{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:08:19Z","timestamp":1789013299268,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Addict"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>Cannabis withdrawal symptoms can be severe and protracted, significantly impeding the ability to abstain from cannabis use, resulting in failed quit attempts and relapse. This clinical trial evaluated safety and efficacy of PP\u201001, a novel dual\u2011mechanism of action, investigational agent, for mitigating cannabis withdrawal symptoms in patients with cannabis use disorder (CUD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This Phase 1b\/2a randomized, double\u2010blind, placebo\u2010controlled, crossover, 5\u2010night, inpatient study evaluated efficacy and safety of PP\u201001 (nabilone and gabapentin) in 14 adults with moderate to severe CUD. Participants with daily\/near daily use of \u22651\u2009gram\/day of cannabis and a history of cannabis withdrawal were randomized to PP\u201001 or placebo. Severity and bothersomeness of withdrawal symptoms were evaluated by patient daily diary. Mixed model repeated measures analysis of variance was used to compare mean differences between PP\u201001 and placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PP\u201001 significantly reduced severity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.0222) and bothersomeness (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.0063) of cannabis withdrawal symptoms within 10 and 4\u2009h post\u2010first dose of PP\u201001, respectively. Sleep quality and cannabis cravings significantly improved following first dose through discharge. Objective withdrawal measures also statistically significantly improved. PP\u201001 was well tolerated; adverse events (AEs) were mild in severity with no serious AEs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusions<\/jats:title>\n                    <jats:p>Investigational PP\u201001 mitigated cannabis withdrawal symptoms in participants with moderate to severe CUD, was safe and well\u2010tolerated in this proof\u2010of\u2010concept study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Scientific Significance<\/jats:title>\n                    <jats:p>PP\u201001 is intended as a potential treatment for cannabis withdrawal syndrome (CWS)\/CUD, a serious and unmet need for which there is no Food and Drug Administration (FDA)\u2010approved medication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ajad.70202","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:33:36Z","timestamp":1789011216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proof\u2010of\u2010concept trial of PP\u201001 for mitigating cannabis withdrawal syndrome in participants with cannabis use disorder"],"prefix":"10.1111","author":[{"given":"Ashley F.","family":"Slagle","sequence":"first","affiliation":[{"name":"Aspen Consulting, LLC Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Constantine","sequence":"additional","affiliation":[{"name":"PleoPharma, Inc Phoenixville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey","family":"Kushner","sequence":"additional","affiliation":[{"name":"Biomedical Computer Research Institute Penn Valley Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelli","family":"Graham","sequence":"additional","affiliation":[{"name":"PleoPharma, Inc Phoenixville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginger","family":"Constantine","sequence":"additional","affiliation":[{"name":"PleoPharma, Inc Phoenixville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Substance Abuse and Mental Health Services Administration (SAMHSA). 2024 NSDUH Detailed Tables.2025. 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