Opinion

"Considerations for the FDA on Postpartum-depression, for the record" - PSA's Sunday Sound-Off: September 20th, 2026

"On Postpartum-depression, for the record: Considerations for the FDA," ICYMI: "What's the most pressing issue facing psychedelics in the U.S.?" plus the PSA NewsWire Highlights of the Week

By PSA Media Team and Stephanie Karzon Abrams

Contributor

September 20, 2026 · 5 min read

PSA’s Sunday Sound-Off: September 20th, 2026

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On Postpartum-depression, for the record Considerations for Potential Future Therapeutic Use of Psychedelic Drugs FDA Public Hearing
ICYMI: “The Most Pressing Issue Facing Psychedelics in The U.S. Today”
PSA NewsWire Highlights of the Week: September 20th, 2026

On Postpartum-depression, for the record

Considerations for Potential Future Therapeutic Use of Psychedelic Drugs FDA Public Hearing

By Stephanie Karzon Abrams

From our friends at GALILEA Health over on Substack.

To the FDA,

Postpartum depression strikes one in seven mothers, it is a leading cause of maternal death by suicide, and it is fundamentally a disorder of a collapsing hormonal environment. This is the one depression we already know is hormone-driven. Ketamine and esketamine cut the risk of postpartum depression roughly in half in over twenty randomized trials, and ketamine’s active metabolites bind the very estrogen receptors that are crashing in these women. Yet not one of those trials measured a mother’s hormone levels, whether she was breastfeeding, or how those factors shaped her response and her infant’s safety. If the FDA wants a proving ground for taking sex and hormonal status seriously in psychedelic and rapid-acting antidepressant development, postpartum depression is it—because here the biology cannot be ignored, and the stakes include two lives.

So my ask is specific and, I believe, incremental. Require that trials of ketamine, esketamine, and psychedelics in perinatal populations measure and analyze what we already know matters: maternal estradiol and progesterone, breastfeeding status, and infant exposure. Pre-specified and not buried in a demographics table. Please include, rather than reflexively exclude, postpartum and lactating women, with infant safety built into the protocol from the start.

We do not yet know whether a mother's hormonal state changes how well these drugs work or how safe they are for her baby, and that uncertainty is exactly the point! We have the biology, we have the signal from more than twenty trials, and we have the tools to measure it. What we lack is the requirement to do so. Postpartum depression is where the science is ready and the need is greatest. Let it be where the FDA sets the standard because getting this right protects two lives, not one. And in some cases, as we have recently learned, more!

Thank you.

Rationale

- Prevalence and mortality. PPD affects roughly 10–17% of women (about one in seven), and suicide accounts for approximately 20% of postpartum deaths.

- PPD is a hormone-withdrawal disorder. Estradiol rises up to ~1000-fold and progesterone to 100–200 ng/mL by term, then both crash to prepregnancy levels within one to two weeks postpartum; this rapid withdrawal is mechanistically tied to PPD onset, and the “hormone sensitivity hypothesis” holds that susceptible women react to this drop. Estrogen withdrawal provokes depressive symptoms in women with PPD histories, and estradiol treatment can prevent relapse.

- Ketamine/esketamine roughly halve PPD incidence. A trial-sequential meta-analysis of 22 RCTs (n=3,463) found perioperative ketamine/esketamine reduced PPD risk at 1 week (RR 0.41) and 4–6 weeks (RR 0.47), with the sequential analysis confirming the evidence was statistically robust, not just significant. A 2025 updated meta-analysis reproduced the ~50% reduction across short- and long-term follow-up.

- The mechanistic overlap. Ketamine and its (2R,6R)/(2S,6S)-HNK metabolites are direct estrogen-receptor-alpha ligands, and estrogen additively augments their AMPA-receptor induction through an ERα-dependent loop—linking the drug’s action directly to the receptor system that is destabilized postpartum.

- The measurement gap. The PPD ketamine trials did not measure or model maternal hormone levels, lactation status, or infant exposure. The women’s-health review explicitly calls for postpartum and lactating women to be included in safety/efficacy assessments and for hormonal status to be stratified.

A caveat: The existing ketamine PPD data are largely prophylactic (perioperative) rather than treatment of established PPD, with predominantly short-term benefit and low-to-very-low GRADE certainty.

For classic psychedelics a preclinical peripartum model found psilocybin failed to help—and sometimes worsened—maternal anxiety, with signs of offspring vulnerability via breastmilk.That is precisely why lactation and infant safety must be built into any postpartum psychedelic protocol.

A significant lactation study was completed with ketamine showing favorable results and a feasible protocol for mother and infant.
The study examined four lactating women given intramuscular (IM) ketamine doses of 0.5 mg/kg and 1.0 mg/kg.

Relative Infant Dose (RID): The mean RID was calculated at 0.650% for the 0.5 mg/kg dose and 0.766% for the 1.0 mg/kg dose. An RID under 10% is generally considered safe and acceptable in lactation pharmacology.
Rapid Decline: Ketamine and its primary active metabolite, norketamine, peaked between 3 to 4 hours and dropped to insignificant levels by the 12-hour mark

The following figure maps how hormonal state cascades through pharmacokinetics, receptor availability, brain networks, and ultimately clinical outcome—useful as a one-slide visual for why hormonal status must be a measured variable:

Figure 2 Multi-level mechanistic model of sex hormone modulation of psychedelic response.

Editor’s Note: This piece was originally published by GALILEA Health Founder Stephanie Karzon Abrams. Check out the sources cited over on Substack, and be sure to like, share, and subscribe!

ICYMI: “The Most Pressing Issue Facing Psychedelics in The U.S. Today”

Feat. Psychedelic Bar Association Board Chair Christian Holden and PSA Founder Jack Gorsline

Psychedelic Bar Association Board Chair Christian Holden breaks it down: the FDA needs to stop the "teeter-totter" approach and acknowledge the importance of this space with open ears and an open mind. Regulators are at a pivotal turning point where they must make a confident choice to unpack the complexities of psychedelc policy, rather than continuing to question whether to address it at all.

Watch the full exchange to hear more on the regulatory decisions shaping the future of this space in the U.S.

Source: "Beyond the FDA hearing: How Psychedelic State(s) of America and The Psychedelic Bar Association are shaping the future of psychedelic discourse" -- powered by Psychedelics Today