I should add the prefix to the subject: "Why I think that", but it would be too long. Consider it added. I'll elaborate some points and quote some sources, but note that many more sources can be found, the conclusion is not based on these sources only.
Note that I'll make a conceptual leap: since basically nothing can be said about HPPD due to lack of research and data, I'll treat it as some form of psychosis/schizophrenia, which is widely studied (although not understood anyway), and REMARKABLY similar to HPPD. At the very least, it could be said that HPPD is a mild form of psychosis/schizophrenia, a subset, etc, but it seems very logical to assume that they will share many characteristics. See second link, about Drug Induced Psychosis
- The causes of schizophrenia are not understood, and many hypothesis have been proposed, notably: serotonergic causes, dopaminergic causes, and glutamate causes.
While the sertonergic idea is the older, newer studies point in other directions, mainly of stimulatory nature
- Recent studies have indicated the importance of the Dopaminergic system in the effects of LSD, distinguishing between phases of the LSD effects according to the main receptors activated, and proposing as a model for schizophrenia.
- While sertonergic system is mainly associated with mood (depression, anti-depressants), the Glutamate system is more related with the information processing and memory formation.
- The relationship between dopamine and glutamate is deep, and many studies are studying their link to each other, and to psychosis.
- Going back to David Nichols study about the 2 different phases (sertonergic and dopaminergic) phases of LSD, and comparing that to the description of HPPD, seems clear that HPPD seems more "phase 2". It's usually describe as "the last part of an LSD trip"
- For drugs or situations that are well known to trigger or worsen HPPD according to the community, it can be found that they act on the dopamine/glutamate system, but NOT (or barely) on the sertonergic system.
- The inverse argument can be seen also: drugs that act directly on the serotonergic system, usually have little effect on HPPD, or make it even worse. Example: anti-depressants (SSRI). Also, the same drugs are not known to cause HPPD.
- Of the drugs that have consistently shown usefulness for the HPPD community, 2 of the 4 target the Glutamate system
- Some HPPD sufferers are experimenting with Ketamine, with good results. Ketamine's main method of action is through the Glutamate system, not serotonin.
- Regarding stress being a trigger for HPPD, the relationship between cortisol and glutamate and PTSD has been already treated, in this example, by no less than David Nutt, one of the most world renowned scientists regarding drugs:
- More about the relationship of psychedelics, anti-psychotics, and 5HT2A and Glutamate receptors can be seen here:
- More on the relationship of excess glutamate in the PFC and schizophrenia:
- Chronic LSD, schizophrenia, glutamate, etc:
In sum, for all of the above, I believe it's pretty clear that HPPD has way bigger chances of being glutamate related, than serotonin related.
I could also keep going on a bit more about in the hypothesis, but I'll leave that for a follow up text.
Looking forward to reading all opinions.