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Combined Treatment with Morphine and Δ 9 ‐Tetrahydrocannibinol (THC) in Rhesus Monkeys: Antinociceptive Tolerance and Withdrawal
Author(s) -
Gerak Lisa,
France Charles
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.616.9
Subject(s) - morphine , nociception , analgesic , pharmacology , opioid , medicine , cannabinoid , drug tolerance , potency , anesthesia , physical dependence , receptor , chemistry , biochemistry , in vitro
Opioid receptor agonists are effective for treating pain; however, tolerance and dependence can develop with repeated treatment. Combining opioids with cannabinoids can enhance their analgesic potency, although it is less clear whether combined treatment alters opioid tolerance and dependence. In this study, 4 monkeys received 3.2 mg/kg morphine alone or in combination with 1 mg/kg THC; the antinociceptive effects (warm water tail withdrawal) of morphine and the cannabinoid receptor agonists WIN 55212 and CP 55940 were determined before and during treatment. To determine whether this treatment produced dependence, behavioral signs indicative of withdrawal were monitored when treatment was discontinued. Before treatment, morphine and the cannabinoids, given alone, increased tail withdrawal latency to 20 sec (maximum possible effect). During treatment, latencies did not exceed 10 sec for any drug, up to doses 3‐ to 10‐fold larger than those that were fully effective before treatment. Rightward and downward shifts in antinociceptive dose‐effect curves were greater in monkeys receiving the morphine/THC combination. Withdrawal signs included increased heart rate, decreased activity, and increased tongue movement, and these signs were similar in monkeys that received morphine alone or in combination with THC. These results demonstrate that antinociceptive tolerance is greater during treatment with the combination, whereas dependence and withdrawal are not changed. When combined with THC, a much smaller dose of morphine is needed to produce antinociceptive effects, and the ability of THC to enhance tolerance to small doses of morphine will be examined in the next study. Supported by R01DA005018 and K05DA17918.