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


OBJECTIVE
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.


CONCLUSIONS
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.
Department Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands. j.ramaekers@maastrichtuniversity.nl
Johannes G
JG
Ramaekers
Eef L
EL
Theunissen
Marjolein
M
de Brouwer
Stefan W
SW
Toennes
Manfred R
MR
Moeller
Gerhold
G
Kauert
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects / Q000523:psychology*; D001288:Attention / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage* / Q000009:adverse effects; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D056344:Executive Function / Q000187:drug effects; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D002189:Marijuana Abuse / Q000150:complications / Q000523:psychology*; D008385:Marijuana Smoking / Q000009:adverse effects / Q000523:psychology*; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D015990:Placebo Effect; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D055815:Young Adult
D002492:Central Nervous System Depressants; D011619:Psychotropic Drugs; D000431:Ethanol; D013759:Dronabinol