Addiction and Substance Use Disorder Clinical Trials 2026: Opioid, Alcohol, and New Treatments

Addiction research has changed more in the past five years than in the preceding two decades. The conversation has moved from symptom management to targeting the specific neurobiological mechanisms of craving, withdrawal, and relapse with a precision that simply wasn't available before. The GLP-1 finding — that drugs originally developed for diabetes appear to reduce cravings for alcohol, opioids, and nicotine through mesolimbic dopamine modulation — was genuinely unexpected and has opened an entirely new research direction. Meanwhile, psilocybin-assisted therapy is approaching Phase 3 for alcohol use disorder, and ibogaine is being evaluated in structured clinical settings following striking results in veterans. The pipeline is broader than most patients realize, and the stigma that historically kept people out of addiction trials is slowly dissolving alongside it.

NIDA Clinical Trials Network: Where Most Patients Can Actually Access Research

The National Institute on Drug Abuse funds the Clinical Trials Network — approximately 16 research nodes conducting trials in real-world community treatment settings rather than exclusively at academic medical centers. This matters enormously for access. CTN trials recruit people already seeking treatment, and the sites are embedded in community programs rather than requiring patients to travel to tertiary care facilities. If you're looking for an addiction trial you can realistically participate in, the CTN network is where to start.

• CTN-0094 (INSPIRE): Comparing extended-release subcutaneous buprenorphine (Sublocade, monthly injection) versus daily sublingual buprenorphine/naloxone for opioid use disorder. The core question is whether the depot formulation improves adherence and reduces diversion — significant practical issues with daily sublingual buprenorphine in community settings. Primary outcomes include illicit opioid use confirmed by urine toxicology and treatment retention at 24 weeks.
• CTN-0099: Evaluating liraglutide (a GLP-1 agonist, 1.8mg daily) versus placebo for reducing alcohol use in heavy drinkers with alcohol use disorder. Recruiting adults who drink ≥14 drinks/week (men) or ≥7 drinks/week (women), motivated to reduce or stop. Primary outcome: reduction in percentage of heavy drinking days over 16 weeks. This is one of several GLP-1 addiction trials feeding into a rapidly growing evidence base.
• Contingency management trials: Multiple CTN trials are evaluating financial incentives for stimulant-negative urine screens — providing prizes up to $599 for confirmed cocaine and methamphetamine abstinence. Contingency management is among the most efficacious behavioral interventions for stimulant use disorder (effect sizes d=0.58 in meta-analyses) but has been historically restricted by federal guidelines that equated it with gambling. SAMHSA policy revisions in 2023 have clarified its permissibility, and pragmatic trials are now validating CM delivery in Medicaid-funded community programs.
• Finding CTN trials: Search ClinicalTrials.gov with "NIDA Clinical Trials Network" as sponsor, or visit the NIDA website for CTN site listings by state. CTN sites are embedded in community treatment programs — coordinators can discuss both standard care and trial participation in the same appointment.

GLP-1 Agonists: The Unexpected Addiction Treatment

The discovery that semaglutide and liraglutide reduce substance cravings may be the most surprising finding in addiction medicine in a generation. In rodent models, GLP-1 receptor agonists reduce alcohol, cocaine, and opioid self-administration by 50–80%. The mechanism appears to involve GLP-1 receptors in the mesolimbic reward circuitry — specifically the nucleus accumbens and ventral tegmental area — where GLP-1 signaling attenuates dopamine release triggered by addictive substances, reducing the rewarding value of the substance and consequently the craving to use it.

Observational data in humans has been consistent with this mechanism. A 2023 analysis of insurance claims (Klausen et al.) found that patients prescribed semaglutide for diabetes or obesity had significantly lower rates of alcohol use disorder diagnoses and opioid overdose events than matched controls on other medications. This is not randomized evidence — confounding is possible — but the signal is large enough and biologically plausible enough to justify the ongoing Phase 2 program.

• NCT05895643 and related semaglutide AUD trials: Phase 2 trials at multiple academic centers testing weekly 0.5–1mg subcutaneous semaglutide in adults with moderate-to-severe DSM-5 alcohol use disorder. Primary outcomes are reduction in heavy drinking days and alcohol craving scores (Penn Alcohol Craving Scale). Several studies include fMRI subsections to assess reward circuit changes. Results expected 2025–2026.
• Semaglutide as adjunct to buprenorphine for OUD: Phase 2 trials evaluating whether adding weekly semaglutide to existing buprenorphine treatment reduces residual opioid cravings and relapse risk in patients already on MOUD. The hypothesis is that GLP-1 signaling addresses the craving component that buprenorphine's partial agonism doesn't fully resolve.
• Eligibility typically requires: Adults 18+, DSM-5 SUD diagnosis, absence of GLP-1 contraindications (personal or family history of medullary thyroid carcinoma or MEN2, prior pancreatitis), not pregnant or planning pregnancy.

Psilocybin for Alcohol Use Disorder: From Landmark Phase 2 Toward Phase 3

The Johns Hopkins psilocybin AUD study (Bogenschutz et al., JAMA Psychiatry 2022) enrolled 93 adults with AUD in a double-blind randomized trial comparing two sessions of high-dose psilocybin (25mg or 40mg) plus motivational enhancement therapy versus diphenhydramine (active placebo) plus MET. The psilocybin group showed an 83% reduction in percentage of heavy drinking days versus 51% in the placebo group (difference −32 percentage points, 95% CI −53 to −10, p=0.0009) at the 32-week endpoint. Eight months after the final psilocybin session, 48% of the psilocybin group had stopped drinking entirely versus 24% in the control group. These are large effect sizes by any metric in addiction research.

