L-tetrahydropalmatine

updated

L-tetrahydropalmatine (L-THP) is a plant alkaloid that a 2012 review says has been approved and used in China as Rotundine, with no US application or label found on 9 October 2026. Human data are a PK study in 12 men and two small randomized trials in drug dependence, in 120 heroin-dependent patients and 24 cocaine-using men. No trial of L-THP alone tested sleep, anxiety or pain, and product and overdose reports describe liver injury and life-threatening toxicity.

Dopamine receptor antagonist (alkaloid from Corydalis and Stephania species)

  • A 2012 review states that L-THP has been approved and used in China under the drug name Rotundine; that is a review statement, not a regulator record, and openFDA and DailyMed queries on 9 October 2026 returned no US application or label.
  • In a pilot trial in 120 heroin-dependent patients, 4 weeks of inpatient L-THP reduced withdrawal-syndrome severity versus placebo; 3-month abstinence was 47.8% versus 15.2% among participants who stayed past the first 2 weeks.
  • In 24 cocaine-using men, L-THP 30 mg twice a day for 4 days was safe and well tolerated and did not change cocaine PK or its acute cardiovascular effects.
  • Terminal half-life was 11.42 plus or minus 2.43 hours after a single 60 mg orally disintegrating tablet in 12 fasted healthy Chinese men.
  • No trial of L-THP alone for sleep, anxiety or pain was found; the one pain trial tested a 10-ingredient product.
  • In a Vietnamese series of 37 acute rotundine poisonings, 4 patients (10.8%) needed mechanical ventilation, and Jin Bu Huan products containing L-THP were tied to hepatitis and to toxicity in children.

What is L-tetrahydropalmatine, and is it approved?

L-THP is a plant alkaloid that a 2012 review says has been approved and used in China as Rotundine. openFDA and DailyMed queries on 9 October 2026 returned no US application or label.

Levo-tetrahydropalmatine is PubChem CID 72301, (13aS)-tetrahydropalmatine, C21H25NO4, 355.4 g/mol, CAS 483-14-7 (PubChem also lists 219697-24-2). Synonyms include (-)-tetrahydropalmatine, (-)-rotundine, gindarine, hyndarine and (-)-corydalis B.

The name rotundine on its own maps in PubChem to a different record, CID 5417, the racemate (D,L-tetrahydropalmatine, CAS 2934-97-6 and 10097-84-4), while the 2012 review and a Vietnamese case series use Rotundine for the L form. Some animal work used the racemate, and herbal products such as Jin Bu Huan tablets or corydalis preparations have L-THP content that the reports reviewed do not define. None of these is interchangeable with purified L-THP.

A 2012 review states that L-THP, a constituent of Stephania and Corydalis species, has been approved and used in China for a number of clinical indications under the drug name Rotundine, and discusses the hurdles to a US FDA approval. That is a review statement, not a Chinese regulator record. In the US, openFDA Drugs@FDA queries for tetrahydropalmatine and for rotundine returned no application, and DailyMed returned no label under either name, on 9 October 2026. The Vietnamese authors state that rotundine is widely used there as an over-the-counter sedative and sleep aid; that is also an author statement, not a regulator record.

PubChem: L-THP identity, with the racemate listed separately

Chemical identity record

National Library of Medicine. PubChem compound record CID 72301 (levo-tetrahydropalmatine, (13aS)-tetrahydropalmatine); racemate CID 5417.

Levo-tetrahydropalmatine is PubChem CID 72301, (13aS)-tetrahydropalmatine, C21H25NO4, 355.4 g/mol, CAS 483-14-7 (PubChem also lists 219697-24-2); synonyms include (-)-tetrahydropalmatine, (-)-rotundine, gindarine, hyndarine, and (-)-corydalis B. The name rotundine on its own maps in PubChem to a different record, CID 5417, the racemate (D,L-tetrahydropalmatine, CAS 2934-97-6 and 10097-84-4).

Participants / model
Chemical identity, not a clinical population
Treatment
Defined L isomer; racemate listed separately
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only. Some animal work used the racemate, and herbal products such as Jin Bu Huan tablets or corydalis preparations have L-THP content that the reports reviewed do not define; none of these is interchangeable with purified L-THP.

Read the original source
2012 review: used in China as Rotundine; D1 and D2 antagonism

Human study

Wang JB et al. Future Med Chem. 2012;4(2):177-86. PMID 22300097.

A 2012 review states that L-THP, a constituent of Stephania and Corydalis species, has been approved and used in China for a number of clinical indications under the drug name Rotundine, and discusses the hurdles to a US FDA approval. It describes the pharmacology as antagonism of dopamine D1 and D2 receptors plus actions at D3, alpha-adrenergic, and serotonin receptors. In the US, openFDA Drugs@FDA queries for tetrahydropalmatine and for rotundine returned no application, and DailyMed returned no label under either name, on 9 October 2026.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Narrative review of pharmacology and regulatory status, with dated openFDA and DailyMed queries
Funding
not stated in the source

This is a review statement, not a Chinese regulator record. The US database queries are dated and US-scoped.

Read the original source
Rotundine overdose in Vietnam: 37 patients, 4 ventilated, no deaths

Human study

Duc ND et al. Toxicol Rep. 2026;17:102312. PMID 42519822.

Central nervous system depression predominated. Severe impairment of consciousness (GCS below 8) occurred in 5.4%, QTc prolongation (440 ms or more) in 16.2%, and 4 patients (10.8%) needed mechanical ventilation and intensive care. No one died. An admission GCS of 12 or less predicted ventilation (sensitivity 100%, specificity 97.0%).

Participants / model
37 consecutive patients with acute rotundine poisoning in Vietnam (April 2024 to June 2026; median age 27, 56.8% female)
Treatment
Acute rotundine poisoning (route and amounts not stated in the abstract)
Follow-up
April 2024 to June 2026
Study design
Retrospective observational case series
Funding
not stated in the source

The authors state that rotundine (L-THP) is widely used in Vietnam as an over-the-counter sedative and sleep aid; that is an author statement, not a regulator record.

Read the original source

What did the trials of L-THP in people find?

A pilot trial in 120 heroin-dependent patients found milder protracted withdrawal syndrome than placebo, and a 24-man cocaine study found L-THP safe and well tolerated. Neither tested sleep, anxiety or pain in healthy people.

In a randomized, double-blind, placebo-controlled pilot trial in 120 heroin-dependent patients, 4 weeks of inpatient L-THP reduced the severity of protracted abstinence withdrawal syndrome versus placebo, including somatic symptoms, mood, insomnia and craving. At 3-month follow-up, among participants who stayed through the first 2 weeks of medication and remained in the program, abstinence was 47.8% (95% CI 33% to 67%) versus 15.2% (7% to 25%) on placebo (log-rank P below 0.0005). The abstract gives no dose, and the abstinence comparison excludes early dropouts.

In 24 cocaine-using men randomized to L-THP 30 mg orally twice a day or placebo for 4 days, with a 40 mg intranasal cocaine challenge on day 4, L-THP was safe and well tolerated and did not affect cocaine PK or its acute cardiovascular effects (cocaine AUC 211.5 versus 261.4 h.ng/mL and Cmax 83.3 versus 104.5 ng/mL, L-THP versus placebo). Side-effect reports did not differ significantly (22 [48%] versus 24 [52%]), and 20 men completed. This is a short safety and interaction study, not an efficacy trial.

The registry separately lists a completed phase 1 L-THP study with cocaine exposure (NCT01631383, enrollment 20, no posted results) and a phase 2 L-THP trial for cocaine use disorder that was withdrawn with enrollment 0 (NCT02139761).

Heroin pilot: 120 patients, 4 weeks inpatient, abstinence at 3 months

Randomized controlled trial

Yang Z et al. Acta Pharmacol Sin. 2008;29(7):781-8. PMID 18565275.

