The Opioid System Question
A 2018 Williams et al. study reignited debate over whether ketamine's antidepressant effect requires mu-opioid receptor activity.
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The debate
- Williams 2018: Naltrexone (opioid blocker) appeared to prevent ketamine's antidepressant effect in 12 patients.
- Yoon 2019, Klein 2020: Replication attempts found no such blockade.
- Current consensus: Opioid system involvement is possible but not established. The glutamate cascade remains the dominant explanation.
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