Five Addiction Treatments That Might Actually Work: A 2025 Assessment

Which of these five innovations will we look back on in 2030 as having actually mattered?

This is a question worth asking, because addiction treatment has a graveyard of promising approaches that never scaled. Virtual reality for cue exposure looked transformative in pilot studies. Ibogaine had fervent advocates and some compelling case reports. Multiple medications have shown efficacy in controlled trials but remain barely used in practice.

Innovation was never a problem; people are very innovative. But ensuring that what works in controlled settings scales to the real world is a formidable challenge. What will actually change outcomes for the 20 million Americans with substance use disorders? Some of these five approaches will hopefully cross that gap. Others won’t, and the reasons for failure may have nothing to do with the underlying science.

Over 100,000 Americans died from drug overdoses in 2023. Behind each number is someone’s child, parent, friend, or partner. Addiction remains one of our most pressing public health challenges, devastating families and communities while straining healthcare systems and social services.

Part of why addiction has been so difficult to treat is that humans are complex entities. Addiction involves reward circuitry, executive control systems, stress responses, social learning, and metabolic processes, all interacting in ways we’re still working to understand. Plus, you add the social context to the already complex biological substrate; a treatment that addresses craving might not solve adherence problems. An intervention that works for someone with intact social support might fail for someone with unstable housing. The heterogeneity of addiction means we are unlikely to find a magic bullet; we’ll need multiple tools.

Several innovations are maturing in 2025, each targeting different aspects of the problem. Some address biological mechanisms we couldn’t reach before. Others solve practical barriers like medication adherence or therapy access. A few are still years from clinical use but represent fundamentally new approaches. None are miracle cures, but together they suggest that treatment might become more precise, matching specific interventions to individual needs.

This is where we are in 2025.

GLP-1 Agonists: Beyond Appetite Suppression

Glucagon-like peptide-1 receptor agonists entered the addiction research space through an unexpected route. These medications, approved for diabetes and obesity, work by enhancing insulin secretion and promoting satiety. But clinicians and patients started noticing something else: people on semaglutide or tirzepatide reported reduced interest in alcohol. Some described it as the urge simply disappearing.

The evidence base for alcohol use disorder is growing. A 2025 JAMA Psychiatry trial tested low-dose semaglutide in 48 adults with alcohol use disorder over 9 weeks. The medication reduced the amount of alcohol consumed in laboratory self-administration sessions and decreased weekly craving compared to placebo. Some measures of weekly consumption improved. Large observational studies from electronic health records show that people prescribed GLP-1 agonists for diabetes or obesity are associated with fewer alcohol-related hospitalizations compared to those on other medications. There is also newer evidence suggesting that, by simply slowing down stomach emptying, GLP-1 agonists may diminish alcohol’s effect and reduce subsequent cravings.

The mechanism probably involves reward-related behavior in the context of bodily states. GLP-1 receptors are expressed throughout reward-related brain regions: the ventral tegmental area, nucleus accumbens, and lateral septum. Preclinical work suggests these receptors may modulate dopamine signaling, though the details remain to be worked out. I have written about this in a previous post.

What comes after semaglutide and tirzepatide? Several next-generation compounds are in Phase 3 trials. CagriSema combines semaglutide with cagrilintide, an amylin agonist. Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors, showing up to 24% weight loss in trials. Survodutide combines GLP-1 with glucagon. Orforglipron is an oral GLP-1 formulation. These trials will complete between 2025 and 2027. There is excitement among addiction researchers around the idea that designing GLP-1 agonists with higher blood-brain barrier penetration and more selective central nervous system targets can be a next frontier in addiction treatment.

Beyond alcohol use, the evidence is lower but the trajectory looks promising. Nicotine trials have shown initial promise. For stimulants and opioids, we currently have only preclinical rodent studies, but these show good effects. The preclinical stimulant data is particularly important given that methamphetamine and cocaine use disorders have no FDA-approved pharmacological treatments. Rodent studies demonstrate that GLP-1 agonists reduce self-administration of both methamphetamine and cocaine, attenuate drug-seeking behavior, and prevent relapse-like patterns. One retrospective study suggested reduced opioid overdose rates in people prescribed GLP-1 agonists. The evidence for alcohol is the strongest, but if CNS-targeted GLP-1 compounds can be developed specifically for addiction, the mechanism may be general enough to work across multiple substance classes. Might we see the first FDA approval of a GLP-1 agonist for addiction in 2030?

