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
Psychopharmacology October 30, 2010 DOI: 10.1007/s00213-010-2042-1 via OpenAlex
Summary
Heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive tasks, but they do not develop cross-tolerance to the impairing effects of alcohol. In a double-blind study, 21 heavy cannabis users received alcohol at three levels (targeting blood alcohol concentrations of 0, 0.5, and 0.7 mg/ml) and smoked a THC cigarette (400 μg/kg) 3 hours after drinking began. Alcohol alone impaired performance on tests of perceptual motor control, divided attention, and motor inhibition, while THC alone generally did not affect performance. However, combining THC and alcohol produced greater impairments in divided attention than alcohol alone, indicating that alcohol can potentiate THC effects in tolerant users.
Study at a glance
| Characteristics | Double-blind, placebo-controlled, three-way study Peer reviewed |
|---|---|
| Sample size | 21 |
| Population | Heavy cannabis users |
| Interventions | Alcohol THC cigarette |
| Dose | 400 μg/kg |
| Duration | 5-h time window for alcohol dosing; performance tests conducted between 0 and 7 h after onset of drinking |
| Topics | Cannabis |
| Keywords | Neurocognitive Cross-tolerance Effects of cannabis Drug tolerance Alcohol tolerance |
| Citations | 168 |
| Key finding | Heavy cannabis users showed tolerance to THC's impairing effects on neurocognitive tasks but did not show cross-tolerance to alcohol; alcohol potentiated THC effects on divided attention. |
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.