Cannabis and Cocaine Reduced Impulse Control and Brain Connectivity, But Only in People With Certain Genetics | Research

The takeaway

Both cannabis and cocaine increased impulsivity and reduced brain reward circuit connectivity, but only in drug users with a genetic variant that predisposes to higher dopamine levels.

Read this if you are interested in how genetics influence individual responses to cannabis and other drugs.

Same doses of cannabis and cocaine impaired impulse control in one genotype group but not another.

What the researchers found

Researchers gave 122 regular drug users acute doses of cannabis, cocaine, and placebo and measured cognitive impulsivity and brain connectivity. The effects of both drugs depended heavily on a specific genetic variant (DBH rs1611115) that controls how efficiently dopamine is converted to noradrenaline.

In participants with the low-activity variant (CT/TT genotype), both cannabis and cocaine increased cognitive impulsivity on a matching task and reduced functional connectivity between the nucleus accumbens (the brain's reward center) and multiple cortical regions. In participants with the high-activity variant (CC genotype), neither drug significantly affected impulsivity or connectivity.

The researchers propose that individuals with low-activity DBH genotypes experience a drug-induced hyperdopaminergic state that disrupts impulse control circuits, while those with high-activity genotypes have enough enzyme activity to buffer the dopamine surge.

Why it matters

This is one of the clearest demonstrations that genetics can determine whether a drug impairs cognitive function. The same dose of cannabis or cocaine had completely different effects depending on a single gene variant. This has implications for understanding why some people are more vulnerable to drug-related impairment and addiction.

The numbers in context

122 drug users. Cannabis dose: 450 micrograms/kg THC. Cocaine dose: 300 mg. CT/TT genotype carriers showed increased impulsivity and reduced corticostriatal connectivity. CC genotype carriers showed no significant effects.

How the study worked

This was a controlled within-subject study. 122 regular drug users received acute doses of cannabis (450 micrograms/kg THC), cocaine (300 mg), and placebo across sessions. Cognitive impulsivity was measured with the Matching Familiar Figures Test. Resting state fMRI was performed in a subset to measure functional connectivity. Participants were genotyped for DBH rs1611115.

What this study cannot tell us

All participants were regular drug users, so results may not apply to occasional users or non-users. The study tested acute effects only; chronic effects may differ. The sample was genotyped after the study, so groups were not balanced by design. The fMRI subset was smaller than the full behavioral sample.

How to read the evidence

Moderate evidence from a controlled within-subject trial with a reasonable sample size, though the genetic analysis was post-hoc rather than prospectively designed.

When this study was published

Published in 2016. Pharmacogenomic approaches to substance use disorders remain an active research area.

The bigger picture

The idea that some people are genetically more vulnerable to drug effects is widely suspected but rarely demonstrated this clearly. By showing that a single genetic variant determines whether cannabis and cocaine impair impulse control, this study provides both a biological mechanism and a potential target for personalized treatment approaches.

Questions still open

Could DBH genotyping help identify individuals at higher risk for drug-related impairment? Would pharmacological approaches targeting dopamine-to-noradrenaline conversion reduce impulsivity in at-risk drug users? Do these genetic effects influence the transition from use to addiction?

Common questions

Do genetics determine how cannabis affects you?

This study found that a specific gene variant (DBH) determined whether cannabis increased impulsivity and disrupted brain connectivity. People with one version of the gene were significantly affected, while those with another version were not.

Could genetic testing predict who is more vulnerable to cannabis impairment?

This study suggests it might be possible. The DBH gene variant identified here affected responses to both cannabis and cocaine, potentially offering a biomarker for vulnerability. However, this would need much more research before any clinical application.

Read the original research

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

Brain imaging and behavior, 10(4), 1254-1263

View on PubMed ↗

Citation

Ramaekers, J G; van Wel, J H; Spronk, D; Franke, B; Kenis, G; Toennes, S W; Kuypers, K P C; Theunissen, E L; Stiers, P; Verkes, R J. (2016). Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes.. Brain imaging and behavior, 10(4), 1254-1263.