Original Article

Neuropsychopharmacology (2008) 33, 1432–1440; doi:10.1038/sj.npp.1301506; published online 18 July 2007

Cannabis Use Disrupts Eyeblink Conditioning: Evidence for Cannabinoid Modulation of Cerebellar-Dependent Learning

Patrick D Skosnik1, Chad R Edwards1, Brian F O'Donnell1, Ashley Steffen1, Joseph E Steinmetz2 and William P Hetrick1

  1. 1Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
  2. 2Department of Psychology, University of Kansas, Lawrence, KS, USA

Correspondence: Dr PD Skosnik, Department of Psychological and Brain Sciences, Indiana University, 1101 East 10th Street, Bloomington, IN 47405, USA. Tel: +1 812 320 2521; Fax: +1 812 855 4691; E-mail: pskosnik@indiana.edu

Received 5 December 2006; Revised 17 May 2007; Accepted 8 June 2007; Published online 18 July 2007.

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Abstract

While the cerebellum contains the highest density of cannabinoid receptor (CB1) in the brain, no studies have assessed the effect of exogenous cannabinoids on cerebellar-dependent learning in humans. The current study, therefore, examined the effect of chronic cannabis use on classical eyeblink conditioning (EBC), a cerebellar-mediated task which has been shown to be disrupted in CB1 knockout mice. Chronic cannabis users (24 h abstinence before study; positive THC urine drug test) free of DSM-IV Axis-I or -II disorders, were evaluated. A delay EBC task was utilized, in which a conditioned stimulus (CS; 400 ms tone) co-terminated with a corneal air puff unconditioned stimulus (US; 50 ms), thus eliciting a conditioned blink response (CR). The cannabis group exhibited markedly fewer, and more poorly timed CRs as compared to drug-naive controls. There were no differences between the groups in either the unconditioned response (UR) or an EEG measure of selective attention to the CS (N100 auditory ERP), indicating that the disruption observed in the cannabis group was specific to CR acquisition. These results suggest that cannabis use is associated with functional deficits in the cerebellar circuitry underlying EBC, a finding which corroborates the recent work in CB1 knockout mice.

Keywords:

THC, cannabinoid, cerebellum, eyeblink conditioning, behavior, human

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