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Ya'el Courtney, PhD @scienceyael.bsky.social · 5h

Thank you!!

Reposted by Ya'el Courtney, PhD

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Anatomically, LSD-exposed mice had enlarged brain ventricles and common callosal abnormalities. Female mice displayed brain and body weight changes. Males had larger testes w repeated dosing.

Midline anatomy screen at P156 (descriptive). Atlas reference levels and representative examples from LSD-exposed adults illustrate lateral ventricular enlargement with frontal-horn predominance, third-ventricle enlargement, asymmetric callosal hypoplasia, a supracallosal diverticulum continuous with the frontal horn, and partial agenesis of the anterior corpus callosum (absent genu/rostrum). Sections were cryostat-prepared for other analyses; sampling was limited and not powered for hypothesis testing.

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Reposted by Ya'el Courtney, PhD

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

And here’s the part that’s hard to quantify on a graph: these mice were weirder than we could measure. 60% of LSD-exposed mice developed continuous stereotypies (backflips, tight circling), which made higher-order tests (novel object, social approach) basically uninterpretable.

(I) Open-field examples: single-animal path traces. (J) Group-mean occupancy heatmaps (50×50 grid). (K) Total rotations by group (negative-binomial GLM, omnibus χ² = 8.02, P = 0.018); back-transformed means ± SE: Control 54.2 ± 12.6, Acute 136.2 ± 31.3, Repeated 81.4 ± 18.8; Tukey Control vs Acute P = 0.013. (L) Proportion of “high-rotators” (threshold = 95th percentile of Control; Fisher exact P = 0.43; n/N shown).

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Reposted by Ya'el Courtney, PhD

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Our first question was “does LSD get to the embryo?” We built a tiny-volume PK pipeline—micro-sampling embryonic CSF and quantifying LSD by targeted LC–MS/MS. After one maternal dose, LSD is in embryonic CSF within ~5–15 min and fades over the next hour.

Fig. 1. Maternal LSD rapidly enters embryonic circulation and CSF. (A) Schematic of the pharmacokinetic study. Pregnant mice received a single subcutaneous injection of LSD (0.3 mg kg⁻¹) at E12 .5 or E16.5. Maternal serum, embryonic serum (E16.5) and embryonic CSF (E12.5, E16.5) were sampled at 5, 15, 30, 60, and 120 min and analyzed by LC-MS/MS. (B) Calibration curve for LSD spiked into serum (R² = 0.996). (C) Calibration curve for LSD spiked into CSF (R² = 0.996). (D) Time course of LSD concentration in maternal serum after 0.3 mg kg⁻¹ LSD (mean ± SEM, n = 3 dams per time point). (E) Time course of LSD concentration in E16.5 serum after 0.3 mg kg⁻¹ maternal LSD (mean ± SEM, n = 3 pooled litters per time point). (F) LSD concentration in embryonic CSF at E12 .5 or E16.5 peaks at 15 min then declines yet remains detectable at 120 min (mean ± SEM, n = 3 pooled litters per time point).

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Reposted by Ya'el Courtney, PhD

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

🚨 Psychedelics in pregnancy - can a single dose reach the embryo and matter? Yes. In mice they hit embryonic CSF within minutes, activate choroid plexus→CSF axis, & shift cortical development with adult behavioral signatures. @lehtinenlab.bsky.social Preprint:

www.biorxiv.org/content/10.1...

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Gestational psychedelic exposure disrupts brain development and offspring behavior in mice

Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg/kg) cross...

www.biorxiv.org

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Ya'el Courtney, PhD @scienceyael.bsky.social · 6d

Thank you! We are doing our best to keep doing great science anyway, and to convince the public and the government why it benefits everyone to fund :)

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Ya'el Courtney, PhD @scienceyael.bsky.social · 6d

You know what’s weird - the mice get preternaturally STILL on acid! Much less grooming, fidgeting, exploring. Though they may respond very differently to a threat, I’m not sure!

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Ya'el Courtney, PhD @scienceyael.bsky.social · 6d

I always summarize the takeaway of this manuscript for folks as “don’t drop acid if you’re pregnant” and they stare at me like “is that seriously a paper??”

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Reposted by Ya'el Courtney, PhD

Tamsin Shaw @professorshaw.bsky.social · 6d

This is so my timeline these days - I doomscroll far enough and I get to pregnant mice on acid

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

🚨 Psychedelics in pregnancy - can a single dose reach the embryo and matter? Yes. In mice they hit embryonic CSF within minutes, activate choroid plexus→CSF axis, & shift cortical development with adult behavioral signatures. @lehtinenlab.bsky.social Preprint:

www.biorxiv.org/content/10.1...

1/13

Gestational psychedelic exposure disrupts brain development and offspring behavior in mice

Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg/kg) cross...

www.biorxiv.org

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Thank you so much!!

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Also thankful for fellowship support from @hhmi.org in my PhD and now from @jcchildsfund.bsky.social!

#Neurodevelopment #Psychedelics #ChoroidPlexus #CSF #DevNeuro #Pregnancy #LSD #Preprint

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Huge thanks to my co-authors: Christian, Jozi, Cody, and @lehtinenlab.bsky.social, to NIDA DSP, & to phenomenal support @harvardmed.bsky.social @harvardbrainsci.bsky.social @hms-nif.bsky.social, @bostonchildrens.bsky.social (esp research controlled substances team!), & @uwmadpharmacy.bsky.social.