TMS: Targeting the Brain Directly

Transcranial magnetic stimulation has been FDA-approved for depression since 2008. The technology is straightforward: electromagnetic coils placed on the scalp induce electrical currents in underlying brain tissue, modulating neural activity. For depression, high-frequency stimulation of the left dorsolateral prefrontal cortex has proven effective. More recently, TMS received FDA clearance for smoking cessation.

The rationale for addiction treatment involves targeting prefrontal-striatal networks that are thought to control goal-directed behavior more generally. Chronic substance use is associated with reduced activity in prefrontal regions involved in executive control and elevated activity in reward-related striatal circuits. High-frequency TMS (typically 10 Hz) applied to the left dorsolateral prefrontal cortex aims to generate perturbations that reduce craving and improve cognitive control. Theta burst stimulation, a more recent variant, delivers similar effects in shorter sessions.

For alcohol use disorder, the evidence is mixed. Meta-analyses show heterogeneous outcomes, with some studies demonstrating positive effects on craving or consumption reduction. Deep TMS using H-coils appeared more effective than standard figure-8 coils, possibly because deeper structures like the insula and nucleus accumbens are better targeted. Studies varied widely in protocol (frequency, intensity, number of sessions), making it difficult to identify optimal parameters.

Tobacco use shows clearer success. Multiple studies demonstrate reduced smoking and nicotine dependence with TMS, leading to the 2020 FDA clearance for the BrainsWay Deep TMS system as an aid for smoking cessation. The typical protocol involves daily sessions over several weeks, targeting the left dorsolateral prefrontal cortex.

For stimulant use disorder, where no FDA-approved medications exist, TMS represents a particularly important opportunity. Several small trials in methamphetamine use disorder show reduced craving with 10 Hz stimulation over the left dorsolateral prefrontal cortex. A 2017 study of 30 participants found that 5 daily sessions significantly reduced craving compared to sham stimulation, with improvements in verbal learning and social cognition.

Cocaine use disorder trials have also shown promise. Studies using 15 Hz stimulation over the left dorsolateral prefrontal cortex demonstrated reductions in both craving and cocaine use measured by urine drug screens. Theta burst protocols targeting the frontal pole reduced days of use and money spent on cocaine in pilot studies.

The largest ongoing trial is STIMULUS, a multi-site study sponsored by the National Drug Abuse Treatment Clinical Trials Network. This double-blind, sham-controlled trial aims to recruit 160 participants with moderate to severe cocaine or methamphetamine use disorder. Participants receive up to 30 sessions of 10 Hz TMS at 120% motor threshold over the left dorsolateral prefrontal cortex, or sham stimulation, across 8 weeks. The primary outcome is feasibility (proportion completing at least 20 sessions), with secondary outcomes examining reduction in stimulant use and craving. The protocol was published in May 2025; and data collection appears to be ongoing. Be on the lookout for the results.

Current limitations are significant. Most completed trials enrolled 30 to 90 participants. Protocols vary widely in frequency, intensity, number of sessions, and targeted brain regions. Most studies measured craving as the primary outcome; actual reduction in substance use is less consistently demonstrated. Long-term outcomes beyond the treatment period are rarely reported. My personal take is that the field needs larger trials with standardized protocols and longer follow-up.

From Figure 1 of Mehta et al. 2023

Long-Acting Injectables: Solving the Adherence Problem

Medication adherence is one of addiction treatment’s most stubborn barriers. Daily oral medications require patients to remember doses, refill prescriptions, and maintain motivation during periods when craving is high and judgment is impaired. Long-acting injectables eliminate this problem by providing steady medication levels for weeks or months from a single administration.

For opioid use disorder, monthly buprenorphine formulations have transformed treatment retention. Sublocade, approved in the US, delivers 100 mg or 300 mg doses that maintain therapeutic levels for a month. Buvidal, available in Europe, UK, and Australia, offers both weekly and monthly formulations. Real-world data from Sweden shows that 82% of patients remained on treatment at 6 months, and 66% at 12 months. A Kentucky study found that utilization doubled after Medicaid removed prior authorization requirements. A 2023 UK trial published in eClinicalMedicine demonstrated that monthly Sublocade was superior to daily standard of care (methadone or sublingual buprenorphine) for maintaining abstinence from non-medical opioid use over 24 weeks.

The market reflects growing adoption, with projections showing substantial growth driven by expanding Medicaid coverage, reduced administrative barriers, and accumulating evidence of improved outcomes compared to daily formulations.