L-THP reduced the severity of protracted abstinence withdrawal syndrome versus placebo, including somatic symptoms, mood, insomnia, and craving. At 3-month follow-up, among participants who stayed through the first 2 weeks of medication and remained in the program, abstinence was 47.8% (95% CI 33% to 67%) versus 15.2% (7% to 25%) on placebo (log-rank P below 0.0005).

Participants / model
120 heroin-dependent patients
Treatment
L-THP for 4 weeks as inpatients (route and dose not stated in the abstract), or placebo
Follow-up
4 weeks of treatment, follow-up to 3 months
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

The abstinence comparison excludes early dropouts. The insomnia result is a withdrawal-syndrome subscale in heroin users, not evidence for sleep in healthy people.

Read the original source
Cocaine safety study: 24 men, 4 days, cocaine challenge

Randomized controlled trial

Hassan HE et al. J Clin Pharmacol. 2017;57(2):151-160. PMID 27363313.

L-THP was safe and well tolerated and did not affect cocaine PK or its acute cardiovascular effects (cocaine AUC 211.5 versus 261.4 h.ng/mL and Cmax 83.3 versus 104.5 ng/mL, L-THP versus placebo). Side-effect reports did not differ significantly (22 [48%] versus 24 [52%]). 20 men completed.

Participants / model
24 adult men who use cocaine (20 completers)
Treatment
Oral L-THP 30 mg twice a day or placebo for 4 days, with an intranasal cocaine 40 mg challenge on day 4
Follow-up
4 days
Study design
Randomized trial of safety, cocaine PK and cardiovascular effects
Funding
not stated in the source

This is a short safety and interaction study, not an efficacy trial. The registry separately lists a completed phase 1 L-THP study with cocaine exposure (NCT01631383, enrollment 20, no posted results) and a phase 2 L-THP trial for cocaine use disorder that was withdrawn with enrollment 0 (NCT02139761).

Read the original source

Does L-THP improve sleep, anxiety or pain?

Sleep, anxiety and pain effects are shown in rodents. In people they appear only through a withdrawal-syndrome subscale in heroin users, a review of capsule studies whose designs need improving, and a 10-ingredient product, and no trial of L-THP alone tested them.

Sellers describe L-THP as giving better sleep, less anxiety and pain relief, and as protecting against dopamine receptor downregulation during stimulant use. The dopamine point has its own section below.

On pain, a PubMed search on 9 October 2026 for tetrahydropalmatine, rotundine or l-THP with pain or analgesia, limited to human studies (36 records, reviewed by title), found no trial of L-THP alone. The one pain trial tested a 10-ingredient product (vitamins B6, B12 and D, white willow bark extract, angelica root extract, acetyl L-carnitine, caffeine, L-theanine, benfotiamine and L-THP). In a three-period crossover in 27 healthy adults aged 22 to 63 with non-pathological aches, 7 days of the product lowered worst-pain scores more than acetaminophen (21.8% versus 9.8% decrease, p=0.026). The design cannot isolate any effect of L-THP. In mice with neuropathic pain from partial sciatic nerve ligation, intraperitoneal L-THP at 5 and 10 mg/kg raised the mechanical threshold by 134.4% and 174.8% and lengthened thermal latency by 49.4% and 69.2% compared with vehicle.

On sleep, a review of post-marketing clinical studies of Fufang Zaoren capsule, a marketed Chinese capsule that the abstract says contains L-THP, concluded that it has some therapeutic effect for insomnia but that the study designs need improving. In the mouse nerve-injury study, 5 and 10 mg/kg increased non-rapid eye movement sleep by 17.5% and 29.6% with less sleep fragmentation. That is sleep in mice in pain, not sleep in people. The heroin trial's insomnia result is a withdrawal-syndrome subscale in heroin users, not evidence for sleep in healthy people.

On anxiety, male rats given L-THP intraperitoneally before single prolonged stress on 8 consecutive days showed, at 50 mg/kg, more open-arm visits and a lower anxiety index in the elevated plus maze, more center time in the open field, less immobility in the forced swim test, and no stress-related fall in hypothalamic NPY or rise in CRF. A PubMed search on 9 October 2026 for tetrahydropalmatine, rotundine or l-THP with anxiety, anxiolytic, insomnia, sleep or hypnotic returned 40 records, and by title none was a human anxiety trial.

Pain product crossover: 27 adults, 10 ingredients, L-THP not isolated

Randomized controlled trial

Evans M et al. Nutrients. 2020;12(6). PMID 32575480.

In a three-period crossover in 27 healthy adults with non-pathological aches, 7 days of the product lowered worst-pain scores more than acetaminophen (21.8% versus 9.8% decrease, p=0.026). The product contained 10 ingredients: vitamins B6, B12 and D, white willow bark extract, angelica root extract, acetyl L-carnitine, caffeine, L-theanine, benfotiamine and L-THP.

Participants / model
27 healthy adults aged 22 to 63 with unresolved, non-pathological aches
Treatment
Oral multi-ingredient product (Pain Bloc-R), 7 days per period
Follow-up
7 days per period
Study design
Three-period randomized crossover; Brief Pain Inventory and musculoskeletal discomfort
Funding
not stated in the source

The design cannot isolate any effect of L-THP. A PubMed search on 9 October 2026 for tetrahydropalmatine, rotundine or l-THP with pain or analgesia, limited to human studies (36 records, reviewed by title), found no trial of L-THP alone for pain.

Read the original source
Capsule review: some effect for insomnia, adverse reactions, design needs improving

Human study

Qing S et al. Zhongguo Zhong Yao Za Zhi. 2013;38(21):3790-4. PMID 24494575.

A review of post-marketing clinical studies of Fufang Zaoren capsule, a marketed Chinese capsule that the abstract says contains L-THP, concluded that it has some therapeutic effect for insomnia but that the study designs need improving. At recommended doses it caused adverse reactions including chills, fever, dizziness, nausea, shortness of breath, chest tightness, and palpitations, and high doses can cause delayed extrapyramidal symptoms. The abstract also reports that a Health Canada web notice linked the L-THP in this capsule to liver damage in pregnant women.

Participants / model
Patients in post-marketing clinical studies (populations not specified in the abstract)
Treatment
Oral capsule containing L-THP (other contents not given in the abstract)
Follow-up
not stated in the source
Study design
Review of post-marketing studies (English abstract only)
Funding
not stated in the source

Authors include staff of an adverse drug reaction monitoring center and of the China Food and Drug Administration's Center for Drug Reevaluation. Only the English abstract of this Chinese-language article was read, and the Health Canada notice is not described here.

Read the original source
Mice with nerve injury: pain relief and more non-REM sleep

Animal study

Liu YY et al. Psychopharmacology (Berl). 2019;236(11):3169-3182. PMID 31172225.

In mice with neuropathic pain from partial sciatic nerve ligation, intraperitoneal L-THP at 5 and 10 mg/kg raised the mechanical threshold by 134.4% and 174.8%, lengthened thermal latency by 49.4% and 69.2%, and increased non-rapid eye movement sleep by 17.5% and 29.6% with less sleep fragmentation, compared with vehicle. A D1 antagonist or a D2 agonist blocked the pain effect and the D2 agonist blocked the sleep effect, so the authors attribute pain relief to D1 agonism plus D2 antagonism and sleep to D2 antagonism.

Participants / model
Mice with experimental neuropathic pain
Treatment
Intraperitoneal L-THP 5 and 10 mg/kg
Follow-up
not stated in the source
Study design
Preclinical study of mechanical allodynia, thermal hyperalgesia and EEG sleep
Funding
not stated in the source

The authors state that L-THP has been used clinically in China for decades as an analgesic with sedative and hypnotic properties. This is sleep in mice in pain, not sleep in people. Its D1 account differs from the review's D1 antagonism.

