Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users

Johannes G Ramaekers, Eef L Theunissen, Marjolein de Brouwer, Stefan W Toennes, Manfred R Moeller, Gerhold Kauert, Johannes G Ramaekers, Eef L Theunissen, Marjolein de Brouwer, Stefan W Toennes, Manfred R Moeller, Gerhold Kauert

Abstract

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.

Figures

Fig. 1
Fig. 1
Mean (SE) BAC as a function of time after onset of alcohol drinking and onset of THC cigarette smoking in the low- and high-dose alcohol condition. Arrows indicate time points at which booster alcohol doses could be administered on an as needed basis to achieve steady BAC levels between 1 and 5 h after onset of drinking
Fig. 2
Fig. 2
Mean (SE) subjective high (lower panel) and drunkenness (middle panel) as a function of time after alcohol and THC administration. The upper panel displays subjective dominance of alcohol or THC over time
Fig. 3
Fig. 3
Mean (SE) lambda-c in the CTT as a function of time after alcohol and THC administration in every treatment condition
Fig. 4
Fig. 4
Mean (SE) tracking error, control losses, correct detections, and reaction time during the DAT as a function of time after alcohol and THC administration in every treatment conditions
Fig. 5
Fig. 5
Mean (SE) stop reaction time and commission errors in the SST as a function of time after alcohol and THC administration in every treatment condition

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