Psychedelics Promote Brain Plasticity by Binding to TrkB receptors

Two years ago, I pondered the possibility of psilocybin binding directly to TrkB receptors - and it seems like the future is here. This recent study, "Psychedelics promote plasticity by directly binding to BDNF receptor TrkB", published in the renowned Nature Neuroscience journal, substantiates this hypothesis.
In this video, I will explore the study's controversial findings regarding how psychedelics like psilocybin may enhance neuroplasticity - the brain's ability to form and reorganize synaptic connections.
To stay up-to-date with the latest developments in this exciting field, don't forget to subscribe and hit the notification bell. Remember, sharing knowledge is the best way to expand it - so, share this video with your friends and colleagues interested in the field of psychedelics and neuropharmacology!
IG: @neuropharmacist
Twitter: @samuelkohtala
www.neuropharmacist.com
Further reading:
Moliner, R., Girych, M., Brunello, C.A. et al. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci 26, 1032-1041 (2023). doi.org/10.1038/s41593-023-01...
Maxemiliano V. Vargas et al. Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors. Science 379,700-706(2023). DOI: 10.1126/science.adf0435
Nardou, R., Sawyer, E., Song, Y.J. et al. Psychedelics reopen the social reward learning critical period. Nature 618, 790-798 (2023). doi.org/10.1038/s41586-023-06...
Referenced videos:
• Three Hypotheses of Ps...
• Psilocybin and 5HT2A r...

[@Neuropharmacist]

Dear viewers, I wish to warn you, a lot of the content in this video is going to be difficult to understand if you don't have any background in a closely related field of study.

[@BasedChadman]

I'm only a 2nd year college student, but this area of fringe research on psychedelics and their efficacy has been my main focus. This is simply the proof in the pudding we have needed for something we could intuitively understand without the mechanism of action, as many cultures throughout history have chocked the outcomes up to a sort of "spiritualism", which is the pinnacle of awareness within our senses, so it only makes sense that it could increase neuroplasticity in such a way. Great content!

[@milothegreatful]

Im here to learn.Thanks for the content.

[@Neuropharmacist]

@@milothegreatful That's a great attitude! However, I feel that with this video, I didn't do a good job of introducing many of the things for someone not used to reading scientific studies, as I kind of wanted to rush through the data and it already took a very long time.

[@jj.296]

@@Neuropharmacist Wanted to say thanks for making these, Im not in the field but I enjoy learning.

[@PPP-on3vl]

@@Neuropharmacist Thank you.

[@jaapmat]

Super cool to see your analysis on this. Glad to have you back!

[@Neuropharmacist]

Thanks! Struggling to find time at the moment, but I had to take on this paper.

[@spiralsun1]

I’m glad you said something about reservations about plasticity. Plasticity alone is not the key-the experience of higher ideas and oneness from the psychedelic experience in combination with the plasticity is key to real positive change. ❤ So microdosing is probably best for people who don’t want the experience to be conscious. Still enhances creativity.

[@joo5070]

// a comment to support this channel // This is truly amazing, thank you for your work! Subscribed and smashed like button.

[@Neuropharmacist]

✨

[@kristaselene]

Hi Samuel! I sent you a message for a press inquiry on your website. I book guests for a live nightly podcast and would enjoy having you on the show! Thanks. -Krista

[@BrianOSheaPlus]

It would be interesting to see if the non-psychedelic 5-HT2A receptor agonist Ariadne binds to TrkB receptors in the same way as psychedelic 5-HT2A receptor agonists.

[@Neuropharmacist]

Would be interesting to see a replication of any of these drugs binding to TrkB!

[@joeybasile1572]

What exactly was your originally thought process years ago, predicting the binding to TrkB receptors?

[@Neuropharmacist]

Truth be told, it was the straightforward "cool story" I saw in that, and scientific publishing is fueled by cool stories. I'm not yet fully convinced these drugs actually bind to TrkB - future replications will either prove or disprove these findings.

[@maurunmal1422]

Wow! Amazing video. Keep 'em coming!

[@Neuropharmacist]

I'll do my best! Thanks for the support!

[@CodeEstLeXIII]

Excellent Video....I love your channel. No BS,

[@Neuropharmacist]

Thank you!

[@ownmicelio]

Really interesting topic and good analisys of the paper!!

[@Neuropharmacist]

Thank you, appreciate it!

[@BigMathis]

Do you think this could be a treatment for tinnitus?

