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9886696 
Journal Article 
Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users 
Ramaekers, JG; Theunissen, EL; de Brouwer, M; Toennes, SW; Moeller, MR; Kauert, G 
2011 
1 
Psychopharmacology
ISSN: 0033-3158
EISSN: 1432-2072 
214 
2 
391-401 
English 
21049267 
INTRODUCTION: Previous research has shown that heavy cannabis users develop tolerance to the impairing effects of Δ9-tetrahydrocannabinol (THC) on neurocognitive functions. Animal studies suggest that chronic cannabis consumption may also produce cross-tolerance for the impairing effects of alcohol, but supportive data in humans is scarce.

PURPOSE: The present study was designed to assess tolerance and cross-tolerance to the neurocognitive effects of THC and alcohol in heavy cannabis users.

METHODS: Twenty-one heavy cannabis users participated in a double-blind, placebo-controlled, three-way study. Subjects underwent three alcohol-dosing conditions that were designed to achieve a steady blood alcohol concentration of about 0, 0.5, and 0.7 mg/ml during a 5-h time window. In addition, subjects smoked a THC cigarette (400 μg/kg) at 3 h post-onset of alcohol dosing during every alcohol condition. Performance tests were conducted repeatedly between 0 and 7 h after onset of drinking and included measures of perceptual motor control (critical tracking task), dual task processing (divided-attention task), motor inhibition (stop-signal task), and cognition (Tower of London).

RESULTS: Alcohol significantly impaired critical tracking, divided attention, and stop-signal performance. THC generally did not affect task performance. However, combined effects of THC and alcohol on divided attention were bigger than those by alcohol alone.

CONCLUSION: In conclusion, the present study generally confirms that heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive task performance. Yet, heavy cannabis users did not develop cross-tolerance to the impairing effects of alcohol, and the presence of the latter even selectively potentiated THC effects on measures of divided attention.