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

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27 Scopus citations

Abstract

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
JournalPsychopharmacology
Volume236
Issue number11
DOIs
StatePublished - Nov 1 2019

Bibliographical note

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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

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