Substance use

What can be done

Actions rated on the strength-rating scale (A strong and replicated, B solid but limited, C weak or debated, D contested or failed), applied to the specific claim made.

• Alcohol taxes (A). Across 112 studies, higher prices consistently reduced drinking (Wagenaar, Salois, and Komro, 2009).
• Minimum unit pricing for alcohol (B). In Scotland, deaths wholly attributable to alcohol fell 13.4%, with the largest gains in the poorest areas (Wyper et al., 2023).
• Limits on hours of alcohol sale (B). Extending on-premises sale hours by two or more raised alcohol-related harms (U.S. Community Preventive Services Task Force).
• Opioid agonist treatment such as methadone (A for staying in treatment and reducing heroin use). Methadone outperformed approaches without medication (Mattick et al., 2009), and in cohort studies, unadjusted death rates were 3.2 times higher out of treatment than in it (C) (Sordo et al., 2017).
• Brief alcohol advice in primary care (A, small effect). Across 69 trials, people drank about 20 grams less alcohol per week a year later (Kaner et al., 2018).
• Naloxone distribution (C, observational). In Massachusetts, opioid overdose death rates were lower in communities with more naloxone training (Walley et al., 2013).
• School and community prevention (B, small effects). School programs combining social skills and resistance to peer influence cut later cannabis use by 17% (Faggiano et al., 2014). Communities That Care raised lifetime abstinence by grade 12 but did not lower current use (Hawkins et al., 2014). The Good Behavior Game reduced later drug problems in Baltimore boys (Kellam et al., 2008), but an English trial did not replicate its effect on disruptive behavior (Troncoso and Humphrey, 2021).
• Not effective or unproven: DARE had no effect on drug use (A for no effect) (West and O'Neal, 2004). Alcohol advertising bans lack robust evidence either way (C) (Siegfried et al., 2014). The Icelandic prevention model has no randomized trial and is rated "additional studies recommended" by the EU drug agency (C) (EUDA).
• Context: Recreational cannabis legalization in the United States has been linked to modest increases in youth use, while medical legalization has not (C) (Pawar et al., 2024).

Proposed and experimental methods

Methods that are proposed, under trial, approved in some places, or tried and then failed. Each shows a stage label and an evidence rating. A stage label shows how far a method has progressed, not whether it works. The stage labels are explained on the biological factor page.

