Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability

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Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Δ9 tetrahydrocannabinol [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4 °C); times to report pain (pain threshold) and withdraw the hand from the water (pain tolerance) were recorded. Abuse-related effects were measured and effects of oxycodone on cannabis self-administration were determined. Alone, 5.0 mg oxycodone increased pain threshold and tolerance (p ≤ 0.05). Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance (p ≤ 0.05). Oxycodone did not increase subjective ratings associated with cannabis abuse, nor did it increase cannabis self-administration. However, the combination of 2.5 mg oxycodone and active cannabis produced small, yet significant, increases in oxycodone abuse liability (p ≤ 0.05). Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis’s abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.

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The authors acknowledge and appreciate the exceptional assistance of Olivia Derella and Bennett Wechsler in data collection and Dr. Richard Foltin for his assistance with regulatory and computer programming aspects of the study.


This research was supported by US National Institute on Drug Abuse Grant DA19239, DA009236, and DA027755. ZDC, GB, DR, RB, SDC, and MH have no competing interests in relation to the work described. ZDC and MH have received research funds and partial salary support from Insys Therapuetics. Over the past 3 years, SDC received compensation (in the form of partial salary support) from studies supported by Braeburn Pharmaceuticals, Cerecor, Indivior, MediciNova, and Reckitt-Benckiser Pharmaceuticals. In addition, SDC has served as a consultant to the following companies over the past 3 years: Advances in Pain Management, AstraZeneca, Clinilabs, Collegium Pharmaceutical, Daiichi Sankyo, Depomed, Egalet, Endo, Guidepoint Global, Heptares Therapeutics Limited, Inspirion Delivery Sciences, IntelliPharmaCeutics, Janssen, KemPharm, Mallinckrodt, Neuromed, Opiant, Orexo, Pfizer, and Shire.

Author information


  1. Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, New York, NY, 10032, USA

    • Ziva D. Cooper
    • , Rebecca Balter
    • , Sandra D. Comer
    •  & Margaret Haney
  2. Orygen National Centre of Excellence in Youth Mental Health, and Center for Youth Mental Health, University of Melbourne, Melbourne, Australia

    • Gillinder Bedi
  3. Center for Advancement in Managing Pain, University of Connecticut School of Nursing, Storrs, CT, USA

    • Divya Ramesh


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The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Ziva D. Cooper.