Marijuana May Cause Psychosis/schizophrenia By Increasing Serotonin Signalling

haidut

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I know the topic of weed is controversial but by now the link between heavy and chronic marijuana use and the risk of psychotic conditions like schizophrenia has been well established. Peat mentioned a few times briefly that cannabis has anti-androgenic effects and should not be used chronically but up until now the mechanism of weed causing psychosis was not officially known. This study below shows that the active cannabis ingredient THC increases expression of the psychedelic receptor 5-HT2A, which is responsible for the sensory overload and auditory hallucinations often reported by people with psychosis.

Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway
The molecular mechanism linking cannabis consumption to the development of schizophrenia is identified for the first time - Biotech Spain

"...The research was led by Leyre Urigüen, and the UPV/EHU researchers and CIBERSAM affiliates Inés Ibarra-Lecue, Irene Mollinedo, Luis F. Callado, Javier Meana and Rebeca Diez-Alarcia participated in it. It analysed the brains of mice to whom THC had begun to be administered chronically during “adolescence, a critical period in brain development which in people corresponds to adolescence”. In the study of the cerebral cortex of these mice the researchers spotted alterations in the serotonin 2A receptor, which is primarily responsible for producing hallucinations that are a feature of psychosis and schizophrenia. Specifically, the research team found that the functionality of this pro-hallucinogenic receptor increases after chronic treatment with cannabis. They also described the means by which this hyperfunctionality takes place. “The description of this hyperactivity of the serotonin 2A receptor, detected for the first time on a molecular level in the brain, is the first step towards exploring other fields,” said Dr Urigüen. At the same time, the researcher maintained that “the final aim is to identify the existence of similar molecular changes in people who consume cannabis to be able to associate them with the risk of developing psychosis or schizophrenia, and also to produce new drugs to alleviate the symptoms of patients with schizophrenia”."
 

Wagner83

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Wouldn't anti-serotonin drugs also increase receptors expression/density/sensitivity to serotonin in the long run ? I don't understand where the line is between increased sensitivity being good or bad.
Do Ray give so much importance to receptors? Why are they so often talked about? Didn't he say the state of metabolism/cells and overall health defines how it responded to its environment/supplements etc..?
 

haidut

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Wouldn't anti-serotonin drugs also increase receptors expression/density/sensitivity to serotonin in the long run ? I don't understand where the line is between increased sensitivity being good or bad.
Do Ray give so much importance to receptors? Why are they so often talked about? Didn't he say the state of metabolism/cells and overall health defines how it responded to its environment/supplements etc..?

As far as I know it is the 5-HT1 receptor that forms a negative feedback mechanism with serotonin release. So, the upregulation of 5-HT2A likely won't downregulate serotonin synthesis but just increase the reaction to endogenous serotonin. The same receptor was found to be upregulated in suicide victims, as far as I can remember.
 
L

lollipop

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I know the topic of weed is controversial but by now the link between heavy and chronic marijuana use and the risk of psychotic conditions like schizophrenia has been well established. Peat mentioned a few times briefly that cannabis has anti-androgenic effects and should not be used chronically but up until now the mechanism of weed causing psychosis was not officially known. This study below shows that the active cannabis ingredient THC increases expression of the psychedelic receptor 5-HT2A, which is responsible for the sensory overload and auditory hallucinations often reported by people with psychosis.

Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway
The molecular mechanism linking cannabis consumption to the development of schizophrenia is identified for the first time - Biotech Spain

"...The research was led by Leyre Urigüen, and the UPV/EHU researchers and CIBERSAM affiliates Inés Ibarra-Lecue, Irene Mollinedo, Luis F. Callado, Javier Meana and Rebeca Diez-Alarcia participated in it. It analysed the brains of mice to whom THC had begun to be administered chronically during “adolescence, a critical period in brain development which in people corresponds to adolescence”. In the study of the cerebral cortex of these mice the researchers spotted alterations in the serotonin 2A receptor, which is primarily responsible for producing hallucinations that are a feature of psychosis and schizophrenia. Specifically, the research team found that the functionality of this pro-hallucinogenic receptor increases after chronic treatment with cannabis. They also described the means by which this hyperfunctionality takes place. “The description of this hyperactivity of the serotonin 2A receptor, detected for the first time on a molecular level in the brain, is the first step towards exploring other fields,” said Dr Urigüen. At the same time, the researcher maintained that “the final aim is to identify the existence of similar molecular changes in people who consume cannabis to be able to associate them with the risk of developing psychosis or schizophrenia, and also to produce new drugs to alleviate the symptoms of patients with schizophrenia”."
This makes sense. Glad to see this coming to light.
 

