PleoPharma has dosed the first patient in its pivotal Phase 3 CAN-004 trial of PP-01 for cannabis use disorder, advancing a Fast Track-designated therapy toward potential FDA submission as the first approved treatment for cannabis withdrawal symptoms.
Written By: Disha Jadhao, BPharm
Reviewed By: Pharmacally Editorial Team
PleoPharma has initiated its pivotal Phase 3 development program for PP-01 after dosing the first participant in the CAN-004 study (NCT07644052), a late-stage clinical trial evaluating the investigational therapy in adults with cannabis use disorder (CUD). The milestone advances development of a treatment that could address a major gap in addiction medicine, where no FDA-approved therapies currently exist for cannabis withdrawal syndrome or CUD.
The Phase 3 program follows encouraging Phase 2b results and is intended to support a future New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA). PP-01 has already received FDA Fast Track designation, highlighting the unmet medical need in this therapeutic area.
Addressing a Growing Public Health Challenge
Cannabis use disorder has become an increasingly common condition in the United States, affecting an estimated 20.6 million people. Despite growing treatment demand, clinicians currently rely on behavioral interventions because no approved pharmacologic therapies are available.
Withdrawal symptoms often emerge rapidly when individuals attempt to reduce or discontinue cannabis use. Common symptoms include anxiety, irritability, cravings, insomnia, decreased appetite, restlessness, depressed mood, and various physical complaints. These symptoms frequently contribute to relapse and can make sustained abstinence difficult.
PP-01 is being developed to help mitigate these withdrawal symptoms and improve the likelihood of successful treatment engagement and recovery.
CAN-004 Phase 3 Trial Design
CAN-004 is a multicenter, randomized, double-blind, placebo- and active-controlled Phase 3 study enrolling adults with moderate-to-severe cannabis use disorder who are actively attempting to discontinue cannabis use.
The trial will evaluate both the efficacy and safety of PP-01 in reducing withdrawal symptoms during cannabis cessation. While detailed endpoint information has not yet been disclosed, the study is expected to provide the pivotal evidence required for regulatory review.
The trial builds on positive findings from the Phase 2b program, which supported advancement into late-stage development.
How PP-01 Works
PP-01 is an investigational oral therapy administered once daily. The candidate employs a dual mechanism of action targeting suppressed cannabinoid type 1 (CB1) receptors and neurotransmitter dysregulation within the brain’s mesolimbic reward pathway, a key neural circuit involved in addiction and substance dependence.
By addressing both cannabinoid receptor signaling and reward-pathway dysfunction, the therapy aims to reduce the physiological and psychological symptoms associated with cannabis withdrawal.
The company reports that PP-01 has demonstrated rapid onset of action along with favorable safety and tolerability in earlier-stage studies.
Clinical Implications
Ginger Constantine, MD, Chief Executive Officer, Co-founder, and Chairperson of PleoPharma, described first-patient dosing as a significant milestone for both the company and patients seeking treatment options for cannabis dependence.
She emphasized that the absence of approved therapies for cannabis withdrawal continues to leave many patients without effective medical support during cessation attempts.
Enrollment and execution of CAN-004 now become key near-term priorities. If successful, the study could support regulatory submission and position PP-01 as the first approved medication specifically indicated for cannabis withdrawal symptoms, potentially establishing a new treatment option for millions of individuals living with cannabis use disorder.
What This Means for Patients
For people living with cannabis use disorder, quitting cannabis can be challenging because withdrawal symptoms often appear within days of stopping use. Anxiety, irritability, strong cravings, sleep problems, and mood changes can make it difficult to remain abstinent and frequently lead to relapse.
There are currently no FDA-approved medications specifically available to help manage cannabis withdrawal symptoms. If PP-01 proves effective in the Phase 3 CAN-004 trial and receives regulatory approval, it could become the first medication specifically indicated for this purpose.
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About the Writer
Disha Sanjay Jadhao (LinkedIn) is a pharmacy graduate and healthcare writer with a strong interest in clinical documentation and simplifying healthcare information for better reader understanding. She is enthusiastic, adaptable, and eager to take on new challenges while contributing to clear, accurate, and engaging medical and pharmaceutical content.