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 similar ...

s that function as

monoamine oxidase inhibitor 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, espe ...

s (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 angiospe ...

s of ''

Peganum harmala ''Peganum harmala'', commonly called wild rue, Syrian rue, African rue, esfand or espand,Mahmoud OmidsalaEsfand: a common weed found in Persia, Central Asia, and the adjacent areasEncyclopedia Iranica Vol. VIII, Fasc. 6, pp. 583–584. Originall ...

'' (also known as ''

Harmal ''Peganum harmala'', commonly called wild rue, Syrian rue, African rue, esfand or espand,Mahmoud OmidsalaEsfand: a common weed found in Persia, Central Asia, and the adjacent areasEncyclopedia Iranica Vol. VIII, Fasc. 6, pp. 583–584. Originall ...

'' 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 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 monoamin ...

harmaline Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine. Occurrence in nature Various plants contain harmaline including ''Peganum harmala'' (Syrian rue) ...

, and

harmalol Harmalol is a bioactive beta-carboline β-Carboline (9''H''- pyrido ,4-''b'' ndole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective ...

, 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 β-Carboline (9''H''- pyrido ,4-''b'' ndole) 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 prima ...

that is structurally related to

, and also found in the vine ''

Banisteriopsis caapi ''Banisteriopsis caapi'', also known as ayahuasca, caapi, soul vine, or yagé (yage), is a South American liana of the family Malpighiaceae. It is one half of ayahuasca, a decoction with a long history of its entheogenic (connecting to spirit) us ...

''.

Tetrahydroharmine Tetrahydroharmine (THH) is a fluorescent indole alkaloid that occurs in the tropical liana species '' Banisteriopsis caapi''. THH, like other harmala alkaloids in ''B. caapi'', namely harmaline and harmine, is a reversible inhibitor of monoam ...

is also found in ''B. caapi'' and ''P. harmala''. Dr.

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. He is credited with introducing 3,4-methylenedioxymethamph ...

has suggested that harmine may be a breakdown product of harmaline. Harmine and harmaline are both a

reversible inhibitor of monoamine oxidase A 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, especia ...

(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 par ...

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 cell ...

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines are ...

compounds such as

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

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 ''

'' 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 ''

'' 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'' descen ...

, 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 ''Passiflora'', known also as the passion flowers or passion vines, is a genus of about 550 species of flowering plants, the type genus of the family Passifloraceae. They are mostly tendril-bearing vines, with some being shrubs or trees. They ...

''. 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 ''

'', 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 Telepathy () is the purported vicarious transmission of information from one person's mind to another's without using any known human sensory channels or physical interaction. The term was first coined in 1882 by the classical scholar Frederic ...

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 "

" from its previous discovery in ''

'' (Syrian Rue).

Uses

As mentioned above, some harmala alkaloids can be used as a

(MAOI) to facilitate the ingestion of

dimethyltryptamine ''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a derivative and a structural analog of tryptamine. It is used as a ...

(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 Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubri ...

. 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 becom ...

. 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 o ...

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

, harmala alkaloids are used as a model for

essential tremor Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations ( oscillations or twitching movements) of certain muscle groups in ...

(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''. Alternatively ...

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 Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine and ...

, harmine and harmaline are reversible and selective meaning they do not have nearly as high a risk for " cheese syndrome" caused by consuming

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-b ...

-containing foods, which is a risk associated with

monoamine oxidase A Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, s ...

inhibitors, but not

monoamine oxidase B Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the ''MAOB'' gene. The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. ...

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 Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

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 ab ...

and

K562 K562 cells were the first human immortalised myelogenous leukemia cell line to be established. K562 cells are of the erythroleukemia type, and the cell line is derived from a 53-year-old female chronic myelogenous leukemia patient in blast cris ...

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 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 monoamin ...

: C₁₃H₁₂N₂O :: 7-Methoxy-1-methyl-9''H''-pyrido ,4-''b''ndole :: ::Harmine is a

(RIMA). *

Harmaline Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine. Occurrence in nature Various plants contain harmaline including ''Peganum harmala'' (Syrian rue) ...

: 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 β-Carboline (9''H''- pyrido ,4-''b'' ndole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective ...

: C₁₂H₁₂N₂O :: 1-Methyl-4,9-dihydro-3''H''-pyrido ,4-''b''ndol-7-ol :: *

: C₁₃H₁₆N₂O :: 1,2,3,4-tetrahydro-harmine :: * Harmalane: C₁₂H₁₀N₂ :: 1-Methyl-3,4''-dihydro''-''beta''-carboline. Harmalan occurs in foodstuffs. :: * Isoharmine: C₁₃H₁₂N₂O ::