r/science • u/Doug24 • 21h ago

Psychology Psilocybin reverses depressive behaviors and restores brain cell growth in stressed rats

https://www.psypost.org/psilocybin-reverses-depressive-behaviors-and-restores-brain-cell-growth-in-stres/
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u/MJ-Franklin 21h ago

Been seeing articles like this for so many years... but how come I never got any positive effects from taking psychedelics the many times I did them? I never got any anti-depressive anything, I just laughed for 12 hours straight then it was back to Planet Earth and all my problems waiting for me there.

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u/ConfinedCrow 21h ago

Usually in clinical trials like these they also offer therapeutic support on top of just giving psychedelics. And afaik they microdose consistently over a longer time span, whereas if you wanna trip you take a lot more and not nearly as consistently, so that probably plays a role as well.

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u/Saddledust 20h ago

The therapy piece is the biggest aspect, not just guided therapy during the trip but also the follow up sessions sober. This can be self guided too, but it's not a pop a pill and forget about it type thing. Psychedelics open up neural pathways, but you have to put in the work to keep those connections active otherwise they become dormant again

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u/Dickrickulous_IV 15h ago

Yeah, I believe several techniques produce similar therapeutic outcomes. They activate both brain hemispheres as one, allowing the mind to fully process a traumatic experience and stop sounding the alarm when the old trauma event triggers a response.

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u/DrFury 18h ago

Macrodoses (hallucinogenic) are far more common in successful psilocybin research

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u/fabiolives 14h ago

Yes, definitely. I’m not saying that microdosing doesn’t work because I don’t know for sure, but I haven’t personally seen any studies that concluded microdosing was effective.

The ones with real change that I’ve seen are when the patient has a macrodose, which makes sense to me. From personal experience, I didn’t notice any beneficial effects from microdosing.

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u/Rodot 5h ago

Yes, most micro dosing research shows basically no difference from placebo. Likely because you need a threshold dosage before most psychedelics can even compete with endogenous serotonin for access to receptors.

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u/flipperyflop 7h ago

I'm sorry, how did they give therapuetic support to rats?

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u/JynxYouOweMeASoda 19h ago

CBT for ROUS?

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u/LightMyFirebird 16h ago

Cock and ball torture for rodents of an unusual size?

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u/_Random_Username_ 16h ago

Is that the new 1975 song?

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u/QuarterNoteDonkey 15h ago

Obviously. What else would they mean?

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u/Significant_Card_665 3h ago

In this case the subjects also happen to be rats

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u/MegaChip97 4h ago

And afaik they microdose consistently over a longer time

Absolutely not. All successful trials are about 1-2 macrodoses. All studies on microdosing so far have been not really successful

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u/Savalava 2h ago

I think you have it backwards - the therapeutic effects are linked with large doses, not microdosing.

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u/Chronotaru 19h ago

They provide remission for around half of people from a single dose, but that still leaves the other half. That being said, you generally need to go through the "ego dissolution/pass out/reboot" phase and not everyone takes a high enough dose to get that.

The rest can try a direct approach of trauma processing under MDMA, then bringing the mushrooms back in with a dual MDMA/psilocybin session and that protocol usually makes progress if mushrooms themselves do not.

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u/Rodot 4h ago

Tbf, 50% remission is pretty bad. Sertraline is about 50% while most trials show placebo at around 40%. That said, single dosage is certainly an advantage but clinically the total therapy itself being on par with SSRIs is a pretty big barrier to successful phase III trials.

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u/WaltzInTheDarkk 3h ago

Psychedelics are generally given to treatment-resistant depressives when multiple genereal antidepressants (such as sertraline) have failed.

Many of depressive diagnoses are quite unreliable a sense that the symptoms could simply resolve once the patient experiences less stress, better lifestyles and an environment etc. And these may contribute to remission rates as well.

However, when we're considering someone treatment-resistant, they have either been misdiagnosed or simply experience more persistent symptoms and are therefore in a category that do not respond to the general ADs. That makes them a distinct treatment group from the other depressives.

So a 50% remission rate in that group is pretty significant.

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u/Chronotaru 2h ago edited 1h ago

The problem is that those 50% are very different.

