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I've always been very, very skeptical of this claim.

If there's an actual natural, identified substance with huge benefits to people, it's going to go gangbusters and you're going to make a lot, LOT of money selling it, even if you're doing it via roadside lemonade stand.

It feels like this claim is usually used to promote cures and treatments with extremely low quality RCTs backing their use as a sort of panacea.

I used to believe the "just do shrooms to cure depression" claims on principle until I looked into the quality of those studies, which is very low. At that point, you're just making stuff up.



Caffeine is an example. Coffee and energy drinks are doing well I'd say.


Caffeine is grandfathered in as a Generally Recognized as Safe food additive. If energy drink companies had to go through clinical trials with no patent protection for each drink formula, they wouldn't make them.


I think the current regulatory regime in many US states allows companies to make a killing off of selling naturally occurring bioactive substances as dietary supplements with few regulatory hurdles.

Kratom, CBD, and delta-8 THC are naturally occurring bioactive substances that are newer to the US market. Both have carved out a pretty nice economic niche with a bunch of claimed health benefits.

A couple of years back, I saw a sign outside a fancy legal highs shop in Fishtown, Philadelphia touting the benefits of kratom as a pre-workout supplement. The insanity that a business was advertising an addictive opioid to healthy, opioid-naive people for better gains in the gym almost makes me want more regulation in this area.


Your point is a bit undermined by the fact that two out of your three examples are cannabis extracts, where cannabis proper - literally a leaf - is still very much illegal and has to be "laundered" through chemical processes to make it less fun and therefore "medicine" instead of "recreational drugs".


I think your point and mine can both be true at the same time. Cannabis is the subject of a past regulatory regime that restricted nearly all psychoactive substances popular at the time (natural or synthetic). The actions of that regime do not go away when the zeitgeist changes. The current regulatory regime is much more dovish, and that is visible in the difference between the controlled status of chemicals that became popular recently versus similar ones that were popular 50 years ago.


Isn't it relatively easy to sell anything "naturally occurring" as a supplement? I think there is very little regulation (of course if you want to claim it's a drug and presumably charge much more for it it's another matter).

Even synthetic research chemicals are generally legal as long as you add a "not for human consumption" label (and they aren't explicitly banned or analogous to other illegal/regulated drugs).


Why was caffeine studied? Why does it continue to be studied?


The global coffee market is worth $138 billion, the soft drink industry is $556 billion (and growing). The vast majority of which being caffeinated. Starbucks the company is #116 on the Fortune 500 and #1 in food services. There's sufficient economic activity to warrant continued research in the area.


It’s a lot cheaper to study something in academia than to do a full clinical trial.


That’s an excellent point


Lithium is a good counter. It is by far the best treatment for bipolar 1, and its cheap and easy to source. Prices for lithium carbonate and other lithium medicament's are not at all cheap, and there are not a lot of medical companies producing it. There has even been shortages. Instead antipsychotics have been pushed as a preferred treatment, even though the outcomes are worse than with lithium.


Lithium in dosages effective in treating a mood disorder is quite toxic (e.g., to the kidneys) so most of the price is probably to offset the risk of lawsuit awards.


With regular blood checks its not an issue. You can catch it before the kidneys take damage. Antipsychotics are literally neurotoxic (first gen atleast).


But antipsychotics cause movement disorders and metabolic syndrome.


> Prices for lithium carbonate and other lithium medicament's are not at all cheap

You can buy a 3 month supply of Lithium Orotate for like $10. I certainly wouldnt recommend self prescribing this kind of thing though.


It’s not enough dosing to treat bipolar.

You have to dose relatively high in order to have an effect. You’re disrupting your neural sodium-potassium pumps with it.

But it’s still pretty cheap. Hard to charge a lot for a fairly abundant element.


I'm skeptical of your claim because if there's any additional margin to be made doing it artificially, at big-pharma scale history shows that they plenty willing to squeeze every penny out that they can even if it's less effective/natural.


That's true, but doesn't really squeeze natural alternatives out of the market if they're effective.

For example, there's a prescription engineered version of melatonin.

Melatonin is still a huge business.


Red Yeast rice exists, and so does lovastatin (Altoprev)


Right, but there is a free rider problem. Why should a company spend $100 million doing clinical trials to get FDA approval if once it is approved, all other companies can sell it, even though they didn't pay anything? Even if every actor in the market thinks there will be a good return on investment if they get FDA approval, there is a strong incentive to instead wait for someone else to do it and free ride on them. The result is no one acts.

Clinical trials are a significant expense in developing a drug. Kind of makes me think we should award patents not for coming up with some molecule, but instead award them for showing a molecule is safe and effective.


CBD, which doesn't appear to have a fraction of the therapeutic efficacy of something like Ozempic, is a multi-hundred billion dollar industry now with a lot of active research.


Do you have a source for that? Everything I can find online puts global CBD industry revenue at less than $10 billion. And that's everything. The only FDA approved use of CBD (treating seizures), I'm sure is only a tiny fraction of that.

In any case, none of that refutes that there is a strong economic incentive for market actors to not fund FDA approval trials since any benefit will be shared by the entire market.


Nitrous Oxide (laughing gas) is both significantly cheaper, and less risky than epidurals for reducing pain during childbirth. Yet, in the US, most hospitals don't even offer it as an option, and I think a major part of that is that patented epidurals have much higher margins, so that is what the medical suppliers push.


I doubt it. It's very commonly offered in the UK and while it's cheap and safe, based on what I've seen it's also not effective at all. Forget the same league, it's not even playing the same game as an epidural. An epidural is a drip of opioids right to your spine. Proper hardcore.




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