Dependence on tetrahydrocannabinol in rhesus monkeys.

The present studies examined whether dependence could be induced by continuous infusion of delta-9-tetrahydrocannabinol (THC), as evidenced by behavioral disruptions during withdrawal of THC administration. Four rhesus monkeys lever pressed under fixed-ratio schedules for their daily food rations during four, daily, 0.5 -hr sessions. Initially, the monkeys were tested before, during and after continuous i.v. infusions of THC. A dosage regimen of 0.05 mg/kg/hr for 10 days for three of the monkeys and a somewhat greater regimen in the fourth had little direct effect on rates of respondings for food during THC infusion, but marked decreases in response rates occurred in each monkey during withdrawal. These effects generally did not occur until the second day of withdrawal, and often lasted for over a week. These initial demonstrations were replicated subsequently with lower solvent concentrations. In the final study, THC was administered for a greater number of days and at higher dosages than during any of the previous studies. Response rate reductions again occurred within 2 to 3 days of withdrawal. When THC was readministered, reversal of the withdrawal effects occurred in that withdrawal-induced rate decreases were halted and rates increased subsequently. Administration of THC was discontinued after 2 to 3 days of its readministration. Response rates again decreased within the first 3 days after this withdrawal and then recovered slowly with time. Withdrawal of THC administration can disrupt operant behavior, and these disruptions can be reversed by resumption of THC administration, indicating that dependence upon this drug can be produced in rhesus monkeys.