Tetrahydrocannabinol potentiates reserpine-induced hypokinesia

Delta-9-tetrahydrocannabinol (THC), a substance in marihuana, was found to produce a profound potentiation of reserpine-induced hypokinesia in rats as measured with a bar test. In these experiments, THC had no hypokinetic effect by itself but produced a more than 20-fold increase in the hypokinesia produced by reserpine. Reserpine-induced hypokinesia has been viewed as animal model of Parkinson's Disease. THC potentiation of reserpine-induced hypokinesia was observed to be both time- and dose-dependent (1 to 10 mg/kg THC). When administered by gavage to reserpine-pretreated subjects (7.5 mg/kg IP, 24 hours before), THC produced a potentiation of hypokinesia that developed fully within 1 hour, lasted at least 5 hours, and was absent by 12 hours after THC administration. This THC effect was slightly increased by physostigmine, a cholinesterase inhibitor, relatively unaffected by scopolamine, a muscarinic antagonist, and almost completely blocked by ethopropazine, an anticholinergic antiparkinson drug. The effect was completely unaffected by naloxone. Insofar as reserpine has been used with some clinical efficacy in hyperkinetic movement disorders such as Huntington's disease and tardive dyskinesia, it may be that potentiation of reserpine's hypokinetic effect by a drug such as THC could greatly increase the clinical value of reserpine or related drugs in the treatment of these disorders.