Several

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of simila ...

s that function as monoamine oxidase inhibitors (MAOIs) are found in the

seed A seed is an embryonic plant enclosed in a protective outer covering, along with a food reserve. The formation of the seed is a part of the process of reproduction in seed plants, the spermatophytes, including the gymnosperm and angiosper ...

s of '' Peganum harmala'' (also known as '' Harmal'' or ''Syrian Rue''), as well as

tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

leaves including harmine, harmaline, and

harmalol Harmalol is a bioactive beta-carboline and a member of the harmala alkaloid Several alkaloids that function as monoamine oxidase inhibitors (MAOIs) are found in the seeds of ''Peganum harmala'' (also known as ''Harmal'' or ''Syrian Rue''), as w ...

, which are members of a group of substances with a similar chemical structure collectively known as ''harmala alkaloids''. These alkaloids are of interest for their use in Amazonian shamanism, where they are derived from other plants. The harmala alkaloid harmine, once known as telepathine and banisterine, is a naturally occurring beta-carboline

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. Harmine and harmaline are both a reversible inhibitor of monoamine oxidase A (RIMAs). They can stimulate the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

by inhibiting the

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...

of monoamine compounds such as serotonin and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

. The harmala alkaloids occur in '' Peganum harmala'' in concentrations of roughly 3%, though tests have documented anywhere from 2-7% or even higher, 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 AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' ( Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' desce ...

, 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. 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 mg%, and 0% harmala alkaloids.

Telepathine

Telepathine was originally thought to be the active chemical constituent of '' Banisteriopsis caapi'', a key plant ingredient in the preparation of

; a sacramental beverage from the Amazon. 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. 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).

Uses

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. In high doses, it acts as purgative. Harmala alkaloids from ''Banisteriopsis caapi'' have been used to treat

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

. As a

benzodiazepine site The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on ...

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. Harmala alkaloids interact with smoked

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: '' Cannabis sativa'', '' C. indica'', and '' C. ruderalis''. Alternative ...

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 Ego death is a "complete loss of subjective self-identity". The term is used in various intertwined contexts, with related meanings. Jungian psychology uses the synonymous term psychic death, referring to a fundamental transformation of the psych ...

, 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. 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 The HL-60 cell line is a human leukemia cell line that has been used for laboratory research on blood cell formation and physiology. HL-60 proliferates continuously in suspension culture in nutrient and antibiotic chemicals. The doubling time is ...

and K562 leukemic cell lines. This action might explain the previously observed cytotoxic effect of '' P. harmala'' on these cancer cells."

Legal status

Australia

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015).Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534 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. 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.

Chemical forms

* Harmine: C₁₃H₁₂N₂O :: 7-Methoxy-1-methyl-9''H''-pyrido ,4-''b''ndole :: ::Harmine is a reversible inhibitor of monoamine oxidase A (RIMA). * Harmaline: C₁₃H₁₄N₂O :: 4,9-Dihydro-7-methoxy-1-methyl-3''H''-pyrido ,4-''b''ndole :: ::Harmaline is also a RIMA. *

Harmalol Harmalol is a bioactive beta-carboline and a member of the harmala alkaloid Several alkaloids that function as monoamine oxidase inhibitors (MAOIs) are found in the seeds of ''Peganum harmala'' (also known as ''Harmal'' or ''Syrian Rue''), as w ...

: C₁₂H₁₂N₂O :: 1-Methyl-4,9-dihydro-3''H''-pyrido ,4-''b''ndol-7-ol :: * Tetrahydroharmine: C₁₃H₁₆N₂O :: 1,2,3,4-tetrahydro-harmine :: * Harmalane: C₁₂H₁₀N₂ :: 1-Methyl-3,4''-dihydro''-''beta''-carboline. Harmalan occurs in foodstuffs. :: * Isoharmine: C₁₃H₁₂N₂O ::