Potential Drug for Mitigation of Cannabis Withdrawal Symptoms Receives FDA Fast Track Designation

The FDA has granted fast track designation (FTD) to PP-01 (PleoPharma), a dual mechanism of action investigational new drug, for the treatment of cannabis withdrawal syndrome in patients with cannabis use disorder, according to a news release from PleoPharma.¹

Cannabis use disorder could affect more individuals as the use of cannabis increases across the country. | Image Credit: © Joshua Resnick - stock.adobe.com

According to investigators, PP-01 is designed as a once-daily oral product to target suppressed CB1 receptors and neurotransmitter dysregulation in the mesolimbic reward pathway. The FTD allows for PP-01 to have a facilitated development and expedited review, given it is poised to fill a major unmet medical need. If approved, PP-01 would become the first-in-class treatment to mitigate withdrawal symptoms that many patients with cannabis use disorder experience.¹

"We are pleased that PP-01 has been granted FTD and are grateful to the FDA for recognizing the significance of cannabis withdrawal for the growing population with cannabis use disorder," Ginger Constantine, MD, CEO of PleoPharma, said in the news release.¹

The safety and efficacy of PP-01 were evaluated in CAN-002, a phase 2b, randomized, double-blind, placebo-controlled study that enrolled 234 participants between the ages of 18 and 55 years across 22 addiction centers that were seeking to cease cannabis use. Investigators in the trial observed statistically significant reductions in the presence of cannabis withdrawal symptoms with PP-01 compared with placebo.²

Furthermore, a dose response was observed in patients with the highest dose, providing mitigation of symptoms with clinically meaningful results (primary endpoint: P = .02), according to the investigators. In an important discovery, PP-01 was found to be well-tolerated among treated patients, with no safety signals observed.²

Based on these positive trial results and the new FTD, PleoPharma is planning a phase 3 clinical trial, in conjunction with the FDA, to further evaluate the effectiveness of PP-01.^1,2

According to US government data, in 2023, approximately 19.2 million Americans reported having cannabis use disorder, with 1.64 million individuals receiving either inpatient or outpatient treatment. In addition, the number of individuals who receive treatment for health problems associated with cannabis has grown by an average of 27% annually from 2018 to 2023.¹

The CDC reports that among individuals who use cannabis, approximately 3 in 10 have cannabis use disorder. The risk of developing cannabis use disorder is even higher for individuals who begin to use the drug before the age of 18. Though it is federally illegal, dozens of states and the District of Columbia have legalized cannabis at the state level, heightening use of the drug nationwide and across multiple age groups. In 2021 alone, 52.5 million people, or about 19% of Americans, used cannabis at least once.³

Critically, there are currently no FDA-approved medications for the treatment of either cannabis use disorder or cannabis withdrawal symptoms, making further research into potential therapies such as PP-01 paramount as cannabis use increases across the country.^1,2

“We recognize that many people do use cannabis without becoming dependent, but as with alcohol, some may develop a dependence (use disorder) that may be sustained and worsened by withdrawal symptoms,” Constantine continued. “Our mission is to provide a treatment option for those who want help discontinuing cannabis."¹

REFERENCES

1. PleoPharma. 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. PR Newswire. News Release. Released February 13, 2025. Accessed February 14, 2025. 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

2. PleoPharma. PleoPharma, Inc. reports positive phase 2b clinical trial data for mitigation of cannabis withdrawal: A potential first in class treatment. News Release. Released September 4, 2024. Accessed February 14, 2025. https://www.pleopharma.com/post/pleopharma-inc-reports-positive-phase-2b-clinical-trial-data-for-mitigation-of-cannabis-withdrawal

3. CDC. Cannabis and Public Health—Cannabis facts and stats. Last Updated February 22, 2024. Accessed February 14, 2025. https://www.cdc.gov/cannabis/data-research/facts-stats/index.html