spec sheet10 rows
Harmine is a beta-carboline alkaloid found in the vine Banisteriopsis caapi and in Peganum harmala (Syrian rue), and it is one of the harmala alkaloids that give ayahuasca its oral activity. Pharmacologically it is a reversible, competitive inhibitor of monoamine oxidase A (MAO-A), the property that protects DMT from breakdown in the ayahuasca brew and raises brain levels of serotonin and other monoamines. Beyond its role as an MAO inhibitor, harmine has attracted intense biomedical interest as a potent inhibitor of the kinase DYRK1A, an action through which it drives replication of human pancreatic beta cells and has become a leading template for diabetes regeneration research. It has additionally shown antidepressant-like, anti-inflammatory, and neuroprotective effects in preclinical models.
- Reversible MAO-A inhibition that enables oral DMT in ayahuasca
- Antidepressant-like and neuroprotective activity in preclinical models
- DYRK1A inhibition that makes adult human beta cells replicate, a landmark diabetes research lead
- Nausea and vomiting
- Tremor and dizziness
- Serotonin syndrome risk with serotonergic drugs
- Blood-pressure changes
- CNS excitation at higher doses
Mechanism
Harmine reversibly and competitively inhibits MAO-A, the flavoenzyme that oxidatively deaminates , , and noradrenaline. By slowing this catabolism it raises monoamine tone, and in the context of ayahuasca it blocks metabolism of DMT and thereby confers oral psychoactivity on the brew. Harmine and its beta-carboline relatives are among the naturally occurring MAO inhibitors identified in foods such as coffee, and their reversible mode of action distinguishes them from older irreversible MAO inhibitor drugs.
The most distinctive modern finding is that harmine is a potent inhibitor of dual-specificity tyrosine-regulated kinase 1A (DYRK1A). Inhibition of DYRK1A, together with the closely related DYRK1B, releases a brake on the cell cycle in adult human beta cells and, acting through the NFAT pathway, induces measurable beta-cell proliferation, an effect amplified by combining harmine with agents that inhibit TGF-beta or SMAD signalling or that stimulate the -1 receptor. These observations have made harmine the founding scaffold for medicinal chemistry aimed at -avoidant, beta-cell selective regenerative drugs for diabetes.
receptor fingerprint
Monoamine oxidase A (MAO-A)Reversible competitive inhibitor
DYRK1A kinaseInhibitor
DYRK1B kinaseInhibitor
receptorWeak agonist
Safetyrisks and cautions, not medical advice
As an MAO-A inhibitor, harmine carries the classic interaction hazards of that drug class: combining it with serotonergic drugs such as SSRIs, with other MAO inhibitors, or with tyramine-rich foods can provoke serotonin syndrome or hypertensive crisis. On its own it can cause nausea, vomiting, tremor, dizziness, and cardiovascular changes, and at higher doses beta-carbolines can be neuroexcitatory. Its DYRK1A and beta-cell effects are experimental and not an approved therapy, and native harmine also acts on the central nervous system, which is why current drug-development efforts specifically try to engineer out its CNS activity. Not medical advice.
Subjective profileweighing the evidence above
A real MAO-A inhibitor with every hazard that class carries, so tyramine-rich foods, SSRIs and other serotonergic drugs all become dangerous around it. This is not a casual supplement. The DYRK1A beta-cell work is a genuinely exciting diabetes lead, and that promise belongs in labs rather than in a capsule.
Resources
This entry is here for reference.
Research
- 2006first citedHuman monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman is…
- 2025most recentDevelopment of a physiologically based pharmacokinetic model of N,N-dimethyltryptamine, harmine…
- 1.Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors.
- 2.A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication.
- 3.Development of a reliable automated screening system to identify small molecules and biologics that promote human β-cell regeneration.
- 4.Combined Inhibition of DYRK1A, SMAD, and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells.
- 5.Pharmacologic and genetic approaches define human pancreatic β cell mitogenic targets of DYRK1A inhibitors.
- 6.Synthesis and Biological Validation of a Harmine-Based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor.
- 7.Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.
- 8.Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee.
- 9.Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents.
- 10.Effects and mechanisms of harmine on ameliorating ethanol-induced memory impairment.
- 11.Development of a physiologically based pharmacokinetic model of N,N-dimethyltryptamine, harmine, and their interactions from ayahuasca in rats and humans.
11 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What makes harmine interesting for diabetes?
Harmine inhibits the kinase DYRK1A, which releases a brake on the cell cycle and prompts adult human insulin-producing beta cells to divide, something few if any other compounds achieve.
Is harmine psychedelic by itself?
Not really. Its main role is inhibiting MAO-A; on its own it is more of a mild sedative and enzyme inhibitor than a hallucinogen, but that MAO-A block is what makes DMT orally active.
Can harmine interact with other drugs?
Yes. As an MAO-A inhibitor it can combine dangerously with SSRIs, other serotonergic agents, and tyramine-rich foods to risk serotonin syndrome or blood-pressure spikes.
Adverse effects
- Nausea and vomiting
- Tremor and dizziness
- Serotonin syndrome risk with serotonergic drugs
- Blood-pressure changes
- CNS excitation at higher doses