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

TL;DR: Maternal psychedelics reach embryonic CSF within minutes, activate the choroid plexus, alter CSF, and shift cortical development in mice—yielding lasting behavioral changes. A discrete embryonic window is vulnerable via the ChP–CSF axis.

www.biorxiv.org/content/10.1...

Gestational psychedelic exposure disrupts brain development and offspring behavior in mice

Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg/kg) cross...

www.biorxiv.org

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Policy-relevant point: as clinical and non-medical psychedelic use expands, pregnancy is a distinct risk context. We need careful, PK/PD-anchored studies to guide evidence-based recommendations. For now, the simple advice stands: don’t use psychedelics during pregnancy

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Limitations to keep in mind: rodent dosing ≠ human exposures; parallel direct effects on embryonic neurons can’t be excluded; we still need to identify the specific CSF proteins that mediate the cortical shift. But the embryo-facing detection mechanism is clear.

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

We did not see overt maternal toxicity or adverse birth outcomes at these doses. Effects show up in offspring brain composition and behavior. These are standard mouse doses known to produce beneficial effects in other contexts; they are not human-equivalent.

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Anatomically, LSD-exposed mice had enlarged brain ventricles and common callosal abnormalities. Female mice displayed brain and body weight changes. Males had larger testes w repeated dosing.

1 1 3

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

And here’s the part that’s hard to quantify on a graph: these mice were weirder than we could measure. 60% of LSD-exposed mice developed continuous stereotypies (backflips, tight circling), which made higher-order tests (novel object, social approach) basically uninterpretable.

1 1 2

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

By adulthood, behavior shifts in specific ways. Males show weaker prepulse inhibition (a test of sensorimotor gating—filtering out a startle). In the open field, we see more repetitive, tight rotations, i.e., stereotypy, rather than flexible exploration.

Fig. 3. Embryonic LSD exposure impairs sensorimotor gating and increases rotational stereotypy. Analyses were blinded; litter was tracked and included as a random intercept in sensitivity models. (A) PPI task schematic. (B) Maternal dosing and testing timeline (acute E12.5; repeated E12.5–E16.5; saline controls). (C–E) Prepulse inhibition (PPI) at P90: (C) sexes pooled, PPI reduced after prenatal LSD; (D) males, reduced PPI after repeated exposure; (E) females, no group-level difference at this N despite individual variability.

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Does a brief hit matter? Yes. After a single exposure in mid-gestation, cortex is already different by postnatal day 8: shifts in layer markers and microglia. With repeated exposures, some of these changes grow.

Fig. 2. Prenatal LSD alters S1 cortical composition with dose- and sex-contingent effects. (A) Experimental design and S1 sampling. Pregnant dams received a single LSD dose at E12.5 (“acute”) or daily doses at E12.5–E16.5 (“repeated”) at 0.3 mg kg⁻¹. Brains were analyzed at P8. S1 was divided into six equal-width bins from pia (Bin 1) to white matter (Bin 6). (B) Total cell density (DAPI⁺ nuclei mm⁻²) across depth. Both regimens reduce nuclei relative to controls; exact post hoc P values are printed above bins.

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

With “it gets there” answered, we asked “who senses it?” The choroid plexus (ChP) does. Using rapid activity mapping (Fos), high-res imaging of ChP apical remodeling, and CSF protein assays, we see the ChP activate within 30 min. Same fast response with psilocybin and 5-MeO-DMT.

Light-sheet fluorescence imaging of optically cleared E12.5 heads stained for c-FOS 30 min post maternal 0.3 mg kg⁻¹ LSD (representative embryo). Cross-sections of whole-head dataset highlight strong activation in 4V ChP and detectable signal in LV ChP (arrows). Scattered bright foci are noncellular artifacts (e.g., vascular-associated antibody retention and secondary antibody pooling) characteristic of this non-perfused, whole-embryo staining method. Scale bars as indicated.

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Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

Our first question was “does LSD get to the embryo?” We built a tiny-volume PK pipeline—micro-sampling embryonic CSF and quantifying LSD by targeted LC–MS/MS. After one maternal dose, LSD is in embryonic CSF within ~5–15 min and fades over the next hour.

1 1 1

Ya'el Courtney, PhD @scienceyael.bsky.social · 7d

🚨 Psychedelics in pregnancy - can a single dose reach the embryo and matter? Yes. In mice they hit embryonic CSF within minutes, activate choroid plexus→CSF axis, & shift cortical development with adult behavioral signatures. @lehtinenlab.bsky.social Preprint:

www.biorxiv.org/content/10.1...

1/13

Gestational psychedelic exposure disrupts brain development and offspring behavior in mice

Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg/kg) cross...

www.biorxiv.org

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Reposted by Ya'el Courtney, PhD

Dr. Lucky Tran @luckytran.com · Aug 12

This is what the audience for a Long COVID conference looked like today. Notice anything? 😷

Audience for a Long COVID conference all wearing masks

160 870 3.7K

Reposted by Ya'el Courtney, PhD

a wicked and unusual boy @myrrlyn.net · Aug 11

every time sama posts about “you could have phd level intelligence i. your pocket” i simply remember that i can text actual phd @scienceyael.bsky.social whenever i want and not burn down a meadow to do it

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