• Current Phase 2 trials (2026): Multiple university centers — Yale, UCSF, UNC Chapel Hill, Ohio State — are running psilocybin-assisted therapy trials for AUD using variations of the Hopkins protocol. Most test 25–30mg psilocybin in 2–3 sessions with trained therapists present, preceded by 2–3 preparatory sessions and followed by 4–6 integration sessions. Total time commitment: approximately 3–4 months.
• USONA Phase 3: USONA Institute is advancing a Phase 3 registration trial for psilocybin in AUD following FDA IND approval. Protocol is in development; enrollment expected to begin mid-2026. This would be the first Phase 3 psychedelic trial for a substance use disorder indication.
• Exclusion criteria: Personal or family history of psychosis, schizophrenia, or bipolar I disorder; current lithium or MAOI use; severe cardiovascular disease or uncontrolled hypertension. Screening is thorough — psychiatric history is evaluated in detail before enrollment.

Ibogaine for Opioid Use Disorder: The Veterans Data

Ibogaine, derived from the West African Tabernanthe iboga plant, has produced some of the most striking case series data in addiction medicine — reportedly interrupting opioid withdrawal and cravings for weeks to months after a single dose. A 2023 Nature Medicine study (Cherian et al.) of 30 Special Operations veterans with treatment-resistant OUD, TBI, and PTSD administered a single dose of ibogaine (median dose 12 mg/kg) with magnesium co-administration for cardiac safety. At one-month follow-up, PTSD symptoms decreased by 88%, disability decreased by 87%, and depression decreased by 86%. Twelve of 30 participants had no PTSD diagnosis at follow-up. These are extraordinary numbers — even accounting for the uncontrolled design and selection bias, the effect sizes are large enough to demand controlled investigation.

• Phase 2 trial (NCT05765981): MAPS-sponsored study evaluating ibogaine with magnesium co-administration for treatment-resistant OUD; recruiting veterans and non-veterans at clinical sites in Canada and Europe (ibogaine remains Schedule I in the US, making US-based trials legally complex without FDA Breakthrough designation or an IND for Schedule I substances).
• Noribogaine (TBX-002, DemeRx): An ibogaine metabolite with a 24+ hour half-life versus ibogaine's 4–6 hours, and a potentially improved cardiac safety profile. Phase 1 studies completed; Phase 2 for OUD in preparation. The longer half-life may allow more gradual and controllable dosing.
• Cardiac safety is the core issue: Ibogaine blocks hERG potassium channels, prolonging the QT interval and carrying arrhythmia risk — the mechanism responsible for deaths associated with uncontrolled ibogaine use outside clinical settings. All formal clinical trials require baseline ECG and cardiology clearance, continuous cardiac monitoring throughout the session, and magnesium supplementation to mitigate QT prolongation. This is non-negotiable and is why these trials are only conducted at specialized clinical sites.

MOUD Optimization: What the Evidence Actually Shows

Medications for opioid use disorder — buprenorphine, methadone, and extended-release naltrexone — are the established evidence-based standard of care, with Phase 3 trial data showing 50–60% reductions in illicit opioid use and significant mortality benefit. The original X:BOT trial (NEJM 2018, Lee et al., n=570) compared extended-release injectable naltrexone (Vivitrol, 380mg monthly IM) versus daily buprenorphine-naloxone. In the intent-to-treat analysis, XR-naltrexone was less effective due to the induction barrier — 28% of patients assigned to naltrexone couldn't complete detoxification to start it. Among patients who successfully initiated, outcomes were comparable. This is the nuance that gets lost in simplistic comparisons: the evidence doesn't say naltrexone is inferior, it says the induction barrier is clinically significant in community settings.

• Low-dose buprenorphine induction (Bernese protocol) trials: Allows patients actively using fentanyl to start buprenorphine without precipitated withdrawal — by initiating at micro-doses (0.5–2mg) and gradually escalating over 4–7 days rather than requiring full opioid abstinence. Pragmatic trials validating the protocol across emergency department and outpatient settings have been published, but standardized implementation protocols are still being established.
• Sublocade long-term outcomes (CTN-0094 extension): Beyond the INSPIRE comparison trial, longer-term outcomes data on monthly subcutaneous buprenorphine in community treatment settings are being collected. The hypothesis is that eliminating daily adherence requirements reduces diversion and improves sustained remission rates over 12+ months.

How to Find Addiction Clinical Trials in 2026

• ClinicalTrials.gov: Search your substance (e.g., "alcohol use disorder" or "opioid use disorder") + "recruiting" + your state. Filter by "Phase 2" or "Phase 3" to find the most advanced studies. Many trials offer compensation and cover transportation costs.
• NIDA Clinical Trials Network: nida.nih.gov lists CTN sites by state — these are embedded in community programs and are the most accessible trials for patients already seeking treatment.
• SAMHSA treatment locator: findtreatment.gov identifies community treatment programs — many serve as CTN research sites and have coordinators who can discuss both standard care and trial participation.
• Psychedelic trial registries: MAPS (maps.org), USONA Institute, and the Multidisciplinary Association for Psychedelic Studies maintain registries for psilocybin, MDMA, and ibogaine studies. These trials are typically smaller, more rigorous, and more selective than CTN trials — screening can take several appointments.