Acute cannabis intoxication impairs executive function, impulse control, attention, and psychomotor function, and increases subjective intoxication, regardless of how frequently a person uses cannabis. In a study of 122 drug users with cannabis use histories ranging from infrequent to daily, cannabis (300 μg/kg THC) produced these deficits compared to placebo, while cocaine (300 mg) improved psychomotor function and attention but impaired impulse control. The absence of tolerance to cannabis's neurocognitive effects suggests that frequent use and intoxication can interfere with performance in daily environments such as school, work, or traffic.
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.