[@Neuropharmacist]

I wouldn't put my money on it, but it remains a possibility. Then again, there are some reports of getting tinnitus from psychedelic use, like this case report: pubmed.ncbi.nlm.nih.gov/33242285/

[@ItsTripTips]

Great video!! I really love your whole channel 🙏🙏

[@Neuropharmacist]

Thank you!

[@jaapmat]

I've watched this like 3 times over lol so I'm commenting again: I disagree with the notion that the subjective experience is key to antidepressant psychedelics (this wasn't your stance, but just something I wanted to comment on). This is such a slippery argument to have because proponers on both sides think either way too much in terms of pharmacology or psychology principles. A little while ago I made a video on the efficacy of behavioural intervention vs stimulants for ADHD, and how the combination of these interventions is greater than the sum of its parts. However, it is still obvious that behavioural intervention is what receives the most benefit from the combination. Stimulants are about 60-70% effective by some measures, whereas CBT is about 30% effective in rough comparisons. Theres no reason not to combine them, but we're kidding ourselves if we say CBT is the most essential component of this combo. This is loosely evidenced by the fact that CBT without stimulants isn't nearly as good (but this is also a bit of an extrapolation). The subjective psychedelic experience is a form of CBT which is why I've made this comparison. ADHD medications are overall much more effective than antidepressant medications but this may soon change. Last I checked, CBT is proportionately much more efficacious in depression relative to pharmacotherapy than it is for ADHD (the efficacy of CBT vs SSRIs appears equal). However, as antidepressants become faster acting and more effective, the same dynamic present between ADHD stimulants and CBT will arise between antidepressants and CBT. Their combination hinges on the neuroplastic amplification of the effects of CBT, but psychoplastogens will always be the essential facilitator of efficacy (though this assumes that plasticity is, in fact, the end target). Just my .02. I'd love to here any comments you have on this!

[@Neuropharmacist]

The end result is likely a combination of both the pharmacological and psychological aspects, but the evidence is still lacking to make any real conclusions. I'm not sure we can even conclude much about the significance of the plasticity promoting effects in rodents, let alone people - and this comes from someone working on mechanisms of plasticity. One example commonly used to illustrate the plasticity promoting effects of antidepressants in rodents is visual cortex plasticity and the rescue of amblyopia in adult mice. However, a human trial attempting the same (with fluoxetine) failed (30150750). Altogether, the idea of antidepressants + therapy working synergistically through plasticity is not new (23842648), but to the best of my knowledge remains without solid evidence.

[@jaapmat]

@@Neuropharmacist Worded first comment weird. I liked this video so much i watched it 3 times! That's better. Yeah its futile to look at most of the cause and effect data we have, even when it comes from well designed experiments/trials, and treat it as anything more than a correlation. I still think that's very useful on its own though. Tying antidepressant efficacy to regional brain plasticity might overlook the cellular mechanisms but 'feeling in the dark' tangential to the state of scientific understanding has historically been the theme for MDD drug development. At some point there will always be a persistent "we don't know" that is at odds with the urge to innovate with some sort of small molecule or biologic. It's tempting to try and solve the issue only as deep as our 'understanding' goes, because further research only ever seems to bring up more questions for MDD. The best moment to create an antidepressant based on our current knowledge is now, but by then the scientific reasoning will already be outdated! I wonder, does that motivate or dissuade you? It definitely dissuades me at times. Great video, again!

[@Neuropharmacist]

@@jaapmat What both motivates and dissuades me is the sad state of rigor in modern biomedical science, which makes me believe we haven't really advanced as much as we want to believe in terms of actual, replicable, scientific findings.

[@sterlinglcannon]

Would be interesting to see the binding affinity of the 5-HT2a antagonist to the TrkB receptor. LSD probably much higher affinity resulting in the persistent spinogenesis.

[@BrianOSheaPlus]

At what doses do psychedelic drugs stimulate neuroplasticity? Do they have this effect at sub-psychedelic doses? Does this differ for different psychedelic drugs?

[@Neuropharmacist]

So far there is only evidence of neuroplasticity promoting effects in rodents and neuronal cultures, with most of the in vivo studies looking at psychedelic doses. It seems like 5HT2A targeting drugs share this property, but it is unclear how well it generalizes across various drugs. "Stimulating neuroplasticity" is also a bit undefined in terms of what it actually means, and the measures of "stimulated neuroplasticity" are somewhat unclear. For example, psychedelics seem to promote dendritic spinogenesis, but in my opinion, we don't thoroughly understand what it means in terms of its neurobiological significance.

