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Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users

J G Ramaekers1, J H van Wel2, D Spronk3

  • 1Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands. j.ramaekers@maastrichtuniversity.nl.

Brain Imaging and Behavior
|December 16, 2015
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Summary
This summary is machine-generated.

Individuals with low dopamine beta-hydroxylase (DBH) activity genotypes show increased drug-induced impulsivity and altered brain connectivity with cannabis and cocaine. This highlights a genetic influence on drug sensitivity and potential targets for pharmacotherapy.

Keywords:
CannabisCocaineDBH genotypeFuctional connectivityImpulse control

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Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Dopamine beta-hydroxylase (DBH) converts dopamine to noradrenaline.
  • DBH enzyme activity influences neurotransmitter levels and brain function.
  • Genetic variations in DBH may affect individual responses to drugs.

Purpose of the Study:

  • To investigate the interaction between DBH genotypes and the effects of cannabis and cocaine on cognitive impulse control.
  • To examine how DBH genotype influences functional connectivity in the brain's reward circuit under drug influence.
  • To explore the neural mechanisms underlying drug sensitivity and seeking behavior.

Main Methods:

  • Recruited 122 regular drug users.
  • Administered acute doses of cannabis (THC), cocaine, and placebo.
  • Assessed cognitive impulse control using the Matching Familiar Figures Test (MFFT).
  • Measured resting-state functional magnetic resonance imaging (fMRI) to determine nucleus accumbens (NAc) connectivity.

Main Results:

  • Cannabis and cocaine increased cognitive impulsivity in individuals with low-activity DBH genotypes (CT/TT) but not high-activity genotypes (CC).
  • Both drugs reduced functional connectivity between the NAc and limbic/cortical areas, particularly in CT/TT genotype individuals.
  • A negative correlation was found between cognitive impulsivity and functional connectivity in subcortical brain regions.

Conclusions:

  • The impact of cannabis and cocaine on impulse control and brain connectivity is dependent on DBH genotype.
  • Findings suggest a genetic basis for differential drug sensitivity and provide a neural substrate for drug seeking.
  • Results support the rationale for genotype-targeted pharmacotherapy in chronic drug users.