{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:41:25Z","timestamp":1787726485024,"version":"build-2784847793"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Targeting peroxisome proliferator-activated receptors (PPARs) has received increasing interest as a potential strategy to treat substance use disorders due to the localization of PPARs in addiction-related brain regions and the ability of PPAR ligands to modulate dopamine neurotransmission. Robust evidence from animal models suggests that agonists at both the PPAR-\u03b1 and PPAR-\u03b3 isoforms can reduce both positive and negative reinforcing properties of ethanol, nicotine, opioids, and possibly psychostimulants. A reduction in the voluntary consumption of ethanol following treatment with PPAR agonists seems to be the most consistent finding. However, the human evidence is limited in scope and has so far been less promising. There have been no published human trials of PPAR agonists for treatment of alcohol use disorder, despite the compelling preclinical evidence. Two trials of PPAR-\u03b1 agonists as potential smoking cessation drugs found no effect on nicotine-related outcomes. The PPAR-\u03b3 agonist pioglitazone showed some promise in reducing heroin, nicotine, and cocaine craving in two human laboratory studies and one pilot trial, yet other outcomes were unaffected. Potential explanations for the discordance between the animal and human evidence, such as the potency and selectivity of PPAR ligands and sex-related variability in PPAR physiology, are discussed.<\/jats:p>","DOI":"10.3390\/cells9051196","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T10:53:55Z","timestamp":1589280835000},"page":"1196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Therapeutic Potential of Peroxisome Proliferator-Activated Receptor (PPAR) Agonists in Substance Use Disorders: A Synthesis of Preclinical and Human Evidence"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-3704","authenticated-orcid":false,"given":"Justin","family":"Matheson","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, 27 King\u2019s College Circle, Toronto, ON M5S 3H7, Canada"},{"name":"Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-4973","authenticated-orcid":false,"given":"Bernard","family":"Le Foll","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, 27 King\u2019s College Circle, Toronto, ON M5S 3H7, Canada"},{"name":"Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada"},{"name":"Addictions Division, Centre for Addiction and Mental Health, 100 Stokes Street, Toronto, ON M6J 1H4, Canada"},{"name":"Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada"},{"name":"Department of Psychiatry, Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada"},{"name":"Institute of Medical Sciences, University of Toronto, 1 King\u2019s College Circle, Room 2374, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Family and Community Medicine, University of Toronto, 500 University Avenue, 5th Floor, Toronto, ON M5G 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"ref_1","unstructured":"UNODC (2020, April 14). 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