Ketamine is a dissociative anesthetic that’s also used (in controlled medical settings) for depression and suicidality, including IV ketamine clinics and intranasal esketamine (Spravato). Its core pharmacology is NMDA-receptor antagonism, which can rapidly shift glutamate signaling and produce short-term changes in perception, mood, and pain. Compared with many classic antidepressants, ketamine’s antidepressant effects—when they occur—can be faster, but the experience is also more acute/“state-changing” (dissociation is common).
Mechanistically, ketamine is often discussed in terms of neuroplasticity: research reviews describe downstream effects that can increase synaptogenesis and synaptic strength, involving AMPA signaling, BDNF/TrkB, and mTOR-related pathways in various models. (ScienceDirect) That said, these are general depression/neuroplasticity frameworks—not PFS/PSSD/PAS-specific mechanisms—and they don’t automatically translate into durable benefit for people whose symptoms are driven by other “stuck” biology.
Anecdotes (Community Reports):
https://www.reddit.com/r/PSSD/comments/1nppzda/ketamine_for_anhedonian/
https://www.reddit.com/r/PSSD/comments/17897gn/ketamine_is_the_shit/
https://www.reddit.com/r/PSSD/comments/1cn7gd8/experienced_with_ketamine/
How to Interpret This Page
This page summarizes anecdotal reports and community observations, not medical evidence. “Risk” here refers to how frequently severe or prolonged symptom worsening is reported, not to proven causation or population-wide probability. Individual responses vary widely, and absence of issues in some users does not rule out significant reactions in others.
Community Reports: Mixed Outcomes & Variable Risk Signal
Overall pattern: In PFS/PSSD/PAS communities, ketamine is usually described as mixed but often “mild”—some people report modest mood relief or temporary stress-buffering, others report no real change, and some report feeling worse (often anxiety, sleep disruption, emotional flattening, or a general destabilized “wired” feeling afterward). The reports that stand out most are often transient (helpful or harmful) rather than dramatic, lasting shifts in baseline.
Why it may not “hit the core mechanism”: Even if ketamine increases neuroplasticity in a broad sense, many users interpret their experience as symptomatic (mood state / stress / sleep) rather than a direct fix for the underlying drivers they associate with PFS/PSSD/PAS. In other words, it may change the “state” without reliably changing the “trait,” and some people find the after-effects (rebound anxiety, sleep issues, emotional weirdness) outweigh any short window of relief.
Practical Caution Signal
Even when people view ketamine as “not a big crasher,” it’s still a high-impact CNS drug. Medical labeling for esketamine includes boxed warnings around sedation, dissociation, respiratory depression, and abuse/misuse risk, and it’s administered under a risk-management/monitoring program. FDA Access Data Separately, frequent/recreational ketamine exposure is strongly associated with ketamine-induced urinary tract injury/cystitis in the medical literature—typically in heavier/chronic use patterns, but important enough to be on the radar.
Evidence Basis
Established pharmacology and clinical use of ketamine/esketamine; mechanistic literature on NMDA antagonism and downstream neuroplasticity pathways (AMPA/BDNF/mTOR); FDA labeling and safety warnings for esketamine; anecdotal reports (online forums, self-reports).