Read the original source
Stressed rats: anxiety-like behavior reduced at 50 mg/kg

Animal study

Lee B et al. Biomol Ther (Seoul). 2014;22(3):213-22. PMID 25009702.

In male rats given L-THP intraperitoneally 30 minutes before single prolonged stress on 8 consecutive days, 50 mg/kg increased the number and duration of open-arm visits in the elevated plus maze and lowered the anxiety index, increased center time in the open field, reduced immobility in the forced swim test, and blocked the stress-related fall in hypothalamic NPY and rise in CRF.

Participants / model
Male rats in a single prolonged stress model
Treatment
Intraperitoneal L-THP, daily for 8 days
Follow-up
8 consecutive days
Study design
Preclinical study of elevated plus maze, open field, forced swim, and hypothalamic NPY and CRF
Funding
not stated in the source

A PubMed search on 9 October 2026 for tetrahydropalmatine, rotundine or l-THP with anxiety, anxiolytic, insomnia, sleep or hypnotic returned 40 records; by title, none was a human anxiety trial.

Read the original source
Heroin pilot: 120 patients, 4 weeks inpatient, abstinence at 3 months

Randomized controlled trial

Yang Z et al. Acta Pharmacol Sin. 2008;29(7):781-8. PMID 18565275.

L-THP reduced the severity of protracted abstinence withdrawal syndrome versus placebo, including somatic symptoms, mood, insomnia, and craving. At 3-month follow-up, among participants who stayed through the first 2 weeks of medication and remained in the program, abstinence was 47.8% (95% CI 33% to 67%) versus 15.2% (7% to 25%) on placebo (log-rank P below 0.0005).

Participants / model
120 heroin-dependent patients
Treatment
L-THP for 4 weeks as inpatients (route and dose not stated in the abstract), or placebo
Follow-up
4 weeks of treatment, follow-up to 3 months
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

The abstinence comparison excludes early dropouts. The insomnia result is a withdrawal-syndrome subscale in heroin users, not evidence for sleep in healthy people.

Read the original source

Does L-THP protect dopamine receptors during stimulant use?

No human study tests it. The closest result is one acute rat experiment on D3 receptor mRNA with methamphetamine, plus an opioid study, and a search for human dopamine receptor imaging returned 0 records.

The closest test of the dopamine claim is a rat study. In rats pretreated with L-THP (10 and 15 mg/kg) before an acute methamphetamine injection, L-THP reduced methamphetamine hyperlocomotion and attenuated the methamphetamine-induced fall in striatal dopamine D3 receptor mRNA, and in mice it reduced serotonin-induced head twitch and dopamine-driven climbing. This is one acute exposure, messenger RNA rather than receptor protein or binding, and the D3 receptor rather than D1 or D2, in rats.

No human study of dopamine receptor levels with L-THP was found: a PubMed search on 9 October 2026 for tetrahydropalmatine or rotundine with PET, positron, SPECT, occupancy, receptor availability or raclopride returned 0 records.

A second rat study used an opioid, not a stimulant. Repeated morphine reduced dopamine D2 receptor protein in the prefrontal cortex, hippocampus and striatum and raised striatal GluA1, and pretreatment with intraperitoneal L-THP at 1.25, 2.5 or 5 mg/kg blocked both changes and inhibited morphine conditioned place preference, without producing preference or aversion on its own.

In people, the only stimulant study is the 24-man cocaine safety and interaction study, which did not measure dopamine receptors or any efficacy outcome.

Rats and mice: acute methamphetamine, D3 receptor mRNA

Animal study

Yun J. Phytomedicine. 2014;21(11):1287-91. PMID 25172791.

In rats pretreated with L-THP (10 and 15 mg/kg) before an acute methamphetamine injection, L-THP reduced methamphetamine hyperlocomotion and attenuated the methamphetamine-induced fall in striatal dopamine D3 receptor mRNA; in mice it reduced serotonin-induced head twitch and dopamine-driven climbing.

Participants / model
Rats (locomotion, striatal mRNA); mice (head twitch, climbing)
Treatment
L-THP 10 and 15 mg/kg pretreatment (route not stated in the abstract); single methamphetamine injection
Follow-up
Single acute exposure
Study design
Preclinical study of locomotor activity, striatal dopamine receptor mRNA, head twitch and climbing
Funding
not stated in the source

This is one acute exposure, messenger RNA rather than receptor protein or binding, and the D3 receptor rather than D1 or D2, in rats. A PubMed search on 9 October 2026 for tetrahydropalmatine or rotundine with PET, positron, SPECT, occupancy, receptor availability or raclopride returned 0 records.

Read the original source
Morphine rats: D2 receptor protein and place preference

Animal study

Jiang WN et al. Eur J Pharmacol. 2020;884:173397. PMID 32717192.

In rats, repeated morphine reduced dopamine D2 receptor protein in the prefrontal cortex, hippocampus, and striatum and raised striatal GluA1; pretreatment with intraperitoneal L-THP at 1.25, 2.5, or 5 mg/kg blocked both changes and inhibited the acquisition and expression of morphine conditioned place preference, without producing preference or aversion on its own.

Participants / model
Rats given repeated morphine
Treatment
Intraperitoneal L-THP 1.25 to 5 mg/kg before morphine
Follow-up
not stated in the source
Study design
Preclinical study of conditioned place preference and D2, GluA1 and GluA2 receptor protein
Funding
not stated in the source

The drug of exposure here is an opioid, not a stimulant.

Read the original source
Cocaine safety study: 24 men, 4 days, cocaine challenge

Randomized controlled trial

Hassan HE et al. J Clin Pharmacol. 2017;57(2):151-160. PMID 27363313.

L-THP was safe and well tolerated and did not affect cocaine PK or its acute cardiovascular effects (cocaine AUC 211.5 versus 261.4 h.ng/mL and Cmax 83.3 versus 104.5 ng/mL, L-THP versus placebo). Side-effect reports did not differ significantly (22 [48%] versus 24 [52%]). 20 men completed.

Participants / model
24 adult men who use cocaine (20 completers)
Treatment
Oral L-THP 30 mg twice a day or placebo for 4 days, with an intranasal cocaine 40 mg challenge on day 4
Follow-up
4 days
Study design
Randomized trial of safety, cocaine PK and cardiovascular effects
Funding
not stated in the source

This is a short safety and interaction study, not an efficacy trial. The registry separately lists a completed phase 1 L-THP study with cocaine exposure (NCT01631383, enrollment 20, no posted results) and a phase 2 L-THP trial for cocaine use disorder that was withdrawn with enrollment 0 (NCT02139761).

Read the original source

How does L-THP work, and what does the body do with it?

A 2012 review describes antagonism of dopamine D1 and D2 receptors plus actions at D3, alpha-adrenergic and serotonin receptors. After a single 60 mg tablet in 12 healthy men, terminal half-life was 11.42 plus or minus 2.43 hours.

A 2012 review describes the pharmacology of L-THP as antagonism of dopamine D1 and D2 receptors plus actions at D3, alpha-adrenergic and serotonin receptors. The sources describe the D1 action differently: a mouse study attributes pain relief to D1 agonism plus D2 antagonism and sleep to D2 antagonism.

After a single 60 mg orally disintegrating tablet in 12 fasted healthy Chinese men, L-THP was absorbed quickly (absorption half-life 0.5 plus or minus 0.054 hours), distributed fast (distribution half-life 0.74 plus or minus 0.088 hours) and eliminated with a terminal half-life of 11.42 plus or minus 2.43 hours, with V1/F of 133.30 plus or minus 30.78 L in a two-compartment model. The tablets were reported as well tolerated. Tmax is not given in the sources reviewed, and this is one small study with one formulation.

2012 review: used in China as Rotundine; D1 and D2 antagonism

Human study

Wang JB et al. Future Med Chem. 2012;4(2):177-86. PMID 22300097.

