Harmine
Encyclopedia
Harmine is a fluorescent harmala alkaloid
belonging to the beta-carboline
family of compounds. It occurs in a number of different plants, most notably the Middle East
ern plant harmal
or Syrian rue (Peganum harmala) and the South America
n vine Banisteriopsis caapi
(also known as "yage" or "ayahuasca"). Harmine reversibly inhibits monoamine oxidase A
(MAO-A), an enzyme
which breaks down monoamines, making it a RIMA
. Harmine selectively binds
to MAO-A but does not inhibit the variant MAO-B.
Monoamines include neurotransmitter
s (serotonin
, dopamine
), hormones (melatonin
) and drugs, including many hallucinogens (psilocybin
, dimethyltryptamine
(DMT), mescaline
). By slowing the breakdown of neurotransmitters, monoamine oxidase inhibitor
s (MAOIs) can help to replenish the body's supply of these chemicals, and many MAOIs are used as antidepressants. Harmine has not been the subject of much clinical research in the treatment of depression, which could be due in part to its restricted legal status in many countries, as well as the existence of synthetic MAOIs with fewer side effects.
P. harmala and B. caapi are both traditionally used for their psychoactive effects. B. caapi has a tradition of use in conjunction with plants containing the drug DMT
. Traditionally, B. caapi is consumed as a drink, with or without the DMT-bearing plants (see Ayahuasca
). Ordinarily, DMT is not active when taken orally, but users report very different effects when DMT is present in such beverages. Harmine and substances containing it have been used in conjunction with many other drugs by modern experimenters. Many hallucinogens appear to exhibit increased potency when used in this way.
Harmine is also a useful fluorescent pH indicator. As the pH of its local environment increases, the fluorescence emission of harmine decreases.
With the radioisotope carbon-11 harmine is used in positron emission tomography
neuroimaging to examine its binding to MAO-A.
Harmine found in root secretions of Oxalis tuberosa has been found to have insecticidal properties.
Harmine has been found to increase EAAT2 glutamate pump expression in central nervous system, therefore reducing glutamate toxicity.
against HL60
and K562 cell lines. This could explain the cytotoxic effect of P. harmala on these cells."
s are generally not considered safe treatments for depression within the medical community. This bias however is primarily built on previous decades of experience with pharmaceutical non-specific MAOIs that block both MAO-A and MAO-B. Inhibiting MAO-A or MAO-B (in high enough doses) while consuming tyramine
-laden foods, e.g. cheese, can cause tyramine, ordinarily metabolized by these enzymes, to accumulate to dangerous levels. Because harmine reversibly inhibits MAO-A, the harmala alkaloid
s (including harmine) are less likely to induce this "cheese syndrome".
It has recently been shown in the Journal of Photochemistry and Photobiology B: Biology that beta-carboline MAO inhibitors, such as harmine, bind with DNA and also exhibit anti-tumor properties. Harmine has been shown to bind one hundred times more effectively than its close analogue harmaline. The consequences of this are currently not well understood.
Rapid discontinuation of MAO inhibitors can cause serious withdrawal syndrome
.
or tachycardia
, blurred vision, hypotension
, paresthesias and hallucinations. Serum or plasma harmine concentrations may be measured as a confirmation of diagnosis. The plasma elimination half-life is on the order of 1–3 hours.
lists about thirty different species known to contain harmine, including seven species of butterfly
in the Nymphalidae
family. The harmine-containing plants listed include tobacco
, two species of passion flower
/passion fruit, and numerous others.
In addition to B. caapi
, at least three members of the Malpighiaceae
contain harmine, including two more Banisteriopsis species and the plant Callaeum antifebrile. Callaway, Brito and Neves (2005)
found harmine levels of 0.31-8.43% in B. caapi samples.
The Zygophyllaceae
family, which harmal
belongs to, contains at least two other harmine-bearing plants: Peganum nigellastrum and Zygophyllum fabago
.
