Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes
Johannes G. Ramaekers, J. H. van Wel, Desirée Spronk, Barbara Franke, Günter Kenis, Stefan W. Toennes, Kim P. C. Kuypers, Eef L. Theunissen, Peter Stiers, Robbert Jan Verkes
Brain Imaging and Behavior December 14, 2015 DOI: 10.1007/s11682-015-9488-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 122 |
| Population | Regular drug users |
| Interventions | Cannabis Cocaine |
| Dose | 450 μg/kg THC, 300 mg cocaine HCl |
| Topics | Cannabis |
| Keywords | Neuropsychology Cognition Impulse control disorder Audiology Clinical psychology |
| Citations | 61 |
| Key findings | Cannabis and cocaine increased cognitive impulsivity and reduced functional corticostriatal connectivity primarily in individuals with low-activity DBH genotypes (CT/TT), not in those with the high-activity CC genotype. |
Abstract
The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes.
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 24
- The neuropsychopharmacology of cannabis: A review of human imaging studies Pharmacology & Therapeutics October 20, 2018
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Reduced responsiveness of the reward system is associated with tolerance to cannabis impairment in chronic users Addiction Biology December 22, 2019
- Functional brain connectomes reflect acute and chronic cannabis use Scientific Reports February 14, 2022
- Cannabis-induced altered states of consciousness are associated with specific dynamic brain connectivity states Journal of Psychopharmacology June 3, 2019
and 19 more in the library
Cites 4
- Single doses of THC and cocaine decrease proficiency of impulse control in heavy cannabis users British Journal of Pharmacology October 11, 2013
- Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users. Journal of Psychopharmacology May 2009
- Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology February 2009
- Elevated impulsivity and impaired decision-making cognition in heavy users of MDMA (“Ecstasy”) Psychopharmacology January 20, 2006