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  • Title: The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys.
    Author: Justinova Z, Tanda G, Munzar P, Goldberg SR.
    Journal: Psychopharmacology (Berl); 2004 Apr; 173(1-2):186-94. PubMed ID: 14668977.
    Abstract:
    RATIONALE: Experimental evidence from animal studies suggests reciprocal functional interactions between endogenous brain cannabinoid and opioid systems. There is recent evidence for a role of the opioid system in the modulation of the reinforcing effects of synthetic cannabinoid CB1 receptor agonists in rodents. Since Delta(9)-tetrahydrocannabinol (THC), the natural psychoactive ingredient in marijuana, is actively and persistently self-administered by squirrel monkeys, this provides an opportunity to directly study involvement of opioid systems in the reinforcing effects of THC in non-human primates. OBJECTIVES: To study the effects of naltrexone, an opioid antagonist, on THC self-administration behavior in squirrel monkeys. METHODS: Monkeys pressed a lever for intravenous injections of THC under a ten-response, fixed-ratio (FR) schedule with a 60-s time-out after each injection. Effects of pre-session treatment with naltrexone (0.03-0.3 mg/kg intramuscularly, 15 min before session) for 5 consecutive days on self-administration of different doses of THC (2-8 microg/kg per injection) were studied. RESULTS: Self-administration responding for THC was significantly reduced by pretreatment with 0.1 mg/kg naltrexone for five consecutive daily sessions. Naltrexone pretreatment had no significant effect on cocaine self-administration responding under identical conditions. CONCLUSIONS: Self-administration behavior under a fixed-ratio schedule of intravenous THC injection was markedly reduced by daily pre-session treatment with naltrexone, but remained above saline self-administration levels. These findings demonstrate for the first time the modulation of the reinforcing effects of THC by an opioid antagonist in a non-human primate model of marijuana abuse.
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