A 2012 review states that L-THP, a constituent of Stephania and Corydalis species, has been approved and used in China for a number of clinical indications under the drug name Rotundine, and discusses the hurdles to a US FDA approval. It describes the pharmacology as antagonism of dopamine D1 and D2 receptors plus actions at D3, alpha-adrenergic, and serotonin receptors. In the US, openFDA Drugs@FDA queries for tetrahydropalmatine and for rotundine returned no application, and DailyMed returned no label under either name, on 9 October 2026.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Narrative review of pharmacology and regulatory status, with dated openFDA and DailyMed queries
Funding
not stated in the source

This is a review statement, not a Chinese regulator record. The US database queries are dated and US-scoped.

Read the original source
Mice with nerve injury: pain relief and more non-REM sleep

Animal study

Liu YY et al. Psychopharmacology (Berl). 2019;236(11):3169-3182. PMID 31172225.

In mice with neuropathic pain from partial sciatic nerve ligation, intraperitoneal L-THP at 5 and 10 mg/kg raised the mechanical threshold by 134.4% and 174.8%, lengthened thermal latency by 49.4% and 69.2%, and increased non-rapid eye movement sleep by 17.5% and 29.6% with less sleep fragmentation, compared with vehicle. A D1 antagonist or a D2 agonist blocked the pain effect and the D2 agonist blocked the sleep effect, so the authors attribute pain relief to D1 agonism plus D2 antagonism and sleep to D2 antagonism.

Participants / model
Mice with experimental neuropathic pain
Treatment
Intraperitoneal L-THP 5 and 10 mg/kg
Follow-up
not stated in the source
Study design
Preclinical study of mechanical allodynia, thermal hyperalgesia and EEG sleep
Funding
not stated in the source

The authors state that L-THP has been used clinically in China for decades as an analgesic with sedative and hypnotic properties. This is sleep in mice in pain, not sleep in people. Its D1 account differs from the review's D1 antagonism.

Read the original source
PK: 12 healthy Chinese men, terminal half-life 11.42 hours

Human study

Chao-Wu L et al. Eur J Drug Metab Pharmacokinet. 2011;36(4):257-62. PMID 21633914.

After a single 60 mg orally disintegrating tablet in 12 fasted healthy Chinese men, L-THP was absorbed quickly (absorption half-life 0.5 plus or minus 0.054 hours), distributed fast (distribution half-life 0.74 plus or minus 0.088 hours), and eliminated with a terminal half-life of 11.42 plus or minus 2.43 hours, with V1/F of 133.30 plus or minus 30.78 L in a two-compartment model. The tablets were reported as well tolerated.

Participants / model
12 healthy Chinese men
Treatment
Single oral 60 mg L-THP orally disintegrating tablet, fasted
Follow-up
Single dose
Study design
Plasma pharmacokinetic study
Funding
not stated in the source

One small study in men of one ethnicity with one formulation. Tmax is not given in the sources reviewed.

Read the original source

What risks do the studies and case reports show?

In a Vietnamese series of 37 rotundine poisonings, 4 patients (10.8%) needed mechanical ventilation and none died. A Chinese capsule review reports adverse reactions at recommended doses and delayed extrapyramidal symptoms at high doses, and the human trials were small.

In a retrospective series of 37 consecutive patients with acute rotundine poisoning at a poison control department in Vietnam (April 2024 to June 2026; median age 27, 56.8% female), central nervous system depression predominated. Severe impairment of consciousness (GCS below 8) occurred in 5.4%, QTc prolongation (440 ms or more) in 16.2%, and 4 patients (10.8%) needed mechanical ventilation and intensive care. No one died. An admission GCS of 12 or less predicted ventilation (sensitivity 100%, specificity 97.0%).

The review of post-marketing studies of Fufang Zaoren capsule, which the abstract says contains L-THP, reports that at recommended doses it caused adverse reactions including chills, fever, dizziness, nausea, shortness of breath, chest tightness and palpitations, and that high doses can cause delayed extrapyramidal symptoms. The abstract also reports that a Health Canada web notice linked the L-THP in this capsule to liver damage in pregnant women. That notice is not described here, and only the English abstract of the Chinese-language review was read.

In the controlled studies, L-THP was reported as well tolerated in 12 healthy men after a single 60 mg tablet, and safe and well tolerated in 24 cocaine-using men over 4 days, with side-effect reports not significantly different from placebo (22 [48%] versus 24 [52%]). Those studies were small and short.

Rotundine overdose in Vietnam: 37 patients, 4 ventilated, no deaths

Human study

Duc ND et al. Toxicol Rep. 2026;17:102312. PMID 42519822.

Central nervous system depression predominated. Severe impairment of consciousness (GCS below 8) occurred in 5.4%, QTc prolongation (440 ms or more) in 16.2%, and 4 patients (10.8%) needed mechanical ventilation and intensive care. No one died. An admission GCS of 12 or less predicted ventilation (sensitivity 100%, specificity 97.0%).

Participants / model
37 consecutive patients with acute rotundine poisoning in Vietnam (April 2024 to June 2026; median age 27, 56.8% female)
Treatment
Acute rotundine poisoning (route and amounts not stated in the abstract)
Follow-up
April 2024 to June 2026
Study design
Retrospective observational case series
Funding
not stated in the source

The authors state that rotundine (L-THP) is widely used in Vietnam as an over-the-counter sedative and sleep aid; that is an author statement, not a regulator record.

Read the original source
Capsule review: some effect for insomnia, adverse reactions, design needs improving

Human study

Qing S et al. Zhongguo Zhong Yao Za Zhi. 2013;38(21):3790-4. PMID 24494575.

A review of post-marketing clinical studies of Fufang Zaoren capsule, a marketed Chinese capsule that the abstract says contains L-THP, concluded that it has some therapeutic effect for insomnia but that the study designs need improving. At recommended doses it caused adverse reactions including chills, fever, dizziness, nausea, shortness of breath, chest tightness, and palpitations, and high doses can cause delayed extrapyramidal symptoms. The abstract also reports that a Health Canada web notice linked the L-THP in this capsule to liver damage in pregnant women.

Participants / model
Patients in post-marketing clinical studies (populations not specified in the abstract)
Treatment
Oral capsule containing L-THP (other contents not given in the abstract)
Follow-up
not stated in the source
Study design
Review of post-marketing studies (English abstract only)
Funding
not stated in the source

Authors include staff of an adverse drug reaction monitoring center and of the China Food and Drug Administration's Center for Drug Reevaluation. Only the English abstract of this Chinese-language article was read, and the Health Canada notice is not described here.

Read the original source
Cocaine safety study: 24 men, 4 days, cocaine challenge

Randomized controlled trial

Hassan HE et al. J Clin Pharmacol. 2017;57(2):151-160. PMID 27363313.

L-THP was safe and well tolerated and did not affect cocaine PK or its acute cardiovascular effects (cocaine AUC 211.5 versus 261.4 h.ng/mL and Cmax 83.3 versus 104.5 ng/mL, L-THP versus placebo). Side-effect reports did not differ significantly (22 [48%] versus 24 [52%]). 20 men completed.

Participants / model
24 adult men who use cocaine (20 completers)
Treatment
Oral L-THP 30 mg twice a day or placebo for 4 days, with an intranasal cocaine 40 mg challenge on day 4
Follow-up
4 days
Study design
Randomized trial of safety, cocaine PK and cardiovascular effects
Funding
not stated in the source

This is a short safety and interaction study, not an efficacy trial. The registry separately lists a completed phase 1 L-THP study with cocaine exposure (NCT01631383, enrollment 20, no posted results) and a phase 2 L-THP trial for cocaine use disorder that was withdrawn with enrollment 0 (NCT02139761).

Read the original source
PK: 12 healthy Chinese men, terminal half-life 11.42 hours

Human study

Chao-Wu L et al. Eur J Drug Metab Pharmacokinet. 2011;36(4):257-62. PMID 21633914.

