What gene is commonly involved in non-responsive patients on MOUD?

• A. ALDH5A1
• B. OPRM1
• C. GABRA6
• D. CYP2D6

Answer: (A)

Understand that how someone responds to medications for opioid use disorder (MOUD) can be shaped by genetics that influence brain signaling beyond just opioid receptors. One important angle is the GABA system, which modulates inhibitory control in reward and withdrawal circuits.

ALDH5A1 encodes an enzyme in the GABA metabolism pathway. Variants in this gene can alter levels of GABA in the brain. When GABA balance is disrupted, the inhibitory tone on reward and stress pathways can change, potentially making standard MOUD regimens less effective for some individuals. This is why ALDH5A1 is considered a gene of interest for non-response to MOUD in this context.

By contrast, OPRM1 involves the mu-opioid receptor and shows some associations with treatment responses, but findings are less consistent across studies. GABRA6, a GABA receptor subunit, has less robust evidence linking it to MOUD outcomes, and CYP2D6 mainly affects the metabolism of other drugs rather than the primary MOUD agents themselves.