Methadone mechanism — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyMethadone mechanismMRCPsych Paper A

A 39-year-old man with opioid dependence is stabilised on once-daily methadone. At an adequate maintenance dose, he has no opioid withdrawal symptoms before the next dose. Which receptor action principally mediates methadone's suppression of opioid withdrawal?

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Correct answer: B — Agonism at mu-opioid receptors

Methadone is a long-acting opioid agonist whose actions are predominantly mediated at mu-opioid receptors. In an opioid-dependent patient, sustained mu-receptor activation substitutes for shorter-acting opioids and prevents withdrawal between doses. Its prolonged and variable elimination also permits once-daily maintenance but creates a risk of accumulation and delayed respiratory depression. NMDA-receptor antagonism is not the principal mechanism responsible for opioid substitution and withdrawal suppression. GABA-B receptor agonism is associated with baclofen, while nicotinic receptor antagonism and dopamine-reuptake inhibition do not account for methadone maintenance treatment. Therefore, the best answer is B.

Reference: Thornton & Ross Ltd. Methadone Mixture 1 mg/ml, Summary of Product Characteristics, sections 4.1, 4.2 and 5.1; revised 18 May 2026. https://www.medicines.org.uk/emc/product/4907/smpc