The Serotonin Hypothesis of Psychosis

Показать описание

Although serotonin receptors and synapses are ubiquitous throughout the brain, the serotonin hyperfunction hypothesis of psychosis suggests that psychosis may be caused by an imbalance in excitatory 5HT2A receptor stimulation of those glutamate pyramidal neurons discussed above that directly innervate VTA/mesostriatal integrated hub dopamine neurons and visual cortex neurons. The hallucinogens LSD, mescaline, and psilocybin, which are all powerful 5HT2A agonists, have long been known to induce psychosis, dissociative experiences, and especially visual hallucinations by overstimulating prefrontal and visual cortex 5HT2A receptors. These symptoms can be blocked by 5HT2A antagonists, demonstrating that hallucinogens cause psychosis by 5HT2A stimulation.

Copyright © Neuroscience Education Institute. All rights reserved.

NEI Psychopharm

Рекомендации по теме

Комментарии

Made the explanation way easier to understand than the book does, and the key sentence of showing how all these hypotheses leads back to dopamine. Thank you.

thwarmngr

3:35 😂laughing out loud in a coffee shop damn it hahahhaha

eugenvataman

"you messah wif my serotonin, I GROW YOU MORE RECPTORS!!" writing a paper on the mechanism/ pathway of LSD and I needed to hear this lol

jaydavis

This is just my opinion/Theory from the research I have done on 5HT2A receptors and their role in the brain. I am wondering if these receptors act naturally as some type of emotional amplifier, giving normal emotions a more sharp edge. this is something I’ve always suspected, but I have more reason to believe this after reading a study on The role of 5HT2A receptors in sleep paralysis hallucinations. The author also claimed that this receptor was involved in the attachment of normally meaningless environmental stimuli to strong emotions. I also read a paper claiming that 5HT2A antagonists could diminish the ability of human subjects to recognise fearful faces, indicating these receptors play a major role in fear. this makes sense since classical psychedelics produce the opposite effects, that is intensified fear and a strange sense of connection to inanimate objects. personally, I’ve never tried psychedelics and never will, and I have a strong dislike for them. this is because, the more I read about their emotional effects, the more disturbing they seem. Additionally, I’ve read stories of peoples lives being destroyed by some type of post traumatic stress disorder triggered by the psychedelic experience. it’s not only flashbacks to the trip that plagued these people, some don’t even have these flashbacks, but do experience severe depression, anxiety, panic attacks, and even psychosis. some say they could not stop questioning their everyday reality and the point of their existence and did not respond to therapy. what is even more unfortunate is that many of these people claim to have been highly motivated, successful or at least happy/laid-back individuals before their experience. I also want to give my rebuttal to the psychedelic enthusiasts Who directly or indirectly tried to claim that we are currently living in a regulated psychedelic state based on the fact that we have these receptors, and an extremely powerful agonist of them, DMT is naturally found in the brain. let’s start with DMT. Firstly, this compound is only present at very low levels in the brain. however, researchers studying its function have found it to be a strong agonist of the Sigma receptor which is not hallucinogenic under normal circumstances. in fact, they found that DMT was synthesised and released very close to these receptors before being rapidly destroyed by monoamine oxidase enzymes before it could reach the serotonergic receptors. therefore, DMT is believed to play a Neuromodulatory and neuroprotective role via Sigma receptor activation. whilst I’m not aware of any studies knocking out DMT production in the brain, we already know that 5HT2A antagonists do not significantly affect the human perception of reality. so what about serotonin and fiveHT2A receptors which are much more abundant than DMT? well, serotonin does not cause us to hallucinate under normal circumstances, even when its levels are strongly elevated. The reason for this is that 5HT2A receptors can activate two different downstream intracellular signalling pathways depending on how an agonist binds to them. basically, unlike its methylated tryptamine metabolites, serotonin activates both pathways in a balanced manner and modulates neuronal function. This binding is possibly involved in emotional amplification to some degree and this receptor is involved in the side-effects of SSRI antidepressants, such as anxiety and initial worsening of depression. however, the methylated tryptamines preferentially activate one pathway and in doing so cause the receptor to form a complex known as a heterodimer with a metabatropic glutamate receptor called MGLU2. MGLU2 serves many protective functions in neurons, but one of its main Rolls is to restrain glutamate release by neurons. When the psychedelic bound 5HT2A receptor forms a complex with MGLU2, The function of MGLU2 is inhibited and a huge amount of glutamate is released. This not only screws up information-processing in the brain, but could also amplify the effects of other neurotransmitters as well as emotions in general associated with those neurotransmitters. despite the so-called benefits of micro dosing, psychedelics, even at low doses, have been found to strongly impaire memory in animals. in an article published in the Guardian, A woman microdoseing LSD for depression noted that she became extremely paranoid that her supplier was an informant for the police. this is whilst she defended the drug and stated that it helped her, but she still acknowledged that it might have been behind her paranoia. I am convinced that it was the microdoses of LSD due to its inappropriate enhancement of glutamate function in certain areas of the brain.

