Time course of the effects of naturally occurring cannabinoids on morphine abstinence syndrome.

The effects of a single intraperitoneal injection (10 mg/kg) of delta9-tetrahydrocannabinol, delta8-tetrahydrocannabinol and 11-hydroxy-delta8-tetrahydrocannabinol on abstinence syndrome were investigated in mice rendered dependent on morphine by pellet implantation. In morphine dependent mice from which the pellets had been removed, delta9-tetrahydrocannabinol inhibited the naloxone-precipitated jumping response as evidenced by an increase in the ED50 of naloxone. This inhibition was evident for 24 hr, the most pronounced effect being produced between two to four hr after delta9-tetrahydrocannabinol administration. Withdrawal defecation was also inhibited for two hours. Similarly, in mice from which pellets were not removed, delta9-tetrahydrocannabinol suppressed the jumping response; however, the intensity of effect was less than when the pellets were removed. delta8-tetrahydrocannabinol and 11-hydroxy-delta8-tetrahydrocannabinol were not effective in suppressing morphine abstinence syndrome two hr following their administration. The suppression of jumping response was specific, since, the vertical jumping behavior induced by coadministration of amphetamine and l-dopa was not affected by cannabinoids. These results demonstrate that single injection of delta9-tetrahydrocannabinol is effective in controlling morphine abstinence syndrome for 24 hr, and that the drugs related to cannabinoids may show promise in narcotic detoxification.