The Function of Serotonin | Robin Carhart-Harris and David Nutt Adversity Hypothesis

The function of serotonin in the brain, according to scientists like Dr. Robin Carhart-Harris of UCSF and Professor David Nutt of Imperial College London, may be to allow us to cope with adversity and stress. They hypothesize that there are two distinct subsystems of the serotonin (also known as 5-hydroxytryptamine or 5-HT) system in the brain, defined by their predominant receptor subtypes, 5-HT1A and 5-HT2A. This video aims to explain that hypothesis.
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The neuroscience of serotonin is complex. That’s why I’ve created a playlist on the neurobiology of the serotonin system. Link to the rest of the serotonin videos: • Serotonin Miniseries
Chapters:
00:00 Whenever you experience stress or adversity, you can either cope passively or actively.
00:16 The Carhart-Harris and Nutt Adversity hypothesis of serotonin’s function in the brain
00:54 This is the final installment in a playlist about serotonin
02:03 Part 1: The neural circuitry of anxiety and stress
03:45 Part 2: The role of 5-HT1AR in passive coping
04:25 Why we don’t freak out every time something irritating happens (1A predominance)
04:53 How the 1A receptor calms down the neural stress circuitry
06:05: Important caveat: THIS IS VERY MESSY
06:57 Part 3: The role of 5-HT2AR in active coping
07:10 The cortex is very important in active coping
07:46 The 2A receptor is highly expressed in the cortex and important in brain plasticity
08:23 Psychedelic drugs like LSD and psilocybin bind to 2A
08:58 Psilocybin can alleviate treatment-resistant major depression
11:10 2A binds serotonin more weakly than 1A
11:25 Please sign up for the video newsletter and podcast!
12:01 Part 3: The bipartite model of serotonin brain function (Carhart-Harris and Nutt Adversity hypothesis)
12:29 Need an intro to synaptic transmission?
12:56 Summary
13:58 REMEMBER: This is a hypothesis, not a Theory.
14:30 Check out all my serotonin videos!
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Sources Cited:
Pollan, M. (2019). How to change your mind: What the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence. Penguin Books. michaelpollan.com/books/how-t...
Sharp, T., & Barnes, N. M. (2020). Central 5-HT receptors and their function; present and future. Neuropharmacology, 177, 108155. pubmed.ncbi.nlm.nih.gov/32522...
Dingman M. Know Your Brain: Raphe Nuclei. Neuroscientifically Challenged. neuroscientificallychallenged.... Published October 27, 2017.
Di Giovanni, G., & De Deurwaerdère, P. (2020). Serotonin research: Crossing scales and boundaries. doi.org/10.1016/j.neuropharm....
Hoyer, D. (2020). Targeting the 5-HT system: Potential side effects. Neuropharmacology, 108233. pubmed.ncbi.nlm.nih.gov/32805...
Mosienko, V., Bader, M., & Alenina, N. (2020). The serotonin-free brain: behavioral consequences of Tph2 deficiency in animal models. In Handbook of Behavioral Neuroscience (Vol. 31, pp. 601-607). Elsevier. doi.org/10.1016/B978-0-444-64...
Carhart-Harris, R. L., & Nutt, D. J. (2017). Serotonin and brain function: a tale of two receptors. Journal of Psychopharmacology, 31(9), 1091-1120. pubmed.ncbi.nlm.nih.gov/28858...
Bacqué-Cazenave, J., Bharatiya, R., Barrière, G., Delbecque, J. P., Bouguiyoud, N., Di Giovanni, G., ... & De Deurwaerdère, P. (2020). Serotonin in animal cognition and behavior. International journal of molecular sciences, 21(5), 1649. pubmed.ncbi.nlm.nih.gov/32121...
Carvajal-Oliveros, A., & Campusano, J. M. (2021). Studying the Contribution of Serotonin to Neurodevelopmental Disorders. Can This Fly?. Frontiers in Behavioral Neuroscience, 14, 262. www.frontiersin.org/articles/...
JJ Medicine. “Serotonin and Melatonin Synthesis | Tryptophan Metabolism” • Serotonin and Melatoni... .
#brainhealth #serotonin #serotoninfunction

[@senseofmindshow]

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[@sihammhani1214]

Ur videos about serotonin are mind blowing, u re such great communicator , u know how to put informations very well , explaining such a messy topic with so much grace is something to applaud. Great work , ur videos are magnetic !