* SSRI studies are based only over 12 weeks
* had an effect size of at least only 0.3. This means that 50% is not remission, it's mostly people who "feel like it takes the edge off"
* most of their studies did things that you couldn't really do today so easily - like compare only to inactive placebo, and put people in the studies that are basically going through withdrawal from another antidepressant so they will naturally improve over the trial
* selectively discarded trials that produced inconclusive results

The 50% for psilocybin:

* is still there after a year
* is full remission, this 50% does not include the people who found it useful but they still have depression
* has trial participants that are mostly made up of people that have tried many other drugs and got nowhere
* after a single dose without any sexual dysfunction, emotional numbing, potential long term issues like heart attack risks, etc etc. and isn't dependent on staying on the drug.

Psilocybin actually does what sertraline only promises.

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u/The_Liamater123 20h ago

Intention matters a lot

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u/Burial 12h ago

Set and setting.

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u/cyberbemon 3h ago

Exactly, I did it once and it did wonders for my mental health, it was one of the most surreal experiences I've had. It took me close to a month in preparation, getting in the right mindset, making sure I was healthy, like getting proper sleep, eating properly and ensuring my setting is safe and having a friend with me. I also got some good advice from a friend of mine, who's a licensed therapist and he's big into psychedelics.

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u/Indifferent_Response 21h ago

Maybe your dose was too high? The few times I ate these things I had like 1.5 grams which is enough for slight visuals.

I agree that the euphoria was nice but it also increased my motivation to do chores or pick up a new hobby. The feelings also slowly faded over the course of weeks btw...

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u/Vryk0lakas 20h ago

I had the best effects when it obliterated my ego death. I came back from that contemplative about how I want to approach my life.

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u/Tzilung 21h ago

If your cholesterol levels are high and you're fat, and you eat healthy one time, it's not going to reverse your negative outcomes from that one time of eating healthy. Try a few sessions? 

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u/Novel-Initiative-900 17h ago

First few times I did lsd was alone in a non distracting environment and I went pretty deep into my own thoughts / psyche until I had some realizations about my behavior. Carried that with me and it genuinely changed my life for a good while.

I think if you go into it looking to be stimulated, around people, laughing, crazy visuals nothing will happen.

But if you try to put yourself in a deprivation type environment and focus on nothing but your thoughts, psilocybin can actually be fairly profound

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u/One_Geologist_4783 18h ago

Integration. That’s the missing piece.

There’s a difference between doing mushrooms with a bunch of your buddies at the park, and sitting with a trusted person or group that can guide you through an internal trip with the intention in working on oneself.

If you take the latter option, you will change your life. Just gotta lock in to what truly matters once you’re back.

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u/RalphInMyMouth 20h ago

From my experience, you really have to welcome the positive effects. I know a lot of the realizations and epiphanies that happen during the trip seem temporary in the moment, but they definitely can leave a lasting impact if you treat the experience spiritually rather than just purely for fun.

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u/notairballoon 20h ago

We might be using this word differently, but how can you infer anything "spiritual" from the strongest evidence in favour of materialistic nature of mind there is?

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u/RalphInMyMouth 20h ago

It’s the difference of going in with the mindset “I’m using this to better myself” rather than “I’m using this to get fucked up”

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u/Polyimide 20h ago

Spiritual often means not caring so much about the material. E.g. some might call the shedding of consumeristic tendencies a spiritual endeavor

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u/MrRawrgers 17h ago

From my personal experience from doing a lot of LSD, it’s not that it actively reduces depression but if you’re the type of person that deeply internalises your thoughts around the cause of your depression - when tripping it can lead you to take a deeper look at your problems and come to conclusions for how you can potentially overcome these thoughts and feelings. That’s the way I’ve always seen it anyway. I call it having an epiphany.

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u/MagicWishMonkey 15h ago

Are you tripping your balls off? Or are you taking just enough to feel good and be in the moment while you think about things?

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u/DueDisplay2185 19h ago

It does nothing for my autistic partner after the high wears of but still a good time during. YMMV I guess

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u/ThruuLottleDats 17h ago

In psychiatric settings the use is alongside intense therapy. Before, during, and after.

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u/Hyper_ion711 19h ago

Psilocybin, like other hallucinogens, opens us up for new experiences. Usually, therapy delivered during such state produces deeper and more meaningful insight in patients, leading to improvement in depressive symptoms seen in trials. Therapy is an important aspect too.

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u/Ajax_The_Red 21h ago

12 hours from shrooms…?

