Dr. Ben Yudkoff, Co-Founder and Chief Medical Officer at Lumin Health, hosted a Reddit AMA on r/TherapeuticKetamine community on March 6th, 2026\. The below blog post is a recap of one of the questions presented on that AMA, syndicated to the Lumin Health blog in the event that it answers any questions about ketamine therapy, Spravato treatment, or general concerns you may have about treatment.
[https://www.reddit.com/r/TherapeuticKetamine/comments/1rj2blv/ama\_im\_dr\_ben\_yudkoff\_psychiatrist\_cofounder/](https://www.reddit.com/r/TherapeuticKetamine/comments/1rj2blv/ama_im_dr_ben_yudkoff_psychiatrist_cofounder/)
Don’t hesitate to get in touch with us if you’re interested in learning more about ketamine for depression at Lumin Health. Thank you once again to the moderators and community members for facilitating such an engaging discussion.
Candlesticcs asks:
Can you discuss the side effects of long-term therapeutic ketamine use, including the high oral doses we often see in this community, 400 plus milligrams to 2 to 3 times weekly? Aside from ketamine cystitis, what issue should we be aware of? And are there any signs that we should slow down or stop taking the medication? I'm especially interested in the effects on the bladder and the liver.
Answer from Dr. Ben Yudkoff, Co-Founder and Chief Medical Officer of Lumin Health:
That's a great question. The most honest answers we don't know and the long term use of high dose ketmaine hasn't been well described. Having said that, there are a number of people who are taking relatively high doses chronically and we haven't seen the kinds of side effects that we've been most concerned about, specifically, like as you named, ketamine-associated ulcerative cystitis or hepatitis. Another concern raised during the exploration of the feasibility of ketamine as a treatment for depression is concern about something called “Olney's lesions” - in animal models, rats provided ketamine in doses of 100-200 times the dose provided for antidepressant effects caused something called vacuolization - empty areas in brain cells began to emerge. It's hard to translate how that evidence comes into a human model when considering this was not represented in non-human primates and the study design is very far away from how ketamine is provided clinically (i.e., the doses were just so much higher and given over multiple injections). It’s also worth mentioning that these vacuolizations resolved. The concern raised the question of neurotoxicity is a concern. But as the expression goes, so the dose has the poison: so as the dose remains responsible ketamine is safe.
Janssen (which produces esketamine (Spravato)) did a 5 year retrospective study on people taking esketamine and there were no identifiable or statistically significant long-term side effects from people who take esketamine clinically, including neurocognitive side effects. And in fact, there may be some signs that it can improve certain elements, certain elements of cognition.
As of right now, from what we know, there are no known extraordinary risks associated with long-term, clinical use use.
Apropos your second target question, specifically around when to slow down or stop the medication: there are lots of signs them. Those could include:
- Developing tolerance to medication.
- Something called “tachyflaxis” - term for why the medication poops out.
- There are financial concerns around the cost of these treatments.
- There's that commitment in time to the treatments that might otherwise be spent doing other things to feel better.
The signs that might instigate slowing down or stopping have less to do with long-term risks of the medicine and more to do with the circumstances of the medication and how it's benefitting a person.