• GLP-1 drugs for alcohol and opioid use disorders (Early trial, B). Using semaglutide and similar drugs, which appear to dampen the brain's reward response, to reduce drinking and drug use. In a 48-person phase 2 trial, low-dose semaglutide reduced alcohol drunk in a laboratory test, drinks per drinking day, and craving, but not drinks per day or the number of drinking days (Hendershot et al., 2025). In a 26-week trial of 108 people with alcohol use disorder and obesity, weekly semaglutide added to cognitive behavioral therapy cut heavy drinking days by 13.7 percentage points more than placebo (Klausen et al., 2026). In U.S. health records of 503,747 people with opioid use disorder and 817,309 with alcohol use disorder, GLP-1 or GIP prescriptions were associated with lower rates of opioid overdose (aIRR 0.60) and alcohol intoxication (aIRR 0.50), though such data cannot rule out other explanations (Qeadan et al., 2025).
• Psilocybin-assisted therapy for alcohol use disorder (Early trial, B). Two high-dose psilocybin sessions combined with talk therapy. In 95 adults, heavy drinking days over 32 weeks were 9.7% with psilocybin versus 23.6% with an active placebo (diphenhydramine), a 13.9 point difference (95% CI 3.0 to 24.7) (Bogenschutz et al., 2022). It is a single trial, and 78.9% of participants were non-Hispanic White.
• Very low nicotine standard for cigarettes (Large trial, B). Cutting the nicotine in cigarettes to levels too low to sustain addiction. In a 6-week trial of 840 smokers, cigarettes with 0.4 mg of nicotine per gram of tobacco cut smoking to 14.9 cigarettes per day versus 22.2 with usual brands, with little sign of compensatory smoking (Donny et al., 2015). The FDA proposed a cap of 0.70 mg per gram on January 16, 2025, and modeled that more than 12.9 million additional people would quit in the first year and 4.3 million deaths would be averted by the end of the century (FDA, 2025). As of September 2026 no final rule had been issued, according to a maker of low-nicotine cigarettes that is urging the FDA to act (22nd Century Group, 2026).
• Supervised consumption sites, also called overdose prevention centers (Approved but not scaled, B). Sites where people use drugs they already have under supervision, with naloxone on hand. The first two sanctioned U.S. sites opened in New York City in November 2021. Compared with areas around 17 syringe service programs, they were not associated with changes in violent or property crime, 911 calls, or 311 complaints, while drug possession arrests nearby fell 82.7%, which the authors linked to police easing enforcement in line with city support for the sites (Chalfin et al., 2023).
• Generational tobacco sales ban (Approved but not scaled, contested, C). Banning tobacco sales to anyone born after a set date, so the legal age for buying tobacco rises every year. The UK Tobacco and Vapes Act received royal assent on 29 April 2026, so that nobody born on or after 1 January 2009 can be sold tobacco (Hart and Caddy, 2026), with the ban coming into force on 1 January 2027 (ASH, 2026). New Zealand passed a similar law but repealed it under urgency, together with its retailer reduction and denicotinization measures, before any of them took effect (1News, 2024), and the repeal became law on 5 March 2024 (New Zealand Parliament, 2024). No health outcome data were found.
• Safer supply, prescribed pharmaceutical alternatives (Approved but not scaled, contested, D). Prescribing pharmaceutical opioids or stimulants to people at high risk of poisoning from the illegal drug supply. Among 5,882 people in British Columbia, receiving prescribed opioids in a given week was associated with lower all-cause death (aHR 0.39) and overdose death (aHR 0.45), with larger effects at four or more days per week (Slaunwhite et al., 2024). A province-level comparison found the policy was associated with 3.2 more opioid poisoning hospitalizations per 100,000 people and no significant change in deaths (Nguyen et al., 2024). In February 2025 British Columbia moved the program from take-home doses to witnessed consumption, citing diversion of the drugs (Judd, 2025).
• Failed: Vaccines against addictive drugs (Failed or reversed, D). Vaccines that make the body produce antibodies that bind nicotine or cocaine so less reaches the brain. A Cochrane review of four trials with 2,642 smokers found no evidence that nicotine vaccines improve long-term quitting, and two phase 3 NicVAX trials reported quit rates of about 11% in both groups (Hartmann-Boyce et al., 2012). A phase 3 cocaine vaccine trial in 300 people found no significant difference in cocaine-positive urine samples over 16 weeks (Kosten et al., 2014).
• Reversed: Drug decriminalization, Oregon Measure 110 (Failed or reversed, contested, D). Replacing criminal penalties for possessing small amounts of drugs with civil fines and treatment funding, in effect from February 1, 2021. One synthetic control study (which compares the state with a weighted mix of similar states) found no association with fatal overdose rates in the first year (Joshi et al., 2023), another estimated 182 extra overdose deaths in 2021, a 23% increase (Spencer, 2023), and a third found that a crude increase disappeared once the arrival of fentanyl was taken into account (estimate -0.51, P = .41) (Zoorob et al., 2024). Oregon made possession a misdemeanor again through House Bill 4002, signed on April 1, 2024, with new charges starting September 1 of that year (Wilson, 2024).

