Harmine

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 Eastern plant harmal or Syrian rue (Peganum harmala) and the South American vine Banisteriopsis caapi ('yage', 'ayahuasca'). Harmine is a RIMA, a reversible inhibitor of monoamine oxidase A (MAO-A), an enzyme which breaks down monoamines. Harmine selectively binds to MAO-A but does not inhibit the variant MAO-B.

Uses


Monoamines include neurotransmitters (serotonin, dopamine), hormones (melatonin) and drugs, including many hallucinogens (psilocybin, dimethyltryptamine (DMT), mescaline). By slowing the breakdown of neurotransmitters, monoamine oxidase inhibitors (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.

Anticancer
"Harmine showed cytotoxicity against HL60 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 alkaloids 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 alkaloids (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-carbolines (MAO Inhibitors), such as harmine, bind into dna, and also exhibit anti-tumor properties. It has been shown to bind one hundred times more effectively than its close analogue harmaline. The consequences of this are currently not well understood.

It is important to remember that discontinuation of MAO inhibitors can cause serious withdrawal syndrome.

Overdosage
Oral or intravenous harmine doses ranging from 30–300 mg have caused agitation, bradycardia 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.

Natural sources
Harmine is found in a wide variety of different organisms, most of which are plants. Shulgin 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.