L-THP

L-THP (levo-tetrahydropalmatine, also written l-tetrahydropalmatine) is a tetrahydroprotoberberine isoquinoline alkaloid found in Corydalis and Stephania plants and in many traditional Chinese herbal preparations (Mantsch et al., 2007; Du et al., 2022).

In the 1990s, Jin Bu Huan tablets containing it were linked to poisoning in children and hepatitis in adults (Horowitz et al., 1996).

PubChem CID 72301, the (-)-tetrahydropalmatine record, lists the same CAS number, formula and weight and is the source of the aliases and structure. PubChem files the name rotundine under CID 5417, a record with undefined stereochemistry that covers racemic tetrahydropalmatine (CAS 2934-97-6), while the literature uses Rotundine for the levo form (Wang and Mantsch, 2012).

Published work on L-THP falls into six areas. Each summary below states the model used. Most data come from rodents; human data include two NIDA-funded studies, a small pharmacokinetic study in healthy volunteers (Chao-Wu et al., 2011), case reports and poisoning series.

Dopamine receptor pharmacology

In brain receptor binding assays, levo tetrahydroprotoberberines acted as dopamine receptor antagonists with a preference for D1; L-THP was an antagonist, while its mirror image, d-THP, showed no D2 affinity (Xu et al., 1989). A NIDA-funded group reported that L-THP is a higher-affinity D1 antagonist and a low-affinity D2 antagonist that also interacts with D3 receptors (Mantsch et al., 2007); a review adds actions at alpha-adrenergic and serotonin receptors (Wang and Mantsch, 2012).

In the rat striatum it raised extracellular dopamine, which the authors read as blockade of presynaptic and postsynaptic receptors (Marcenac et al., 1986). One mouse study instead describes partial agonism at D1 (Liu et al., 2019). Models: binding assays, rat striatum and mice.

Pain models in rodents

In the rat tail-flick test, the analgesic effect of L-THP at 40 mg/kg disappeared after lesions of the hypothalamic arcuate nucleus, and naloxone given into the periaqueductal gray reduced it, implicating arcuate beta-endorphin neurons (Hu and Jin, 2000). In mice with partial sciatic nerve ligation, 5 and 10 mg/kg raised mechanical thresholds by 134 and 175 percent and lengthened thermal latency. A D1 antagonist or a D2 agonist prevented this effect (Liu et al., 2019). Models: rats and mice.

Sedation and EEG sleep measures in rodents

A 1986 paper called L-THP a Chinese neuroleptic and noted sedation in rats and mice at 5 to 10 mg/kg (Marcenac et al., 1986). In the nerve-injured mice above, it increased EEG-scored non-rapid eye movement sleep by 18 and 30 percent, an effect the D2 agonist quinpirole blocked (Liu et al., 2019). In rats, 10 mg/kg but not 1 to 3 mg/kg suppressed locomotion and sucrose self-administration (Xi et al., 2007). Models: rats and mice.

Cocaine self-administration studies supported by NIDA

PubMed grant records list US National Institute on Drug Abuse (NIDA) support for all three studies below. In rats responding for cocaine and food on separate levers, 3.75 to 15 mg/kg shifted the cocaine response curve rightward and downward and blunted cocaine-induced reinstatement; cocaine intake fell at amounts that left food responding unchanged, although L-THP also reduced food responding and locomotion (Mantsch et al., 2007).

At NIDA's intramural program, low amounts reduced progressive-ratio cocaine responding and cocaine-enhanced brain-stimulation reward but raised fixed-ratio intake, which the authors read as compensation for weaker reward (Xi et al., 2007). Given by oral gavage, 3 mg/kg reduced reinstatement triggered by cocaine, footshock stress or drug-paired cues without lowering food responding (Figueroa-Guzman et al., 2011). Models: rats.

Opioid studies and human research

In rats, 2.5 and 5 mg/kg lowered heroin self-administration, and 1.25 to 5 mg/kg reduced heroin-primed reinstatement (Yue et al., 2012). In a NIDA-supported pilot trial from China, 120 heroin-dependent participants were randomized, double-blind, to L-THP or placebo for 4 weeks on an inpatient ward. L-THP lowered protracted withdrawal ratings, including craving; among participants who stayed past the first 2 weeks, 47.8 percent were abstinent at the 3-month follow-up against 15.2 percent on placebo (Yang et al., 2008).

In a NIDA-funded laboratory study, 24 men who used cocaine received oral L-THP or placebo twice daily for 4 days, double-blind, with an intranasal cocaine challenge on day 4. L-THP did not change cocaine's pharmacokinetics or cardiovascular effects, and side-effect counts were similar (Hassan et al., 2017). Models: rats and human studies.

Jin Bu Huan, liver injury and poisoning reports

A Denver poison center described three children with life-threatening neurologic and cardiovascular effects after one ingestion of Jin Bu Huan Anodyne Tablets, and three adults with hepatitis after long-term use. The tablets contained L-THP, and the package misidentified their ingredients (Horowitz et al., 1996). In seven previously healthy people, acute hepatitis appeared after a mean of 20 weeks of use and resolved in six; renewed use in two brought it back abruptly (Woolf et al., 1994).

LiverTox, the NIH liver-injury database, counts more than a dozen such cases and judges a contaminant of the products, rather than the Jin Bu Huan herb itself, the likely cause; a letter it cites argued that the contaminant was a plant rich in L-THP (LiverTox, 2018).

In Vietnam, where the authors say rotundine is widely used over the counter, a hospital reviewed 37 acute rotundine poisonings: central nervous system depression dominated, 16 percent showed QTc prolongation, four people needed mechanical ventilation, and none died (Duc et al., 2026). Models: case reports, case series and a poisoning study.