Naltrexone, an opioid antagonist, is also available as a monthly injection (Vivitrol) for both alcohol and opioid use disorder. A 2025 JAMA Internal Medicine trial compared oral versus extended-release injectable naltrexone in 248 hospitalized patients with alcohol use disorder. Both groups showed substantial reductions in heavy drinking days (38 percentage points for oral, 46 percentage points for injectable), with no statistically significant difference between them. The study suggests that when adherence is supported, oral naltrexone may work as well as the injectable formulation.

The main barrier for naltrexone is initiation. Because naltrexone precipitates withdrawal in people with physiological opioid dependence, patients must be opioid-free for 7 to 10 days before starting. This creates a dangerous window when patients are vulnerable to relapse and overdose. A 2024 study (SWIFT) tested a rapid initiation protocol: one day of buprenorphine, a 24-hour opioid-free period, then gradual titration of low-dose oral naltrexone before the injection. This approach was more successful than the standard protocol, though significant challenges remain.

Longer-acting formulations are in development. Delpor, funded by the NIH HEAL Initiative, is developing a titanium implant designed to release naltrexone steadily for one year. The company plans to file an Investigational New Drug application within two years, with potential FDA approval as early as 2026. A 6-month naltrexone implant developed in Australia has shown efficacy in trials. A Russian study of 306 patients found that 53% of those receiving the implant remained in treatment without relapse at 6 months, compared to 16% on oral naltrexone. Columbia University is conducting Phase 2 trials of a similar 6-month implant. No naltrexone implants are currently FDA-approved in the United States.

From Nkanga et al., 2020, an industry piece on long-acting injectable formulations

Vaccines: A Long Road Ahead

The concept is appealing: train the immune system to produce antibodies that bind to drug molecules in the bloodstream, preventing them from crossing the blood-brain barrier and producing their euphoric effects. For someone trying to maintain abstinence, a vaccine could provide months of protection, eliminating the reward if they relapse.

Fentanyl vaccines are the furthest along. The University of Houston, in partnership with the biotech startup Ovax, plans to begin Phase 1 clinical trials in the second quarter of 2025. Boston Children’s Hospital has a second fentanyl vaccine that may enter Phase 1 trials in early 2026 if licensing negotiations succeed. The University of Montana is advancing both fentanyl and heroin vaccines through Phase 1 trials, supported by a $33.4 million NIH HEAL Initiative contract. All have shown efficacy in animal models, blocking fentanyl’s effects and preventing overdose in rodents and non-human primates.

The timeline is sobering. Phase 1 trials establish safety in a small number of people. Phase 2 trials test efficacy. Phase 3 trials compare the vaccine to standard treatments in larger populations. Even with expedited development, vaccines typically take 5 to 10 years from Phase 1 to market approval. FDA approval for a fentanyl vaccine is probably not before 2030.

Past vaccine efforts provide cautionary context. Fifteen clinical trials tested nicotine vaccines; none succeeded. Six trials tested cocaine vaccines; the largest found that only 38% of participants achieved sufficient antibody levels to show clinical benefit. High variability in individual immune response has been the consistent problem. Some people mount robust antibody responses while others produce too few antibodies to be effective. Those with high antibody levels in cocaine vaccine trials did show reduced cocaine use and less subjective high, but the proportion who achieved this was too low for regulatory approval.

Methamphetamine vaccines have advanced to Phase 1 safety testing, with one trial (IXT-m200) completed, though peer-reviewed results are not yet available. Oxycodone vaccines demonstrated protection against respiratory depression in preclinical work.

Monoclonal antibodies represent an alternative approach. Rather than relying on the patient’s immune system to produce antibodies, these treatments deliver lab-produced antibodies directly. Cessation Therapeutics recently began the first government-approved clinical trial of an anti-fentanyl monoclonal antibody. Anti-methamphetamine monoclonal antibodies have completed Phase 1 trials showing acceptable safety profiles. Monoclonal antibodies offer more predictable effects than vaccines, with less individual variability. The downside is cost and the need for frequent infusions, probably monthly.

VR and AI: Distinguishing Pilot Data from Proven Interventions

Virtual reality creates immersive environments that can be used therapeutically in ways traditional therapy cannot replicate. For addiction, VR has been explored primarily for cue exposure therapy, where patients are gradually exposed to drug-related cues in a controlled setting to reduce the conditioned craving response.

Recent systematic reviews have identified a small but growing number of pilot studies and randomized controlled trials testing VR for substance use disorders. The interventions targeted alcohol, tobacco, cannabis, opioids, and stimulants using various headsets (Oculus Rift, HTC Vive, others). VR reliably elicits craving and physiological responses comparable to real-world exposure, which is necessary for effective cue exposure therapy.

