Naltrexone Mechanism — MRCPsych Paper B MCQ

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ModerateSubstance MisuseNaltrexone MechanismMRCPsych Paper B

A 45-year-old man with alcohol dependence has completed assisted withdrawal and is taking oral naltrexone 50 mg daily alongside a psychological intervention for relapse prevention. He reports reduced alcohol craving. Which pharmacological action most directly accounts for this effect?

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Correct answer: E — Competitive antagonism at opioid receptors, attenuating endogenous opioid reward signalling

Explanation lettering: B = shown as A · E = shown as B · A = shown as C · C = shown as E

Naltrexone is a long-acting competitive opioid receptor antagonist with clinically important activity at μ-opioid receptors. Alcohol consumption stimulates endogenous opioid (notably beta-endorphin) release, which contributes to activation of mesolimbic reward pathways. By blocking this signalling, naltrexone attenuates alcohol's rewarding and reinforcing effects, reducing craving and the risk that a lapse progresses to full relapse; NICE CG115 recommends oral naltrexone with psychological intervention after successful withdrawal. NMDA-related glutamatergic modulation (A) is associated with acamprosate, the other first-line relapse-prevention agent. GABA-A positive allosteric modulation (B) is the mechanism of benzodiazepines used for withdrawal, not relapse prevention. Dopamine D2 agonism (D) would enhance rather than dampen reward signalling. Serotonin-transporter inhibition (E) is the mechanism of SSRIs, which have no established role in reducing alcohol craving.

Reference: Electronic Medicines Compendium (eMC). Adepend 50 mg film-coated tablets, Summary of Product Characteristics, sections 4.1 and 5.1 (pharmacodynamic properties). https://www.medicines.org.uk/emc/medicine/29642