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.
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.
Authors: J M Fletcher; J B Page; D J Francis; K Copeland; M J Naus; C M Davis; R Morris; D Krauskopf; P Satz Journal: Arch Gen Psychiatry Date: 1996-11
Authors: F Rodríguez de Fonseca; M A Gorriti; J J Fernández-Ruiz; T Palomo; J A Ramos Journal: Pharmacol Biochem Behav Date: 1994-01 Impact factor: 3.533
Authors: Laura Cutando; Arnau Busquets-Garcia; Emma Puighermanal; Maria Gomis-González; José María Delgado-García; Agnès Gruart; Rafael Maldonado; Andrés Ozaita Journal: J Clin Invest Date: 2013-06-24 Impact factor: 14.808
Authors: Ashley M Schnakenberg Martin; Dae-Jin Kim; Sharlene D Newman; Hu Cheng; William P Hetrick; Ken Mackie; Brian F O'Donnell Journal: J Psychopharmacol Date: 2021-05-25 Impact factor: 4.153