Harmala alkaloid
Several alkaloids that function as monoamine oxidase inhibitors are found in the seeds of Peganum harmala , including harmine, harmaline, and harmalol, which are members of a group of substances with a similar chemical structure collectively known as harmala alkaloids...
belonging to the beta-carboline
Beta-carboline
β-Carboline is an organic amine that is the prototype of a class of compounds known as β-carbolines.-Pharmacology:...
family of compounds. It occurs in a number of different plants, most notably the Middle East
Middle East
The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East...
ern plant harmal
Harmal
Harmal is a plant of the family Nitrariaceae, native from the eastern Mediterranean region east to India. It is also known as Wild Rue or Syrian Rue because of its resemblance to plants of the rue family....
or Syrian rue (Peganum harmala) and the South America
South America
South America is a continent situated in the Western Hemisphere, mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. The continent is also considered a subcontinent of the Americas. It is bordered on the west by the Pacific Ocean and on the north and east...
n vine Banisteriopsis caapi
Banisteriopsis caapi
Banisteriopsis caapi, also known as Ayahuasca, Caapi or Yage, is a South American jungle vine of the family Malpighiaceae. It is used to prepare Ayahuasca, a decoction that has a long history of entheogenic uses as a medicine and "plant teacher" among the indigenous peoples of the Amazon Rainforest...
(also known as "yage" or "ayahuasca"). Harmine reversibly inhibits monoamine oxidase A
Monoamine Oxidase A
Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAO-A gene. Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine , epinephrine , serotonin, and dopamine...
(MAO-A), an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
which breaks down monoamines, making it a RIMA
Reversible inhibitor of monoamine oxidase A
Reversible inhibitors of monoamine oxidase A are a class of drugs which selectively and reversibly inhibit the enzyme monoamine oxidase A . They are used clinically in the treatment of depression and dysthymia, though they have not gained widespread market share due to limited efficacy relative to...
. Harmine selectively binds
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
to MAO-A but does not inhibit the variant MAO-B.
Uses
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s (serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
), hormones (melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
) and drugs, including many hallucinogens (psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...
, dimethyltryptamine
Dimethyltryptamine
N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...
(DMT), mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
). By slowing the breakdown of neurotransmitters, monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
s (MAOIs) can help to replenish the body's supply of these chemicals, and many MAOIs are used as antidepressants. Harmine has not been the subject of much clinical research in the treatment of depression, which could be due in part to its restricted legal status in many countries, as well as the existence of synthetic MAOIs with fewer side effects.
P. harmala and B. caapi are both traditionally used for their psychoactive effects. B. caapi has a tradition of use in conjunction with plants containing the drug DMT
Dimethyltryptamine
N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...
. Traditionally, B. caapi is consumed as a drink, with or without the DMT-bearing plants (see Ayahuasca
Ayahuasca
Ayahuasca is any of various psychoactive infusions or decoctions prepared from the Banisteriopsis spp. vine, usually mixed with the leaves of dimethyltryptamine-containing species of shrubs from the Psychotria genus...
). Ordinarily, DMT is not active when taken orally, but users report very different effects when DMT is present in such beverages. Harmine and substances containing it have been used in conjunction with many other drugs by modern experimenters. Many hallucinogens appear to exhibit increased potency when used in this way.
Harmine is also a useful fluorescent pH indicator. As the pH of its local environment increases, the fluorescence emission of harmine decreases.
With the radioisotope carbon-11 harmine is used in positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
neuroimaging to examine its binding to MAO-A.
Harmine found in root secretions of Oxalis tuberosa has been found to have insecticidal properties.
Harmine has been found to increase EAAT2 glutamate pump expression in central nervous system, therefore reducing glutamate toxicity.
Anticancer
"Harmine showed cytotoxicityCytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
against HL60
HL60
The HL-60 cell line is a leukemic cell line that has been used for laboratory research on how certain kinds of blood cells are formed. HL-60 proliferates continuously in suspension culture in nutrient medium supplemented with fetal bovine serum, L-glutamine, HEPES and antibiotic chemicals. The...
and K562 cell lines. This could explain the cytotoxic effect of P. harmala on these cells."
