Chronic Δ9-tetrahydrocannabinol exposure during adolescence is associated with persistent behavioural tolerance in adult nonhuman primates.
Yasaman Razavi, Stephen J Kohut, Jack Bergman, Brian D Kangas
British journal of pharmacology November 1, 2025 Peer reviewed DOI: 10.1111/bph.70179 via PubMed
Summary
Chronic exposure to Δ9-THC during adolescence in nonhuman primates leads to increased tolerance to its attention-impairing effects in adulthood, even after a year of abstinence. Adult animals that had received high or low doses of Δ9-THC as adolescents required higher acute doses of the drug to impair performance on a touchscreen-based psychomotor vigilance task compared to those that had received vehicle. The results suggest that adolescent cannabis use may cause lasting changes that manifest as reduced sensitivity to cannabis's cognitive effects later in life.
Study at a glance
| Design | experimental study |
|---|---|
| Population | adolescent nonhuman primates |
| Key finding | Adolescent Δ9-THC exposure increased tolerance to Δ9-THC-induced attentional deficits in adulthood, as measured by the Psychomotor Vigilance Task. |
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.