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Robbert Jan Verkes

2 papers in the library · 76 citations · publishing 2015-2024

Papers

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes

Brain Imaging and Behavior December 14, 2015 Johannes G. Ramaekers, J. H. van Wel, Desirée Spronk et al. 61 citations

The 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.

The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

Journal of psychopharmacology (Oxford, England) May 1, 2024 Thomas Knuijver, Rob Ter Heine, Arnt Schellekens et al. 15 citations

Ibogaine, a hallucinogenic drug being studied for opioid use disorder, shows highly variable pharmacokinetics strongly linked to CYP2D6 genotype. In 14 patients given a single 10 mg/kg dose, ibogaine clearance increased by 30.7 L/h per point of CYP2D6 activity score, from a baseline of 0.82 L/h. Higher ibogaine plasma concentrations correlated significantly with QTc prolongation and cerebellar ataxia, while noribogaine did not. Neither ibogaine nor its metabolite correlated with opioid withdrawal severity. These findings suggest that cardiac and neurological side effects are driven more by ibogaine itself, and that lower or genotype-personalized dosing may improve safety.