# Substance Use Disorder Pharmacotherapy > Substance use disorder pharmacotherapy in MBBS Pharmacology: buprenorphine, methadone, naltrexone, naloxone rescue, varenicline and bupropion. - Canonical URL: https://prepelephant.com/topics/mbbs/pharmacology/substance-use-disorder-pharmacotherapy - Exam / course: MBBS · Subject: Pharmacology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Substance Use Disorder Pharmacotherapy", PrepElephant, https://prepelephant.com/topics/mbbs/pharmacology/substance-use-disorder-pharmacotherapy ## Direct answer Because withdrawal and craving, not weak will, drive relapse in opioid use disorder, medication is first-line treatment: buprenorphine, a partial mu agonist with a ceiling on respiratory depression, and methadone, a full agonist with a long variable half-life, both hold withdrawal at bay without euphoria; naltrexone blocks opioids but only after seven to ten detoxified days. Tobacco dependence has three evidence-based options — nicotine replacement, varenicline and bupropion. Cannabis and stimulant use disorders still lack approved pharmacotherapy and rest on psychosocial intervention. Naloxone reverses overdose, and its short half-life of 30 to 90 minutes makes take-home naloxone and repeat dosing core harm reduction. ## What you must remember - **Buprenorphine properties:** sublingual partial agonist, high receptor affinity (it displaces full agonists — hence precipitated withdrawal if started too early), ceiling on respiratory depression; combined with naloxone to deter injection. - **Induction timing:** wait for mild-to-moderate withdrawal (COWS around 8 or more) before the first buprenorphine dose; starting early trades craving for precipitated misery. - **Methadone:** once-daily full agonist, half-life 24-36 hours and variable — accumulation risk, QT prolongation, and only licensed centres dispense it in India. - **Naltrexone rules:** only after 7-10 days opioid-free; on relapse the blocked tolerance has vanished, making overdose the lethal risk; monthly injection exists for adherence. - **Naloxone rescue:** 0.4-0.8 mg IV or intranasal, short-acting — expect re-narcotisation and repeat dosing; prescribe it to patients and families. - **Varenicline:** partial alpha-4 beta-2 nicotinic agonist — start one week before the quit date, titrate to 1 mg twice daily; nausea and vivid dreams; most effective single agent. - **Bupropion:** NDRI, contraindicated with seizures, eating disorders and MAOIs; halves craving and limits weight gain after quitting. - **Vacuum areas:** no approved drugs for cannabis, cocaine or methamphetamine dependence — contingency management and behavioural therapy carry those. ## Starting buprenorphine without precipitating withdrawal The first buprenorphine dose is the whole examination. A man using heroin by injection presents in early withdrawal — yawning, lacrimation, pilomotor erection, COWS 6. Dosing now would flood high-affinity receptors with a partial agonist and hurl him into full withdrawal; wait until the score passes 8-12, then give 2-4 mg sublingually and observe. Titrate over two days to a dose that abolishes craving without sedation. The naloxone component stays sublingually inactive but punishes injection. If he later chooses abstinence, naltrexone follows only after a naloxone challenge or ten clean days. Tobacco runs in parallel: combination nicotine replacement (patch plus gum for breakthrough craving) doubles quit rates over placebo; varenicline outperforms both single-mode therapies and suits the smoker with past depression concerns; bupropion serves the one who cannot stop while also on an antidepressant. Every quit attempt deserves at least 12 weeks of pharmacotherapy. ## Indian programme context India delivers opioid substitution therapy through NACO-supported targeted-intervention centres under the National AIDS Control Programme, dispensing free buprenorphine-naloxone to injecting drug users — a harm-reduction pathway an MBBS graduate should be able to describe. Methadone is confined to designated government centres. De-addiction services cluster around "Nasha Mukti" centres and hospital psychiatry departments; the NDPS Act schedules most agents involved. Over-the-counter codeine and tramadol misuse supplies a steady stream of iatrogenic dependence — prescribe, count and report misuse patterns to the PvPI. ## Frequently asked questions ### Why is buprenorphine combined with naloxone? Naloxone is inactive sublingually but, if the tablet is dissolved and injected, it precipitates withdrawal — pure deterrence while oral-sublingual therapy proceeds normally. ### What is precipitated withdrawal and how is it avoided? High-affinity buprenorphine displaces full agonists from receptors; waiting until mild-to-moderate withdrawal (COWS 8 or more) before induction prevents it. ### Why prescribe take-home naloxone? Its half-life of 30-90 minutes is shorter than most opioids, so reversed patients re-sedate; families equipped and trained with intranasal naloxone bridge the gap to hospital. ### What is varenicline's mechanism and main adverse effects? Partial agonism at alpha-4 beta-2 nicotinic receptors eases craving while blocking reinforcement; nausea, vivid dreams and insomnia head the adverse profile. ### Which substance use disorders have no approved pharmacotherapy? Cannabis and stimulant (cocaine, amphetamine-type) dependence — psychosocial and contingency-based interventions remain the standard of care.