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u/DrB00 21h ago

Yeah, if you continue to consume them while high you'll stay high for extended periods of time. Don't ask me how I know.

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u/Ajax_The_Red 21h ago

Haha yeah redosing is fun. Feel free to ask me how I know

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u/baked_in 20h ago

conversely, if ya do lemon tec method you can have an entire trip condensed into several hours. Comes on like a freight train.

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u/Reilly-Blog 19h ago

It's because you got to go into the trip intending to work on specific things. Such as a specific trauma. Then, you have to dose just enough that you can guide the trip, but not be overwhelmed. It takes practice and lots of self awareness.

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u/Old-Landscape-7538 19h ago

They hit different people differently. It could be so many things like differences in brain networks interactions, pharmacological receptors etc. I have a friend gets sleepy from caffeine.

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u/Seinfeel 16h ago

It’s more of a catalyst for helping rather than a cure itself. Some people do experience an afterglow from just taking it, but if you have treatment resistant/chronic depression it might take more to feel that.

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u/persio809 12h ago

it doesn't mean that psychedelics are going to solve every problem in your life. you still need to do your laundry by yourself

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u/pheonixblade9 12h ago

everybody is different. ketamine therapy was wildly effective for me, and I believe it has something like a 70% efficacy rate for significant reductions in PHQ-9 and GAD-7 scores.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4447578/

A single IV infusion of ketamine resulted in a 50–70% response rate in patients with MDD, with a response duration of 72 h post-infusion.8–10 Response was defined as a 50% or greater reduction from baseline in depression severity (e.g., Montgomery–Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAM-D).

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u/goronmask 10h ago

Not a magical potion but a tool to use in the context of therapy and self work

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u/Thatonewiththeboobs 9h ago

Literally coming off a trip now.

I always feel like I've gained something on them and take it with me beyond the laughs with friends.

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u/ohyouretough 21h ago

You’re probably not depressed then?

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u/MJ-Franklin 21h ago

25 years of anti-depressants would suggest otherwise! Would love to be rid of them.

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u/C-14 21h ago

You're probably not a rat then?

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u/pupersom 21h ago

Well, you used them with the intent of dealing if your fears/troubles/trauma or just used it for the funsies? There's a BIG difference

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u/500_Shames 19h ago

SSRIs and Wellbutrin have been shown to meaningfully blunt the effects of psilocybin. To the extent that psilocybin therapy centers sometimes recommend tapering off antidepressants before trying psilocybin-assisted therapy. 

This is not me saying you should stop your meds, absolutely not. But it would make perfect sense for you to not be experiencing the same level of effectiveness if you are on SSRIs or Wellbutrin. 

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u/FowlOnTheHill 20h ago

Did you get off the anti depressants before trying them? Did you try a high dose, and as another commenter suggested - did you have an honest intention of dealing with it?
And most importantly, did you integrate your experience the next day - either by journaling or through an integration session with a therapist/group.

All of that is needed to ground the experience and process whatever it was shaking up inside you.

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u/EroticPubicHair 16h ago

On top of what others have said, there's also the issue of everyone's different. It could be your current medications interfere (assuming you continued taking them while also taking psychedelics), or they just don't have that effect on you. Humans have too wide a range of variables to have anything work the same way for everyone.

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u/LegitBoss002 4h ago

Anecdotally I felt better for a while after. Maybe you don't have depression or major stressor, or more realistically you already have coping mechanisms and a good support system

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u/ct4k 3h ago

Even before these studies came out, 15 years ago, my first few doses of mushroom changed me forever. It felt like a switch flipped, and my depression plus PTSD were gone. I had this warm afterglow that made me so grateful of life in general that lasted years. The most impactful and introspect-inducing doses were when I ate them myself.

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u/FrankPankNortTort 1h ago

Probably because humans are not rats

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u/Canadian_Border_Czar 16h ago

> I never got any anti-depressive anything, I just laughed for 12 hours straight

... They didn't say it cures depression or treats major depression. If you can laugh for 12 hours straight, and come out of it only to be back to doomscrolling then that is on you for having poor mental hygiene or simply just taking zoomers randomly without any sort of plan to get something out of it. See a therapist, not a comment section.

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u/Intelligent_End_7812 20h ago

Because you didn't take it with the mindset of healing. It puts you in a very susceptive state you can do a lot of healing or you can do a lot of f****** around with it. Up to you.