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 75mg subcutaneously, 150 to 200mg intravenously, and 300mg or more orally. However, in other reports, hallucinogenic effects were minimal at doses of up to 960mg orally and 750mg sublingually. In a modern clinical trial, harmine given orally did not produce hallucinogenic effects in humans at doses of up to 300mg. 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 8hours, by intramuscular injection is 3 to 5hours, and by intravenous injection is 30 to 45minutes.
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 190mg orally, whereas smaller doses in the range of 120 to 140mg 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 300mg 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 2.7mg/kg represents a more useful threshold than fixed dosing.
Pharmacology Pharmacodynamics + Target Affinity (Ki, nM) 5-HT1A >10,000 5-HT1B 5-HT1D >10,000 (calf/pig) 5-HT1E 5-HT1F 5-HT2A 230–397 (rat) 5-HT2B 5-HT2C 5,340 (rat) 5-HT3 5-HT4 5-HT5A 5-HT6 5-HT7 α1A–α1D α2 >10,000 (rat) α2A–α2C β1–β3 D1 D2 >10,000 D3–D5 H1–H4 M1–M5 I1 629 () I2 10 σ1, σ2 MOR >100,000 (bovine) DOR >100,000 (bovine) DOR >100,000 (bovine) >10,000 (rat) 11,000–41,000 () (mouse) 22,000 () (mouse) 12,000 () 1.0–16.9 (Ki)1.0–380 () 120,800 (Ki) () 12–700 () Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs:
The pharmacology of harmine has been studied. It showed affinity (Ki) for the serotonin 5-HT2A receptor (Ki = 230–397nM) and for the serotonin 5-HT2C receptor (Ki = 5,340nM), but not for the serotonin 5-HT1A receptor, the dopamine D2 receptor, or the benzodiazepine site of the GABAA receptor (all Ki = >10,000nM). The drug showed among the highest affinity for the serotonin 5-HT2A receptor of any other β-carboline, with a few exceptions. However, in contrast to serotonergic psychedelics, harmine has been found to be inactive as an agonist of the serotonin 5-HT2A receptor. In addition, other β-carbolines like harmaline did not activate the serotonin 5-HT2A receptor in terms of PI hydrolysis even at very high concentrations in vitro. Harmine has been found to be antagonistic to serotonin in certain tissues similarly to LSD. Harmine has been found to increase dopamine release in the nucleus accumbens in a serotonin 5-HT2A receptor-dependent manner as evidenced by reversal by ketanserin, but this may instead be via indirect serotonin 5-HT2A receptor activation.
Harmine has also shown affinity for the imidazoline I2 receptor (Ki = 10nM). It has been suggested that this action might be involved in or responsible for its hallucinogenic effects. The drug is a potent inhibitor of DYRK1A (Ki or = 33–700nM) and a very weak dopamine reuptake inhibitor ( = 12,000nM). Conversely, it is not a dopamine transporter (DAT) substrate or dopamine releasing agent. Harmine is a highly potent inhibitor of monoamine oxidase A (MAO-A) (Ki = 16.9nM, = 2.0–380nM). It shows 10,000-fold selectivity for MAO-A over monoamine oxidase B (MAO-B). Unlike ibogaine and noribogaine, harmine does not bind to the κ-opioid receptor or other opioid receptors.
In contrast to harmaline and 6-methoxyharmalan, which fully substituted for the psychedelic drug DOM in rodent drug discrimination tests, but similarly to harmane, harmine failed to significantly substitute for DOM and produced behavioral disruption at higher doses. Similarly, harmine did not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents. However, in a subsequent study, harmine did produce the head-twitch response. In addition, as with other MAOIs, harmine can potentiate the head-twitch response induced by 5-hydroxytryptophan (5-HTP).
Pharmacokinetics The pharmacokinetics of harmine have been studied and described. The plasma elimination half-life of harmine is about 1.3 to 1.9hours or with a range of 1 to 3hours.
Chemistry Harmine, also known as 7-methoxy-1-methyl-β-carboline, is a substituted β-carboline and cyclized tryptamine derivative. Analogues of harmine include harmaline and tetrahydroharmine, among others. A positional isomer of harmine is 6-methoxyharman and analogues of that isomer include 6-methoxyharmalan and 6-methoxytetrahydroharmine (6-MeO-THH).
Synthesis The chemical synthesis of harmine has been described.
Natural occurrence Harmine is found in a wide variety of different organisms, most of which are plants.
Alexander Shulgin lists about thirty different species known to contain harmine, including seven species of butterfly in the family Nymphalidae.
The harmine-containing plants include tobacco, Peganum harmala, two species of passiflora, and numerous others. Lemon balm (Melissa officinalis) contains harmine.
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 family Zygophyllaceae, which P. harmala belongs to, contains at least two other harmine-bearing plants: Peganum nigellastrum and Zygophyllum fabago.
Biosynthesis The coincident occurrence of β-carboline alkaloids and serotonin in Peganum harmala indicates the presence of two very similar, interrelated biosynthetic pathways, which makes it difficult to definitively identify whether free tryptamine or L-tryptophan is the precursor in the biosynthesis of harmine. However, it is postulated that L-tryptophan is the most likely precursor, with tryptamine existing as an intermediate in the pathway.
The following figure shows the proposed biosynthetic scheme for harmine. The Shikimate acid pathway yields the aromatic amino acid, L-tryptophan. Decarboxylation of L-tryptophan by aromatic L-amino acid decarboxylase (AADC) produces tryptamine (I), which contains a nucleophilic center at the C-2 carbon of the indole ring due to the adjacent nitrogen atom that enables the participation in a Mannich-type reaction. Rearrangements enable the formation of a Schiff base from tryptamine, which then reacts with pyruvate in II to form a β-carboline carboxylic acid. The β-carboline carboxylic acid subsequently undergoes decarboxylation to produce 1-methyl β-carboline III. Hydroxylation followed by methylation in IV yields harmaline. The order of O-methylation and hydroxylation have been shown to be inconsequential to the formation of the harmaline intermediate. In the last step V, the oxidation of harmaline is accompanied by the loss of water and effectively generates harmine.