying and Unconcerning'". erowid.org. Retrieved 19 May 2022.
  13. ↑ "Syrian Rue & Cannabis - Erowid Exp - 'Testing Its Power'". erowid.org. Retrieved 19 May 2022.
  14. ↑ McKenna DJ, Callaway JC, Grob CS (1998). "The scientific investigation of Ayahuasca: a review of past and current research". The Heffter Review of Psychedelic Research. 1 (65–77): 195–223. Archived from the original on 8 October 2007. Retrieved 4 June 2007.
  15. ↑ Jahaniani F, Ebrahimi SA, Rahbar-Roshandel N, Mahmoudian M (July 2005). "Xanthomicrol is the main cytotoxic component of Dracocephalum kotschyii and a potential anti-cancer agent". Phytochemistry. 66 (13): 1581–92. Bibcode:2005PChem..66.1581J. doi:10.1016/j.phytochem.2005.04.035. PMID   15949825.
  16. 1 2 3 Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534
  17. ↑ Herraiz T, Guillén H (2018). "Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions". BioMed Research International. 2018: 4810394. doi: 10.1155/2018/4810394 . PMC   5820675 . PMID   29568754.
  18. ↑ Massaro EJ (2002). Edward J. Massaro, Handbook of Neurotoxicology. Humana Press. ISBN   978-0-89603-796-0 . Retrieved 4 June 2020.[ permanent dead link ]
  19. ↑ Herraiz T (November 2004). "Relative exposure to beta-carbolines norharman and harman from foods and tobacco smoke". Food Additives and Contaminants. 21 (11): 1041–50. doi:10.1080/02652030400019844. PMID   15764332. S2CID   216644379.
  20. ↑ Ayoub Mikdad T., Rashan L.J. (1991). "Isoharmine, a β-carboline alkaloid from Peganum harmala seeds". Phytochemistry. 30 (3): 1046–1047. Bibcode:1991PChem..30.1046A. doi:10.1016/0031-9422(91)85312-N.
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