The alkaloids includeharmine,harmaline,harmalol, and their derivatives, which have similar chemical structures, hence the name "harmala alkaloids". These alkaloids are of interest for their use in Amazonianshamanism, where they are derived from other plants. Harmine, once known astelepathine andbanisterine, is a naturally occurringβ-carbolinealkaloid that is structurally related to harmaline, and also found in the vineBanisteriopsis caapi.Tetrahydroharmine is also found inB. caapi andP. harmala. Dr.Alexander Shulgin has suggested that harmine may be a breakdown product of harmaline.[3] Harmine and harmaline are reversible inhibitors ofmonoamine oxidase A (RIMAs). They can stimulate thecentral nervous system by inhibiting themetabolism ofmonoamine compounds such asserotonin andnorepinephrine.
The harmala alkaloids occur inPeganum 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 theBanisteriopsis 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, whenhypnagogic visions, alongside vomiting and diarrhea, become the main effect.
Harmala alkaloids are also found in many other plants, such asPassiflora. The leaves ofP. incarnata have been reported variously to give 0.005%, 0.12%, and 0% harmala alkaloids.[6]
Telepathine was originally thought to be the active chemical constituent ofBanisteriopsis 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 inPeganum harmala (Syrian rue).[9]
As mentioned above, some harmala alkaloids can be used as amonoamine oxidase inhibitor (MAOI) to facilitate the ingestion ofdimethyltryptamine (DMT) and other tryptamines; while not generally used as a hallucinogen alone, there are reports of such use.[10] In high doses, it acts aspurgative. Harmala alkaloids fromBanisteriopsis caapi have been used to treatParkinson's disease[citation needed]. As abenzodiazepine siteinverse agonist, harmala alkaloids are used as a model foressential 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 smokedcannabis[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 asphenelzine, harmine and harmaline arereversible andselective meaning they do not have nearly as high a risk for "cheese syndrome" caused by consumingtyramine-containing foods, which is a risk associated with monoamine oxidase A inhibitors, but notmonoamine 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.
Isolated harmine was found to exhibit acytotoxic effect onHL60 andK562 leukemic cell lines. This action might explain the previously observed cytotoxic effect ofP. harmala on these cancer cells."[18]
Harmala alkaloids are considered Schedule 9 prohibited substances under thePoisons 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]
^Kivell BM, Danielson K (2016).Neuropathology of Drug Addictions and Substance Misuse. Elsevier.
^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.PMID16139309.
^Shulgin A, Shulgin A."#13. HARMALINE".Tryptamines i Have Known And Loved: The Chemistry Continues. Erowid.
^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.PMID20036304.
^Callaway JC, Brito GS & Neves ES (2005).Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis Journal of Psychoactive Drugs 37(2): 145-150.
^abGrella 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.PMID9649961.
^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.hdl:11380/17721.PMID10940539.
