Lower Striatal Dopamine D2 Receptor Availability in Individuals Who Test Positive for Quantitated Urine Metabolites of Tobacco and/or Marijuana Smoke.
| Title: | Lower Striatal Dopamine D2 Receptor Availability in Individuals Who Test Positive for Quantitated Urine Metabolites of Tobacco and/or Marijuana Smoke. |
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| Authors: | Yoder KK; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN United States.; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN United States.; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN United States.; Carpenter S; Department of Psychological Science, Ball State University, Muncie, IN United States.; Illinois Behavioral Health Workforce Center, University of Illinois-Chicago, Chicago, IL United States.; Hile KL; Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN United States.; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN United States.; Dzemidzic M; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN United States.; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN United States.; Durazzo TC; War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA United States.; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA United States. |
| Source: | Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco [Nicotine Tob Res] 2026 Apr 22; Vol. 28 (5), pp. 791-798. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9815751 Publication Model: Print Cited Medium: Internet ISSN: 1469-994X (Electronic) Linking ISSN: 14622203 NLM ISO Abbreviation: Nicotine Tob Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Oxford : Oxford University Press; Original Publication: Abingdon, Oxfordshire, UK : Carfax Pub. and Society for Research on Nicotine and Tobacco, c1999- |
| MeSH Terms: | Receptors, Dopamine D2*/metabolism ; Marijuana Smoking*/urine ; Marijuana Smoking*/metabolism ; Corpus Striatum*/metabolism ; Corpus Striatum*/diagnostic imaging; Dronabinol/urine ; Dronabinol/analogs & derivatives ; Cotinine/urine ; Nicotine/urine ; Humans ; Male ; Female ; Adult ; Positron-Emission Tomography ; Raclopride ; Young Adult ; Middle Aged |
| 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.; (© The Author(s) 2025. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| References: | J Chromatogr. 1977 Jan 21;131:422-4. (PMID: 853102); J Psychopharmacol. 2012 Jan;26(1):144-9. (PMID: 21890594); Neurosci Lett. 2008 Jan 3;430(1):38-42. (PMID: 18060695); Brain Imaging Behav. 2013 Sep;7(3):326-34. (PMID: 23649848); Alcohol Clin Exp Res. 2019 Jun;43(6):1170-1179. (PMID: 30977902); J Epidemiol Community Health. 1984 Dec;38(4):335-9. (PMID: 6512488); Int J Neuropsychopharmacol. 2012 Aug;15(7):989-94. (PMID: 22243762); Synapse. 1993 Apr;13(4):350-6. (PMID: 8480281); Am J Psychiatry. 2001 Dec;158(12):2015-21. (PMID: 11729018); Science. 2001 Aug 10;293(5532):1164-6. (PMID: 11498597); Synapse. 2009 Aug;63(8):681-9. (PMID: 19360907); Biochem Biophys Res Commun. 2005 Jan 14;326(2):378-86. (PMID: 15582589); Nat Neurosci. 2020 Nov;23(11):1421-1432. (PMID: 32989295); Biol Psychiatry. 2012 Feb 1;71(3):192-8. (PMID: 22015315); Eur J Nucl Med Mol Imaging. 2012 Feb;39(2):220-5. (PMID: 22009382); Synapse. 2007 Aug;61(8):637-45. (PMID: 17492764); Biol Psychiatry. 2020 Nov 15;88(10):788-796. (PMID: 32507390); Addict Behav. 1994 Jan-Feb;19(1):33-9. (PMID: 8197891); J Neurosci. 2014 Dec 10;34(50):16851-5. (PMID: 25505336); J Cereb Blood Flow Metab. 1997 Sep;17(9):932-42. (PMID: 9307606); Drug Alcohol Depend. 2023 May 1;246:109860. (PMID: 37004462); J Cereb Blood Flow Metab. 2007 Mar;27(3):606-17. (PMID: 16788713); J Cereb Blood Flow Metab. 2003 Sep;23(9):1096-112. (PMID: 12973026); Clin Pharmacol Ther. 1983 Nov;34(5):604-11. (PMID: 6627820); Int J Environ Res Public Health. 2015 Jul 16;12(7):8198-213. (PMID: 26193290); Addict Behav. 1986;11(2):149-61. (PMID: 3739800); Synapse. 1993 Jun;14(2):169-77. (PMID: 8101394); Addict Biol. 2024 Nov;29(11):e70008. (PMID: 39576234); JAMA. 1983 Nov 25;250(20):2796-800. (PMID: 6644957); J Anal Toxicol. 2001 Oct;25(7):531-7. (PMID: 11599596); Drug Alcohol Depend. 2013 Feb 1;128(1-2):52-7. (PMID: 22909787); Am J Psychiatry. 2008 Apr;165(4):507-14. (PMID: 18316420); Nature. 1997 Apr 24;386(6627):830-3. (PMID: 9126741); J Cereb Blood Flow Metab. 1998 Nov;18(11):1196-210. (PMID: 9809509); Biomed Mass Spectrom. 1983 May;10(5):316-23. (PMID: 6305440); J Stud Alcohol. 1994 Mar;55(2):149-58. (PMID: 8189735); Int J Neuropsychopharmacol. 2008 May;11(3):413-7. (PMID: 17949514); J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9. (PMID: 17519979); Synapse. 2011 Dec;65(12):1344-9. (PMID: 21780185); Am J Public Health. 1988 Jun;78(6):699-701. (PMID: 3369604) |
| Grant Information: | R01 AA018354 United States AA NIAAA NIH HHS; R01 AA026014 United States AA NIAAA NIH HHS; R21 AA022650 United States AA NIAAA NIH HHS |
| Substance Nomenclature: | 0 (Receptors, Dopamine D2); 7J8897W37S (Dronabinol); K5161X06LL (Cotinine); 430K3SOZ7G (Raclopride); 6M3C89ZY6R (Nicotine) |
| Entry Date(s): | Date Created: 20251127 Date Completed: 20260422 Latest Revision: 20260423 |
| Update Code: | 20260423 |
| PubMed Central ID: | PMC12767398 |
| DOI: | 10.1093/ntr/ntaf249 |
| PMID: | 41307548 |
| Database: | MEDLINE |
Journal Article