After a single 60 mg orally disintegrating tablet in 12 fasted healthy Chinese men, L-THP was absorbed quickly (absorption half-life 0.5 plus or minus 0.054 hours), distributed fast (distribution half-life 0.74 plus or minus 0.088 hours), and eliminated with a terminal half-life of 11.42 plus or minus 2.43 hours, with V1/F of 133.30 plus or minus 30.78 L in a two-compartment model. The tablets were reported as well tolerated.

Participants / model
12 healthy Chinese men
Treatment
Single oral 60 mg L-THP orally disintegrating tablet, fasted
Follow-up
Single dose
Study design
Plasma pharmacokinetic study
Funding
not stated in the source

One small study in men of one ethnicity with one formulation. Tmax is not given in the sources reviewed.

Read the original source

What happened with Jin Bu Huan products that contain L-THP?

Jin Bu Huan Anodyne Tablets were tied to life-threatening toxicity in children and to hepatitis in adults, with recurrence on rechallenge in two. NIH LiverTox judges the liver injury likely due to a contaminant, so the reports do not settle whether purified L-THP injures the liver.

Jin Bu Huan Anodyne Tablets caused distinct syndromes in 3 children and 3 adults. A single acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular effects, while long-term use in adults was associated with hepatitis. The product contains levo-tetrahydropalmatine, and its package misidentified the constituents, which delayed identification of the responsible alkaloid. The authors cite the concentrated formulation, lack of childproof packaging, and an insert listing serious medical indications as contributing factors.

A separate series described 7 previously healthy patients who developed acute hepatitis after a mean of 20 weeks (range 7 to 52) of taking the tablets. It resolved in 6 within a mean of 8 weeks (range 2 to 30), and the seventh was improving. Symptoms and signs included fever, fatigue, nausea, pruritus, abdominal pain, jaundice and hepatomegaly. Lowering the dose improved liver tests in one patient, and taking the product again caused abrupt recurrence of hepatitis in two others. The abstract names the product's labeled botanical as Lycopodium serratum and does not mention L-THP.

The NIH LiverTox entry (updated 26 April 2018) describes Jin Bu Huan as a Chinese herb used as a mild sedative and analgesic and marketed for insomnia, pain and gastrointestinal complaints. Products were implicated in more than a dozen cases of idiosyncratic, clinically apparent acute liver injury, but LiverTox judges the hepatotoxicity likely due to a contaminant rather than Jin Bu Huan itself; the summary does not name the contaminant. These product reports therefore do not settle whether purified L-THP injures the liver.

Jin Bu Huan: 3 children and 3 adults, two distinct syndromes

Case report

Horowitz RS et al. Arch Intern Med. 1996;156(8):899-903. PMID 8774209.

Jin Bu Huan Anodyne Tablets caused distinct syndromes in 3 children and 3 adults: a single acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular effects, while long-term use in adults was associated with hepatitis. The product contains levo-tetrahydropalmatine, and its package misidentified the constituents, which delayed identification of the responsible alkaloid.

Participants / model
3 children after acute ingestion; 3 adults after long-term use
Treatment
Oral Jin Bu Huan Anodyne Tablets
Follow-up
Single acute ingestion in children; long-term use in adults
Study design
Case series
Funding
not stated in the source

The authors cite the concentrated formulation, lack of childproof packaging, and an insert listing serious medical indications as contributing factors. The product is a multi-constituent herbal tablet, not purified L-THP.

Read the original source
Jin Bu Huan hepatitis: 7 patients, recurrence on rechallenge in two

Case report

Woolf GM et al. Ann Intern Med. 1994;121(10):729-35. PMID 7944049.

Seven previously healthy patients developed acute hepatitis after a mean of 20 weeks (range 7 to 52) of taking Jin Bu Huan Anodyne Tablets; it resolved in 6 within a mean of 8 weeks (range 2 to 30), and the seventh was improving. Symptoms and signs included fever, fatigue, nausea, pruritus, abdominal pain, jaundice, and hepatomegaly. Lowering the dose improved liver tests in one patient, and taking the product again caused abrupt recurrence of hepatitis in two others.

Participants / model
7 previously healthy patients
Treatment
Oral Jin Bu Huan Anodyne Tablets, long-term
Follow-up
Mean 20 weeks (range 7 to 52) before hepatitis
Study design
Retrospective case series with liver histology and rechallenge
Funding
not stated in the source

The abstract names the product's labeled botanical as Lycopodium serratum and does not mention L-THP; a separate case series links the product to L-THP.

Read the original source
LiverTox: Jin Bu Huan liver injury likely due to a contaminant

Regulatory record

Jin Bu Huan. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643477.

The entry (updated 26 April 2018) describes Jin Bu Huan as a Chinese herb used as a mild sedative and analgesic and marketed for insomnia, pain, and gastrointestinal complaints. Jin Bu Huan products were implicated in more than a dozen cases of idiosyncratic, clinically apparent acute liver injury, but LiverTox judges the hepatotoxicity likely due to a contaminant rather than Jin Bu Huan itself; the summary does not name the contaminant.

Participants / model
People with liver injury after Jin Bu Huan products
Treatment
Oral Jin Bu Huan products
Follow-up
not stated in the source
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

These product reports do not settle whether purified L-THP injures the liver.

Read the original source

Why does L-THP sit in C tier?

L-THP has a reported record of medical use in China, human PK data and two small randomized trials in drug dependence. No trial of L-THP alone tested sleep, anxiety or pain, and product and overdose reports describe liver injury and life-threatening toxicity.

The C reflects a long reported record of medical use in China, human PK data, and two small randomized trials in drug dependence: a 120-patient heroin pilot with a positive abstinence result limited to participants who stayed past the first 2 weeks, and a 24-man cocaine safety study.

There is no trial of L-THP alone for sleep, anxiety or pain. The safety record holds the grade back: Jin Bu Huan products containing L-THP were tied to acute hepatitis with recurrence on rechallenge and to life-threatening neurologic and cardiovascular toxicity in children, although LiverTox attributes the liver injury most likely to a contaminant. Overdose of over-the-counter rotundine in Vietnam put 4 of 37 patients on mechanical ventilation, and a Chinese post-marketing review reports delayed extrapyramidal symptoms at high doses of an L-THP-containing capsule.

On the supplier's claims, sleep, anxiety and pain effects are shown in rodents, and in people only through a withdrawal-syndrome subscale in heroin users, a review of capsule studies whose designs need improving, and a 10-ingredient product. Protection against stimulant-related dopamine receptor downregulation rests on one acute rat mRNA result for the D3 receptor, plus an opioid study, with no human data.

2012 review: used in China as Rotundine; D1 and D2 antagonism

Human study

Wang JB et al. Future Med Chem. 2012;4(2):177-86. PMID 22300097.

A 2012 review states that L-THP, a constituent of Stephania and Corydalis species, has been approved and used in China for a number of clinical indications under the drug name Rotundine, and discusses the hurdles to a US FDA approval. It describes the pharmacology as antagonism of dopamine D1 and D2 receptors plus actions at D3, alpha-adrenergic, and serotonin receptors. In the US, openFDA Drugs@FDA queries for tetrahydropalmatine and for rotundine returned no application, and DailyMed returned no label under either name, on 9 October 2026.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Narrative review of pharmacology and regulatory status, with dated openFDA and DailyMed queries
Funding
not stated in the source

This is a review statement, not a Chinese regulator record. The US database queries are dated and US-scoped.

Read the original source
PK: 12 healthy Chinese men, terminal half-life 11.42 hours

Human study

Chao-Wu L et al. Eur J Drug Metab Pharmacokinet. 2011;36(4):257-62. PMID 21633914.

