Cannabinoid modulation of opioid analgesia and subjective drug effects in healthy humans

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21 Scopus citations


Rationale: Dozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of μ-opioid agonists. Objectives: The aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models. Methods: Healthy participants (n = 10) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Nine 8-h sessions were completed during which dronabinol (0, 2.5, 5 mg, p.o.) was administered 1 h before oxycodone (0, 5, 10 mg, p.o.) for a total of 9 test conditions. Outcomes included sensory threshold and tolerance from four experimental pain models (cold pressor, pressure algometer, hot thermode, cold hyperalgesia), along with participant- and observer-rated, performance and physiological effects. Results: Oxycodone produced miosis (p < 0.05) and analgesic responses (e.g., pressure algometer [p < 0.05]), while dronabinol did not (p > 0.05). Depending on the dose combination, dronabinol attenuated or did not alter oxycodone analgesia; for example, dronabinol (2.5 mg) decreased the analgesic effects of oxycodone (10 mg) on pressure tolerance. Conversely, dronabinol increased oxycodone subjective effects (e.g., drug liking) (p < 0.05); oxycodone (5 mg) ratings of “high” were potentiated by 5 mg dronabinol (p < 0.05; placebo = 1.1 [± 0.7]; 5 mg oxycodone = 4.7 [± 2.2]; 5 mg dronabinol = 9.9 [± 8.4]; 5 mg oxycodone + 5 mg dronabinol = 37.4 [± 11.3]). Conclusions: This study indicates that dronabinol did not enhance the analgesic effects of oxycodone and increased abuse- and impairment-related subjective effects. These data suggest that dronabinol may not be an effective or appropriate opioid adjuvant; it could potentially increase opioid dose requirements, while increasing psychoactive opioid effects.

Original languageEnglish
Pages (from-to)3341-3352
Number of pages12
Issue number11
StatePublished - Nov 1 2019

Bibliographical note

Funding Information:
Grants from the National Center for Research Resources and National Center for Advancing of Translational Sciences (KL2TR000116-04 [SB]; UL1TR001998 [UK CTSA]) and the University of Kentucky Center for Clinical and Translation Science provided support for this research. We thank Anne Estrup Olesen (Aalborg University Hospital, Denmark) for feedback on the experimental pain protocols; the staff at the University of Kentucky (UK) Center on Drug and Alcohol Research for research support: Amanda Kopca, Matthew Taylor, and Victoria Vessels; the UK Investigational Pharmacy for preparing study medication; and Dr. Samy-Claude Elayi for patient support.

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.


  • Cannabinoid
  • Dronabinol
  • Human
  • Opioid
  • Opioid sparing
  • Pain

ASJC Scopus subject areas

  • Pharmacology


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