Harmaline is a

fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, ...

indole Indole is an aromatic heterocyclic organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other c ...

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 ...

from the group of

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 well as tobacco leaves including harmine, harmaline, and harmalol, which a ...

s and

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 ...

s. 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 organic ...

form of

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 ...

Occurrence in nature

Various plants contain harmaline including ''

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 ...

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

, which is traditionally brewed using ''

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 ...

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

Effects

Harmaline is a

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 ...

stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...

and a "reversible

inhibitor Inhibitor or inhibition may refer to: In 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 neurotra ...

MAO Mao Zedong pronounced ; also romanised traditionally as Mao Tse-tung. (26 December 1893 – 9 September 1976), also known as Chairman Mao, was a Chinese communist revolutionary who was the founder of the People's Republic of China (PRC ...

-A ( RIMA)". 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 blood ...

-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 class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine an ...

. The harmala alkaloids are psychoactive in humans. Harmaline is shown to act as an

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and ...

. Harmaline also stimulates

striatal The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...

dopamine release in rats at very high dose levels. Since harmaline is a reversible inhibitor of monoamine oxidase A, it could, in theory, induce both

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

and

hypertensive crises Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 120—sometimes termed malignant or accelerated hypertension) is referred to as a hypertensive crisis, as blood pressure at this level confers a high risk ...

in combination with tyramine, serotonergics, catecholaminergics drugs or prodrugs. Harmaline-containing plants and tryptamine-containing plants are used in ayahuasca brews. The inhibitory effects on monoamine oxidase allows dimethyltryptamine (DMT), the psychoactively prominent chemical in the mixture, to bypass the extensive first-pass metabolism it undergoes upon ingestion, allowing a psychologically active quantity of the chemical to exist in the brain for a perceivable period of time. Harmaline forces the anabolic metabolism of serotonin into N-acetylserotonin (normelatonin), and then to

melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrat ...

, the body's principal sleep-regulating hormone and a powerful antioxidant. United States

Patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A ...

Number 5591738 describes a method for treating various chemical dependencies via the administration of harmaline and or other beta-carbolines. A study has reported the antiviral activity of Harmaline against

Herpes Simplex Virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names '' Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral in ...

1 and 2 (

HSV-1 Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...

and HSV-2) by inhibiting immediate early transcription of the virus at noncytotoxic concentration. Harmaline is known to act as a

histamine N-methyltransferase Histamine ''N''-methyltransferase (HNMT, HMT) is an enzyme involved in the metabolism of histamine. It is one of two enzymes involved in the metabolism of histamine in mammals, the other being diamine oxidase (DAO). HNMT catalyzes the methylation ...

inhibitor. This explains how harmaline elicits its wakefulness-promoting effects.

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 The ''Controlled Drugs and Substances Act'' (french: Loi réglementant certaines drogues et autres substances) (the ''Act'') is Canada's federal drug control statute. Passed in 1996 under Prime Minister Jean Chrétien's government, it repeal ...

. 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

TIHKAL, #13
* {{Tryptamines Reversible inhibitors of MAO-A Antidepressants Beta-Carbolines Tryptamine alkaloids Entheogens Monoamine oxidase inhibitors Acetylcholinesterase inhibitors Phenol ethers Oneirogens