Is Ketamine Neurotoxic?

I discuss ketamine, and my person experience with it, in more detail here.

At recreational doses, ketamine is addictive, destroys the bladder, and is toxic to the central nervous system. Microscopic lesions (including but not limited to so-called “Olney’s lesions”) in both grey and white matter are evident already after three months of high-dose ketamine use.

By year three of heavy use, MRI scans of ketamine users often reveal a brain that looks like a mix between multiple sclerosis (white matter lesions) and Alzheimer’s disease (grey matter atrophy).

Ketamine abuse is well known to cause widespread cognitive and neurological impairment. However, the average ketamine “user” consumes 500-1000mg of ketamine per day, which is 100-300x as much as therapeutic use (0.5mg/kg). One glass of wine per week is surely different from a gallon of vodka per day.

Nonetheless, it’s widely recognized that individuals who occasionally use ketamine find they need significantly higher doses than when they first started, even after prolonged periods of abstinence.

For instance, after a few months of using therapeutic doses of ketamine (around 0.5mg/kg per week), I noticed that its impact was much less pronounced compared to my initial experiences with the substance. Even extended breaks did not bring back my virgin response – in an analogous way that MDMA users never recapture the magic of their first few trips.

This form of “permatolerance” may point to neurotoxicity.

Researchers are still unsure whether it is safe to use ketamine at low therapeutic doses at reasonable frequencies for a couple of weeks to a couple of months. However, in the case of otherwise untreatable depression, the risks and side effects need to be weighed against the risks and side effects of ongoing depression. Furthermore, depression itself is quite damaging to brain health itself.

The above is only a fraction of the article. This article is currently undergoing final revisions and is expected to be published within the next few weeks to months. To receive a notification upon its release, sign up for my newsletter.