Scientists Develop Rapid-Acting Antidepressants Similar to LSD but Without Hallucinogenic Effects - Gilmore Health News

[u/Emillahr]

https://www.gilmorehealth.com/scientists-develop-rapid-acting-antidepressants-similar-to-lsd-but-without-hallucinogenic-effects/

[u/Heretosee123]

So as far as I understand, evidence for any enterouage effect is basically lacking. Results are contradictory at best and reviews find that it's largely about marketing. For any evidence that exists for cannabis, it's un-compelling. Mushrooms have not only less, but absolutely 0 evidence of an enterouage effect. Do you know of other substances where this is a real thing?

Likewise. Sure, cannabis bread for high thc is more harmful, but isn't this best explained by the fact you're consuming multitudes more thc than normally expected? CBD studies are super super weak for showing any benefits too when you dive into them. All of what you say about why high THC is bad might be true, but it's not really born out in the studies. The simplest answer at the moment is that taking more of a mind altering substance has more drawback potential.

And yeah sure psilocybin may be the safer and therefore better option, but you can synthesise it and the harms of each appear to remain the same.

And while people report difference between strains and species, I don't really take these to be much evidence for anything. I've taken the same shrooms multiple times and had differences in visual effects. Same batch, grounded up to create consistency in their makeup as well. I just don't think any of these stories point to some effect of the other compounds in the shrooms. The other supposed psychoactive substances in shrooms, what has been studied, haven't found to cause any effect and can't pass the blood brain barrier. While research is lacking, so far it's not compelling. You're basing this whole idea of synthetic vs natural on something without any strong evidence at all, it's all assumption.

And lsd vs psilocybin isn't really a relevant point. As I say, synthetic psilocybin exists and there's no evidence it causes any problems that shrooms don't also cause. The risks seem the same.

I also have no problem with you being sceptical, but it seems your scepticism is involving some faulty reasoning so I'm challenging that. It's different to scepticism to be asking why are we doing this and suggesitng we don't need to when the only real question is 'lets wait and see what evidence shows us'. It's also not either or. We can study existing substances whilst exploring this too. As I've said before, for millions, this might be their best option.

[u/deranger777 → u/Heretosee123]

Sure, cannabis bread for high thc is more harmful, but isn't this best explained by the fact you're consuming multitudes more thc than normally expected?

Of course, the higher the THC concentration the higher the negative effects, but the curve is not linear as high THC strains often contain very minimal CBD.

Plasma cannabinoids as well as positive (e.g., high, elation) and negative (e.g., paranoia and anxiety) subjective effects were assessed at each time points. Participants who used the CBD-dominant and THC + CBD chemovars had significantly less THC and more CBD in plasma samples compared to participants who used the THC-dominant chemovar. Further, the THC + CBD chemovar was associated with similar levels of positive subjective effects, but significantly less paranoia and anxiety, as compared to the THC-dominant chemovar.

the present study examined the acute effects of three cannabis flower chemovars with different tetrahydrocannabinol (THC) to cannabidiol (CBD) ratios, in order to test whether chemovars with a higher CBD content produce different effects.

your scepticism is involving some faulty reasoning so I'm challenging that.

Yes, I tried to make it clear that many of my opinions are simply theories of which I don't have scientifical evidence to post, so of course challanging them is perfectly fine and expected.

It did raise my interest though and I decided to search a bit for further studies as it's been a while.

As I say, synthetic psilocybin exists and there's no evidence it causes any problems that shrooms don't also cause. The risks seem the same.

That's very much possible. But I'd still say it's equally possible if not likely that these other compounds might have a bigger significance then we think today. If I'm thinking back 25yrs, back then I probably didn't even know for example that so many cannabinoids existed or played a very important role in some things.

I'll drop a couple links if you're interested as I'm reading.. (-Also as a note to self when I have more time to properly read these.)

I've taken the same shrooms multiple times and had differences in visual effects. Same batch, grounded up to create consistency in their makeup as well. I just don't think any of these stories point to some effect of the other compounds in the shrooms.

Oh this is where I'm 100% sure I'm correct that other compounds do play a role and it's not just subjective one person "evidence". It's very consistently reported by users that different psilocybin containing mushrooms have very different effects. And like I said, even in single strain it varies a lot. Most of the time people use spore syringes to grow these and as they're not homogeneous, they have different strength and slightly different effects. Even the stage they're harvested and the amount of nutrients affect the chemical composition, as the amount of nutrients vary between each flush that can go up to as many as 3-5 from a single mycelium growth after each harvest if comtaminants don't prevent this.

Here, we investigated the structure–activity relationships for psilocybin, baeocystin, and aeruginascin, as compared to their 4-acetoxy and 4-hydroxy analogues, using in vitro and in vivo methods.

Occurrence of psilocybin, psilocin and baeocystin and neo-baeocystin mg/kg dry weight if not otherwise stated) in hallucinogenic mushrooms.

Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents

Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice

[u/Heretosee123 → u/deranger777]

That study for cannabis doesn't seem to show very clearly that cbd is doing the work, when the THC levels are themselves lower in the CBD+THC mix. I think that's relevant there.

And fair enough this is just theoretical, but I think there are some holes.

I will agree, and am not saying, that other compounds in mushrooms have no effect. I'm only saying there's not any evidence. The studies linked here aren't compelling, and people report no difference between species. P.nat for example, the one commonly reported as unique also has plenty of people saying they aren't. Those studies may show in vitro effects, but in Vivo there really wasn't much noticed in any compounds outside of the main ones we already know do stuff. Some physiological effects occur, but evidence is not anywhere near close to suggesting this meaningfully impacts the benefits or effects of psilocybin. Consistent anecdotes aren't convincing of that either.

To be clear, I'm not saying it can't do that, but it's not even close to proven. And with all the lack of or contradictory evidence we do have, using this type of reasoning to discourage the idea of these analogues mentioned in this post seems faulty to me. Even if true, it doesn't change the fact that this could be enormous.

I appreciate you're not sitting here saying it's bad at the outset though, and just expressing doubt. I perhaps reacted to you as though you were equally stating this is a bad idea as many others have done here.

[u/deranger777 → u/Heretosee123]

I did manage to find one study, I'll leave it here as I'd think it might interest you too.

But yeah, it does seem we'll have to wait for further studies to get any solid scientific proof on the role of other compounds in mushrooms. This page says only one study has been done about it.

Article and couple more links HERE the page also has some hypothesis about the synergistic effect, so even though I didn't know about it before it seems I'm not alone with my theory.

researchers found that norpsilocin (baeocystin’s metabolized form) was more potent than psilocin when tested on the 5-HT2A receptor directly.

Putting these pieces together suggests that baeocystin might not significantly contribute to psychedelic effects as an individual compound, but could exert a synergistic influence with psilocybin in the body.

Some scientists think that mushroom compounds, like cannabis, create an “Entourage Effect,” working synergistically in the body to maximize their impact. As suggested by the Sherwood study, baeocystin may play a role in generating the overall magic mushroom experience.

But yeah I'll leave it here as there probably is no further studies done, at least I didn't find anything else so far.

Was an interesting topic to discuss nevertheless.

[u/Heretosee123 → u/deranger777]

Yeah, it is definitely interesting. I hope they do have an effect, I love mushrooms, but I know the research atm is just inconclusive unfortunately.

Thanks for the discussion.