Levo-tetrahydropalmatine (l-THP)

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Overview

Levo-tetrahydropalmatine, usually written l-THP, is an isoquinoline alkaloid found in plants of the Corydalis and Stephania genera. It is not a new compound. It has been approved and used in China for decades under the drug name Rotundine for several clinical indications, mainly as an analgesic with sedative and hypnotic effects (PMID: 22300097, PMID: 27606501). Outside China it is known in two very different contexts: as a candidate treatment for cocaine and opioid addiction, and as the active constituent of the herbal product Jin Bu Huan that caused a cluster of poisonings in the United States during the 1990s. Its pharmacology is dopamine receptor antagonism. Radioligand and behavioral work in rats found higher-affinity antagonism at D1 receptors, lower-affinity antagonism at D2 receptors and interaction with D3 receptors, and reviews add activity at alpha adrenergic and serotonin receptors (PMID: 17361394, PMID: 22300097). In C57BL/6J mice, treatment reduced voluntary ethanol drinking and altered D2 receptor-linked protein kinase A signaling in the caudate-putamen but not the nucleus accumbens (PMID: 23376703). The animal addiction work is consistent. In rats, l-THP shifted the cocaine self-administration dose-response curve down and to the right and reduced cocaine-induced reinstatement at doses that did not change food-reinforced responding (PMID: 17361394); reduced reinstatement triggered by cocaine, stress or drug-associated cues after oral administration (PMID: 21196089); reduced cocaine self-administration under a progressive ratio schedule (PMID: 20816889); and reduced nicotine self-administration and reinstatement (PMID: 27817750). Human work is real but small. A randomized, double-blind, placebo-controlled study gave 24 adult male cocaine users l-THP 30 mg twice daily or placebo for four days, with an intranasal cocaine challenge on the fourth day. The short course was safe and well tolerated, side effect counts matched placebo, and l-THP did not change cocaine exposure or its acute cardiovascular effects (PMID: 27363313). Registered work at the University of Maryland includes that Phase 1 study (NCT01631383), a completed 63-participant study in schizophrenia (NCT02118610) and a Phase 2 cocaine use disorder trial that was withdrawn before enrolment (NCT02139761). No adequately powered efficacy trial has been published. The safety record deserves weight. Jin Bu Huan Anodyne tablets, which contain l-THP and were mislabelled on the package as a Lycopodium product, caused acute hepatitis in seven previously healthy adults after a mean of 20 weeks of use, with recurrence on rechallenge in two of them (PMID: 7944049). A separate case series described life-threatening neurological and cardiovascular effects including coma in three young children after single acute ingestions, alongside hepatitis in three adults on long-term use (PMID: 8774209), and chronic hepatitis with moderate fibrosis has been reported after two months of use (PMID: 9537855). In human liver microsomes, tetrahydropalmatine is a mechanism-based inhibitor of CYP2D6 and is itself metabolized by CYP2C19, CYP3A4, CYP1A2 and CYP2D6, which makes interaction with CYP2D6 substrates a live concern (PMID: 41876357). l-THP has no FDA or EMA authorization. Capsules sold on the research chemical and supplement market are not the Chinese pharmaceutical product and are not made to a pharmacopoeial standard.

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Research Disclaimer

This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.

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Tracking since Sep 7, 2026 · 1 data point

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