People's primary concern regarding adverse effects of various drugs seems to always be outright neurotoxicity - I think people should be aware that drugs can cause horrible deficits/side effects without being outright neurotoxic.
Its still unknown if chronic NMDA antagonist abuse is capable of inducing olney's lesions in humans, it seems as though they don't occur in higher primates at least. There is a MRI study from China showing that chronic ketamine abusers brains are atrophied et cetera, but I don't think its clear as to whether or not that is due to being in a K-hole every day for years, or if its actually due to a direct neurotoxic effect. In other words, you can lose muscle by not using it, or a muscle can be outright damaged. Both can result in similar dysfunction that we hope to avoid.
Even if 5-HT2A agonists protect against a supposed direct neurotoxic effect, I would throw caution to the wind with regards to what effect adding in a psychedelic may have on NMDA antagonist abuse related side effects that aren't due to neurotoxicity.
As an example, one of the issues with NMDA antagonist abuse (that likely contributes to psychosis as a side effect) is a decrease in expression of GAD67 and parvalbumin. A decrease in GAD67 and parvalbumin can also been seen in animals given MDMA and this seems to be downstream of 5-HT2A activation.
Granted, MDMA is a different animal, and that is also activation of 5-HT2A by endogenous serotonin which produces a different response than psychedelic activation of 5-HT2A, but the downstream effect that leads to a decrease in GAD67/PV expression is glutamate release, and psychedelics are known to cause (asynchronous) glutamate release.
In other words, one of the main concerns with NMDA antagonist abuse is psychosis, and I don't know if psychedelics will help decrease the incidence of psychosis with disso use. One of the main findings in abstinent ketamine abusers is an increased rate of delusional and psychotic symptoms.
CY
