Cannabis

Neuropsychopharmacology (2009) 34, 2368–2375 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00
www.neuropsychopharmacology.org

A Transcranial Magnetic Stimulation Study of the Effects of Cannabis Use on Motor Cortical Inhibition and Excitability
                                            

Paul B Fitzgerald*,1, SuzanneWilliams2 and Zafiris J Daskalakis3
1

Alfred Psychiatry Research Centre, The Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, Commercial Rd Melbourne, Victoria, Australia; 2Monash University Department of Epidemiology and Preventive Medicine, The Alfred Hospital, Commercial Rd Melbourne, Victoria, Australia; 3Centre for Addiction and Mental Health,University of Toronto, Toronto, Ontario, Canada

Active compounds in cannabis such as tetrahydrocannabinol (THC) interact with the inhibitory neurotransmitter d-aminobutyric acid (GABA) but little is known about the functional effects of cannabis on human cortical brain processes. Therefore, the aim of the study was to investigate whether patients with chronic cannabis use demonstrate abnormalities incortical inhibition or excitability. In all, 42 chronic cannabis using subjects (divided into heavy and light using subjects) and 19 controls were included in the study. Single and paired pulse transcranial magnetic stimulation were used to assess a number of parameters of cortical inhibition and cortical excitability. In addition, psychomotor function and THC plasma levels were measured. Bothcannabis using groups (heavy and light use) demonstrated a reduction in short interval cortical inhibition compared with healthy controls, but there was no difference in other measures of cortical inhibition or cortical excitability. There was also no difference between the two groups on measures of psychomotor performance. Chronic cannabis use is associated with a reduction in cortical inhibitionpotentially related to activity at the GABAA receptors. Further research is required to explore whether this results from chronic cannabis use or reflects an underlying predisposition to developing chronic substance use problems. Neuropsychopharmacology (2009) 34, 2368–2375; doi:10.1038/npp.2009.71; published online 1 July 2009 Keywords: transcranial magnetic stimulation; cannabis; marijuana;cortical inhibition; cortical excitability

INTRODUCTION
Cannabis is the third most widely used recreational drug in the world, being consumed by approximately 4% of the world adult population (UNODC, 2006). Over recent years, there has been a considerable escalation of research into the effects of cannabis, particularly at a basic neurochemical level (eg, see review in Fattore et al, 2008). However,less research has focused on the effects of cannabis at a functional neurophysiological level, especially in human subjects. The one area in which there is neurochemical evidence for the effect of cannabis on the human brain is in the interaction between the endogenous cannabinoid system and the functional inhibitory neuronal networks. For example, there is a complex interaction betweencannabinoid and d-aminobutyric acid (GABA) systems in brain areas such as the nucleus accumbens and hippocampus, potentially relevant to both the addictive and neurocognitive effects of cannabis (Hoffman and Lupica,
*Correspondence: Professor PB Fitzgerald, Alfred Psychiatry Research Centre, First Floor, Old Baker Building, The Alfred, Commercial Rd Melbourne, Victoria 3004, Australia, Tel: + 61 3 90766552, Fax: + 61 3 9076 6588, E-mail: paul.fitzgerald@med.monash.edu.au Received 26 February 2009; revised 14 May 2009; accepted 22 May 2009

2000, 2001). The interaction between these systems at a neurochemical level is complex, however, with variations of the effects of cannabinoid stimulation on GABAergic neurons based on the GABA receptor subtype and brain region. To date, little research has...