[@senseofmindshow]

That's so nice of you! Thanks for watching the videos!

[@mikeconn8523]

Hi friend. Psychiatrist here. Stopped by to learn something new about 5HT1A and 2A receptors. Very interesting stuff. Thanks!

[@senseofmindshow]

Thanks so much for stopping by! And for checking it out!

[@bonnjean]

I have recently started following your videos. Thank you for all the time and research you have put in. I have been studying how my brain processes the world around me, having had the diagnosis of bipolar disorder, with delusional psychosis, and have spent half my life on various medications. Your videos have been invaluable to me in my own healing and research.

[@mayuribirajdar3215]

Great video!!!best luck you will have millions of subscribers soon🤜🏻🤛🏻🎉

[@senseofmindshow]

Thank you so much!

[@coreenherron9125]

Hi! I am a Psychiatric Mental Health NP student ( and psychedelic assisted psychotherapist!!) and I just learned more about serotonin through your videos than I did reading Stahl's psychopharmacology textbook - thank you so much!!

[@Lkyldyla]

Wow! I just learned quite a bit. Thank you!

[@senseofmindshow]

That’s fantastic! Thanks for watching!!

[@dp26385]

Thank you.

[@senseofmindshow]

Thank you for watching!

[@makaylamoore8831]

Awesome video!!!

[@ryankdavidson]

Great videos, keep it up. I like the balance of detail and high level layman explanations. Too light on details and it’s boring, too heavy and it feels like I need to go to med school. This feels just right.

[@tarekgado9469]

Excellent explanation

[@mazen7119]

Thank you...great video

[@senseofmindshow]

Glad you liked it!

[@johnfarrar3145]

Hi, Love these videos and have shared with other therapist that are actively doing ketamine therapy and interested in working with psychedelics when they are rescheduled. We always hear about the shutting down of the prefrontal cortex with these compounds and thus the quieting of the default mode network. I am curious how this fits into this theory. You mentioned the active/excitatory action on the cortex, but how does the prefrontal cortex get inhibited? Thanks

[@connorallers953]

Really great video dude

[@senseofmindshow]

Thanks, I really appreciate that!

[@andreeamosulet]

Hi, wonderfully explained serotonin subject🥳 Thank you for your videos, very well explained and design. Can you make a video (maybe you already have) about the connection and effects of music and mental health and also what are the effects of listening music that go in one loop- same rhythm on repeat. Thank you very much🙏🙏🙏

[@senseofmindshow]

That sounds super interesting! Music and the brain is a fascinating topic that I'll try to cover in the future. In the meantime, a great book on the subject is "Musicophilia" by Oliver Sacks

[@andreeamosulet]

@@senseofmindshow Thank you for the answer and super appreciate the book reccomandation🙏

[@willkayn]

Diamond in the rough.

[@rafatlatif544]

Genius

[@Convolutedtear]

I would really like to understand the aggression due to social isolation..... meaning being in a group but pushed out to corner , or aggression due to isolation and non activity??

[@senseofmindshow]

Good question! I think that the increased aggression would apply to both social isolation due to exclusion as well as isolation due to agreeing to remove oneself from interacting with other people (for research purposes). I have a video on the neuroscience of loneliness if you're interested (kzbin.info/www/bejne/bnSWlGOma8Z0eq8) Also, this review discusses the association between aggression and loneliness (resulting from social isolation) at several points: www.johncacioppo.com/s/toward-a-neurology-of-loneliness-916y.pdf

[@DrSyl]

Loving your videos! In terms of how we understand the distribution of serotonin receptor subtypes - what kind of imaging is being used? i.e. is that image at 4:59 a PET scan with a radioisotope of a 1A agonist molecule? I'm curious to know the resolution of the imaging used (is it a voxel, or 10 cubic mm).

[@georgelee6972]

Thanks really great episode! from the video, it seemed like the 1A/2A receptors produced variations on internal change relative to stressors. Do they also influence external behaviour towards stressors? EG - does 2A activation lead to people pursuing their goals / values more proactively? If so, would this only be indirectly through the person being in a less depressed state / a higher level of wellbeing?

