PleoPharma Wins Federal NIDA Grant to Fund Phase 3 Cannabis Withdrawal Trial

I can’t apply these corrections as specified, and I want to be transparent about why rather than hand back the article with a false implication that it has been verified and repaired.

• Corrections 1, 2, 3, 4, and 6 are not text edits — they instruct me to supply, fetch, or check figures against external source texts (the NIDA award record, SAMHSA’s NSDUH, the September 2024 CAN-002 announcement, the ClinicalTrials.gov record for NCT07644052, and company materials describing PP-01). None of those texts were provided, and I have no ability to retrieve them. Fabricating “fetched” source text, or silently returning the article as though verification had occurred, would be worse than the original problem. Those passages therefore remain unchanged and unverified below; they should not be published until the source bundle is actually supplied.
• Correction 5 offered an executable alternative — “or cut the claim.” Since no source exists here to attribute the NIDA-portfolio characterization to, I applied the cut. That is the only change made.

—

A federal grant is now bankrolling what could become the first medication approved specifically for cannabis withdrawal. PleoPharma, Inc., a clinical-stage company based in Phoenixville, Pennsylvania, announced on August 20, 2026 that the National Institute on Drug Abuse has awarded it a $6.5 million, three-year grant to support the pivotal Phase 3 trial of PP-01, its investigational treatment for adults with cannabis use disorder.

The funding, made through NIDA, a division of the National Institutes of Health, backs the company’s CAN-004 trial, which is testing whether PP-01 can ease the withdrawal symptoms that surface when heavy, long-term cannabis users try to stop. It is a meaningful infusion of public money into a treatment gap that has drawn increasing research attention: more than 19 million people in the United States were reported by the Substance Abuse and Mental Health Services Administration to have cannabis use disorder, and there are currently no FDA-approved medications for either cannabis withdrawal syndrome or the disorder itself.

“Receiving this NIDA award is an important validation of the substantial unmet need for a treatment for cannabis use disorder and the potential of PP-01 to alleviate the withdrawal symptoms that can stand in the way of recovery,” said Shelli Grahm, the company’s senior vice president of medical and clinical research.

Withdrawal is the engine the treatment is aimed at. When people who use cannabis heavily try to quit or cut back, symptoms such as sleep problems, anxiety, irritability, restlessness, cravings, and physical discomfort commonly appear, and they are a documented driver of relapse. That cycle is precisely what PP-01 is designed to interrupt.

What PP-01 Is and How It Works

PP-01 is a once-daily oral product built on two active ingredients that are already familiar to clinicians: nabilone, a synthetic cannabinoid that acts partially at the same CB1 receptor that THC targets, and gabapentin, a drug that modulates GABA-related neurotransmitter activity. The company describes it as a dual-mechanism agent that addresses suppressed CB1 receptors and the neurotransmitter dysregulation in the brain’s reward pathway that heavy cannabis use leaves behind.

The logic is substitution plus stabilization. The nabilone component gives the downregulated cannabinoid system a partial, controlled signal during abstinence, while the gabapentin component targets the broader neurotransmitter imbalance. Both are tapered and titrated over the dosing period rather than given at a flat dose. This mechanistic rationale matters for readers because it explains why a cannabis-derived target is being used to treat cannabis withdrawal: the goal is to blunt the receptor-level shock of abrupt cessation, not to substitute one intoxicant for another.

What the Phase 2B Trial Found

The Phase 3 program rests on results from the company’s earlier CAN-002 trial. That study enrolled 234 participants between the ages of 18 and 55 who were seeking to discontinue cannabis, across 22 U.S. addiction centers, and randomly assigned them to PP-01, placebo, or the active comparators nabilone and gabapentin alone. According to the company’s September 2024 results announcement, participants on PP-01 showed statistically significant reductions in cannabis withdrawal symptoms versus placebo, with a dose response in which the highest dose produced what the company characterized as clinically meaningful relief on the primary endpoint (p = 0.02). The drug was well tolerated, with no safety signal detected.

A later analysis, presented at the 2025 College on Problems of Drug Dependence annual meeting, added detail. Baseline cannabis use in the treatment-seeking group averaged 4.6 grams per day, and 84 percent of participants met criteria for severe cannabis use disorder. PP-01 significantly reduced withdrawal scores compared with placebo (p < 0.02), and a secondary endpoint showed roughly five-fold greater cannabis abstinence two weeks after treatment compared with placebo. The most common adverse events were mild: headache, somnolence, fatigue, nausea, and dizziness, with no serious adverse events reported. The company also reported that the degree of withdrawal reduction during the first week of treatment predicted later abstinence, an observation that, if it holds up in Phase 3, would give clinicians an early marker of who is responding.

These are company-reported results from a completed trial, not yet findings confirmed in a peer-reviewed publication, and Phase 2 effects do not always carry into larger pivotal studies. That is the correct frame for reading the new grant: NIDA is funding the test of whether the effect is real at scale, not certifying that it is.

What the CAN-004 Phase 3 Trial Will Measure

The CAN-004 trial, registered as NCT07644052, is recruiting an estimated 420 adults with moderate to severe cannabis use disorder across roughly two dozen U.S. sites. It is a randomized, double-blind trial with quadruple masking, meaning participants, care providers, investigators, and outcome assessors are all blinded to assignment. Participants receive PP-01, the active comparator nabilone, or placebo daily for 34 days, with a total study duration of about 78 days that includes a one-week inpatient stay followed by clinic visits and telemedicine check-ins.

The primary endpoints are specific. One compares PP-01 against placebo on the area under the curve of a cannabis withdrawal score over days two through seven. The other compares PP-01 against nabilone over days 25 through 35 to assess rebound, the return of symptoms after dosing tapers off. Secondary endpoints break the withdrawal picture into its component domains: irritability, sleep, and craving. Notably, the design builds in the rebound question, which is the central concern with any cannabinoid-based withdrawal treatment and a sign the program is testing the risk a critic would raise.

The trial dosed its first patient in June 2026. PP-01 also holds Fast Track designation from the FDA, a status the agency grants to drugs aimed at serious conditions with unmet need, which allows more frequent interaction with regulators and the possibility of rolling review. The study’s estimated primary completion date is July 2027.

Why NIDA Funding This Work Is Notable

The grant is worth reading as more than a financing event. A three-year federal award to a private, clinical-stage company to run a pivotal Phase 3 program signals that the agency views the lack of any approved cannabis withdrawal or cannabis use disorder medication as a genuine public-health gap worth closing with public funds.

It also reflects where the underlying numbers have moved. The company’s June 2026 announcement cited an estimated 20.6 million people in the United States with cannabis use disorder, with more than 1.4 million receiving treatment in 2024 despite the absence of any approved medication to support them. For a condition of that scale, the treatment pipeline has been thin, and most people who try to quit do so without pharmacologic help. Whether PP-01 ultimately succeeds will be decided by the CAN-004 data over the next two years, but the federal government has now put money behind getting an answer.