The most developed application comes from Indiana University, where researchers created a VR experience that allows people in early recovery to interact with age-progressed avatars representing their future selves: one avatar shows their life trajectory if they return to substance use, another shows their recovery trajectory. A 2022 pilot study of 21 adults in early recovery (less than 1 year abstinent) found that the intervention increased future self-continuity and delayed reward preference while reducing craving. At 30-day follow-up, 18 of 21 participants remained abstinent. Those who showed increased connection to their future self after VR remained abstinent; those who relapsed showed no effect or decreased future self-similarity. The intervention is now being tested in larger NIH-funded trials with remote delivery via wireless headsets for at-home use.

A 2023 study tested VR cue exposure therapy in alcohol-dependent patients, finding reduced craving and improved physiological responses in the treatment group compared to controls. Avatar therapy for cannabis use disorder showed moderate reductions in use (Cohen’s d = 0.611) in a small trial.

The cost and technical requirements of VR systems remain barriers to widespread clinical adoption. Most importantly, these are pilot feasibility studies. We don’t know which VR approaches work best for which substances, which patients benefit most, or whether effects persist long-term.

The term “AI-augmented therapy” often refers to digital tools that deliver cognitive behavioral therapy or motivational interviewing via smartphone apps or chatbots. Some systems use reinforcement learning algorithms to personalize interventions based on user responses. The evidence here is even thinner than for VR. Most published work describes system design and feasibility rather than clinical outcomes. Rigorous randomized trials are largely absent.

VR and AI represent interesting possibilities for scaling therapy access and creating experiences that traditional approaches cannot deliver. But we should distinguish genuine promise from marketing. The pilot data is encouraging enough to justify continued research, but not yet sufficient to recommend these interventions as standard practice.

Figure 1 of Bell et al., 2024

Which Innovations Will Make it?

It is not clear at this point which of these approaches will be successful, and time will tell how many will scale to real-world clinical use.

The safest bet: Long-acting injectables. These solve a real problem (adherence) with proven technology. The market is growing, payers are covering them, and the evidence keeps accumulating. Incremental but effective. This is what progress usually looks like.

The highest ceiling: GLP-1 agonists. If CNS-targeted (or perhaps craving-optimized) compounds can be developed, these could address multiple substance use disorders with a single mechanism. The existing drugs already work well enough that off-label use is happening. The pharmaceutical industry knows how to develop these compounds and has massive incentive to do so. The question is whether the mechanism is as general as preclinical data suggests.

The implementation nightmare: TMS. Even with positive trials, let’s ask ourselves: who pays for 30 sessions of brain stimulation? How many clinics can actually deliver this? The FDA cleared TMS for depression in 2008. Seventeen years later, most depressed patients have never heard of it. Stimulant use disorders desperately need treatment options, but access barriers could prevent TMS from reaching the people who need it most.

The long game: Vaccines. These won’t arrive before 2030, and even then, individual immune response variability may limit effectiveness. But for highly lethal drugs like fentanyl, even a vaccine that works for 40% of recipients could save thousands of lives annually. My hope is that funding agencies and pharmaceutical companies will maintain commitment through the long development timeline.

The wild card: VR. This could scale beautifully, because headsets are getting cheaper, experiences can be delivered remotely, and the technology improves every year. Or it could join the long list of digital health interventions that work in research settings but never achieve clinical adoption. Upcoming large trials will tell us whether this is transformative or just interesting.

The innovations surveyed here share something important: they address different barriers. But a real challenge will likely be matching specific tools to specific patients and actually getting those tools into clinical practice. Someone with methamphetamine use disorder and unstable housing might benefit more from long-acting buprenorphine (if they also use opioids) than from weekly TMS sessions requiring reliable transportation. Someone with alcohol use disorder who has failed multiple medications might be a candidate for off-label GLP-1 treatment. Someone with excellent social support and stable housing might be ideal for a VR-based intervention.

This is one argument for expanding precision psychiatry: treatment should match the person’s specific barriers and vulnerabilities. Neural substrates matter, but so do the practical realities of someone’s life, the economics of delivery, and the political decisions about coverage and access.

The future may be less about a single breakthrough that solves addiction, and more gradual expansion of our toolkit. This would allow clinicians to target specific mechanisms and overcome specific barriers. Some of these tools are available now. Others are in clinical trials. A few remain years away. And some that look promising today will fail for reasons that have nothing to do with efficacy.

That’s where we are in 2025. A moment where multiple distinct approaches are maturing simultaneously, each with different mechanisms, different use cases, and different chances of actually making it from trials to treatment rooms.

