Examining the effects of former cannabis use on cerebellum-dependent eyeblink conditioning in humans

Abstract

Rationale: Previous work in humans has shown that chronic cannabis users exhibit disruptions in classical eyeblink conditioning (EBC), a form of associative learning that is known to be dependent on the cerebellum. Based upon previous work in animals, it was hypothesized that these learning deficits were related to cannabinoid receptor (CB1R) downregulation. However, it remains unclear whether there is a recovery of cerebellum-dependent learning after the cessation of cannabis use.

Methods: Therefore, former cannabis users (n=10), current cannabis users (n=10), and cannabis-naïve controls (n=10), all free of DSM-IV Axis-I or -II disorders, were evaluated. A standard delay EBC procedure was utilized in which paired presentations of a conditioned stimulus (CS; e.g., tone) and a co-terminating unconditioned stimulus (US; e.g., ocular airpuff) were administered, thus eliciting a conditioned eyeblink response (CR). The primary dependent measures were percentage of CRs and CR latency across conditioning blocks.

Results: Similar to prior studies, current cannabis users exhibited marked impairments in both the acquisition and timing of CRs compared to controls. Although former cannabis users showed intact CR acquisition compared to controls, they exhibited significantly impaired (shorter) CR latencies. In both cannabis groups, UR amplitude did not differ from controls, indicating normal US processing.

Conclusions: These data suggest that a recovery of function has occurred for the learning of the CS-US association, while the accurate timing of the CR shows lasting impairments. Taken together, these results suggest that heavy cannabis use can disrupt timing-related synaptic plasticity within the cerebellum, even after the cessation of cannabis use.

Fig. 1

CR percentage for the current users (green triangles), former users (red squares), and controls (black circles) during ten blocks of delay eyeblink conditioning. Current users exhibited an impairment in acquisition as compared to controls, whereas former users did not differ from either the control or current using groups

Fig. 2

CR peak latency for current users (green triangles), former users (red squares), and controls (black circles) during ten blocks of delay eyeblink conditioning. Current and former cannabis-using groups showed significantly (p<0.05) earlier peak latencies of the CR than control participants