High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control Johannes G Ramaekers* ,1 , Gerhold Kauert 2 , Peter van Ruitenbeek 1 , Eef L Theunissen 1 , Erhard Schneider 3 and Manfred R Moeller 4 1 Experimental Psychopharmacology Unit, Department of Neurocognition, Faculty of Psychology, Maastricht University, Maastricht, The Netherlands; 2 Department of Forensic Toxicology, Institute of Legal Medicine, Goethe University of Frankfurt, Frankfurt, Germany; 3 Landeskriminalamt, Kriminaltechnisches Institut, Baden-Wu¨rttemberg, Germany; 4 Unikliniken des Saarlandes, Homburg, Germany Human performance studies have usually relied on low-potency marijuana (4% THC) for determining THC-induced impairment. The present study was designed to assess the effects of high-potency marijuana (13% THC) on human performance. In all, 20 recreational users of marijuana participated in a double-blind, placebo controlled, three way cross-over study. The treatments consisted of single doses of 0, 250, and 500 mg/kg THC. Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control (Critical tracking task), executive function (Tower of London) motor impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task. In addition, THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC  Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 mg/kg were relatively low but generally increased by a factor of two in case of THC 500 mg/kg. These data suggest that high potency marijuana consistently impairs executive function and motor control. Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies. Neuropsychopharmacology advance online publication, 29 March 2006; doi:10.1038/sj.npp.1301068 Keywords: THC; potency; cognition; impulsivity; motor control; acute                                                   INTRODUCTION The acute effects of D 9 -tetrahydrocannabinol (THC) on isolated cognitive functions have been assessed in numer- ous experimental studies employing within subject, double blind, placebo controlled designs. These have generally shown that THC in doses up to 300 mg/kg (ie about 15– 20 mg) causes a dose-related reduction in performance at laboratory tasks measuring memory, divided and sustained attention, reaction time, tracking and motor function (reviews: Ameri, 1999; Hall and Solowij, 1998; Iversen, 2003; Lichtman et al, 2002; Ramaekers et al, 2004). One of the most consistently reported behavioural effects of THC is a disruption in the free recall of previously learned information. Recall of items learned before cannabis use is generally not affected, suggesting that THC impairs learning and the acquisition of information but not its retrieval from memory (Curran et al, 2002; D’Souza et al, 2004; Hampson and Deadwyler, 1999; Leweke et al, 1998). However, the severity of such performance deficits has also been challenged by a number of studies that failed to demonstrate any substantial impairment of simple psycho- motor function or complex cognitive task performance after acute doses of THC (Fant et al, 1998; Hart et al, 2001; Heishman et al, 1997). Some researchers have noted that marijuana smokers are very much aware of their intoxica- tion and take appropriate precautions to compensate for the impairing effects of marijuana smoking. For example, on- the-road and simulator driving studies have found that cannabis drivers tended to reduce their driving speed and drive at greater headway while under influence of THC (Robbe, 1994; Sexton et al, 2000; Smiley, 1999). These results have been interpreted to indicate that marijuana causes drivers to be more cautious and reduce risk taking behaviours, as compared to alcohol-intoxicated drivers (Robbe, 1994; Sexton et al, 2000; Smiley, 1999). A potential drawback that may pertain to marijuana studies on human performance to date is that doses of THC that have been administered are less than those frequently found in marijuana cigarettes or sought by marijuana smokers to achieve their desired high. Most controlled Online publication: 21 February 2006 at http://www.acnp.org/citations/ Npp022106050610/default.pdf Received 6 October 2005; revised 14 February 2006; accepted 17 February 2006 *Correspondence: Dr JG Ramaekers, Experimental Psychopharmaco- logy Unit, Department of Neurocognition, Faculty of Psychology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands, Tel: + 31 43 3881951, Fax: + 31 43 3884125, E-mail: j.ramaekers@psychology.unimaas.nl Neuropsychopharmacology (2006), 1–8 & 2006 Nature Publishing Group All rights reserved 0893-133X/06 $30.00 www.neuropsychopharmacology.org