Tetrahydroharmine

Overview

Tetrahydroharmine (THH), also known as 7-methoxy-1,2,3,4-tetrahydroharman (7-MeO-THH), is a fluorescent indole alkaloid and β-carboline that occurs in the tropical liana species Banisteriopsis caapi. It is an oneirogenic hallucinogen similarly to harmaline. Conversely however, in contrast to other harmala alkaloids, it is very weak as a monoamine oxidase inhibitor (MAOI).[1–7] WP

Uses, dosage and effects

Use and effects

THH has been reported to produce psychoactive effects similar to those of harmaline in humans. It has been reported to be about one-third as potent as harmaline at a dose of 300 mg orally. THH is believed to be one of the constituents of Banisteriopsis caapi responsible for the hallucinogenic effects of the plant. The duration of THH is unknown.[2–5] WP

Pharmacology

Pharmacodynamics

THH, like other harmala alkaloids in B. caapi, namely harmaline and harmine, is a reversible inhibitor of monoamine oxidase A (RIMA), but it also inhibits the reuptake of serotonin. THH contributes to B. caapi's psychoactivity as a serotonin reuptake inhibitor. Although THH is a RIMA, it is 200-fold less potent than harmine and harmaline in this regard and hence is very weak (IC₅₀ (half-maximal inhibitory concentration) = 14,000 nM vs. 60–80 nM, respectively). In addition, its serotonin reuptake inhibition is very weak as well (IC₅₀ (half-maximal inhibitory concentration) = 3,400 nM).[6–10] WP

In contrast to other β-carbolines, THH shows minimal affinity for the serotonin 5-HT2A receptor (Kᵢ = >10,000 nM for racemic THH and R(+)-THH, Kᵢ = 5,890 nM for S(–)-THH). Similarly, THH shows negligible affinity for the serotonin 5-HT1A and 5-HT2C receptors and the dopamine D₂ receptor. THH is inactive as an agonist of the serotonin 5-HT2A receptor, but has been found to be a very weak antagonist of the receptor (IC₅₀ (half-maximal inhibitory concentration) = 48,000 nM). It is the first and only harmala alkaloid known to show any functional activity (agonist or antagonist) at the serotonin 5-HT2A receptor.[4][6][11] WP

Pharmacokinetics

The elimination half-life of THH is 4.7 to 8.8 hours.[12][13] WP

History

History

THH was first described in the scientific literature by Otto Fischer by 1889. Its hallucinogenic effects were described by Claudio Naranjo in 1967. Subsequently, its hallucinogenic effects were further described by Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved) in 1997.[2][3][5][14][15] WP

Legal status

Australia

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015). A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[16] WP

Canada

THH is not a controlled substance in Canada as of 2025.[17] WP

Chemistry

Formula

C13H16N2O PC

CAS number

17019-01-1 PC

Molar mass (g/mol)

216.28 PC

IUPAC name (computed by PubChem)

7-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole PC

SMILES

CC1C2=C(CCN1)C3=C(N2)C=C(C=C3)OC PC

InChIKey

ZXLDQJLIBNPEFJ-UHFFFAOYSA-N PC

PubChem CID

159809

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Callaway JC. Various alkaloid profiles in decoctions of Banisteriopsis caapi. Journal of Psychoactive Drugs. June 2005. doi:10.1080/02791072.2005.10399796 · PMID 16149328
2. Other Brimblecombe RW, Pinder RM. Hallucinogenic Agents. 1975
3. Other CiteTiHKAL
4. Journal / agency Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, Glennon RA. Investigation of hallucinogenic and related beta-carbolines. Drug and Alcohol Dependence. April 1998. doi:10.1016/s0376-8716(97)00163-4 · PMID 9649961
5. Other Naranjo C. Ethnopharmacologic Search for Psychoactive Drugs. 1967
6. Other Rolquin JD. Examining Ayahuasca Constituents at 5-HT2A Receptors in Search of Antidepressant Action. 3 May 2022
7. Journal / agency Buckholtz NS, Boggan WO. Monoamine oxidase inhibition in brain and liver produced by beta-carbolines: structure-activity relationships and substrate specificity. Biochemical Pharmacology. November 1977. doi:10.1016/0006-2952(77)90007-7 · PMID 921812
8. Journal / agency Morales-García JA, de la Fuente Revenga M, Alonso-Gil S, Rodríguez-Franco MI, Feilding A, Perez-Castillo A, Riba J. The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific Reports. July 2017. doi:10.1038/s41598-017-05407-9 · PMID 28706205 · PMC5509699
9. Journal / agency Callaway JC, McKenna DJ, Grob CS, Brito GS, Raymon LP, Poland RE, Andrade EN, Andrade EO, Mash DC. Pharmacokinetics of Hoasca alkaloids in healthy humans. Journal of Ethnopharmacology. June 1999. doi:10.1016/S0378-8741(98)00168-8 · PMID 10404423
10. Journal / agency Buckholtz NS, Boggan WO. Inhibition by beta-carbolines of monoamine uptake into a synaptosomal preparation: structure-activity relationships. Life Sciences. June 1977. doi:10.1016/0024-3205(77)90190-4 · PMID 18641
11. Journal / agency Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV. Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors. Drug and Alcohol Dependence. August 2000. doi:10.1016/s0376-8716(99)00148-9 · PMID 10940539
12. Journal / agency Berlowitz I, Egger K, Cumming P. Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca. Frontiers in Pharmacology. 2022. doi:10.3389/fphar.2022.886408 · PMID 35600851 · PMC9121195
13. Journal / agency Brito-da-Costa AM, Dias-da-Silva D, Gomes NG, Dinis-Oliveira RJ, Madureira-Carvalho Á. Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact. Pharmaceuticals. October 2020. doi:10.3390/ph13110334 · PMID 33114119 · PMC7690791
14. Journal / agency Fischer O. Ueber Harmin und Harmalin. II. Berichte der deutschen chemischen Gesellschaft. 1889. doi:10.1002/cber.188902201146
15. Journal / agency Perkin WH, Robinson R. CXC.—Harmine and harmaline. Part I. J. Chem. Soc., Trans. 1912. doi:10.1039/CT9120101775
16. Other Poisons Standard October 2015. September 2015
17. Other Controlled Drugs and Substances Act

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