Chronic Δ9-tetrahydrocannabinol exposure during adolescence is associated with persistent behavioural tolerance in adult nonhuman primates.

Adolescent monkeys exposed daily to the cannabis compound Δ9-THC for six months, then tested about a year later as adults on a touchscreen attention task, required higher acute doses of Δ9-THC to impair their performance compared with animals that had not been exposed during adolescence. The impairment itself was dose-related and occurred whether the drug was given by injection or orally, though potency and timing differed. These results suggest that heavy cannabis use during adolescence can produce a lasting tolerance that persists into adulthood, even after a long period of abstinence.

Study at a glance

Abstract

Legalisation of Cannabis use has led to considerable increases in the availability and potency of Cannabis products, as well as evolving patterns in methods of their consumption. Adolescent Cannabis use has increased, which can impair cognitive function during this critical developmental stage. The persistence of such effects into adulthood, however, is unclear. The present study examined whether chronic Δ9-tetrahydrocannabinol (Δ9-THC) exposure during adolescence modifies subsequent Δ9-THC-induced cognitive deficits during adulthood. Female and male adolescent nonhuman primates were treated intramuscular daily for 6 months with either vehicle, a low dose of Δ9-THC (0.32 mg kg-1 day-1), or a high dose (3.2 mg kg-1 day-1). Approximately 1 year after discontinuing chronic exposure, these subjects, now adults, were trained on a touchscreen-based Psychomotor Vigilance Task (PVT) to examine attentional processes. Acute doses of Δ9-THC were administered prior to select test sessions via two routes, intramuscular or oral, to evaluate the roles of adolescent drug history and method of consumption on Δ9-THC-induced attentional deficits. Results confirm dose-related Δ9-THC impairment of PVT performance by both intramuscular and oral routes of administration, notwithstanding differences in potency and onset of action. Adolescent drug history modified tolerance to Δ9-THC impact on attentional processes, where subjects exposed to chronic Δ9-THC during adolescence required higher doses of Δ9-THC during adulthood to impair PVT performance. These findings suggest a persistent impact of adolescent Δ9-THC use that, even following extended abstinence, may present itself during adulthood via increased tolerance to Cannabis products.