Role of Levo-tetrahydropalmatine and its metabolites for management of chronic pain and opioid use disorders

Jing Liu; Ronghua Dai; Roxana Damiescu; Thomas Efferth; David Y W Lee

doi:10.1016/j.phymed.2021.153594

Role of Levo-tetrahydropalmatine and its metabolites for management of chronic pain and opioid use disorders

Phytomedicine. 2021 Sep:90:153594. doi: 10.1016/j.phymed.2021.153594. Epub 2021 May 25.

Authors

Jing Liu¹, Ronghua Dai², Roxana Damiescu³, Thomas Efferth³, David Y W Lee⁴

Affiliations

¹ Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
² Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
³ Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, 55128 Mainz, Germany.
⁴ Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. Electronic address: dlee@mclean.harvard.edu.

PMID: 34144869
DOI: 10.1016/j.phymed.2021.153594

Abstract

Background: Opioids have been prescribed to reduce suffering from pain and to enhance quality of life. Due to the addictive potential and the lack of other effective alternatives to treat severe acute and chronic pains, opioids remain a serious public health issue. While, opioids directly influence the drug-seeking behavior, tolerance and withdrawal processes, through neuroadaptation, the brain's endogenous opioid system also adapts in the presence of chronic pain and could contribute to the difficulty of treatment. Despite the seemingly obvious interaction between the presence of pain and opioid-abuse, little is known about the underlying mechanisms in the brain.

Purpose: To review the current understanding of the interaction mechanisms of neurotransmitter circuitries in pain modulation and reward in the brain and the effects of L-tetrahydropalmatine (L-THP) and its metabolites in pain management and opioid use disorder and gain a better insight on the pharmacological profile and in vivo effects of L-THP and its metabolites.

Method: A detailed literature search on available (preclinical and clinical) studies about the effects of L-THP and its metabolites against drug addiction and chronic pain has been performed. The data was collected using various search engines such as PubMed, ScienceDirect, Google scholar and articles in English up to December 2020 were included in this review.

Results: L-THP and its metabolites demonstrated analgesic and anti-addiction effects. Due to their dual pharmacological properties (D1 partial agonist and D2 antagonist) these compounds could be used as molecular tools to provide a better understanding of the interactions between pain and addiction.

Conclusion: The available data confirms the potential of L-THP and its metabolites to treat both chronic pain and drug addiction. However, further clinical trials are needed to establish safety and efficacy.

Keywords: Addiction; L-THP; Natural products; Neuro-circuitries; Opioid use disorders (OUDs); Pain.

Publication types

Review

MeSH terms

Analgesics, Opioid / adverse effects
Berberine Alkaloids* / pharmacology
Chronic Pain* / drug therapy
Humans
Opioid-Related Disorders* / drug therapy
Quality of Life

Substances

Analgesics, Opioid
Berberine Alkaloids
tetrahydropalmatine