Plain Language SummaryThis guidance aims to help healthcare professionals make decisions about prescribing medication to treat addictions to nicotine, alcohol, heroin and other drugs (also known as substance dependence). Shared decision-making and safe prescribing are key principles of this guidance. Effective treatment for substance dependence typically combines medication with psychosocial intervention e.g. cognitive behavioural therapy, motivational interviewing and other activities such as group work and recovery communities. Treatment is often divided into stages with different goals, such as reducing the harms caused by the substance, stabilising or reducing substance use to support further treatment, withdrawal from the substance under clinical supervision, preventing relapse back into substance use, and then recovery, an ongoing process which varies for each person. Treatment should be adjusted to the needs of each person, which may change, for example at different points in their lives, and when people have physical and mental health conditions at the same time as substance dependence.This guidance recommends that for people with: Alcohol dependence a supervised reducing regime of benzodiazepines is the first-line treatment for withdrawal symptoms, alongside thiamine to prevent brain damage. There are several medications with good evidence to help prevent relapse back to heavy drinking or maintain abstinence. Benzodiazepine dependence is best managed through gradual dose reduction, with careful monitoring. Opioid dependence is most effectively managed with substitution therapies like methadone or buprenorphine rather than immediate withdrawal. Long-acting injectable buprenorphine is a newer option. Take Home Naloxone should be provided to people who use opioids as well as their friends and family alongside training to reverse overdose, and naltrexone may help prevent relapse following discontinuation of substitution treatment. Nicotine dependence is most harmful when tobacco is smoked, and has the strongest evidence base for treatment, including nicotine replacement therapy, varenicline, cytisine, and e-cigarettes. In Cannabis dependence the evidence is mixed. Reducing THC content and avoiding tobacco co-use can reduce harm. Stimulant and dissociative drug dependence currently lack approved medications, and more research is needed. Overall, the guidance emphasizes safe prescribing, shared decision-making, and integrating pharmacological treatment with psychosocial care to improve outcomes for people with substance dependence.