RESEARCH MONOGRAPH · KDC-MN-338

Harmine

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

72/100

Beta-carboline with a recently fascinating second life as a DYRK1A inhibitor, relevant to beta-cell biology and Down syndrome

Harmine is the harmaline-adjacent beta-carboline that's gotten genuinely interesting in the last decade because of work showing it's one of the more potent natural DYRK1A inhibitors. Thats opened up a research direction that has nothing to do with the ayahuasca pharmacology and is potentially much more interesting biologically.

Standard mechanism: reversible MAO-A selective inhibitor similar to harmaline but with slightly different kinetics, 5-HT2A partial agonist activity, beta-carboline scaffold pharmacology. The MAO-A inhibition is the part that matters for the natural-product use case in ayahuasca.

The DYRK1A story is what we actually find interesting. DYRK1A is a dual-specificity tyrosine-phosphorylation kinase implicated in pancreatic beta-cell proliferation (downstream of DREAM complex modulation, the Stewart lab and Kushner lab work), in cardiac fibrosis, and in Down syndrome neurodevelopmental biology (DYRK1A is on chromosome 21 so trisomy increases dosage). Harmine inhibits DYRK1A at low-micromolar concentrations and Wang, Stewart, et al's 2015 Nat Med paper showing harmine-induced human beta-cell proliferation was a meaningful result. Theres been a wave of medicinal chemistry trying to make selective DYRK1A inhibitors from the harmine scaffold (without the MAO-A activity) and some of those are looking interesting in beta-cell regeneration research.

Down syndrome cognitive research has also picked up on DYRK1A inhibition as a target, partly because of work in Ts65Dn mouse models. Harmine has shown effects there but the off-target MAO-A activity makes interpretation difficult.

For research the dual mechanism makes harmine a useful tool depending on what you care about: as a reference DYRK1A inhibitor in beta-cell proliferation work, or as a MAO-A inhibitor in beta-carboline pharmacology studies. The MAO-A activity confounds the DYRK1A studies and vice versa, which is why the selective DYRK1A inhibitors derived from the scaffold matter.

Sourcing: harmine hydrochloride is widely available, similar QC profile to harmaline, often even cheaper because demand is lower. HPLC verification, natural and synthetic sources both fine.

What we like: dual mechanism creates two genuinely interesting research angles, the beta-cell proliferation story is one of the more exciting directions in diabetes research, well-characterized natural product.

What we dont like: the MAO-A activity confounds DYRK1A interpretation, and the broader DYRK1A target validation is still ongoing.

Underrated research compound with a fascinating second act. Worth knowing.

Evidence: 65
Mechanism: 78
Reliability: 70
Safety: 65
Sourcing: 80
Value: 78
Signal: 70
Staying power: 70

Plain-language summary Intrigue 68 / 100

Harmine is the second major beta-carboline in ayahuasca and Syrian rue, with the same reversible MAO-A inhibition that lets oral DMT work. What makes harmine separately interesting is its activity as a DYRK1A kinase inhibitor at low nanomolar potency. DYRK1A regulates pancreatic beta-cell proliferation, and harmine has emerged as a tool compound for stimulating beta-cell regrowth in diabetes research, where adult beta-cells have been considered essentially non-replicative. That diabetes angle is genuinely novel and has driven medicinal chemistry programs to build cleaner DYRK1A inhibitors without the MAO baggage. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Beta-carboline reversible MAO-A inhibitor (DYRK1A inhibitor)

A beta-carboline alkaloid from Peganum harmala; a reversible MAO-A inhibitor and DYRK1A kinase inhibitor of interest in beta-cell biology.

Abstract

Harmine (7-methoxy-1-methyl-9H-pyrido[3,4-b]indole; CAS 442-51-3; molecular formula C13H12N2O; molecular weight 212.25) is a beta-carboline alkaloid from Peganum harmala and Banisteriopsis caapi. The compound is a reversible MAO-A inhibitor with similar selectivity profile to harmaline but with the additional well-characterized activity of DYRK1A kinase inhibition (IC50 approximately 30 nM). The DYRK1A activity has generated substantial interest in diabetes research: harmine and related DYRK1A inhibitors stimulate human pancreatic beta-cell proliferation in vitro and in vivo, a long-sought target for diabetes regenerative therapy. Phase 1 trials of derivatives are underway. Plasma half-life is approximately 1 to 3 hours. Used as a research probe for both ayahuasca pharmacology and beta-cell regenerative biology.

Mechanism of action

Reversible MAO-A inhibitor; DYRK1A kinase inhibitor (IC50 ~30 nM). DYRK1A activity stimulates pancreatic beta-cell proliferation.

Reported research dose ranges

Research 100 to 300 mg in the published literature; rodent diabetes studies 10 to 30 mg/kg.

References

Wang P, et al. A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nat Med 2015.
Brierley DI, Davidson C. Developments in harmine pharmacology - implications for ayahuasca use and drug-dependence treatment. Prog Neuropsychopharmacol Biol Psychiatry 2012.
Frost D, et al. beta-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation. PLoS ONE 2011.

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KDC-MN-338

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

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Harmine

Abstract

Mechanism of action

Reported research dose ranges

References

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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