After a single 60 mg orally disintegrating tablet in 12 fasted healthy Chinese men, L-THP was absorbed quickly (absorption half-life 0.5 plus or minus 0.054 hours), distributed fast (distribution half-life 0.74 plus or minus 0.088 hours), and eliminated with a terminal half-life of 11.42 plus or minus 2.43 hours, with V1/F of 133.30 plus or minus 30.78 L in a two-compartment model. The tablets were reported as well tolerated.

Participants / model
12 healthy Chinese men
Treatment
Single oral 60 mg L-THP orally disintegrating tablet, fasted
Follow-up
Single dose
Study design
Plasma pharmacokinetic study
Funding
not stated in the source

One small study in men of one ethnicity with one formulation. Tmax is not given in the sources reviewed.

Read the original source
Heroin pilot: 120 patients, 4 weeks inpatient, abstinence at 3 months

Randomized controlled trial

Yang Z et al. Acta Pharmacol Sin. 2008;29(7):781-8. PMID 18565275.

L-THP reduced the severity of protracted abstinence withdrawal syndrome versus placebo, including somatic symptoms, mood, insomnia, and craving. At 3-month follow-up, among participants who stayed through the first 2 weeks of medication and remained in the program, abstinence was 47.8% (95% CI 33% to 67%) versus 15.2% (7% to 25%) on placebo (log-rank P below 0.0005).

Participants / model
120 heroin-dependent patients
Treatment
L-THP for 4 weeks as inpatients (route and dose not stated in the abstract), or placebo
Follow-up
4 weeks of treatment, follow-up to 3 months
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

The abstinence comparison excludes early dropouts. The insomnia result is a withdrawal-syndrome subscale in heroin users, not evidence for sleep in healthy people.

Read the original source
Cocaine safety study: 24 men, 4 days, cocaine challenge

Randomized controlled trial

Hassan HE et al. J Clin Pharmacol. 2017;57(2):151-160. PMID 27363313.

L-THP was safe and well tolerated and did not affect cocaine PK or its acute cardiovascular effects (cocaine AUC 211.5 versus 261.4 h.ng/mL and Cmax 83.3 versus 104.5 ng/mL, L-THP versus placebo). Side-effect reports did not differ significantly (22 [48%] versus 24 [52%]). 20 men completed.

Participants / model
24 adult men who use cocaine (20 completers)
Treatment
Oral L-THP 30 mg twice a day or placebo for 4 days, with an intranasal cocaine 40 mg challenge on day 4
Follow-up
4 days
Study design
Randomized trial of safety, cocaine PK and cardiovascular effects
Funding
not stated in the source

This is a short safety and interaction study, not an efficacy trial. The registry separately lists a completed phase 1 L-THP study with cocaine exposure (NCT01631383, enrollment 20, no posted results) and a phase 2 L-THP trial for cocaine use disorder that was withdrawn with enrollment 0 (NCT02139761).

Read the original source
Jin Bu Huan: 3 children and 3 adults, two distinct syndromes

Case report

Horowitz RS et al. Arch Intern Med. 1996;156(8):899-903. PMID 8774209.

Jin Bu Huan Anodyne Tablets caused distinct syndromes in 3 children and 3 adults: a single acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular effects, while long-term use in adults was associated with hepatitis. The product contains levo-tetrahydropalmatine, and its package misidentified the constituents, which delayed identification of the responsible alkaloid.

Participants / model
3 children after acute ingestion; 3 adults after long-term use
Treatment
Oral Jin Bu Huan Anodyne Tablets
Follow-up
Single acute ingestion in children; long-term use in adults
Study design
Case series
Funding
not stated in the source

The authors cite the concentrated formulation, lack of childproof packaging, and an insert listing serious medical indications as contributing factors. The product is a multi-constituent herbal tablet, not purified L-THP.

Read the original source
Jin Bu Huan hepatitis: 7 patients, recurrence on rechallenge in two

Case report

Woolf GM et al. Ann Intern Med. 1994;121(10):729-35. PMID 7944049.

Seven previously healthy patients developed acute hepatitis after a mean of 20 weeks (range 7 to 52) of taking Jin Bu Huan Anodyne Tablets; it resolved in 6 within a mean of 8 weeks (range 2 to 30), and the seventh was improving. Symptoms and signs included fever, fatigue, nausea, pruritus, abdominal pain, jaundice, and hepatomegaly. Lowering the dose improved liver tests in one patient, and taking the product again caused abrupt recurrence of hepatitis in two others.

Participants / model
7 previously healthy patients
Treatment
Oral Jin Bu Huan Anodyne Tablets, long-term
Follow-up
Mean 20 weeks (range 7 to 52) before hepatitis
Study design
Retrospective case series with liver histology and rechallenge
Funding
not stated in the source

The abstract names the product's labeled botanical as Lycopodium serratum and does not mention L-THP; a separate case series links the product to L-THP.

Read the original source
LiverTox: Jin Bu Huan liver injury likely due to a contaminant

Regulatory record

Jin Bu Huan. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643477.

The entry (updated 26 April 2018) describes Jin Bu Huan as a Chinese herb used as a mild sedative and analgesic and marketed for insomnia, pain, and gastrointestinal complaints. Jin Bu Huan products were implicated in more than a dozen cases of idiosyncratic, clinically apparent acute liver injury, but LiverTox judges the hepatotoxicity likely due to a contaminant rather than Jin Bu Huan itself; the summary does not name the contaminant.

Participants / model
People with liver injury after Jin Bu Huan products
Treatment
Oral Jin Bu Huan products
Follow-up
not stated in the source
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

These product reports do not settle whether purified L-THP injures the liver.

Read the original source
Rotundine overdose in Vietnam: 37 patients, 4 ventilated, no deaths

Human study

Duc ND et al. Toxicol Rep. 2026;17:102312. PMID 42519822.

Central nervous system depression predominated. Severe impairment of consciousness (GCS below 8) occurred in 5.4%, QTc prolongation (440 ms or more) in 16.2%, and 4 patients (10.8%) needed mechanical ventilation and intensive care. No one died. An admission GCS of 12 or less predicted ventilation (sensitivity 100%, specificity 97.0%).

Participants / model
37 consecutive patients with acute rotundine poisoning in Vietnam (April 2024 to June 2026; median age 27, 56.8% female)
Treatment
Acute rotundine poisoning (route and amounts not stated in the abstract)
Follow-up
April 2024 to June 2026
Study design
Retrospective observational case series
Funding
not stated in the source

The authors state that rotundine (L-THP) is widely used in Vietnam as an over-the-counter sedative and sleep aid; that is an author statement, not a regulator record.

Read the original source
Capsule review: some effect for insomnia, adverse reactions, design needs improving

Human study

Qing S et al. Zhongguo Zhong Yao Za Zhi. 2013;38(21):3790-4. PMID 24494575.

A review of post-marketing clinical studies of Fufang Zaoren capsule, a marketed Chinese capsule that the abstract says contains L-THP, concluded that it has some therapeutic effect for insomnia but that the study designs need improving. At recommended doses it caused adverse reactions including chills, fever, dizziness, nausea, shortness of breath, chest tightness, and palpitations, and high doses can cause delayed extrapyramidal symptoms. The abstract also reports that a Health Canada web notice linked the L-THP in this capsule to liver damage in pregnant women.

Participants / model
Patients in post-marketing clinical studies (populations not specified in the abstract)
Treatment
Oral capsule containing L-THP (other contents not given in the abstract)
Follow-up
not stated in the source
Study design
Review of post-marketing studies (English abstract only)
Funding
not stated in the source

Authors include staff of an adverse drug reaction monitoring center and of the China Food and Drug Administration's Center for Drug Reevaluation. Only the English abstract of this Chinese-language article was read, and the Health Canada notice is not described here.

Read the original source

Studies and sources

PubChem: L-THP identity, with the racemate listed separately

Chemical identity record

National Library of Medicine. PubChem compound record CID 72301 (levo-tetrahydropalmatine, (13aS)-tetrahydropalmatine); racemate CID 5417.

