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

Background and Purpose

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.

Experimental Approach

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.

Key Results

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.

Conclusions and Implications

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.