People who tested positive for tobacco and/or cannabis metabolites had 13% lower striatal dopamine D2 receptor availability on PET imaging, particularly in the nucleus accumbens and putamen.
Addiction researchers, neuroscientists, people interested in how smoking affects the brain, and clinicians advising on cannabis consumption methods.
What the researchers found
Individuals positive for urine metabolites of tobacco and/or cannabis had an average 13.1% lower D2 receptor availability across all striatal subregions compared to negative individuals, with the most significant differences in reward-related brain areas.
Why it matters
Lower D2 receptors in reward circuits are associated with addiction vulnerability and reduced reward sensitivity. Finding that both tobacco and cannabis smoke lower D2 availability suggests shared mechanisms of combustible smoke impact on the brain's reward system.
The numbers in context
29 participants. 13.1% average lower D2 BPND in analyte-positive group (range: 6.6-20.0%). Significant differences in nucleus accumbens and putamen. No effects of alcohol use disorder.
How the study worked
Cross-sectional PET imaging study using [11C]raclopride in 29 participants, comparing striatal D2 receptor availability between those with quantified positive vs. negative urine metabolites for nicotine (cotinine) and THC (THCA).
What this study cannot tell us
Very small sample of 29. Cross-sectional design cannot determine if low D2 preceded or resulted from substance use. Cannot separate tobacco from cannabis effects within the positive group.
How to read the evidence
Novel use of biomarker-verified exposure improves on self-report studies, but very small sample limits confidence in the findings.
When this study was published
Recent study introducing objective metabolite verification to PET imaging research on substance effects on dopamine systems.
The bigger picture
This study uniquely uses objective biomarkers (urine metabolites) rather than self-report to classify smoke exposure, revealing that combustible smoke products — regardless of source — may share neurotoxic effects on dopamine systems.
Questions still open
- Do non-combusted cannabis products (edibles, vapes) also affect D2 receptors? Are the D2 changes reversible with smoking cessation?
Common questions
Does smoking cannabis lower dopamine receptors?
What does lower D2 availability mean?
Read the original research
Lower striatal dopamine D2 receptor availability in individuals who test positive for quantitated urine metabolites of tobacco and/or marijuana smoke.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
Citation
Yoder, Karmen K; Carpenter, Samantha; Hile, Karen L; Dzemidzic, Mario; Durazzo, Timothy C. (2025). Lower striatal dopamine D2 receptor availability in individuals who test positive for quantitated urine metabolites of tobacco and/or marijuana smoke.. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. https://doi.org/10.1093/ntr/ntaf249
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