L‑THP
Corydalis alkaloid anxiolytic and dopamine D1/D2 antagonist with a sedative and analgesic profile.
Pharmacology
Contents
WHAT IS L-THP?
Detailed overview
L-THP (levo-tetrahydropalmatine, rotundine) is an isoquinoline alkaloid derived from Corydalis yanhusuo and Stephania rotunda, used for decades in traditional Chinese medicine as a sedative and pain reliever. Its primary mechanism is antagonism of dopamine D1 and D2 receptors, accompanied by D3 modulation, alpha4beta2 nicotinic inhibition and serotonergic activity; by lowering rewarding dopamine signaling it produces anxiolytic, sedative and analgesic effects. In preclinical studies it reduced the self-administration and rewarding effects of cocaine, nicotine, methamphetamine and morphine, making it a promising candidate for stimulant and opioid addiction research. In humans, a randomized, placebo-controlled study confirmed its pharmacokinetics and good tolerability in cocaine users, though efficacy testing is still at an early stage.
Mechanism
Dopamine D1/D2 antagonist (+ D3, nicotinic, 5-HT)
Evidence
Human PK/safety RCT + robust preclinical
Legal status
Rx in China (Rotundine); supplement/research elsewhere
Receptor profile
- Dopamine D1 and D2 receptors (antagonist)Strong
- Dopamine D3 receptorsModerate
- Alpha4beta2 nicotinic acetylcholine receptorsModerate
- Serotonergic (5-HT) neuronal activityWeak
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Drowsiness, sedation and dizziness, especially at higher doses or daytime use
- Blood pressure reduction (hypotension) that may cause headache or lethargy
- Rare liver enzyme elevation; some case reports have described hepatotoxicity
- Additive sedative effect with other CNS depressants (alcohol, benzodiazepines, opioids)
- Theoretical extrapyramidal (movement) risk with prolonged use from dopamine D2 blockade
- Fatigue or next-day grogginess due to the sedative profile
Contraindications · 5
- Pregnancy and breastfeeding: safety not established, avoid
- Parkinson's disease or other movement disorders: dopamine D2 antagonism may worsen symptoms
- Avoid combining with alcohol, sedatives or other depressants due to additive sedation
- Liver disease: caution warranted due to rare hepatotoxicity reports
- Low blood pressure: the hypotensive effect may be amplified
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Pharmacokinetics and Safety Assessment of l-Tetrahydropalmatine in Cocaine Users: A Randomized, Double-Blind, Placebo-Controlled Study
Hassan HE, Kelly D, Honick M, Shukla S, Ibrahim A, Gorelick DA, Glassman M, McMahon RP, Wehring HJ, Kearns AM, Feldman S, Yu M, Bauer K, Wang JB
l-tetrahydropalmatine reduces nicotine self-administration and reinstatement in rats
Faison SL, Schindler CW, Goldberg SR, Wang JB
Dopamine D1 and D2 receptors mediate analgesic and hypnotic effects of l-tetrahydropalmatine in a mouse neuropathic pain model
Liu YY, Wang TX, Zhou JC, Qu WM, Huang ZL
L-tetrahydropalmatine inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal activity and dopamine D3 receptor expression
Yun J
Corydaline and l-tetrahydropalmatine attenuate morphine-induced conditioned place preference and the changes in dopamine D2 and GluA1 AMPA receptor expression in rats
Jiang WN, Jing X, Li M, Deng H, Jiang T, Xiong KZ, Chen Y, Wang XF, Wang QJ
Effect of l-tetrahydropalmatine on dopamine release and metabolism in the rat striatum
Marcenac F, Jin GZ, Gonon F
FAQ
FAQ
Corydalis alkaloid anxiolytic and dopamine D1/D2 antagonist with a sedative and analgesic profile.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.