Addressing the Treatment Gap in Cannabis Use Disorder

PP-01, PleoPharma's investigational oral therapy for cannabis withdrawal syndrome in patients with moderate to severe cannabis use disorder (CUD), works through a dual mechanism of action that targets suppressed CB1 receptors and corrects neurotransmitter dysregulation in the mesolimbic reward pathway. Medication-assisted therapy and behavioral therapy can function together rather than independently in the treatment of cannabis use disorder (CUD), said Shelli Graham, PhD. Medication addresses one component of cannabis withdrawal, while behavioral therapy addresses secondary, underlying issues that require continual management throughout recovery, Graham said. The 2 approaches work hand in hand rather than as substitutes for one another, she noted.

PleoPharma's phase 3 program was designed to confirm efficacy signals identified in the company's earlier phase 1b, 2a, and 2b trials, which demonstrated that PP-01 mitigated cannabis withdrawal symptoms in adults with moderate to severe CUD. "So for us that is the ultimate milestone that we're hoping to achieve is that we will see that confirmation of that of the results that we've already seen in earlier clinical trials," Graham said.

"There's so many people who are impacted by cannabis use disorder and cannabis withdrawal with no approved FDA approved medication," she noted.¹ PleoPharma's phase 3 program, including the CAN-004 trial, was designed to generate rigorous, evidence-based data supporting PP-01 specifically in patients with moderate to severe CUD experiencing cannabis withdrawal. CAN-004 enrollment outpaced projections, reflecting substantial unmet need, according to Graham. The National Institute on Drug Abuse awarded funding to support the study, and the FDA granted PP-01 Fast Track designation—developments Graham cited as validation of the program and the seriousness of the condition.²

Rising CUD prevalence, particularly among patients with moderate to severe disease, underscored the need for pharmacologic support during cessation attempts, Graham said. Withdrawal symptoms frequently drove patients who wanted to stop using cannabis back to use, undermining cessation efforts. PleoPharma's primary goal was to offer a treatment that mitigates withdrawal symptoms so that patients attempting to quit could get through the withdrawal period and stop using cannabis as intended, Graham noted.

Dr Graham is senior vice president of medical and clinical research at PleoPharma.

References

1. Kuntz L. NIDA awards PleoPharma $6.5 million grant to advance phase 3 trial of PP-01 for cannabis use disorder. Psychiatric Times. August 20, 2026. https://www.psychiatrictimes.com/view/nida-awards-pleopharma-6-5-million-grant-to-advance-phase-3-trial-of-pp-01-for-cannabis-use-disorder

2. PleoPharma, Inc. announces first patient dosed in pivotal phase 3 clinical trial of PP-01 (CAN-004) for mitigation of cannabis withdrawal symptoms in patients with cannabis use disorder. Press release. June 18, 2026. Accessed September 15, 2026. https://www.prnewswire.com/news-releases/pleopharma-inc-announces-first-patient-dosed-in-pivotal-phase-3-clinical-trial-of-pp-01-can-004-for-mitigation-of-cannabis-withdrawal-symptoms-in-patients-with-cannabis-use-disorder-302803987.html