This is a big issue. Clinical studies to get a chemical approved for therapeutical use are very expensive, and since most of the chemicals were first explored a long time ago, they can't be patented anymore, so no pharmaceutical company would fund the studies since they won't be able to be the sole provider of that drug (at a premium cost), and public funding for clinical studies is quite low.

There is nothing stopping them from making a patentable analogue. Happens a lot right now.

Well, except for this: https://en.wikipedia.org/wiki/Federal_Analogue_Act

Meh... that already isn't a barrier. Analogues of heroin (fentanyl, etc) are legitimate Rx drugs today.

I guess that leaves academia?

No, it does not. "Academia" generally means studies funded by public grants (which, as I said above, very rarely would cover drug approval studies) and in some cases academia might implement studies funded by the pharmaceutical companies, but they're not really an independent source of funding for research, at least not in expensive/labor intensive fields like medicine.

In fields where solid research can't be done by a single part-time person (e.g. a teaching professor), research happens only to the extent and in the direction where there's available funding. Even putting a couple grad students on a project for a year (i.e., a very small project) requires external funding, much less the extensive studies needed to prove that a particular chemical is safe for human use and has a therapeutic effect.

It’s true in general that economics, with patents being part of that, is the dominant influence on r&d resources.

However the effective research ban is by far the bigger limiting factor in this case, because it rules out most options before even getting started.

For example, it’s not unusual for unpatentable substances to be studied, in the hope that understanding the fundamental mechanism could allow a (sometimes) improved alternative to be developed that could be profitable.

There is also at least some research not controlled by big pharma that could have conceivably targeted these areas 40 years ago.

I have trouble believing the patent argument. If folks can patent certain strains of crop seeds, why would they not be able to patent a GMO mushroom or a process for GMO yeast to produce such things?

Would they not be able to profit from the stability of lab-produced drugs? Would the generic market not want to produce these? After all, some of the drug manufacturers produce both brand-name and generic drugs [1].

Regardless of patent, I'm pretty sure some players would happily get into the prescription market. On top of this, I'm going to guess since it seems some of these drugs out-perform the available prescription drugs and is cheaper in the long run, insurance companies and governments alike (since some places have universal care and even the US is invested in some forms of healthcare) stand to profit from having this sort of thing be the first line of treatment when possible.

[1] http://www.pharmaceutical-technology.com/features/featurethe...

As I understand it, the problem with drugs that aren't patentable is there is no way for those who pay for clinical testing to re-coup their investment. Phase I-IV clinical testing usually goes well over 100 million USD [1] so drug companies need to recoup that money, if the drug isn't protected under patent, once approved, any manufacturer can produce it. Sure they could patent GMO organism that produces it, but the process to produce it chemically is already well understood, Shulgin has published recipes to produce virtually every psychedelic chemically pure in Pikal and Tikal.

[1]https://aspe.hhs.gov/report/examination-clinical-trial-costs...

Wait, you think drug companies are conspiring to stop MDMA trials?

Having worked for a few drug companies I can assure you most don't even know what MDMA is.