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References

Centers for Disease Control and Prevention. (2024). Provisional Drug Overdose Death Counts. National Center for Health Statistics.

Hendershot CS, Bremmer MP, Paladino MB, et al. (2025). Once-weekly semaglutide in adults with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 82(4), 395-405.

Aranäs C, Edvardsson CE, Shevchouk OT, et al. (2023). Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. EBioMedicine, 93, 104642.

Chuong V, Farokhnia M, Khom S, et al. (2023). The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight, 8(12), e170671.

Lähteenvuo M, Tiihonen J, Solismaa A, et al. (2025). Repurposing semaglutide and liraglutide for alcohol use disorder. JAMA Psychiatry, 82(1), 94-98.

Wang W, Volkow ND, Berger NA, et al. (2024). Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nature Communications, 15, 5177.

Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. (2022). The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. British Journal of Pharmacology, 179, 625-641.

Diana M, Raij T, Melis M, et al. (2017). Rehabilitating the addicted brain with transcranial magnetic stimulation. Nature Reviews Neuroscience, 18, 685-693.

Zangen A, Moshe H, Martinez D, et al. (2021). Repetitive transcranial magnetic stimulation for smoking cessation: A pivotal multicenter double-blind randomized controlled trial. World Psychiatry, 20(3), 397-404.

Su H, Zhong N, Gan H, et al. (2017). High frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex for methamphetamine use disorders: A randomised clinical trial. Drug and Alcohol Dependence, 175, 84-91.

Hanlon CA, Dowdle LT, Austelle CW, et al. (2015). What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals. Brain Research, 1628(Pt A), 199-209.

Sahlem GL, Baker NL, George MS, et al. (2022). Transcranial magnetic stimulation for stimulant use disorder (STIMULUS): Study protocol for a randomized controlled trial. Contemporary Clinical Trials, 116, 106746.

Lofwall MR, Walsh SL, Nunes EV, et al. (2018). Weekly and monthly subcutaneous buprenorphine depot formulations vs daily sublingual buprenorphine with naloxone for treatment of opioid use disorder. JAMA Internal Medicine, 178(6), 764-773.

Frost MC, Viglione J, Evans E, et al. (2023). Utilization of extended-release buprenorphine after policy change removing prior authorization in Kentucky Medicaid. JAMA Health Forum, 4(4), e230070.

Kimber J, Mooney ME, Jones HE, et al. (2023). A randomised clinical trial of monthly depot buprenorphine for treatment of opioid use disorder. eClinicalMedicine, 63, 102164.

Reoux JP, Saxon AJ, Malte CA, et al. (2025). Oral vs extended-release injectable naltrexone for alcohol use disorder. JAMA Internal Medicine, 185(2), 143-152.

Mannelli P, Wu LT, Peindl KS, et al. (2024). SWIFT: Short-term outpatient treatment for opioid use disorder with extended-release naltrexone. Drug and Alcohol Dependence, 243, 109758.

Nasser AF, Greenwald MK, Vince B, et al. (2016). Sustained-release buprenorphine (RBP-6000) blocks the effects of opioid challenge with hydromorphone in subjects with opioid use disorder. Journal of Clinical Psychopharmacology, 36(1), 18-26.

Haney M, Kosten TR. (2021). Therapeutic vaccines for substance use disorders. Annual Review of Medicine, 72, 223-236.

Bremer PT, Kimishima A, Schlosburg JE, et al. (2017). Combating synthetic designer opioids: A conjugate vaccine ablates lethal doses of fentanyl class drugs. Angewandte Chemie, 129(11), 3067-3070.

Comer SD, Sullivan MA, Yu E, et al. (2006). Injectable, sustained-release naltrexone for the treatment of opioid dependence. Archives of General Psychiatry, 63(2), 210-218.

Martell BA, Orson FM, Poling J, et al. (2009). Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients. Archives of General Psychiatry, 66(10), 1116-1123.

Segawa T, Baudry T, Bourla A, et al. (2020). Virtual reality (VR) in assessment and treatment of addictive disorders: A systematic review. Frontiers in Neuroscience, 13, 1409.

Shen YI, Nelson AJ, Oberlin BG. (2022). Virtual reality intervention effects on future self-continuity and delayed reward preference in substance use disorder recovery: Pilot study results. Discover Mental Health, 2(1), 19.

Giroux I, Faucher-Gravel A, St-Hilaire A, et al. (2013). Gambling exposure in virtual reality and modification of urge to gamble. Cyberpsychology, Behavior, and Social Networking, 16(3), 224-231.