Alleviation of Opioid Withdrawal by Cannabis and Delta-9-tetrahydrocannabinol: A Systematic Review of Observational and Experimental Human Studies

Overview

Journal Drug Alcohol Depend

Publisher Elsevier

Specialty Psychiatry

Date 2022 Nov 26

PMID 36434879

Authors

Joao P De Aquino

Anees Bahji

Oscar Gomez

Mehmet Sofuoglu

Affiliations

Soon will be listed here.

Abstract

Background: While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.

Methods: We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.

Results: Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.

Conclusions: Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.

Citing Articles

A preliminary investigation of the acute effects of delta-9-tetrahydrocannabinol on pain and opioid attentional bias among persons with opioid use disorder.

Wolkowicz N, Sofuoglu M, Pittman B, Meyerovich J, MacLean R, Aquino J J Psychiatr Res. 2024; 177:90-95.

PMID: 38991269 PMC: 11371499. DOI: 10.1016/j.jpsychires.2024.06.047.

Examining the Gateway Hypothesis and Mapping Substance Use Pathways on Social Media: Machine Learning Approach.

Yuan Y, Kasson E, Taylor J, Cavazos-Rehg P, De Choudhury M, Aledavood T JMIR Form Res. 2024; 8:e54433.

PMID: 38713904 PMC: 11109860. DOI: 10.2196/54433.

The Role of Medicinal Cannabis as an Emerging Therapy for Opioid Use Disorder.

Le K, Le K, Nguyen J, Hua J, Munday S Pain Ther. 2024; 13(3):435-455.

PMID: 38676910 PMC: 11111657. DOI: 10.1007/s40122-024-00599-1.

Chemistry and Pharmacology of Delta-8-Tetrahydrocannabinol.

Abdel-Kader M, Radwan M, Metwaly A, Eissa I, Hazekamp A, ElSohly M Molecules. 2024; 29(6).

PMID: 38542886 PMC: 10976172. DOI: 10.3390/molecules29061249.

Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study.

Aquino J, Meyerovich J, Xie C, Ranganathan M, Compton P, Pittman B Addict Biol. 2023; 28(9):e13317.

PMID: 37644897 PMC: 10468603. DOI: 10.1111/adb.13317.

References

Lucas P, Baron E, Jikomes N . Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients. Harm Reduct J. 2019; 16(1):9. PMC: 6350348. DOI: 10.1186/s12954-019-0278-6. View

Scavone J, Sterling R, Van Bockstaele E . Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience. 2013; 248:637-54. PMC: 3742578. DOI: 10.1016/j.neuroscience.2013.04.034. View

McGilveray I . Pharmacokinetics of cannabinoids. Pain Res Manag. 2005; 10 Suppl A:15A-22A. DOI: 10.1155/2005/242516. View

Hagemeier N . Introduction to the opioid epidemic: the economic burden on the healthcare system and impact on quality of life. Am J Manag Care. 2018; 24(10 Suppl):S200-S206. View

Jicha C, Lofwall M, Nuzzo P, Babalonis S, Elayi S, Walsh S . Safety of oral dronabinol during opioid withdrawal in humans. Drug Alcohol Depend. 2015; 157:179-83. PMC: 4663169. DOI: 10.1016/j.drugalcdep.2015.09.031. View

Lake S, Pierre M . The relationship between cannabis use and patient outcomes in medication-based treatment of opioid use disorder: A systematic review. Clin Psychol Rev. 2020; 82:101939. DOI: 10.1016/j.cpr.2020.101939. View

Spahn V, Fischer O, Endres-Becker J, Schafer M, Stein C, Zollner C . Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner. Pain. 2013; 154(4):598-608. DOI: 10.1016/j.pain.2012.12.026. View

Langleben D, Ruparel K, Elman I, Busch-Winokur S, Pratiwadi R, Loughead J . Acute effect of methadone maintenance dose on brain FMRI response to heroin-related cues. Am J Psychiatry. 2007; 165(3):390-4. DOI: 10.1176/appi.ajp.2007.07010070. View

Suzuki J, Weiss R . Cannabinoids for the Treatment of Opioid Use Disorder: Where is the Evidence?. J Addict Med. 2020; 15(2):91-92. PMC: 7986228. DOI: 10.1097/ADM.0000000000000711. View

10.

Evans E, Yoo C, Huang D, Saxon A, Hser Y . Effects of access barriers and medication acceptability on buprenorphine-naloxone treatment utilization over 2 years: Results from a multisite randomized trial of adults with opioid use disorder. J Subst Abuse Treat. 2019; 106:19-28. PMC: 6756169. DOI: 10.1016/j.jsat.2019.08.002. View

11.

Kanof P, Handelsman L, ARONSON M, Ness R, Cochrane K, Rubinstein K . Clinical characteristics of naloxone-precipitated withdrawal in human opioid-dependent subjects. J Pharmacol Exp Ther. 1992; 260(1):355-63. View

12.

Coloma-Carmona A, Carballo J, Rodriguez-Marin J, Perez-Carbonell A . Withdrawal symptoms predict prescription opioid dependence in chronic pain patients. Drug Alcohol Depend. 2018; 195:27-32. DOI: 10.1016/j.drugalcdep.2018.11.013. View

13.

Dunn K, Weerts E, Huhn A, Schroeder J, Tompkins D, Bigelow G . Preliminary evidence of different and clinically meaningful opioid withdrawal phenotypes. Addict Biol. 2018; 25(1):e12680. PMC: 6546557. DOI: 10.1111/adb.12680. View

14.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151(4):264-9, W64. DOI: 10.7326/0003-4819-151-4-200908180-00135. View

15.

Meacham M, Nobles A, Tompkins D, Thrul J . "I got a bunch of weed to help me through the withdrawals": Naturalistic cannabis use reported in online opioid and opioid recovery community discussion forums. PLoS One. 2022; 17(2):e0263583. PMC: 8824349. DOI: 10.1371/journal.pone.0263583. View

16.

Calhoun S, Galloway G, Smith D . Abuse potential of dronabinol (Marinol). J Psychoactive Drugs. 1998; 30(2):187-96. DOI: 10.1080/02791072.1998.10399689. View

17.

van Rijswijk S, van Beek M, Schoof G, Schene A, Steegers M, Schellekens A . Iatrogenic opioid use disorder, chronic pain and psychiatric comorbidity: A systematic review. Gen Hosp Psychiatry. 2019; 59:37-50. DOI: 10.1016/j.genhosppsych.2019.04.008. View

18.

Hine B, Friedman E, Torrelio M, Gershon S . Morphine-dependent rats: blockade of precipitated abstinence by tetrahydrocannabinol. Science. 1975; 187(4175):443-5. DOI: 10.1126/science.1167428. View

19.

Voelker R . States Move to Substitute Opioids With Medical Marijuana to Quell Epidemic. JAMA. 2018; 320(23):2408-2410. DOI: 10.1001/jama.2018.17329. View

20.

Hausner E, Guddat C, Hermanns T, Lampert U, Waffenschmidt S . Prospective comparison of search strategies for systematic reviews: an objective approach yielded higher sensitivity than a conceptual one. J Clin Epidemiol. 2016; 77:118-124. DOI: 10.1016/j.jclinepi.2016.05.002. View