Harmine, also known as banisterine or telepathine, as well as 7-methoxyharman or 7-methoxy-1-methyl-β-carboline, is a β-carboline and a harmala alkaloid which has hallucinogenic effects and monoamine oxidase inhibitor (MAOI) activity. It occurs in a number of different plants, most notably Peganum harmala and Banisteriopsis caapi. Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamines, making it a reversible inhibitor of monoamine oxidase A (RIMA). Harmine does not inhibit MAO-B. Harmine is found in various plants—including tobacco, Passiflora species, lemon balm, and several Banisteriopsis species—as well as in some butterflies of the Nymphalidae family. It was first isolated and named by German chemist Julius Fritzsche in 1847 from Peganum harmala seeds, later identified in Banisteriopsis caapi under various names, with its structure determined in 1927. The biosynthesis of harmine likely begins with L-tryptophan, which is decarboxylated to tryptamine—an intermediate also used in serotonin synthesis—before undergoing a series of reactions to form harmine, with feeding experiments supporting tryptamine’s role as an intermediate rather than a primary precursor. It is essential for enabling the oral activity of DMT in ayahuasca and is also used as a fluorescent pH indicator and in PET imaging to study MAO-A-related brain disorders. Pharmaceutical-grade harmine hydrochloride is safe and well-tolerated at oral doses below 2.7 mg/kg in healthy adults, with higher doses causing mild to moderate gastrointestinal and neurological side effects and limited psychoactive effects. Recent patents focus on creating harmine derivatives with reduced toxicity.
Use and effects
Hallucinogen Harmine is a hallucinogen at reported doses of 25 to 75 mg subcutaneously, 150 to 200 mg intravenously, and 300 mg or more orally. However, in other reports, hallucinogenic effects were minimal at doses of up to 960 mg orally and 750 mg sublingually. In a modern clinical trial, harmine given orally did not produce hallucinogenic effects in humans at doses of up to 300 mg. The effects of harmine include euphoria, hallucinogenic effects, confusion, drowsiness, sleepiness, perceptual disturbances, closed-eye visuals, vertigo, lightheadedness, ataxia, speech impairment, and unpleasantness. The hallucinogenic effects of harmine and other β-carbolines are said to be qualitatively distinct from and unlike those of serotonergic psychedelics like LSD but similar to those of ibogaine. Along with harmaline and tetrahydroharmine, harmine is one of the psychoactive constituents of Banisteriopsis caapi. These other constituents, particularly harmaline, may be the more relevant hallucinogenic constituents of this plant. The onset of harmine is not described, whereas its duration by oral administration is 6 to 8 hours, by intramuscular injection is 3 to 5 hours, and by intravenous injection is 30 to 45 minutes.
Monoamine oxidase inhibitor Harmine is a reversible inhibitor of monoamine oxidase A (RIMA), a type of monoamine oxidase inhibitor (MAOI) as it reversibly inhibits monoamine oxidase A (MAO-A), but not monoamine oxidase B (MAO-B). Doses of harmine that are active as a RIMA in combination with dimethyltryptamine (DMT) are in the range of 140 to 190 mg orally, whereas smaller doses in the range of 120 to 140 mg were ineffective. However, its RIMA activity at the preceding effective doses was described as significant but modest. Oral or intravenous harmine doses ranging from 30 to 300 mg may cause agitation, bradycardia or tachycardia, blurred vision, hypotension, and paresthesias. Medically significant amounts of harmine occur in the plants Syrian rue and Banisteriopsis caapi. These plants also contain notable amounts of harmaline, which is also a RIMA. The psychoactive ayahuasca brew is made from B. caapi stem bark usually in combination with dimethyltryptamine (DMT) containing Psychotria viridis leaves. DMT is a psychedelic drug, but it is not orally active unless it is ingested with MAOIs. This makes harmine a vital component of the ayahuasca brew with regard to its ability to induce a psychedelic experience. Syrian rue or synthetic harmine is sometimes used to substitute B. caapi in the oral use of DMT. Harmine was used or investigated as an antiparkinsonian medication since the late 1920s until the early 1950s. It was replaced by other medications.
Other uses
Harmine is a useful fluorescent pH indicator. As the pH of its local environment increases, the fluorescence emission of harmine decreases. Due to its MAO-A specific binding, carbon-11 labeled harmine can be used in positron emission tomography to study MAO-A dysregulation in several psychiatric and neurologic illnesses.
Adverse effects
A 2024 Phase 1 clinical trial investigating pharmaceutical-grade harmine hydrochloride in healthy adults found that the maximum tolerated dose (MTD) is approximately 2.7 mg/kg body weight. Below this threshold, harmine is generally well-tolerated with minimal adverse effects. Above 2.7 mg/kg, common adverse effects include nausea and vomiting, which typically occur 60–90 minutes after ingestion. Other reported effects include drowsiness, dizziness, and impaired concentration. These effects are generally mild to moderate in severity and resolve within several hours. No serious adverse cardiovascular effects were observed at any dose tested (up to 500 mg), though rare instances of transient hypotension occurred during episodes of vomiting. Unlike some traditional preparations containing harmine (such as Ayahuasca), pure harmine did not cause diarrhea in study participants. The study found that adverse effects were more common in participants with lower body weight when given fixed doses, leading the researchers to conclude that 2.7 mg/kg represents a more useful threshold than fixed dosing.
Pharmacology
Pharmacodynamics
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