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).
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 300mg 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.
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 ( = 14,000nM vs. 60–80nM, respectively). In addition, its serotonin reuptake inhibition is very weak as well ( = 3,400nM).
In contrast to other β-carbolines, THH shows minimal affinity for the serotonin 5-HT2A receptor (Ki = >10,000nM for racemic THH and R(+)-THH, Ki = 5,890nM 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 ( = 48,000nM). It is the first and only harmala alkaloid known to show any functional activity (agonist or antagonist) at the serotonin 5-HT2A receptor.
Pharmacokinetics The elimination half-life of THH is 4.7 to 8.8hours.
Chemistry Synthesis The chemical synthesis of THH has been described.
Analogues Analogues of THH include harmine, harmaline, and 6-MeO-THH, among others.
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.
Society and culture 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.
Canada THH is not a controlled substance in Canada as of 2025.
See also Substituted β-carboline Harmala alkaloid Ayahuasca
References
External links THH - Isomer Design Tetrahydroharmine - PsychonautWiki Harmala Alkaloids - Erowid Tetrahydroharmine - TiHKAL - Erowid Tetrahydroharmine - TiHKAL - Isomer Design