Adverse effects
Harmine, and plants containing significant amounts of harmine and other harmala alkaloidHarmala alkaloid
Several alkaloids that function as monoamine oxidase inhibitors are found in the seeds of Peganum harmala , including harmine, harmaline, and harmalol, which are members of a group of substances with a similar chemical structure collectively known as harmala alkaloids...
s are generally not considered safe treatments for depression within the medical community. This bias however is primarily built on previous decades of experience with pharmaceutical non-specific MAOIs that block both MAO-A and MAO-B. Inhibiting MAO-A or MAO-B (in high enough doses) while consuming tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
-laden foods, e.g. cheese, can cause tyramine, ordinarily metabolized by these enzymes, to accumulate to dangerous levels. Because harmine reversibly inhibits MAO-A, the harmala alkaloid
Harmala alkaloid
Several alkaloids that function as monoamine oxidase inhibitors are found in the seeds of Peganum harmala , including harmine, harmaline, and harmalol, which are members of a group of substances with a similar chemical structure collectively known as harmala alkaloids...
s (including harmine) are less likely to induce this "cheese syndrome".
It has recently been shown in the Journal of Photochemistry and Photobiology B: Biology that beta-carboline MAO inhibitors, such as harmine, bind with DNA and also exhibit anti-tumor properties. Harmine has been shown to bind one hundred times more effectively than its close analogue harmaline. The consequences of this are currently not well understood.
Rapid discontinuation of MAO inhibitors can cause serious withdrawal syndrome
Withdrawal syndrome
A withdrawal syndrome, also called a discontinuation syndrome, occurs when a person suddenly stops taking or reduces the dosage of some types of medications...
.
Overdosage
Oral or intravenous harmine doses ranging from 30–300 mg have caused agitation, bradycardiaBradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
or tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, blurred vision, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, paresthesias and hallucinations. Serum or plasma harmine concentrations may be measured as a confirmation of diagnosis. The plasma elimination half-life is on the order of 1–3 hours.
Natural sources
Harmine is found in a wide variety of different organisms, most of which are plants. Shulginlists about thirty different species known to contain harmine, including seven species of butterfly
Butterfly
A butterfly is a mainly day-flying insect of the order Lepidoptera, which includes the butterflies and moths. Like other holometabolous insects, the butterfly's life cycle consists of four parts: egg, larva, pupa and adult. Most species are diurnal. Butterflies have large, often brightly coloured...
in the Nymphalidae
Nymphalidae
The Nymphalidae is a family of about 5,000 species of butterflies which are distributed throughout most of the world. These are usually medium sized to large butterflies. Most species have a reduced pair of forelegs and many hold their colourful wings flat when resting. They are also called...
family. The harmine-containing plants listed include tobacco
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
, two species of passion flower
Passion flower
Passiflora, known also as the passion flowers or passion vines, is a genus of about 500 species of flowering plants, the namesakes of the family Passifloraceae. They are mostly vines, with some being shrubs, and a few species being herbaceous. For information about the fruit of the passiflora...
/passion fruit, and numerous others.
In addition to B. caapi
Banisteriopsis caapi
Banisteriopsis caapi, also known as Ayahuasca, Caapi or Yage, is a South American jungle vine of the family Malpighiaceae. It is used to prepare Ayahuasca, a decoction that has a long history of entheogenic uses as a medicine and "plant teacher" among the indigenous peoples of the Amazon Rainforest...
, at least three members of the Malpighiaceae
Malpighiaceae
Malpighiaceae is a family of flowering plants in the order Malpighiales. It comprises approximately 75 genera and 1300 species, all of which are native to the tropics and subtropics...
contain harmine, including two more Banisteriopsis species and the plant Callaeum antifebrile. Callaway, Brito and Neves (2005)
found harmine levels of 0.31-8.43% in B. caapi samples.
The Zygophyllaceae
Zygophyllaceae
The Zygophyllaceae is a family of flowering plants that contains the bean-caper and caltrop. It includes around 285 species in 22 genera.In the APG III system of classification, the families Zygophyllaceae and Krameriaceae compose the order Zygophyllales...
family, which harmal
Harmal
Harmal is a plant of the family Nitrariaceae, native from the eastern Mediterranean region east to India. It is also known as Wild Rue or Syrian Rue because of its resemblance to plants of the rue family....
belongs to, contains at least two other harmine-bearing plants: Peganum nigellastrum and Zygophyllum fabago
Zygophyllum fabago
Zygophyllum fabago is a species of plant known by the common name Syrian bean-caper. It is considered a noxious weed of economic importance in many of the western United States. It is native to Asia and the Middle East.-Growth:...
.