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

• Published in: Psychopharmacologia Vol. 214; no. 2; pp. 391 - 401
• Main Authors: Ramaekers, Johannes G., Theunissen, Eef L., de Brouwer, Marjolein, Toennes, Stefan W., Moeller, Manfred R., Kauert, Gerhold
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-03-2011; Springer; Springer Nature B.V
• Subjects: Administration, Inhalation; Administration, Oral; Adult; Alcohol; Alcohol Drinking - adverse effects; Alcohol Drinking - psychology; Alcohol use; Analysis; Attention; Attention - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood; Blood levels; Cannabinoids; Cannabis; Central Nervous System Depressants - administration & dosage; Central Nervous System Depressants - adverse effects; Central Nervous System Depressants - blood; Cigarettes; Cognition; Cognition & reasoning; Cognition - drug effects; Cross-tolerance; Double-Blind Method; Drinking behavior; Dronabinol - administration & dosage; Dronabinol - adverse effects; Drug abuse; Drug Tolerance; Effects; Ethanol; Ethanol - administration & dosage; Ethanol - adverse effects; Ethanol - blood; Executive Function - drug effects; Female; Humans; Impulsive Behavior; Inhibition; Male; Marijuana; Marijuana Abuse - complications; Marijuana Abuse - psychology; Marijuana Smoking - adverse effects; Marijuana Smoking - psychology; Medical sciences; Motor Activity - drug effects; Motor control; Motor performance tests; Motor task performance; Neuropsychological Tests; Neurosciences; Original Investigation; Pharmacology/Toxicology; Placebo Effect; Psychiatry; Psychotropic Drugs - administration & dosage; Psychotropic Drugs - adverse effects; Tetrahydrocannabinol; Time Factors; Tobacco; Young Adult; Tolerance; Alcohol; Impulsivity; Cognition; Performance; THC; Cannabidaceae; Alcoholic beverage; Cannabis; Dicotyledones; Angiospermae; Spermatophyta; Drug of abuse; Recreational drug
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-010-2042-1

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.