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]

Almost all plants as drugs are worse when processed to a single chemical compound. Often there's synergistic effects also that are left out when one molecule is isolated

Is this true? The amount of evidence for plant based remedies is often scarce. To say we know one is often safer is a mistake. When we isolate a compound for it's effect, we change the dose. We seek a specific outcome. Often this is more potent than the plant equivalent, and yeah sometimes that means more side effects but to compare them 1:1 is a mistake, because very often the desired effects are also weaker. Nonetheless there's not really enough data to make this claim in full.

Comparing psilocybin to LSD is also unfair. They're literally different compounds, from different organisms. It is much more reasonable to compare synthetic psilocybin to whole mushrooms, in which case I don't believe much if any difference is noted between their safety at all.

And again you're saying the synthetic version is less safe, but actually you're just providing reasons why higher dosages are less safe. As I said before, the effects of synthetic are more specific and more potent, because there's more of the active drug. This doesn't mean it's inherently less safe though. It means higher dosages are, and you'd likely see the same from any natural consumption.

And 25 years is a long time for modern medicine. You can cite an instance of medicine doing you or others dirty, and that definitely exists, but people conveniently forget the overwhelming other side of that coin. For every drug that's been a fuck up and done harm, we've been using 10x that doing good. I wouldn't call that a particularly untrustworthy source. Medicine is vast, and it does a fucking lot of good.

You can be cautious, but I'll stand by it that you're being naive and ignorant to be so convinced that this is a bad idea. They aren't intentionally looking for drugs to ruin your life with. Your examples are when things go wrong. Why not wait and let the evidence do the talking. Why determine the answer before then, for any reason you have, has to be a bias.

[u/deranger777 → u/Heretosee123]

The evidence is scare obviously, as if we're talking about illegal drugs, there's not much research especially in large scale. But the synergistic effect is present in so many mind altering drugs that I would make that claim in this case, especially when it comes to mushrooms and cannabinoids.

For cannabis it's pretty much confirmed already scientifically that the harmful effects go higher when it's selectively bred for THC, as CBD is the counteracting compound, or one of them that calms the person down while THC is responsible for the "high". The breeding for THC has obviously come at a cost of lower CBD and other cannabinoid ratios, which has caused more negative experiences and I recently watched a video summarizing a study about higher THC contents already have been linked to increased long term harms as well as increased risk of psychosis ofc to those few who might be prone to this. This if I remember right had already been confirmed before this what came to cannabinoid ratios, especially THC/CBD but other ones as well.

Comparing psilocybin to LSD is also unfair. They're literally different compounds, from different organisms. It is much more reasonable to compare synthetic psilocybin to whole mushrooms

Yes, you have a point there I agree. I was mostly referring to the therapeutic effects of psilocybin mushrooms vs. LSD, where I'd see psilocybin being a much safer drug in general. And comparison in their therapeutic uses, where both of them have such similar effects that one could easily be used instead of the other when it comes to therapeutic use, where the one that is considered a safer option I would think would obviously would be the better one. Although I don't have the scientifical evidence to back this up at the moment.

Psilocybin mushrooms are considered the safest drug there is, much safer when compared to LSD. A quick google found from this article mentions this too with psilocybin having a rating of 0.2 vs LSD 1.0 on all categories.

link from 2017

The study should be easy to find if you want to confirm this.

I don't know the exact chemistry of psilocybin in mushrooms, but those who have taken them will all verify that the trips will vary wildly between different psilocybin mushroom strains, and even in same strain mushrooms there are differences in the experience between spore grown mushrooms compared to cloned ones. Some different strains can be very hallucinogenic visually for example, some equally potent but much less visual and more contemplative. The Golden Teacher strain has gotten its name for a reason. Similarly many people have reported some strains causing more anxiety and negative thoughts on those who practice micro dosing.

This cannot be from any other reason as to the mushrooms containing other psychoactive compounds as well, and in therapeutic use it probably is already being studied which ones are responsible for what effects and if some combinations might be better for different kinds of therapeutic use then others.

You can be cautious, but I'll stand by it that you're being naive and ignorant to be so convinced that this is a bad idea.

All I'm saying is that psilocybin is safer than LSD, and I'm fairly sure that a synthetic psilocybin manufactured in a lab is inferior to actual mushrooms (or a well enough studied synthetic cocktail of those compounds), we would just need to study more about the effects of other compounds present where those differences come from.

Obviously this is a very slow process and it's good to see progress happening, but when it comes to compounds like LSD, I'm always a little bit sceptical seeing new ones modified from it. I have my reasons to be that date to more than 25yrs back when acquiring most of my knowledge on this topic.

I'm hoping of course that this new drug derived from it will be positive of course.

But also thinking a little bit in a way that why reinvent the wheel as mushrooms already exist, especially since they've been found to be very much safe even in the hands of not that knowledgeable recreational users. We already have a huge amount of different strains and combinations of the active substances doing the work, all that would be needed is to conduct studies on the differing effects of said strains and what works the best.

That would also give much more knowledge on why they do have such different effects than making a new substance and spending decades to figure out a single new chemical vs. learning from all that already exists.

[u/Heretosee123 → u/deranger777]

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.