Levo-tetrahydropalmatine is PubChem CID 72301, (13aS)-tetrahydropalmatine, C21H25NO4, 355.4 g/mol, CAS 483-14-7 (PubChem also lists 219697-24-2); synonyms include (-)-tetrahydropalmatine, (-)-rotundine, gindarine, hyndarine, and (-)-corydalis B. The name rotundine on its own maps in PubChem to a different record, CID 5417, the racemate (D,L-tetrahydropalmatine, CAS 2934-97-6 and 10097-84-4).

Participants / model
Chemical identity, not a clinical population
Treatment
Defined L isomer; racemate listed separately
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only. Some animal work used the racemate, and herbal products such as Jin Bu Huan tablets or corydalis preparations have L-THP content that the reports reviewed do not define; none of these is interchangeable with purified L-THP.

Read the original source
2012 review: used in China as Rotundine; D1 and D2 antagonism

Human study

Wang JB et al. Future Med Chem. 2012;4(2):177-86. PMID 22300097.

A 2012 review states that L-THP, a constituent of Stephania and Corydalis species, has been approved and used in China for a number of clinical indications under the drug name Rotundine, and discusses the hurdles to a US FDA approval. It describes the pharmacology as antagonism of dopamine D1 and D2 receptors plus actions at D3, alpha-adrenergic, and serotonin receptors. In the US, openFDA Drugs@FDA queries for tetrahydropalmatine and for rotundine returned no application, and DailyMed returned no label under either name, on 9 October 2026.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Not applicable
Study design
Narrative review of pharmacology and regulatory status, with dated openFDA and DailyMed queries
Funding
not stated in the source

This is a review statement, not a Chinese regulator record. The US database queries are dated and US-scoped.

Read the original source
PK: 12 healthy Chinese men, terminal half-life 11.42 hours

Human study

Chao-Wu L et al. Eur J Drug Metab Pharmacokinet. 2011;36(4):257-62. PMID 21633914.

After a single 60 mg orally disintegrating tablet in 12 fasted healthy Chinese men, L-THP was absorbed quickly (absorption half-life 0.5 plus or minus 0.054 hours), distributed fast (distribution half-life 0.74 plus or minus 0.088 hours), and eliminated with a terminal half-life of 11.42 plus or minus 2.43 hours, with V1/F of 133.30 plus or minus 30.78 L in a two-compartment model. The tablets were reported as well tolerated.

Participants / model
12 healthy Chinese men
Treatment
Single oral 60 mg L-THP orally disintegrating tablet, fasted
Follow-up
Single dose
Study design
Plasma pharmacokinetic study
Funding
not stated in the source

One small study in men of one ethnicity with one formulation. Tmax is not given in the sources reviewed.

Read the original source
Heroin pilot: 120 patients, 4 weeks inpatient, abstinence at 3 months

Randomized controlled trial

Yang Z et al. Acta Pharmacol Sin. 2008;29(7):781-8. PMID 18565275.

L-THP reduced the severity of protracted abstinence withdrawal syndrome versus placebo, including somatic symptoms, mood, insomnia, and craving. At 3-month follow-up, among participants who stayed through the first 2 weeks of medication and remained in the program, abstinence was 47.8% (95% CI 33% to 67%) versus 15.2% (7% to 25%) on placebo (log-rank P below 0.0005).

Participants / model
120 heroin-dependent patients
Treatment
L-THP for 4 weeks as inpatients (route and dose not stated in the abstract), or placebo
Follow-up
4 weeks of treatment, follow-up to 3 months
Study design
Randomized, double-blind, placebo-controlled pilot trial
Funding
not stated in the source

The abstinence comparison excludes early dropouts. The insomnia result is a withdrawal-syndrome subscale in heroin users, not evidence for sleep in healthy people.

Read the original source
Cocaine safety study: 24 men, 4 days, cocaine challenge

Randomized controlled trial

Hassan HE et al. J Clin Pharmacol. 2017;57(2):151-160. PMID 27363313.

L-THP was safe and well tolerated and did not affect cocaine PK or its acute cardiovascular effects (cocaine AUC 211.5 versus 261.4 h.ng/mL and Cmax 83.3 versus 104.5 ng/mL, L-THP versus placebo). Side-effect reports did not differ significantly (22 [48%] versus 24 [52%]). 20 men completed.

Participants / model
24 adult men who use cocaine (20 completers)
Treatment
Oral L-THP 30 mg twice a day or placebo for 4 days, with an intranasal cocaine 40 mg challenge on day 4
Follow-up
4 days
Study design
Randomized trial of safety, cocaine PK and cardiovascular effects
Funding
not stated in the source

This is a short safety and interaction study, not an efficacy trial. The registry separately lists a completed phase 1 L-THP study with cocaine exposure (NCT01631383, enrollment 20, no posted results) and a phase 2 L-THP trial for cocaine use disorder that was withdrawn with enrollment 0 (NCT02139761).

Read the original source
Pain product crossover: 27 adults, 10 ingredients, L-THP not isolated

Randomized controlled trial

Evans M et al. Nutrients. 2020;12(6). PMID 32575480.

In a three-period crossover in 27 healthy adults with non-pathological aches, 7 days of the product lowered worst-pain scores more than acetaminophen (21.8% versus 9.8% decrease, p=0.026). The product contained 10 ingredients: vitamins B6, B12 and D, white willow bark extract, angelica root extract, acetyl L-carnitine, caffeine, L-theanine, benfotiamine and L-THP.

Participants / model
27 healthy adults aged 22 to 63 with unresolved, non-pathological aches
Treatment
Oral multi-ingredient product (Pain Bloc-R), 7 days per period
Follow-up
7 days per period
Study design
Three-period randomized crossover; Brief Pain Inventory and musculoskeletal discomfort
Funding
not stated in the source

The design cannot isolate any effect of L-THP. A PubMed search on 9 October 2026 for tetrahydropalmatine, rotundine or l-THP with pain or analgesia, limited to human studies (36 records, reviewed by title), found no trial of L-THP alone for pain.

Read the original source
Capsule review: some effect for insomnia, adverse reactions, design needs improving

Human study

Qing S et al. Zhongguo Zhong Yao Za Zhi. 2013;38(21):3790-4. PMID 24494575.

A review of post-marketing clinical studies of Fufang Zaoren capsule, a marketed Chinese capsule that the abstract says contains L-THP, concluded that it has some therapeutic effect for insomnia but that the study designs need improving. At recommended doses it caused adverse reactions including chills, fever, dizziness, nausea, shortness of breath, chest tightness, and palpitations, and high doses can cause delayed extrapyramidal symptoms. The abstract also reports that a Health Canada web notice linked the L-THP in this capsule to liver damage in pregnant women.

Participants / model
Patients in post-marketing clinical studies (populations not specified in the abstract)
Treatment
Oral capsule containing L-THP (other contents not given in the abstract)
Follow-up
not stated in the source
Study design
Review of post-marketing studies (English abstract only)
Funding
not stated in the source

Authors include staff of an adverse drug reaction monitoring center and of the China Food and Drug Administration's Center for Drug Reevaluation. Only the English abstract of this Chinese-language article was read, and the Health Canada notice is not described here.

Read the original source
Mice with nerve injury: pain relief and more non-REM sleep

Animal study

Liu YY et al. Psychopharmacology (Berl). 2019;236(11):3169-3182. PMID 31172225.

In mice with neuropathic pain from partial sciatic nerve ligation, intraperitoneal L-THP at 5 and 10 mg/kg raised the mechanical threshold by 134.4% and 174.8%, lengthened thermal latency by 49.4% and 69.2%, and increased non-rapid eye movement sleep by 17.5% and 29.6% with less sleep fragmentation, compared with vehicle. A D1 antagonist or a D2 agonist blocked the pain effect and the D2 agonist blocked the sleep effect, so the authors attribute pain relief to D1 agonism plus D2 antagonism and sleep to D2 antagonism.

