Psychopharmacology (2002) 164:61–70 DOI 10.1007/s00213-002-1169-0 ORIGINAL INVESTIGATION H. Valerie Curran · Catherine Brignell · Sally Fletcher · Paul Middleton · John Henry Cognitive and subjective dose-response effects of acute oral D 9 -tetrahydrocannabinol (THC) in infrequent cannabis users Received: 31 January 2002 / Accepted: 3 June 2002 / Published online: 23 July 2002  Springer-Verlag 2002 Abstract Rationale: Although some aspects of memory functions are known to be acutely impaired by D 9 - tetrahydrocannabinol (D 9 -THC; the main active con- stituent of marijuana), effects on other aspects of memory are not known and the time course of functional impairments is unclear. Objective: The present study aimed to detail the acute and residual cognitive effects of D 9 -THC in infrequent cannabis users. Methods: A bal- anced, double-blind cross-over design was used to compare the effects of 7.5 mg and 15 mg D 9 -THC with matched placebo in 15 male volunteers. Participants were assessed pre and 1, 2, 4, 6, 8, 24 and 48 h post-drug. Results: D 9 -THC 15 mg impaired performance on two explicit memory tasks at the time of peak plasma concentration (2 h post-drug). At the same time point, performance on an implicit memory task was preserved intact. The higher dose of D 9 -THC resulted in no learning whatsoever occurring over a three-trial selective remind- ing task at 2 h. Working memory was generally unaffected by D 9 -THC. In several tasks, D 9 -THC in- creased both speed and error rates, reflecting “riskier” speed-accuracy trade-offs. Subjective effects were also most marked at 2 h but often persisted longer, with participants rating themselves as “stoned” for 8 h. Par- ticipants experienced a strong drug effect, liked this effect and, until 4 h, wanted more oral D 9 -THC. No effects of D 9 -THC were found 24 or 48 h following ingestion indicating that the residual effects of oral D 9 -THC are minimal. Conclusions: These data demonstrate that oral D 9 -THC impairs episodic memory and learning in a dose- dependent manner whilst sparing perceptual priming and working memory. Keywords Cannabis · Marijuana · THC · Memory · Priming · Subjective effects Introduction Marijuana (cannabis) remains one of the most widely used social drugs in the world and is generally perceived by users to be a relatively benign substance (Ashton 2001). However, several studies comparing marijuana users with non-drug using controls suggest that pro- longed, frequent use of this drug can impair aspects of cognitive functioning. Among these, a study by Block and Ghoneim (1993) found heavy marijuana users displayed subtle deficits in retrieval and mathematical reasoning, along with improved concept formation. A large prospec- tive study by Fletcher et al. (1996) which successfully matched non-using controls with marijuana users reported that prolonged use of the drug was associated with deficits on recall of word lists and with impairments in both selective and divided attention. More recently, Pope et al. (2001) showed word recall deficits in heavy marijuana users (compared with controls) when tested 1 and 7 days following last use of the drug but these were no longer evident after 28 days of abstinence. Pope et al. (2001) conclude that verbal recall impairments detectable a few days after heavy cannabis use are related to recent cannabis exposure and are reversible with abstention from use. Verbal recall impairments are one of the more consistent findings of laboratory studies of the acute effects of cannabinoids. These studies have administered either marijuana in the natural plant form of cannabis or its primary active ingredient, D 9 -tetrahydrocannabinol (D 9 -THC). Natural cannabis preparations contain many cannabinoid constituents besides D 9 -THC (Turner et al. 1980) and in the current debate on the medical use of cannabinoids, a central issue concerns whether the effects of the whole plant differ from those of pure D 9 -THC (e.g. Joy et al. 1999; Wachtel et al. 2002). Studies of acute cognitive effects have differed widely in methodology, H.V. Curran ( ) ) · C. Brignell · S. Fletcher Psychopharmacology Laboratories, Clinical Health Psychology, University College London, Gower Street, London WC1 6BT, UK e-mail: v.curran@ucl.ac.uk Tel.: +44-207-6791898 Fax: +44-207-9161989 P. Middleton · J. Henry Imperial College London, London, UK