L-Tetrahydropalmatine (L-THP) is a non-peptide isoquinoline alkaloid naturally occurring in Corydalis yanhusuo and Stephania rotunda. It acts as a mixed dopamine receptor antagonist with affinity for D1, D2, D3, serotonin 5-HT1A, and alpha-1 adrenergic receptors, and facilitates GABA-A receptor binding. One randomized controlled trial in schizophrenia found no efficacy on psychiatric symptoms and unexpectedly raised inflammatory markers. Widely sold by gray-market vendors as a research chemical labeled “not for human consumption.”
Mechanism of Action
L-THP acts as a mixed dopamine receptor antagonist, binding D1 (Ki ~124 nM), D2 (Ki ~388 nM), and D3 receptors (Ki ~1420 nM), with additional affinity for serotonin 5-HT1A receptors (Ki ~340 nM) and alpha-1 adrenergic receptors; it also facilitates GABA-A receptor binding. In vivo microdialysis in rats indicates predominantly postsynaptic (not presynaptic) dopamine receptor antagonism underlies its effects on drug reward. L-THP modestly elevates extracellular nucleus accumbens dopamine alone but dose-dependently potentiates cocaine-induced dopamine elevation while reducing cocaine’s rewarding effects, consistent with postsynaptic antagonism.
Research Summary
One completed randomized, double-blind, placebo-controlled trial (NCT02118610; 63 adults with schizophrenia, 60 mg/day L-THP vs placebo for 4 weeks) found no significant benefit on positive, negative, depressive, or global symptom measures. The trial did show reduced extrapyramidal symptoms (p<.001, possibly confounded by anticholinergic co-medication) but unexpectedly raised inflammatory markers (sICAM-1 p=.004, CRP p=.039) rather than lowering them as animal data had suggested. Preclinical studies in rats demonstrated dose-dependent reductions in methamphetamine self-administration and reinstatement (1.25–5.0 mg/kg IP), reduced cocaine self-administration breaking points and discrimination (1.875–7.5 mg/kg), and decreased voluntary ethanol drinking in mice (10 mg/kg) via D2-receptor-mediated PKA signaling in dorsal striatum, without affecting locomotor activity at lower doses.
Verified testing for L-Tetrahydropalmatine (L-THP)
Aggregated from 2 lab-verified Certificates of Analysis uploaded directly by labs. Purity averages exclude values outside [50%, 100%] to filter unit-misreads.
Unexpectedly raised inflammatory markers (sICAM-1, CRP) in the single human RCT, contrary to animal data
Theoretical risk of extrapyramidal effects/sedation as a dopamine antagonist (though RCT found reduced EPS vs placebo in medicated schizophrenia patients)
No long-term human safety data available
No data on use in pregnancy, hepatic/renal impairment, or drug-drug interactions
Generally well tolerated in 4-week trial with no significant excess adverse events vs placebo
Contraindications
Pregnancy and lactation (no human data)
Hepatic or renal impairment (no safety data)
Concurrent use with other dopamine antagonists or CNS depressants (no interaction data)
Unmedicated individuals seeking dopamine antagonism (safety data limited to patients already on antipsychotics)
(-)-Tetrahydropalmatine, PubChem Compound Summary for CID 72301.
L-Tetrahydropalamatine: A Potential New Medication for the Treatment of Cocaine Addiction. 2013.
Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement. 2016. PMID 26806555.
Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats. 2010. PMID 20816889.
Frequently asked questions
Has L-Tetrahydropalmatine (L-THP) been independently lab-tested?
Disclosed Labs has collected 2 Certificates of Analysis (COA) for L-Tetrahydropalmatine (L-THP) from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.1% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/l-thp/testing.
How does L-Tetrahydropalmatine (L-THP) work?
L-THP acts as a mixed dopamine receptor antagonist, binding D1 (Ki ~124 nM), D2 (Ki ~388 nM), and D3 receptors (Ki ~1420 nM), with additional affinity for serotonin 5-HT1A receptors (Ki ~340 nM) and alpha-1 adrenergic receptors; it also facilitates GABA-A receptor binding. In vivo microdialysis in rats indicates predominantly postsynaptic (not presynaptic) dopamine receptor antagonism underlies its effects on drug reward. L-THP modestly elevates extracellular nucleus accumbens dopamine alone but dose-dependently potentiates cocaine-induced dopamine elevation while reducing cocaine’s rewarding effects, consistent with postsynaptic antagonism.
What does the research say about L-Tetrahydropalmatine (L-THP)?
One completed randomized, double-blind, placebo-controlled trial (NCT02118610; 63 adults with schizophrenia, 60 mg/day L-THP vs placebo for 4 weeks) found no significant benefit on positive, negative, depressive, or global symptom measures. The trial did show reduced extrapyramidal symptoms (p<.001, possibly confounded by anticholinergic co-medication) but unexpectedly raised inflammatory markers (sICAM-1 p=.004, CRP p=.039) rather than lowering them as animal data had suggested. Preclinical studies in rats demonstrated dose-dependent reductions in methamphetamine self-administration and reinstatement (1.25–5.0 mg/kg IP), reduced cocaine self-administration breaking points and discrimination (1.875–7.5 mg/kg), and decreased voluntary ethanol drinking in mice (10 mg/kg) via D2-receptor-mediated PKA signaling in dorsal striatum, without affecting locomotor activity at lower doses.
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