PleoPharma Doses First Patient in Pivotal Phase 3 Trial of PP-01 for Cannabis Withdrawal, Presents Phase 2 Data Showing 43% Reduction in Irritability
Key Insights
PleoPharma (search) has dosed the first patient in CAN-004, a pivotal Phase 3 trial evaluating PP-01 for cannabis withdrawal symptoms in adults with cannabis use disorder (search), a condition affecting an estimated 20.6 million people in the U.S.
At CPDD 2026, the company presented Phase 2 CAN-002 data showing PP-01 HD produced a statistically significant 43% reduction in the Irritability Domain versus placebo (P = 0.01) during Days 2-5, with a dose response observed.
PP-01 is a dual-mechanism, once-daily oral investigational therapy targeting suppressed CB1 receptors (search) and neurotransmitter dysregulation, and has received FDA Fast Track designation.
PleoPharma (search) has reached a significant clinical milestone with the dosing of the first patient in CAN-004, a pivotal Phase 3 clinical trial evaluating PP-01, an investigational once-daily oral therapy for the mitigation of cannabis withdrawal symptoms in adults with cannabis use disorder (search) (CUD). The announcement, made June 18, 2026, comes just days after the company presented encouraging Phase 2 data at the College on Problems of Drug Dependence (CPDD) 88th Annual Scientific Meeting in Portland, Oregon.
Cannabis use disorder (search) affects an estimated 20.6 million people in the United States, according to the 2024 National Survey on Drug Use and Health. More than 1.4 million people received treatment for CUD in 2024 despite the absence of any FDA-approved medication-assisted treatment. "Despite the growing prevalence of cannabis use disorder, there are currently no FDA-approved treatments for cannabis withdrawal syndrome or cannabis use disorder," said Ginger Constantine, M.D., chief executive officer, co-founder and chairperson of the board of PleoPharma (search).
Phase 2 CAN-002 Results Presented at CPDD
At the CPDD meeting, PleoPharma (search) presented two posters detailing the patient experience of cannabis withdrawal and efficacy data from the Phase 2 CAN-002 trial (NCT05494437). The trial demonstrated that PP-01 HD produced a statistically significant 43% reduction in the Irritability Domain versus placebo (P = 0.01) during Days 2-5, with a dose response observed.
"These findings provide important qualitative insight into the severity and speed of onset of cannabis withdrawal symptoms in individuals with cannabis use disorder (search)," said Ashley Slagle, M.S., Ph.D., chief clinical outcome officer, consultant. "These data capture the patient voice directly, advancing a clearer understanding of the burden of cannabis withdrawal and the need for effective treatment options."
A qualitative patient-reported outcomes study of 15 adults characterized the severity, onset, and impact of cannabis withdrawal in adults with CUD. The findings underscored the meaningful burden withdrawal symptoms can place on patients attempting to stop or reduce cannabis use.
Ginger Constantine, M.D., added, "The CAN-002 findings add to the growing body of evidence supporting PP-01 and its potential role in addressing cannabis withdrawal symptoms in patients with cannabis use disorder (search). We are pleased to share these data at CPDD and remain focused on advancing a potential new treatment option in an area of substantial unmet medical need."
Phase 3 CAN-004 Trial Design
CAN-004 (NCT07644052) is a Phase 3, multicenter, randomized, double-blind, placebo and active-controlled study evaluating the efficacy and safety of PP-01 in adults with moderate to severe CUD who are seeking to discontinue cannabis use. The study builds upon the positive Phase 2b clinical data and is intended to support an FDA submission of a new drug application for PP-01.
PP-01 has received Fast Track designation from the U.S. Food and Drug Administration and has the potential to become the first approved treatment specifically designed to mitigate cannabis withdrawal symptoms.
Mechanism of Action and Clinical Profile
PP-01 is a dual mechanism of action investigational product that targets suppressed CB1 receptors (search) and neurotransmitter dysregulation in the mesolimbic reward pathway. The therapy is intended as a once-daily oral product with a rapid onset of action and excellent safety and tolerability. Many people with CUD experience a rapid onset of withdrawal symptoms when they attempt to stop or reduce cannabis, leading to relapse. Typical symptoms include anxiety, irritability, cravings, sleep disturbance, decreased appetite, restlessness, depression, mood disturbances, and physical symptoms.
"Dosing the first patient in our Phase 3 trial is a significant milestone for PleoPharma (search) and an important step forward to help those patients with cannabis use disorder (search) who are seeking to quit or reduce cannabis," said Dr. Constantine.