Three Hypotheses of Psychedelic Action

[@lucacantoni794]

Thanks for the video! So, if we will find something that acts on 5HT-2A without psychedelic effects, it would be something like biased-agonism? From my point of view, I really think that the psychedelic experience it is fundamental in the re-wiring of the brain, both in the acute phase and in the chronic phase. I don't think that the lone activation of 5-ht2a can have that greatness of therapeutic effects but probably I'm biased 😬

[@Neuropharmacist]

I think so. And I also think it may turn out impossible to retain the therapeutic effects while getting rid of the psychedelic experience.

[@godgodgnipael]

I am micro-dosing 0.15 grams strictly at night, while I sleep. Ground mushroom capsules. It still works to cure mild depression. See my post above.

[@godgodgnipael]

I think macro-dosing has a different effect. Allowing one to rewrite their life narrative. Micro-dosing is more like a powerful healing drug, that works over weeks or months of treatment.

[@BrianOSheaPlus]

The closest thing I am aware of is Ariadne. www.ncbi.nlm.nih.gov/pmc/articles/PMC10147382/

[@adamsusel3801]

I find the second hypothesis most convincing as well. My question for you is this: what level of analysis is the right one to study? There is much theoretical work to be done in neuroscience with regards to network dynamics, computational power, information processing, etc. How do we balance the mechanistic biochemistry of the brain with it’s incredible mathematical power?

[@Neuropharmacist]

These are very good questions and there are no simple answers. I don't think there's a right level. All levels of analysis are likely useful to some extent. I think we need much more basic research of the underlying principles, from molecular to cellular to network and computational aspects of brain function, to really start to even grasp the mechanisms of complex psychiatric disorders and their treatments. One thing is that we need more theoretical work, besides massive data generation.

[@adamsusel3801]

@@Neuropharmacist agree 100% on the need for theoretical work. That’s why I’m doing my undergrad as Math BS!

[@Freakoutski]

A really clear introductory video! Thanks for the further reading references. Do you think you might make one on neuroplasticity? It's a subject that seems to be glossed-over a lot in the context of psychedelics. Subbed, and Like smashed!

[@Neuropharmacist]

Thank you! That's a good idea, although quite difficult. While many speak of neuroplasticity, actually framing what it is can be a complex topic.

[@RyanHellyer]

But is there any dose which doesn't have a psychedelic effect? I can consume 1 mg of psilocybin and not notice it. But when I go to sleep, I am guaranteed to experience psychedelic effects during the process of going to sleep and when I wake up at night. It's not a sufficient dosage to cause the abrupt awake effects of a macro-dose, but I definitely notice the effects given the correct setting.

[@Neuropharmacist]

That's actually a very interesting anecdote - microdosing and sleep. Is it the microdose that wakes you up once it peaks? Can you get sleep after that? Are you experiencing the psychedelic effects when you are falling asleep?

[@candy_helpsoninstagram3878]

Get psychs here👆look up 🔝..

[@themothman3726]

What I don't get is that with 60 years of known use to draw from we know that it works, we also know the risks are relatively low. Why are we still waging a war on these things?

[@godgodgnipael]

I am treating myself for mild depression with psilocybin at night, while I sleep. I take 0.15 gram capsule before bed. Like clockwork, I wake up about 5 hours after falling asleep, at which point I sometimes take a second capsule.

[@godgodgnipael]

I have been doing this for about 6 weeks, 4 days on, 3 days rest.

[@godgodgnipael]

I have found the treatment has put my depression in remission. Furthermore, it has drastically improved my verbal fluency, positively impacting my sociability.

[@godgodgnipael]

Short term memory seems much improved. Positive signs of neural plasticity as well!

[@godgodgnipael]

Do you know anything about heart valve damage from doing this?

[@Neuropharmacist]

​@@godgodgnipael There are several drugs that have been taken out of the market due to valvulopathy risk via 5HT2B activation. I think chronic psilocin could have a similar risk, but there is little known at the moment.

[@joo5070]

Thank you for the video! Amazing channel!

[@Neuropharmacist]

Thanks for watching! :)

[@BrianOSheaPlus]

"Like" button smashed to oblivion. Thanks, very interesting video.

[@mightyscienceforall4188]

Very interesting topic.

[@Neuropharmacist]

Thanks! I'll try to go more in depth to this topic in future videos.

[@mightyscienceforall4188]

@@Neuropharmacist That would be awesome. Most psychedelic videos on YT attribute positive changes on the experience of the psychedelic trips....it's nice that your video discusses other possible explanations.