RESEARCH MONOGRAPH · KDC-MN-339

Tetrahydroharmine (THH)

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

Our opinion on this compound

47/100

Minor ayahuasca beta-carboline with serotonin reuptake activity, niche research interest

Tetrahydroharmine is the reduced beta-carboline that accompanies harmaline and harmine in Banisteriopsis caapi at smaller concentrations. Where harmaline and harmine are primarily reversible MAO-A inhibitors, THH's main pharmacology is weak serotonin reuptake inhibition with minimal MAO activity. Thats a meaningfully different profile within the same scaffold class.

Mechanism: weak SSRI-like activity with IC50 in the low-micromolar range at SERT, which is well above clinical SSRI potency. Minimal MAO-A inhibition compared to harmaline/harmine. Some 5-HT2A binding at higher concentrations. Riba and colleagues had the better pharmacological characterization in the ayahuasca context.

The role of THH in the ayahuasca experience is somewhat ambiguous. The standard story is that it modulates serotonin tone during the experience and may contribute to mood-related effects post-experience, but the actual experimental evidence for this at the concentrations achieved is thin. Plasma exposures from typical ayahuasca preparations dont obviously hit pharmacologically meaningful SERT inhibition.

For research THH is mostly a niche tool. It's not particularly useful as a selective SERT inhibitor compared to citalopram or fluoxetine. It's not a useful MAO inhibitor compared to harmaline or harmine. The interesting use case is really beta-carboline structure-activity work and as a chemical marker in ayahuasca pharmacology research where you want to track all three principal beta-carbolines simultaneously.

Honestly the literature on THH specifically is thin enough that we hesitate to make strong claims. Most of what gets cited about it traces back to the same few Callaway and Riba papers, and the receptor-binding profile has been characterized but not deeply explored in vivo. If THH has independent therapeutic-like effects they havent been clearly demonstrated.

Sourcing: THH is harder to find than harmaline or harmine, fewer suppliers offer synthetic material, natural-source material from caapi extracts is more common but variable in purity. HPLC verification is essential. Cost per gram is meaningfully higher because supply is limited.

What we like: useful as a structural variation in beta-carboline SAR studies, complete-set ayahuasca pharmacology research.

What we dont like: thin pharmacology characterization, limited supplier base, no clear standalone use case as a research tool.

Hold opinions loosely on this one. Mostly a completionist beta-carboline rather than a working research compound.

Evidence: 30
Mechanism: 50
Reliability: 45
Safety: 65
Sourcing: 50
Value: 50
Signal: 40
Staying power: 45

Plain-language summary Intrigue 48 / 100

Tetrahydroharmine is the third major harmala alkaloid in the ayahuasca vine, distinguished from harmine and harmaline by being a reduced (saturated) version of the beta-carboline scaffold. The reduction changes the pharmacology substantially: it is a moderate serotonin reuptake inhibitor with only minor MAO-A activity, more like an SSRI than the parent compounds. In the context of ayahuasca it likely contributes a serotonergic flavor to the experience that complements the MAO inhibition from harmine and harmaline. Standalone clinical data are essentially absent. 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 (tetrahydro reduced)

A reduced tetrahydro-beta-carboline from Banisteriopsis caapi; a serotonin reuptake inhibitor and minor MAO-A inhibitor in ayahuasca.

Abstract

Tetrahydroharmine (THH, 7-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole; CAS 17019-01-1; molecular formula C13H16N2O; molecular weight 216.28) is a tetrahydro-reduced beta-carboline alkaloid from Banisteriopsis caapi, the third major harmala alkaloid alongside harmine and harmaline. Distinct from the parent oxidized beta-carbolines by a different mechanism: THH is a moderate serotonin reuptake inhibitor (SRI) rather than an MAO-A inhibitor; the MAO-A activity is minor compared to harmine/harmaline. The SRI activity contributes a distinct serotonergic component to ayahuasca pharmacology beyond the MAO-mediated DMT potentiation. Plasma half-life is comparable to other beta-carbolines (approximately 2 to 3 hours). Used as a reference SRI beta-carboline in ayahuasca pharmacology research.

Mechanism of action

Tetrahydro-reduced beta-carboline; moderate serotonin reuptake inhibitor with minor MAO-A activity (distinct from parent harmine/harmaline).

Reported research dose ranges

Ayahuasca-context use 50 to 100 mg in the published literature (component of brew).

References

Callaway JC, et al. Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca. J Anal Toxicol 1996.
Riba J, et al. Pharmacology of ayahuasca administered in two repeated doses. Psychopharmacology 2003.
McKenna DJ. Clinical investigations of the therapeutic potential of ayahuasca. Pharmacol Ther 2004.

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KDC-MN-339

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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Tetrahydroharmine (THH)

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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