Dr. Ben Yudkoff, Co-Founder and Chief Medical Officer at Lumin Health, hosted a Reddit AMA on the Spravato community on November 21, 2025. 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/Spravato/comments/1p2ar6v/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.
Delicious_Delilah asks
I've been doing an experiment the past month and a half (with the blessing of my psychiatrist) where I drink grapefruit juice before spravato because I read that it increases the amount of spravato in your blood stream. My theory is that more spravato in the blood stream means more spravato getting to your brain...which may make spravato actually work for me.
I'm super treatment resistant to more than just psych drugs, so I'm just trying to increase the chance of spravato working for me.
Do you think my experiment of drinking grapefruit juice before ketamine or Spravato could work?
My psychiatrist hasn't read any of the papers about grapefruit juice and spravato, so she could only say that, in theory, it could work. For me personally? Possibly not since my body is stupid.
Answer:
Grapefruit juice inhibits a liver enzyme called CYP4503A4 (commonly referred to as "3A4"). Liver enzymes are these little tiny machines in the liver that help to break down molecules so we can clear things from our system. If I can refram Delila's question: "if I take something that blocks my liver's ability from metabolizing the ketamine, might it change the amount in my bloodstream?"
The answer is that drinking a glass of grapefruit juice just once before treatment is unlikely to inhibit this particular enzyme sufficiently that it actually makes a difference. I don't know that for sure, but my intuition is that it might not make such a difference. If a person were to drink multiple glasses of grapefruit juice per day consistently, it's possible that it might impact this enzyme sufficiently that it impairs the clearance of Spravato. But metabolism is only part of the question: not only is ketamine broken down to jnoretamine by these enzymes, but it's also extensively renally cleared, meaning the kidney also does quite a bit of work in clearing Spravato and norketamine from the system. The extent of the impact of blocking 3A4 is unclear.
It's also worth mentioning that experimenting with levels in this uncertain environment presents some risks as well. I would urge some caution, here, because you wouldn't want to have an uncertain amount of Spravato in your system. But if you find that the dose of Spravato may not be sufficient to be helpful, there may be other things to consider. Some clinics will offer additional ketamine on top of the esketamine to get a predictable amount of total ketamine in one's system so that one actually does experience relief and a response. This is more controlled and predictable.
Some people might just forgo Spravato and choose ketamine, either intravenously or intramuscularly. While some people can't make that switch because some insurances don't cover the cost of intravenous ketamine, still some insurances do, and you have a much wider dose range of ketamine available to you than you do with Spravato.
In sum: drinking grapefruit juice will inhibit the metabolism of esketamine. My hunch is that drinking a glass before the esketamine treatment is probably not doing all that much. Drinking grapefruit juice regularly probably would have an impact on how long the esketamine stays in your system and how high the level would get to, but it's not clear by how much. The word of warning is that this all sends us into a direction that's slightly less certain and has more potential risk. You may be able to get the exact same results with a higher degree of certainty and safety by speaking with your providers about having a higher overall dose with your clinic and thinking through other options, or by considering intravenous ketamine checking in to see if your insurance company either pays for it or would create a single case agreement with a provider in your area who offers it.
Also worth mentioning: blocking the activity of 3A4 may also impact other medications you take -- definitely worth checking in with your doctors to make sure there aren't other implications of blocking this enzyme (which breaks down a lot of psychiatric medications, as well).
