Tolerance to the behavioral effects of marihuana in chimpanzees

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Abstract

Two experiments were conducted in which adult chimpanzees were first trained to respond under time-based reinforcement schedules that required a temporal spacing of successive responses. The chimpanzees were then given 14 consecutive daily doses of either a totally synthetic Δ9-trans-tetrahydrocannabinol (Δ9-THC) or a marihuana extract containing a known amount of Δ9-THC. In Experiment 1 the drug dose was increased from 1 mg/kg to 4 mg/kg Δ9-THC. The amount of drug repeatedly administered in Experiment 2 was 3 mg/kg Δ9-THC. In both experiments the first administration of Δ9-THC produced a significant behavioral change from nondrug control responding which was followed in subsequent sessions by the rapid development of tolerance. That is, the behavioral effects intially produced by Δ9-THC progressively decreased with repeated drug administrations. Consistent but temporary departures from control responding occurred during postdrug sessions. The possibility that the development of tolerance to marihuana may be, in part, due to the learning of responses which compensate for marihuana-produced behavioral effects was discussed.

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    The authors wish to thank David Billings for his help in collecting the data and Dr. Monique Braude for her valuable advice. Research supported by National Institute of Mental Health Contract No. HSM-42-71-15. Synthetic Δ9-THC and Marihuana Extract Distillate obtained by approval of the FDA-NIMH Psychotomimetic Agents Advisory Committee. The animals involved in this study were maintained in accordance with “Guide for Laboratory Animal Facilities and Care” as published by the National Academy of Sciences-National Research Council.

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