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 via OpenAlex
Summary
AI-generated from the abstractThe dopamine β-hydroxylase (DβH) enzyme converts dopamine into noradrenaline. People with low-activity DBH genotypes (rs1611115 CT/TT) appear more sensitive to cannabis and cocaine's effects on cognitive impulse control and brain connectivity. In 122 regular drug users, acute doses of cannabis (450 μg/kg THC) and cocaine (300 mg) increased cognitive impulsivity and reduced functional connectivity between the nucleus accumbens and limbic, prefrontal, striatal, and thalamic areas, primarily in those with CT/TT genotypes, not in those with the CC genotype. A negative association emerged between impulsivity and subcortical connectivity. The findings suggest DBH genotype influences how these drugs affect impulse control and brain networks, potentially explaining progression to drug seeking and informing targeted pharmacotherapy.
Study at a glance
| 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 |
| Citations | 61 |
| Key finding | 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.