Sources cited on this page

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2. WHO: Congenital disorders fact sheet (2023) B Moderate
3. WHO: Nearly 1.8 billion adults not doing enough physical activity (2024) B Moderate: agency estimate
4. Faggiano, F., Minozzi, S., Versino, E., & Buscemi, D. (2014). Universal school-based prevention for illicit drug use. Cochrane Database of Systematic Reviews, 2014(12), CD003020. link B Moderate
5. Hawkins, J. D., Oesterle, S., Brown, E. C., Abbott, R. D., & Catalano, R. F. (2014). Youth problem behaviors 8 years after implementing the Communities That Care prevention system: A community-randomized trial. JAMA Pediatrics, 168(2), 122-129. link B Moderate
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7. Kaner, E. F. S., Beyer, F. R., Muirhead, C., Campbell, F., Pienaar, E. D., Bertholet, N., et al. (2018). Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database of Systematic Reviews, 2018(2), CD004148. link A Strong
8. Kellam, S. G., Brown, C. H., Poduska, J. M., Ialongo, N. S., Wang, W., Toyinbo, P., et al. (2008). Effects of a universal classroom behavior management program in first and second grades on young adult behavioral, psychiatric, and social outcomes. Drug and Alcohol Dependence, 95(Suppl. 1), S5-S28. link B Moderate
9. Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), CD002209. link A Strong: for retention and heroin use
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11. Pawar, A. K. S., Firmin, E. S., Wilens, T. E., & Hammond, C. J. (2024). Systematic review and meta-analysis: Medical and recreational cannabis legalization and cannabis use among youth in the United States. Journal of the American Academy of Child and Adolescent Psychiatry, 63(11), 1084-1113. link C Limited
12. Siegfried, N., Pienaar, D. C., Ataguba, J. E., Volmink, J., Kredo, T., Jere, M., & Parry, C. D. H. (2014). Restricting or banning alcohol advertising to reduce alcohol consumption in adults and adolescents. Cochrane Database of Systematic Reviews, 2014(11), CD010704. link C Limited
13. Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ, 357, j1550. link C Limited
14. Troncoso, P., & Humphrey, N. (2021). Playing the long game: A multivariate multilevel non-linear growth curve model of long-term effects in a randomized trial of the Good Behavior Game. Journal of School Psychology, 88, 68-84. link B Moderate
15. Wagenaar, A. C., Salois, M. J., & Komro, K. A. (2009). Effects of beverage alcohol price and tax levels on drinking: A meta-analysis of 1003 estimates from 112 studies. Addiction, 104(2), 179-190. link A Strong
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17. West, S. L., & O'Neal, K. K. (2004). Project D.A.R.E. outcome effectiveness revisited. American Journal of Public Health, 94(6), 1027-1029. link A Strong
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21. Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., et al. (2022). Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 79(10), 953-962. link B Moderate
22. Chalfin, A., del Pozo, B., & Mitre-Becerril, D. (2023). Overdose prevention centers, crime, and disorder in New York City. JAMA Network Open, 6(11), e2342228. link B Moderate
23. Donny, E. C., Denlinger, R. L., Tidey, J. W., Koopmeiners, J. S., Benowitz, N. L., Vandrey, R. G., et al. (2015). Randomized trial of reduced-nicotine standards for cigarettes. New England Journal of Medicine, 373(14), 1340-1349. link B Moderate
24. Hart, H., & Caddy, P. (2026, May 7). Tobacco and Vapes Act 2026 becomes law. Lewis Silkin. link B Moderate
25. Hartmann-Boyce, J., Cahill, K., Hatsukami, D., & Cornuz, J. (2012). Nicotine vaccines for smoking cessation. Cochrane Database of Systematic Reviews, 2012(8), CD007072. link A Strong
26. Hendershot, C. S., Bremmer, M. P., Paladino, M. B., Kostantinis, G., Gilmore, T. A., Sullivan, N. R., et al. (2025). Once-weekly semaglutide in adults with alcohol use disorder: A randomized clinical trial. JAMA Psychiatry, 82(4), 395-405. link B Moderate
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28. Judd, A. (2025, February 19). B.C. overhauls safe supply program, moving to witnessed model. Global News. link B Moderate
29. Klausen, M. K., Justesen, S. K., Pedersen, J. N., Rasmussen, L., Jensen, A., Jensen, M. E., et al. (2026). Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: A randomised, double-blind, placebo-controlled trial. The Lancet, 407(10540), 1687-1698. link B Moderate
30. Kosten, T. R., Domingo, C. B., Shorter, D., Orson, F., Green, C., Somoza, E., et al. (2014). Vaccine for cocaine dependence: A randomized double-blind placebo-controlled efficacy trial. Drug and Alcohol Dependence, 140, 42-47. link B Moderate
31. Nguyen, H. V., Mital, S., Bugden, S., & McGinty, E. E. (2024). British Columbia's Safer Opioid Supply policy and opioid outcomes. JAMA Internal Medicine, 184(3), 256-264. link C Limited
32. Qeadan, F., McCunn, A., & Tingey, B. (2025). The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction, 120(2), 236-250. link C Limited
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34. Spencer, N. (2023). Does drug decriminalization increase unintentional drug overdose deaths? Early evidence from Oregon Measure 110. Journal of Health Economics, 91, 102798. link D Contested
35. Wilson, C. (2024, April 1). Oregon governor signs bill criminalizing drug possession. Oregon Public Broadcasting. link B Moderate
36. Zoorob, M. J., Park, J. N., Kral, A. H., Lambdin, B. H., & del Pozo, B. (2024). Drug decriminalization, fentanyl, and fatal overdoses in Oregon. JAMA Network Open, 7(9), e2431612. link B Moderate

Every source for this factor is listed on the biological factor page.