saifmohsin

And 5HT2c receptors are a funny beast on the one hand they are an “excitatory receptor” but they also inhibit tonic dopamine function via GABAergic neurons and taking an antagonist or inverse agonist of the 5ht2c receptor can disinhibit dopamine and norepinephrine by dampening tonic GABAergic signalling.

sevenman

Saving this to my erectile dysfunction playlist, can you make a video on how 5ht2a plays a role in anti fibrosis of tissue.

fmoney

Would benzodiazepine help with the lost GABA inhibition?

lui

Does anyone has an idea, where can i get all these videos in full version for free??

shivanktomer

Coud DT in OH withdrawal be explained by this lack of inhibition of glutamate?

algernonis

In my opinion, there needs to be much more media attention on 5HT2A antagonists. The research is all there, showing they are extremely beneficial in the treatment of psychiatric disorders. Yes, they might have failed in the treatment of psychosis, but their effects on anxiety/panic and sleep quality are much more promising. unfortunately, no one has really pushed for their public acknowledgement because they lack addiction potential so pharmaceutical companies probably aren’t that interested. Likewise, I assume their lack of hallucinogenic effects means no one from the general public is really that interested in learning about them, let alone lobbying for them as people have done with psychedelics. finally, it’s interesting to note that the supposedly very subtle psychoactive effects of selective 5HT2A might remove an element of placebo effect, tricking patients into thinking these medicines are not working. for example, in a study of 5HT2A antagonists for insomnia patients, researchers noted clear improvements in sleep quality, including a significant increase of slow wave (deep sleep) using brain scans. unfortunately, patience themselves generally said they found these medications ineffective in improving the subjective quality of their sleep. Researchers put this down to The patient believing they have not slept. traditional insomnia drugs like benzodiazepines, The Z drugs and even powerful first generation antihistamines generate a so-called sleep queue, that is a signal for the patient to go to sleep. Furthermore, decreased consciousness and memory formation can create the illusion that the patient has slept, thus changing their perspective and making them more psychologically prepared to face the day. ironically, most benzodiazepines and Z drugs actually worsen sleep quality and continue to cause drowsiness and memory impairment the next day. this is why some researchers have suggested using drugs like S mirtazapine and its analogues, which combine serotonin2A antagonism with histamine H1 antagonism. whilst antagonism of both receptor types promotes efficient sleep and diminish frequency of awakenings, the antiserotonergic effect boosts deep sleep, whilst the antihistamine effect helps transition from the waking to the sleep state but also generates a heavy sense of drowsiness which acts as a signal for the patient to psychologically prepare for sleep. if I remember correctly, these drugs lack anticholinergic effects at reasonable doses so shouldn’t impede memory formation or promote dementia.

saifmohsin

visual snow syndrome? do this explain?

MrWeinfook

I dont understand any of these stuff. But I hope for KarXT because schizophrenia is hard to live with

jeanpaultongeren

Pretty simple, So its best to give a dopomine and serotonine blcoker combined 2nd gen antipsychotics, till the time recommended cource time. If it still occurs then its probably genetics. Hope thier side effects are droped to 0 tho

sirijanthakur

Don't know about all this science but for me carbohydrates ( from real whole foods ) have a natural anti stress effect, genetics play a part and they tell me carbohydrates are what works best for me 😊 all my life...

Starchaser