Lower striatal dopamine D2 receptor availability in individuals who test positive for quantitated urine metabolites of tobacco and/or marijuana smoke

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.

Keywords: combustible smoke products; dopamine D2 receptor; marijuana; positron emission tomography; tobacco; urinalysis.

Figure 1.

Boxplots of extracted striatal RAC BP_ND by group with individual participant data points shown. Data are from the regions of interest (ROIs) with the highest and lowest effect sizes across ROIs, which showed significant differences between analyte negative (AN_neg) and analyte positive (AN_pos) individuals. Left: Data from the left (L) nucleus accumbens dorsal anterolateral ROI, Cohen’s d = 1.55. Right: Data from the right putamen dorsal anterior (DA) ROI, Cohen’s d = 0.77. Box extent illustrates the 25^th to the 75th percentiles (first and third interquartile range, IQR). The line inside the box is the median; whiskers demarcate data points within 1.5 times the IQR from the 25^th and 75^th percentiles. Outliers are denoted by unfilled circles with a blue outline. Mean ± s.d. values are presented in Table 2. Note: The data for the AN_neg group in the right putamen DA appear not to have an upper whisker. However, the whisker happens to have a value identical to the upper bound of the quartile box (2.81).