Harmaline, also known as 7-methoxyharmalan or as 3,4-dihydro-7-methoxy-1-methyl-β-carboline, is a

fluorescent Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with color ...

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

from the group of

harmala alkaloid 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), leave ...

s and β-carbolines. It is the partly

hydrogenated Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organi ...

form of harmine. It is a reversible monoamine oxidase inhibitor (RIMA). It produces vivid

dream A dream is a succession of images, ideas, emotions, and sensation (psychology), sensations that usually occur involuntarily in the mind during certain stages of sleep. Humans spend about two hours dreaming per night, and each dream lasts around ...

-like

visual effects Visual effects (sometimes abbreviated as VFX) is the process by which imagery is created or manipulated outside the context of a live-action shot in filmmaking and video production. The integration of live-action footage and other live-action fo ...

and physical discomfort at

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

doses of 300 to 400mg, often leading users to seek

solitude Solitude, also known as social withdrawal, is a state of seclusion or isolation, meaning lack of socialisation. Effects can be either positive or negative, depending on the situation. Short-term solitude is often valued as a time when one may wo ...

in a quiet, dark environment. Plants containing harmaline are combined in

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 ...

to inhibit monoamine oxidase, allowing orally ingested

DMT Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a serotonergic hallucinogen and investigational drug of the tryptamine family that occurs naturally in many plants and animals, including humans. D ...

to remain active in the brain and produce psychoactive effects. Harmala alkaloids, including harmaline, are psychoactive on their own in humans, with harmaline being particularly hallucinogenic, although other compounds such as harmine and

tetrahydroharmine Tetrahydroharmine (THH) is a fluorescent indole alkaloid and β-carboline that occurs in the tropical liana species ''Banisteriopsis caapi''. Effects THH has been reported to produce psychoactive effects similar to those of harmaline in human ...

have also been reported to produce hallucinogenic effects as well. Harmaline exhibits weak affinity for 5-HT_2A and 5-HT_2C receptors, partially substitutes for the psychedelic DOM in rodents, inhibits

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

and

histamine N-methyltransferase Histamine ''N''-methyltransferase (HNMT) is a protein encoded by the ''HNMT'' gene in humans. It belongs to the methyltransferases Enzyme superfamily, superfamily of enzymes and plays a role in the inactivation of histamine, a biomolecule that ...

, and stimulates

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

release at high doses. Harmaline is present in ''

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 areasEncyclopædia Iranica Vol. VIII, Fasc. 6, pp. 583–584. Origina ...

'' (Syrian rue). Syrian rue seeds contain about 3% harmala alkaloids by dry weight. Harmaline was first isolated from plants in 1841, its chemical structure identified in 1919, and it was first synthesized in 1927.

Use

Harmaline-containing plants and tryptamine-containing plants are used in

brews. The inhibitory effects on monoamine oxidase allows

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT), the psychoactively prominent chemical in the mixture, to bypass the extensive

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

it undergoes upon ingestion, allowing a psychologically active quantity of the chemical to exist in the brain for a perceivable period of time.

Effects

The harmala alkaloids are psychoactive in humans. According to

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American biochemist, broad researcher of synthetic psychoactive compounds, and author of works regarding these, who independently explored the organic chemistry and ph ...

, harmaline is the only harmala alkaloid that has a reputation of being

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic. However, other harmala alkaloids and β-carbolines, like harmine,

(THH),

6-methoxyharmalan 6-Methoxyharmalan, or 6-methoxyharmalane, also known as 6-methoxy-1-methyl-3,4-dihydro-β-carboline, is a naturally occurring serotonin receptor modulator, monoamine oxidase inhibitor, and hallucinogen of the β-carboline family related to harm ...

, and 6-methoxytetrahydroharman, have also been reported to be hallucinogenic.

Interactions

Harmaline is a reversible

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

of MAO-A (

RIMA Rima, also known as Rima the Jungle Girl, is the fictional heroine of W. H. Hudson's 1904 novel '' Green Mansions: A Romance of the Tropical Forest''. In it, Rima, a primitive girl of the shrinking rain forest of South America, meets Abel, a pol ...

)". This means that the risk of a hypertensive crisis, a dangerous high blood pressure crisis from eating

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 bl ...

-rich foods such as cheese, is likely lower with harmaline than with irreversible 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 family which is primarily used as an antidepressant and anxiolytic to treat depression and a ...

. Since harmaline is a RIMA, it could, in theory, induce both

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

and hypertensive crises in combination with tyramine, serotonergics, catecholaminergics drugs or prodrugs.

Pharmacology

Harmaline shows weak but significant

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_2A and 5-HT_2C receptors (in the low

micromolar Molar concentration (also called molarity, amount concentration or substance concentration) is the number of moles of solute per liter of solution. Specifically, It is a measure of the concentration of a chemical species, in particular, of a s ...

range). Harmaline and the

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

DOM partially substitute for each other in rodent

drug discrimination Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...

tests. Harmaline was much more effective in substituting for DOM than harman and harmine, which did not achieve significant generalization and produced behavioral disruption at higher doses. On the other hand, harmaline and 6-methoxyharman were comparable in terms of DOM substitution. Harmaline shows high affinity for the

imidazoline Imidazoline is a heterocycle formally derived from imidazole by the reduction of one of the two double bonds. Three isomers are known, 2-imidazolines, 3-imidazolines, and 4-imidazolines. The 2- and 3-imidazolines contain an imine center, whereas t ...

I₂ receptor (K_i = 22nM).

Chemistry

Harmaline, also known as 7-methoxyharmalan or 3,4-dihydro-7-methoxy-1-methyl-β-carboline, is a β-carboline and a

cyclized tryptamine Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all trypt ...

analogue of 6-methoxy-DMT. It is

under

ultraviolet light Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of th ...

Natural occurrence

Various plants contain harmaline including ''

'' (Syrian rue) as well as the hallucinogenic beverage

, which is traditionally brewed using ''

Banisteriopsis caapi ''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 fam ...

''. Present at 3% by dry weight, the harmala alkaloids may be extracted from the Syrian rue seeds.

History

Harmaline was first

isolated Isolation is the near or complete lack of social contact by an individual. Isolation or isolated may also refer to: Sociology and psychology *Social isolation *Isolation (psychology), a defense mechanism in psychoanalytic theory *Emotional iso ...

from

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

s in 1841. The

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

of harmaline was not correctly identified until 1919. Harmaline was first synthesized in 1927.

Society and culture

Legal status

Australia

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

Canada

Harmaline and Harmalol are considered Schedule III controlled substances by the

Controlled Drugs and Substances Act Control may refer to: Basic meanings Economics and business * Control (management), an element of management * Control, an element of management accounting * Comptroller (or controller), a senior financial officer in an organization * Controll ...

. Every person found to be in possession of a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding three years; or for a first offence, guilty on summary conviction, to a fine not exceeding one thousand dollars or to imprisonment for a term not exceeding six months, or to both. Every person found to be trafficking a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding ten years, or is guilty on summary conviction (first-time offenders) and liable to imprisonment for a term not exceeding eighteen months.

References

External links

Harmaline - Isomer Design

Harmaline - TiHKAL - Erowid
{{Tryptamines Acetylcholinesterase inhibitors Antidepressants Beta-Carbolines Entheogens Hallucinogens N-Monoalkyltryptamines Monoamine oxidase inhibitors Oneirogens Phenol ethers Reversible inhibitors of MAO-A Psychedelic tryptamines Serotonin receptor modulators Tryptamine alkaloids

Use