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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 CBD |
| Keywords | Neurocognitive Cross-tolerance Effects of cannabis Drug tolerance Alcohol tolerance Clinical psychology Pharmacology Cognition |
| Citations | 168 |
| Key points | 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: CBD No effect
Heavy cannabis users showed tolerance to THC's impairing effects on neurocognitive tasks and no cross-tolerance to alcohol; THC generally did not affect task performance, though combined THC and alcohol worsened divided attention.
Synthesized
Comparable studies
Other randomized controlled trials on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants | 2012 | Randomized controlled trial | n = 48 |
| Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... | 2009 | Double-blind, randomized, placebo-controlled crossover trial | n = 15 |
| Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects | 2012 | Randomized controlled trial | n = 16 |
| Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... | 2009 | Randomized controlled trial | n = 15 |
| Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Healthy volunteers with a history of light cannabis use | 2019 | Randomized, double-blind, within-subjects crossover | n = 14 |
Citations in the library
Cited by 30
- Smoked Cannabis' Psychomotor and Neurocognitive Effects in Occasional and Frequent Smokers Journal of Analytical Toxicology March 4, 2015
- Cannabis and tolerance: acute drug impairment as a function of cannabis use history Scientific Reports May 26, 2016
- Cannabis‐related deficits in real‐world memory Human Psychopharmacology: Clinical and Experimental March 1, 2012
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
- Cognitive motor deficits in cannabis users Current Opinion in Behavioral Sciences July 19, 2016
and 25 more in the library
Cites 7
- Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. Journal of Psychopharmacology May 2009
- Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology September 2008
- Abnormal brain activity in prefrontal brain regions in abstinent marijuana users. Neuroimage November 2004
- Effects of acute smoked marijuana on complex cognitive performance. Neuropsychopharmacology November 2001
- The effects of cannabinoids on the brain. Progress in Neurobiology July 1999
and 2 more in the library