Proof‐of‐concept trial of PP‐01 for mitigating cannabis withdrawal syndrome in participants with cannabis use disorder
- 1Aspen Consulting, LLC Denver Colorado USA
- 2PleoPharma, Inc Phoenixville Pennsylvania USA
- 3Biomedical Computer Research Institute Penn Valley Pennsylvania USA
Abstract
Background and Objectives: Cannabis withdrawal symptoms can be severe and protracted, significantly impeding the ability to abstain from cannabis use, resulting in failed quit attempts and relapse. This clinical trial evaluated safety and efficacy of PP‐01, a novel dual‑mechanism of action, investigational agent, for mitigating cannabis withdrawal symptoms in patients with cannabis use disorder (CUD).
Methods: This Phase 1b/2a randomized, double‐blind, placebo‐controlled, crossover, 5‐night, inpatient study evaluated efficacy and safety of PP‐01 (nabilone and gabapentin) in 14 adults with moderate to severe CUD. Participants with daily/near daily use of ≥1 gram/day of cannabis and a history of cannabis withdrawal were randomized to PP‐01 or placebo. Severity and bothersomeness of withdrawal symptoms were evaluated by patient daily diary. Mixed model repeated measures analysis of variance was used to compare mean differences between PP‐01 and placebo.
Results: PP‐01 significantly reduced severity (p = .0222) and bothersomeness (p = .0063) of cannabis withdrawal symptoms within 10 and 4 h post‐first dose of PP‐01, respectively. Sleep quality and cannabis cravings significantly improved following first dose through discharge. Objective withdrawal measures also statistically significantly improved. PP‐01 was well tolerated; adverse events (AEs) were mild in severity with no serious AEs.
Discussion and Conclusions: Investigational PP‐01 mitigated cannabis withdrawal symptoms in participants with moderate to severe CUD, was safe and well‐tolerated in this proof‐of‐concept study.
Scientific Significance: PP‐01 is intended as a potential treatment for cannabis withdrawal syndrome (CWS)/CUD, a serious and unmet need for which there is no Food and Drug Administration (FDA)‐approved medication.
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BibTeX
@article{slagle2026proofofconcept,
title = {{Proof‐of‐concept trial of PP‐01 for mitigating cannabis withdrawal syndrome in participants with cannabis use disorder}},
author = {Ashley F. Slagle and Jay Constantine and Harvey Kushner and Shelli Graham and Ginger Constantine},
journal = {The American Journal on Addictions},
year = {2026},
month = sep,
doi = {10.1111/ajad.70202},
url = {https://doi.org/10.1111/ajad.70202},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Proof‐of‐concept trial of PP‐01 for mitigating cannabis withdrawal syndrome in participants with cannabis use disorder
AU - Ashley F. Slagle
AU - Jay Constantine
AU - Harvey Kushner
AU - Shelli Graham
AU - Ginger Constantine
PY - 2026
DA - 2026/09/09
JO - The American Journal on Addictions
DO - 10.1111/ajad.70202
UR - https://doi.org/10.1111/ajad.70202
AB - Background and Objectives: Cannabis withdrawal symptoms can be severe and protracted, significantly impeding the ability to abstain from cannabis use, resulting in failed quit attempts and relapse. This clinical trial evaluated safety and efficacy of PP‐01, a novel dual‑mechanism of action, investigational agent, for mitigating cannabis withdrawal symptoms in patients with cannabis use disorder (CUD). Methods: This Phase 1b/2a randomized, double‐blind, placebo‐controlled, crossover, 5‐night, inpatient study evaluated efficacy and safety of PP‐01 (nabilone and gabapentin) in 14 adults with moderate to severe CUD. Participants with daily/near daily use of ≥1 gram/day of cannabis and a history of cannabis withdrawal were randomized to PP‐01 or placebo. Severity and bothersomeness of withdrawal symptoms were evaluated by patient daily diary. Mixed model repeated measures analysis of variance was used to compare mean differences between PP‐01 and placebo. Results: PP‐01 significantly reduced severity (p = .0222) and bothersomeness (p = .0063) of cannabis withdrawal symptoms within 10 and 4 h post‐first dose of PP‐01, respectively. Sleep quality and cannabis cravings significantly improved following first dose through discharge. Objective withdrawal measures also statistically significantly improved. PP‐01 was well tolerated; adverse events (AEs) were mild in severity with no serious AEs. Discussion and Conclusions: Investigational PP‐01 mitigated cannabis withdrawal symptoms in participants with moderate to severe CUD, was safe and well‐tolerated in this proof‐of‐concept study. Scientific Significance: PP‐01 is intended as a potential treatment for cannabis withdrawal syndrome (CWS)/CUD, a serious and unmet need for which there is no Food and Drug Administration (FDA)‐approved medication.
SN - 1055-0496
SN - 1521-0391
ER -