Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis.
Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED50) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED50of morphine alone. In addition, the ED50for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED50of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.
The National Drug and Alcohol Research Centre, The University of New South Wales, Sydney, NSW, Australia.|Drug and Alcohol Services, South Eastern Sydney Local Health District, Surry Hills, NSW, Australia.
Suzanne
http://orcid.org/0000-0001-5341-1055
S
Nielsen
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Pamela
P
Sabioni
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Jose M
JM
Trigo
Departments of Anaesthesia and Family Medicine, McGill University, Montreal, QC, Canada.
Mark A
MA
Ware
School of Public Health and Community Medicine, The University of New South Wales, Sydney, NSW, Australia.
Brigid D
BD
Betz-Stablein
Discipline of Addiction Medicine, University of Sydney, Sydney, NSW, Australia.|Pain Management Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Bridin
B
Murnion
Drug and Alcohol Services, South Eastern Sydney Local Health District, Surry Hills, NSW, Australia.|Discipline of Addiction Medicine, University of Sydney, Sydney, NSW, Australia.
Nicholas
N
Lintzeris
Department of Pain Management, Prince of Wales Hospital, Randwick, NSW, Australia.
Kok Eng
KE
Khor
The National Drug and Alcohol Research Centre, The University of New South Wales, Sydney, NSW, Australia.
Michael
M
Farrell
Pain and Addiction Medicine, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Andrew
A
Smith
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Bernard
B
Le Foll
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage*; D004357:Drug Synergism; D006801:Humans; D010146:Pain / Q000188:drug therapy*
D000701:Analgesics, Opioid; D002186:Cannabinoids