[@lui8885]

So, if I take magic truffles with risperidone, can I get the neurotropic benefits?

[@Neuropharmacist]

If you are a mouse eating magic truffles, you might get neurotrophic effects. Not sure what happens if you are a mouse eating risperidone, and then eating truffles.

[@aldobayliss1271]

nice video cna you make a video about Ibogaine?

[@Neuropharmacist]

Maybe at some point.

[@admino96]

But by doing so in the mesolimbic system, wouldnt be detrimental for depression treatment?

[@Neuropharmacist]

The scientific evidence isn't there to really say anything about that, but if long lasting juvenile-like plasticity is activated in various systems, one could expect the possibility of a multitude of potential negative outcomes exists as well.

[@gweettoesan1864]

The dark arts of western blotter 😂😂😂

[@jameswestconsultant]

I am Count Plasticula 🧛‍♂️ Seriously through, I just survived a stroke last week and my right hand articulation has already improved using only 250mg of shrooms. I don’t think my neurologist will approve, however 😂

[@jameswestconsultant]

@PayP67 thx 🙏🏻

[@BeanDar]

Have you heard of Hallucinogen Persisting Perception Disorder? It’s caused by taking psychedelics, basically a never ending mild acid trip. It’s a real risk, and needs to be addressed in this new psychedelic frontier.

[@Neuropharmacist]

Yes, I have it on my long to-do list.

[@BeanDar]

I’m not sure what is on your list but your research and input could bring a major breakthrough. Essentially one of the main theories we have come up with in our own research in the main support group, is that is a sort of drug induced autoimmune encephalitis caused by taking psychedelics. The inflammation is too mild or localized to appear on an MRI, and antibodies are specific to the psychedelic and won’t shop up on blood tests or lumbar punctures, thus difficult to detect. I think the condition should be worth mentioning as a risk to taking psychedelics in each of your videos in your disclaimer of potential risks. Right now there is this huge push to try psychedelics and and that they are this magical drug with little to no risks, sure it is new and needs to be studied, but who cares give it a try! Then you have thousands of people who ruin their lives and they are never talked about by the mainstream, and the condition just keeps growing.

[@Lady.Kitty.purr.purr.purr.12]

I have it, it doesn't bother me bc it's quite mild, only happens when l'm really tired or when I focus on for example pattern on the floor and actively try to experience it. I think LSD is more likely to cause it than psylocybine as it doesn't happen as often and intense now when I stick to schrooms only. while for me it's fun side effect for some people it's debilitating disorder. Other risk is triggering schizophrenia in people predisposed to this disease. But every substance / medicine that actually works carries risk of side effects, psylocybine helped me overcome traumatic episode which greatly improved my quality of life. sorry for bad english as it's not my first language and my keyboard is broken

[@Neuropharmacist]

@@BeanDar I do not recommend anyone to use these drugs without medical supervision, or promote drug use in general. Still, I agree with you that the current hype climate can downplay the negatives associated with psychedelic use. I will certainly do a video on HPPD at some point. My hypothesis is that it could be related to the putative plasticity promoting effects on visual (and other) systems.

[@BeanDar]

@Neuropharmacist Yay! Thank you, and yes likely so. If you want there is a group of about 20 of us collecting data and research. I know Hopkins is conducting research and put out a survey recently. And the visual snow initiative is gaining a lot of traction, which is related to HPPD

[@driggerfireon5760]

All psychedelics encourage plasticity? 5ht2a ? That’s also what MDMA activates, a soft psychedelic.

[@Neuropharmacist]

Not known at this point. Some of them do seem to do it in mice at least.

[@assessmenttreatment8445]

This is only anecdotal - I feel like MDMA just makes users brains into plastic. The people I know at least. 😮

[@donnieptheg360]

Mdma is an amphetamine that is similar to psychs but is more neurotoxic at higher doses due to the amphetamine content. Mdma is being used in circles focused on trauma and ptsd. Psychedelics are being used in depression treatments but I find that psychedelics can cover a far broader range of minor and major issues. I have seen it used for all types of pain and arthritis successfully. Shrooms are potent anti inflammatories.

[@assessmenttreatment8445]

@@donnieptheg360 I appreciate your content. I work in hospice. But my state has yet to legalize its use. I’m curious how a therapy session goes for someone on hospice and how it actually works in the acceptance of succumbing to a disease process.