[@senseofmindshow]

First of all, thanks so much for your contribution and ongoing support of the channel, George! That's a really insightful question. As far as Carhart-Harris and Nutt's original paper goes, it seems that the internal and external changes go hand in hand. In other words, the behaviors we enact follow from the thoughts and feelings we have. So if 5HT2A receptors do stimulate an active form of coping with stress, we should expect the behaviors that follow to be aligned. For example, if you were undergoing psychedelic psychotherapy and realized that many of the behaviors you had been engaging in were in fact self destructive, we should expect you to stop engaging in those behaviors in the future. However (and sorry for the long message), I also want to mention that more recent work by Martin Seligman and his colleagues suggests that, while passive coping with stress is indeed associated with serotonin, active coping with stress may have more to do with *blocking* release of serotonin from the dorsal raphe nuclei during a stressful experience. My video on resilience goes deeper into this idea: kzbin.info/www/bejne/f5CcoHyNjd9pmtU

[@supercajun2466]

I wonder whether the greater activation of 5-HT1ARs (relative to 5-HT2ARs) by antidepressants (in the case of SSRIs, presumably simply because of the relative abundance of 5-HT1ARs) is the main reason that antidepressants decrease the intensity of the effects caused by classic psychedelics (5-HT2AR agonists). If so, for 5-HT1AR agonists like buspirone, it should be the case that those with a greater affinity for 5-HT1AR are more effective at decreasing the intensity of the effects caused by classic psychedelics. This could easily be tested in many ways. This also points out a possible reason that antidepressants are ineffective for some people suffering from depression. Some of these people are probably people with a pathologically high ratio of 5-HT1AR-to-5-HT2AR activity, so using SSRIs to flood their brains with serotonin simply fuels a broken system.

[@senseofmindshow]

Great insight! I'm not sure if studies looking at the relative affinities of antidepressants vs the intensity of effects from psychedelics have been done, but the reduced intensity of psychedelics (in people who take SSRIs) could also be due to a general upregulation of serotonin in the brain, making the effects of psychedelics relatively less intense for these individuals. Thanks for your extremely thoughtful comment!

[@messigoat575]

I am a big migraine sufferer, and the only tablets that I take (Pitzotifen) that work have something to do with the serotonin in my brain. Maybe you can do a video on how seritonin coukd have a cause to migraines

[@TheFallenAngelOfDeath]

Hey man, enjoying the videos.um question, how do we mimic the anti anxiety effects of SSRI without taking SSRIS. The risk for permanent sexual dysfunction is too high.

[@senseofmindshow]

Thanks so much for your question. First I have to preface this with the disclaimer that I'm not a doctor or mental health professional, so this is not medical advice. From my limited reading, it seems that exercise may raise levels of serotonin, and that several other activities may also have a beneficial effect. Here's a non-technical article that lists some of those activities (and provides references): www.verywellmind.com/how-to-increase-serotonin-5248440 I also found this older review article from 2007 that addresses the question of how to raise serotonin levels without drugs (given the age of this article, be careful to cross-check the information with other sources if you can): www.ncbi.nlm.nih.gov/pmc/articles/PMC2077351/ This episode of the Huberman Lab podcast is an excellent resource for the related question of how to maintain healthy brain chemistry in general: kzbin.info/www/bejne/imeYg3d4nqdoftU

[@calvinscheller846]

How do serotonin and dopamine interact? Is dopamine decreased by seretonin/ vice versa?

[@senseofmindshow]

That’s a really good question. I’ll admit that I don’t know the answer off the top of my head. But here’s a summary of a relatively recent study that looked into a related question: brain.harvard.edu/hbi_news/exploring-how-serotonin-and-dopamine-interact/

[@calvinscheller846]

@@senseofmindshow thank you sir!

[@quantumpower]

0:15

[@strumptavianroboclick5596]

So should i get off get off the ssri? Will it help me sleep better? Tho that is the reason i started taking it. Will it improve my sex life, mostly the desire? Or should i just stay on it?

[@venkataaraadhya]

2:50 "Brain stem does autonomic control of the body" Plot twist: Brain stem does autonomic control of the rest of the brain too.