Participants / model
Mice with experimental neuropathic pain
Treatment
Intraperitoneal L-THP 5 and 10 mg/kg
Follow-up
not stated in the source
Study design
Preclinical study of mechanical allodynia, thermal hyperalgesia and EEG sleep
Funding
not stated in the source

The authors state that L-THP has been used clinically in China for decades as an analgesic with sedative and hypnotic properties. This is sleep in mice in pain, not sleep in people. Its D1 account differs from the review's D1 antagonism.

Read the original source
Stressed rats: anxiety-like behavior reduced at 50 mg/kg

Animal study

Lee B et al. Biomol Ther (Seoul). 2014;22(3):213-22. PMID 25009702.

In male rats given L-THP intraperitoneally 30 minutes before single prolonged stress on 8 consecutive days, 50 mg/kg increased the number and duration of open-arm visits in the elevated plus maze and lowered the anxiety index, increased center time in the open field, reduced immobility in the forced swim test, and blocked the stress-related fall in hypothalamic NPY and rise in CRF.

Participants / model
Male rats in a single prolonged stress model
Treatment
Intraperitoneal L-THP, daily for 8 days
Follow-up
8 consecutive days
Study design
Preclinical study of elevated plus maze, open field, forced swim, and hypothalamic NPY and CRF
Funding
not stated in the source

A PubMed search on 9 October 2026 for tetrahydropalmatine, rotundine or l-THP with anxiety, anxiolytic, insomnia, sleep or hypnotic returned 40 records; by title, none was a human anxiety trial.

Read the original source
Rats and mice: acute methamphetamine, D3 receptor mRNA

Animal study

Yun J. Phytomedicine. 2014;21(11):1287-91. PMID 25172791.

In rats pretreated with L-THP (10 and 15 mg/kg) before an acute methamphetamine injection, L-THP reduced methamphetamine hyperlocomotion and attenuated the methamphetamine-induced fall in striatal dopamine D3 receptor mRNA; in mice it reduced serotonin-induced head twitch and dopamine-driven climbing.

Participants / model
Rats (locomotion, striatal mRNA); mice (head twitch, climbing)
Treatment
L-THP 10 and 15 mg/kg pretreatment (route not stated in the abstract); single methamphetamine injection
Follow-up
Single acute exposure
Study design
Preclinical study of locomotor activity, striatal dopamine receptor mRNA, head twitch and climbing
Funding
not stated in the source

This is one acute exposure, messenger RNA rather than receptor protein or binding, and the D3 receptor rather than D1 or D2, in rats. A PubMed search on 9 October 2026 for tetrahydropalmatine or rotundine with PET, positron, SPECT, occupancy, receptor availability or raclopride returned 0 records.

Read the original source
Morphine rats: D2 receptor protein and place preference

Animal study

Jiang WN et al. Eur J Pharmacol. 2020;884:173397. PMID 32717192.

In rats, repeated morphine reduced dopamine D2 receptor protein in the prefrontal cortex, hippocampus, and striatum and raised striatal GluA1; pretreatment with intraperitoneal L-THP at 1.25, 2.5, or 5 mg/kg blocked both changes and inhibited the acquisition and expression of morphine conditioned place preference, without producing preference or aversion on its own.

Participants / model
Rats given repeated morphine
Treatment
Intraperitoneal L-THP 1.25 to 5 mg/kg before morphine
Follow-up
not stated in the source
Study design
Preclinical study of conditioned place preference and D2, GluA1 and GluA2 receptor protein
Funding
not stated in the source

The drug of exposure here is an opioid, not a stimulant.

Read the original source
Jin Bu Huan: 3 children and 3 adults, two distinct syndromes

Case report

Horowitz RS et al. Arch Intern Med. 1996;156(8):899-903. PMID 8774209.

Jin Bu Huan Anodyne Tablets caused distinct syndromes in 3 children and 3 adults: a single acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular effects, while long-term use in adults was associated with hepatitis. The product contains levo-tetrahydropalmatine, and its package misidentified the constituents, which delayed identification of the responsible alkaloid.

Participants / model
3 children after acute ingestion; 3 adults after long-term use
Treatment
Oral Jin Bu Huan Anodyne Tablets
Follow-up
Single acute ingestion in children; long-term use in adults
Study design
Case series
Funding
not stated in the source

The authors cite the concentrated formulation, lack of childproof packaging, and an insert listing serious medical indications as contributing factors. The product is a multi-constituent herbal tablet, not purified L-THP.

Read the original source
Jin Bu Huan hepatitis: 7 patients, recurrence on rechallenge in two

Case report

Woolf GM et al. Ann Intern Med. 1994;121(10):729-35. PMID 7944049.

Seven previously healthy patients developed acute hepatitis after a mean of 20 weeks (range 7 to 52) of taking Jin Bu Huan Anodyne Tablets; it resolved in 6 within a mean of 8 weeks (range 2 to 30), and the seventh was improving. Symptoms and signs included fever, fatigue, nausea, pruritus, abdominal pain, jaundice, and hepatomegaly. Lowering the dose improved liver tests in one patient, and taking the product again caused abrupt recurrence of hepatitis in two others.

Participants / model
7 previously healthy patients
Treatment
Oral Jin Bu Huan Anodyne Tablets, long-term
Follow-up
Mean 20 weeks (range 7 to 52) before hepatitis
Study design
Retrospective case series with liver histology and rechallenge
Funding
not stated in the source

The abstract names the product's labeled botanical as Lycopodium serratum and does not mention L-THP; a separate case series links the product to L-THP.

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LiverTox: Jin Bu Huan liver injury likely due to a contaminant

Regulatory record

Jin Bu Huan. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643477.

The entry (updated 26 April 2018) describes Jin Bu Huan as a Chinese herb used as a mild sedative and analgesic and marketed for insomnia, pain, and gastrointestinal complaints. Jin Bu Huan products were implicated in more than a dozen cases of idiosyncratic, clinically apparent acute liver injury, but LiverTox judges the hepatotoxicity likely due to a contaminant rather than Jin Bu Huan itself; the summary does not name the contaminant.

Participants / model
People with liver injury after Jin Bu Huan products
Treatment
Oral Jin Bu Huan products
Follow-up
not stated in the source
Study design
NIH drug-induced liver injury reference (LiverTox)
Funding
not stated in the source

These product reports do not settle whether purified L-THP injures the liver.

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Rotundine overdose in Vietnam: 37 patients, 4 ventilated, no deaths

Human study

Duc ND et al. Toxicol Rep. 2026;17:102312. PMID 42519822.

Central nervous system depression predominated. Severe impairment of consciousness (GCS below 8) occurred in 5.4%, QTc prolongation (440 ms or more) in 16.2%, and 4 patients (10.8%) needed mechanical ventilation and intensive care. No one died. An admission GCS of 12 or less predicted ventilation (sensitivity 100%, specificity 97.0%).

Participants / model
37 consecutive patients with acute rotundine poisoning in Vietnam (April 2024 to June 2026; median age 27, 56.8% female)
Treatment
Acute rotundine poisoning (route and amounts not stated in the abstract)
Follow-up
April 2024 to June 2026
Study design
Retrospective observational case series
Funding
not stated in the source

The authors state that rotundine (L-THP) is widely used in Vietnam as an over-the-counter sedative and sleep aid; that is an author statement, not a regulator record.

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Why is L-tetrahydropalmatine in C tier?

C fits a compound with a long reported record of medical use in China, human PK data and two small randomized trials in drug dependence. It is held back by the absence of any trial of L-THP alone for sleep, anxiety or pain, and by safety reports: hepatitis and life-threatening toxicity with Jin Bu Huan products that contain L-THP, and mechanical ventilation in 4 of 37 rotundine overdoses in Vietnam. The grade does not cover the supplier's sleep, anxiety, pain and dopamine claims.