“Ketamine part 2: What do in vitro studies tell us about safety?” by Elizabeth

Ketamine is an anesthetic with growing popularity as an antidepressant. As an antidepressant, it's quite impressive. When it works, it's often within hours- a huge improvement over giving a suicidal person a pill that might work 6 weeks from now. And it has a decent success rate in people who have been failed by several other antidepressants and are thus most in need of a new option.

The initial antidepressant protocols for ketamine called for a handful of uses over a few weeks. Scott Alexander judged this safe, and I’m going to take that as a given for this post. However, new protocols are popping up for indefinite, daily use. Lots of medications are safe or worth it for eight uses, but harmful and dangerous when used chronically. Are these new continuous use protocols safe?

That's a complicated question that will require several blog posts to [...]

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Outline:

(01:15) Reasons to doubt my results

(03:09) Tl;dr

(08:58) Papers

(09:51) Ketamine Increases Proliferation of Human iPSC-Derived Neuronal Progenitor Cells via Insulin-Like Growth Factor 2 and Independent of the NMDA Receptor

(11:57) Ketamine Induces Toxicity in Human Neurons Differentiated from Embryonic Stem Cells via Mitochondrial Apoptosis Pathway

(14:42) (2R,6R)-Hydroxynorketamine promotes dendrite outgrowth in human inducible pluripotent stem cell-derived neurons through AMPA receptor with timing and exposure compatible with ketamine infusion pharmacokinetics in humans

(16:18) Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons

(18:05) Ketamine Prevents Inflammation-Induced Reduction of Human Hippocampal Neurogenesis via Inhibiting the Production of Neurotoxic Metabolites of the Kynurenine Pathway

(19:11) The effects of ketamine on viability, primary DNA damage, and oxidative stress parameters in HepG2 and SH-SY5Y cells (the negative one)

(21:25) Why In Vitro Studies?

(25:09) Conclusion

(25:28) Thanks

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First published:

September 7th, 2025

Source:

https://www.lesswrong.com/posts/kjbq7T7Z2vEDoPw95/ketamine-part-2-what-do-in-vitro-studies-tell-us-about

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Narrated by TYPE III AUDIO.

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