Cognitive and subjective dose-response effects of acute oral Δ9-tetrahydrocannabinol (THC) in infrequent cannabis users

Rationale: Although some aspects of memory functions are known to be acutely impaired by Delta(9)-tetrahydrocannabinol (Delta(9)-THC; the main active constituent 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 Delta(9)-THC in infrequent cannabis users. Methods: A balanced, double-blind cross-over design was used to compare the effects of 7.5 mg and 15 mg Delta(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: Delta(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 Delta(9)-THC resulted in no learning whatsoever occurring over a three-trial selective reminding task at 2 h. Working memory was generally unaffected by Delta(9)-THC. In several tasks, Delta(9)-THC increased 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. Participants experienced a strong drug effect, liked this effect and, until 4 h, wanted more oral Delta(9)-THC. No effects of Delta(9)-THC were found 24 or 48 h following ingestion indicating that the residual effects of oral Delta(9)-THC are minimal. Conclusions: These data demonstrate that oral Delta(9)-THC impairs episodic memory and learning in a dose-dependent manner whilst sparing perceptual priming and working memory.