Potential Pharmacokinetic Drug-Drug Interactions Between Cannabinoids and Drugs Used for Chronic Pain

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2020 Aug 29

PMID 32855964

Citations 16

Authors

Marta Vazquez

Natalia Guevara

Cecilia Maldonado

Paulo Caceres Guido

Paula Schaiquevich

Affiliations

Soon will be listed here.

Abstract

Choosing an appropriate treatment for chronic pain remains problematic, and despite the available medication for its treatment, still, many patients complain about pain and appeal to the use of cannabis derivatives for pain control. However, few data have been provided to clinicians about the pharmacokinetic drug-drug interactions of cannabinoids with other concomitant administered medications. Therefore, the aim of this brief review is to assess the interactions between cannabinoids and pain medication through drug transporters (ATP-binding cassette superfamily members) and/or metabolizing enzymes (cytochromes P450 and glucuronyl transferases).

Citing Articles

Therapeutic Efficacy of Medicinal Plants with Allopathic Medicine in Musculoskeletal Diseases.

Rajalekshmi R, Agrawal D Int J Plant Anim Environ Sci. 2025; 14(4):104-129.

PMID: 39866300 PMC: 11765655. DOI: 10.26502/ijpaes.4490170.

Utilization of Cannabidiol in Post-Organ-Transplant Care.

Koyama S, Etkins J, Jun J, Miller M, So G, Gisch D Int J Mol Sci. 2025; 26(2).

PMID: 39859413 PMC: 11765766. DOI: 10.3390/ijms26020699.

Green rush and red warnings: Retrospective chart review of adverse events of interactions between cannabinoids and psychotropic drugs.

Chrobak A, Woron J, Siwek M Front Pharmacol. 2024; 15:1500312.

PMID: 39502532 PMC: 11534596. DOI: 10.3389/fphar.2024.1500312.

Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.

Carrascosa A, Navarrete F, Saldana R, Garcia-Gutierrez M, Montalban B, Navarro D Int J Mol Sci. 2024; 25(11).

PMID: 38892456 PMC: 11172912. DOI: 10.3390/ijms25116268.

Human Data on Pharmacokinetic Interactions of Cannabinoids: A Narrative Review.

Maldonado C, Peyraube R, Fagiolino P, Oricchio F, Cunetti L, Vazquez M Curr Pharm Des. 2024; 30(4):241-254.

PMID: 38288797 DOI: 10.2174/0113816128288510240113170116.

References

Hicks J, Sangkuhl K, Swen J, Ellingrod V, Muller D, Shimoda K . Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2016; 102(1):37-44. PMC: 5478479. DOI: 10.1002/cpt.597. View

Mazaleuskaya L, Sangkuhl K, Thorn C, FitzGerald G, Altman R, Klein T . PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015; 25(8):416-26. PMC: 4498995. DOI: 10.1097/FPC.0000000000000150. View

Degenhardt L, Lintzeris N, Campbell G, Bruno R, Cohen M, Farrell M . Experience of adjunctive cannabis use for chronic non-cancer pain: findings from the Pain and Opioids IN Treatment (POINT) study. Drug Alcohol Depend. 2014; 147:144-50. DOI: 10.1016/j.drugalcdep.2014.11.031. View

Jornil J, Nielsen T, Rosendal I, Ahlner J, Zackrisson A, Boel L . A poor metabolizer of both CYP2C19 and CYP2D6 identified by mechanistic pharmacokinetic simulation in a fatal drug poisoning case involving venlafaxine. Forensic Sci Int. 2013; 226(1-3):e26-31. DOI: 10.1016/j.forsciint.2012.12.020. View

Vuckovic S, Srebro D, Savic Vujovic K, Vucetic C, Prostran M . Cannabinoids and Pain: New Insights From Old Molecules. Front Pharmacol. 2018; 9:1259. PMC: 6277878. DOI: 10.3389/fphar.2018.01259. View

Yekehtaz H, Farokhnia M, Akhondzadeh S . Cardiovascular considerations in antidepressant therapy: an evidence-based review. J Tehran Heart Cent. 2015; 8(4):169-76. PMC: 4434967. View

Feinshtein V, Erez O, Ben-Zvi Z, Eshkoli T, Sheizaf B, Sheiner E . Cannabidiol enhances xenobiotic permeability through the human placental barrier by direct inhibition of breast cancer resistance protein: an ex vivo study. Am J Obstet Gynecol. 2013; 209(6):573.e1-573.e15. DOI: 10.1016/j.ajog.2013.08.005. View

Wang J, Ruan Y, Taylor R, Donovan J, Markowitz J, Devane C . Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood-brain barrier of Abcb1a gene knockout mice. Psychopharmacology (Berl). 2004; 173(1-2):132-8. DOI: 10.1007/s00213-003-1718-1. View

Hassan H, Myers A, Lee I, Coop A, Eddington N . Oxycodone induces overexpression of P-glycoprotein (ABCB1) and affects paclitaxel's tissue distribution in Sprague Dawley rats. J Pharm Sci. 2007; 96(9):2494-506. PMC: 3401599. DOI: 10.1002/jps.20893. View

10.

Alsherbiny M, Li C . Medicinal Cannabis-Potential Drug Interactions. Medicines (Basel). 2018; 6(1). PMC: 6473892. DOI: 10.3390/medicines6010003. View

11.

Lalovic B, Phillips B, Risler L, Howald W, Shen D . Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004; 32(4):447-54. DOI: 10.1124/dmd.32.4.447. View

12.

Bockbrader H, Wesche D, Miller R, Chapel S, Janiczek N, Burger P . A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010; 49(10):661-9. DOI: 10.2165/11536200-000000000-00000. View

13.

Ewing L, McGill M, Yee E, Quick C, Skinner C, Kennon-McGill S . Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration. Molecules. 2019; 24(12). PMC: 6630875. DOI: 10.3390/molecules24122256. View

14.

Chaves C, Remiao F, Cisternino S, Decleves X . Opioids and the Blood-Brain Barrier: A Dynamic Interaction with Consequences on Drug Disposition in Brain. Curr Neuropharmacol. 2017; 15(8):1156-1173. PMC: 5725546. DOI: 10.2174/1570159X15666170504095823. View

15.

Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen L, Shen D . Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther. 2006; 79(5):461-79. DOI: 10.1016/j.clpt.2006.01.009. View

16.

Thompson S, Koszdin K, Bernards C . Opiate-induced analgesia is increased and prolonged in mice lacking P-glycoprotein. Anesthesiology. 2000; 92(5):1392-9. DOI: 10.1097/00000542-200005000-00030. View

17.

Opitz B, Ostroff M, Whitman A . The Potential Clinical Implications and Importance of Drug Interactions Between Anticancer Agents and Cannabidiol in Patients With Cancer. J Pharm Pract. 2019; 33(4):506-512. DOI: 10.1177/0897190019828920. View

18.

Rottmann C . SSRIs and the syndrome of inappropriate antidiuretic hormone secretion. Am J Nurs. 2007; 107(1):51-8. DOI: 10.1097/00000446-200701000-00022. View

19.

Qian Y, Gurley B, Markowitz J . The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications. J Clin Psychopharmacol. 2019; 39(5):462-471. DOI: 10.1097/JCP.0000000000001089. View

20.

Zheng Y, Chen X, Benet L . Reliability of In Vitro and In Vivo Methods for Predicting the Effect of P-Glycoprotein on the Delivery of Antidepressants to the Brain. Clin Pharmacokinet. 2015; 55(2):143-67. PMC: 5674979. DOI: 10.1007/s40262-015-0310-2. View