Treating Cannabis Use Disorder & Withdrawal With PP-01: NIDA Grant Accelerates Phase 3 Trial

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. The dual approach is intended to address withdrawal symptoms—including irritability, sleep disruption, and cravings—that can emerge within hours of cannabis cessation as well as symptoms that develop later in the withdrawal process, Shelli Graham, PhD, said.

More than 19 million Americans are affected by CUD, and no treatment approved by the US Food and Drug Administration (FDA) currently exists for the condition.¹ Clinicians are instead limited to off-label therapies that may address isolated symptoms but have not been evaluated in rigorous trials specifically targeting withdrawal in this population, according to Graham.

The FDA has granted PP-01 Fast Track designation, a status reserved for products addressing a serious condition with an unmet medical need; the designation allows PleoPharma more frequent communication with the agency regarding the clinical development program.² PleoPharma also received a $6.5 million, 3-year grant from NIDA to help fund a pivotal phase 3 trial of PP-01, which is ongoing, Graham said. The Fast Track designation and NIDA funding, in combination, validate CUD as a serious condition warranting a specifically studied, FDA-approved medication, Graham highlighted.

PP-01 is a once-daily investigational medication-assisted therapy for patients with CUD who are experiencing withdrawal symptoms and have attempted to quit cannabis use. It is intended to help patients get through the difficult withdrawal period and support successful recovery, Graham said. "The phase 3 program that's ongoing is enrolling extremely rapidly and ahead of projections, which really speaks to and confirms the large unmet need for an FDA approved product in this population," Graham said.

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. FDA grants Fast Track designation to PleoPharma, Inc's investigational new drug, PP-01, for the mitigation of cannabis withdrawal symptoms in patients with cannabis use disorder: a potential first in class treatment. Press release. February 13, 2025. Accessed September 14, 2026. https://www.prnewswire.com/news-releases/fda-grants-fast-track-designation-to-pleopharma-incs-investigational-new-drug-pp-01-for-the-mitigation-of-cannabis-withdrawal-symptoms-in-patients-with-cannabis-use-disorder-a-potential-first-in-class-treatment-302376117.html