Work

Lower Striatal Dopamine D2 Receptor Availability in Individuals Who Test Positive for Quantitated Urine Metabolites of Tobacco and/or Marijuana Smoke

Year: 2025

Type: article

Abstract: INTRODUCTION: The status of striatal dopamine (DA) D2 receptors in cigarette smoking is equivocal. One potential explanation is unreliability of self-report of smoking status, which may not accurately reflect exposure to combustible smoke products and thus contribute variance to estimations of D2 availability (a compound index that is comprised of both DA levels and D2 density). Given that tobacco and marijuana smoke share hundreds of toxic compounds that could have similar effects on striatal D2 availability, we determined urine metabolites for both and compared striatal [11C]raclopride (RAC) positron emission tomography (PET) D2 availability between analyte negative (ANneg) and positive (ANpos) groups. We hypothesized that the ANpos group (positive for cigarette and/or marijuana metabolites) would have lower D2 availability than ANneg. METHODS: Twenty-nine participants had resting RAC scans and quantitative urinalysis data for the major metabolites of nicotine (cotinine) and Δ9-tetrahydrocannabinol (THC; 11-nor-∆9-tetrahydrocannabinol-9-carboxylic acid [THCA]). Participants were classified as ANneg or ANpos. Parametric images of binding potential (BPND) were generated with MRTM2. Average BPND values were extracted from striatal subregions. RESULTS: Across all subregions, ANpos had an average of 13.1% lower BPND relative to ANneg (range: 6.6-20.0%). Significant differences were primarily in the nucleus accumbens and putamen. There were no effects of alcohol use disorder (AUD; secondary analysis). Within the ANpos group, there were no effects of self-reported cigarette smoking or analyte subgroups. CONCLUSION: ANpos individuals had lower striatal D2 availability relative to ANneg. Quantitative characterization of combustible smoke metabolites in PET studies of the dopaminergic system is recommended. IMPLICATIONS: We demonstrate for the first time that individuals who test positive for urine metabolites of recent tobacco and marijuana combustible smoke exposure (via quantitative gas chromatography/mass spectroscopy) have lower striatal D2 receptor availability. This effect is apparently independent of both presence of alcohol use disorder and endorsement of cigarette smoking status. We emphasize both the importance of characterizing study participants beyond self-report of smoking status and the need to ensure that control samples are well-matched for smoking status of target neuropsychiatric populations.

Source: Nicotine & Tobacco Research

DOI: 10.1093/ntr/ntaf249

Authors: Karmen K Yoder, Samantha Carpenter, Karen L Hile, Mario Dzemidzic, Timothy C Durazzo