Aaron

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Makes some sense in explaining the psychedelic properties of cannabis. Producing some of the symptoms of schizophrenia and psychosis (temporarily) seems to be an effect of most psychedelic drugs. I'm still undecided whether experiencing that "loopiness" could be beneficial when trying to improve or evaluate oneself under a different light. I feel I become a little too "sane," or trapped in my patterns and behaviors, when I go too long without using some kind of psychoactive substance, psychedelic or otherwise. However, I definitely notice those "self-evaluative" benefits are replaced by legitimate mental illness symptoms with chronic use of marijuana.

Perhaps the exacerbation of schizophrenic neurochemistry can help people oblivious to their psychological condition (or those who know them) recognize that they have schizophrenia in the first place. I'm not convinced it would actually trigger the condition.
 

Stramonium

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I saw this reported in a clinical case I was translating. Chronic cannabis use was linked to a case of a shared psychotic disorder in 3 individuals. The patients described things like hearing voices or being possessed by entities which led one of them to burn the other two with a clothing iron.
 

haidut

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I feel I become a little too "sane," or trapped in my patterns and behaviors, when I go too long without using some kind of psychoactive substance, psychedelic or otherwise

This tends to be caused by verbal overload - i.e. too much reading or talking. I have experienced it myself and find that not using any computer or watching TV or avoiding spending hours talking about pointless stuff helps a lot. I try to have that non-verbal experience one day of the week. Peat also mentioned this and said his method is not talking at all for one day of the week and just painting. Small children, who dwarf adults in terms of intelligence, do not talk much. They just observe and learn. This state of mind is what the philosophical field of Phenomenology tries to induce purposefully - i.e. the return to the pure "experiential" state of consciousness that children have. The technique the phenomenologists have to achieve this is called "epoche". Google it for more info...but after you spend a day away from computers:):
 

haidut

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isn't high dopamine one of the causes of Schizophrenia ?

Nope. This has been discredited independently by many groups around the world over the last 20 years. Most of the newly approved antipsychotic drugs are the so-called "atypical antipsychotics" - i.e. none of them are dopamine antagonists and many of the are partial serotonin antagonists. Clozapine is the most well-know example. In addition, several newly approved drugs are exclusively selective serotonin antagonists (usually 5-HT6 or 5-HT7). Finally, the original gold standard in antipsychotic drugs haloperidol turned out to be a potent antagonist on one of the 5-HT2 receptors (I am blanking on which one exactly). It is also a dopamine antagonist and since this is its most well-known mechanisms everybody assumed dopamine is the cause of psychosis, but that theory has been (quietly) debunked by now.
https://www.medscape.org/viewarticle/423111
 

LeeRoyJenkins

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This tends to be caused by verbal overload - i.e. too much reading or talking. I have experienced it myself and find that not using any computer or watching TV or avoiding spending hours talking about pointless stuff helps a lot. I try to have that non-verbal experience one day of the week. Peat also mentioned this and said his method is not talking at all for one day of the week and just painting. Small children, who dwarf adults in terms of intelligence, do not talk much. They just observe and learn. This state of mind is what the philosophical field of Phenomenology tries to induce purposefully - i.e. the return to the pure "experiential" state of consciousness that children have. The technique the phenomenologists have to achieve this is called "epoche". Google it for more info...but after you spend a day away from computers:):

There's a saying in the Jewish community, Jews haven't kept the Sabbath as much as the Sabbath has kept the Jewish people.

Fascinating finds on marijuana from personal experience I completely agree. It's EXTREMELY powerful and is very similar to pyschosis/schizophrenic/serotonin symptoms. It can open one's eyes, but perhaps a little too much.
 

Aaron

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This tends to be caused by verbal overload - i.e. too much reading or talking. I have experienced it myself and find that not using any computer or watching TV or avoiding spending hours talking about pointless stuff helps a lot. I try to have that non-verbal experience one day of the week. Peat also mentioned this and said his method is not talking at all for one day of the week and just painting. Small children, who dwarf adults in terms of intelligence, do not talk much. They just observe and learn. This state of mind is what the philosophical field of Phenomenology tries to induce purposefully - i.e. the return to the pure "experiential" state of consciousness that children have. The technique the phenomenologists have to achieve this is called "epoche". Google it for more info...but after you spend a day away from computers:):

I believe it. We are essentially being programmed each day by the flow of nonsense information we receive from other people in various forms. It's especially hard to disrupt that when the flow is actually meant to trap you and make you rely on it for information about the world and maintaining your own self-image, like Facebook for example. An extra day of painting in nature may be in order for me.

But it's also possible to smoke some really good weed and realize Facebook is lame, and hit the button that permanently deletes your account after 30 days like I did.

I think your suggestion would cater to that experiential state of consciousness more than smoking a joint, but it requires me to disrupt my programming just a bit more to achieve, which is probably why I haven't done it. But I will. This is exactly the advice I needed actually. I am fairly new to Peat but I love poring over the insights I've found here, especially since the suggestions tend to be simple, manageable, and intuitive. Thanks.
 

jandrade1997

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I'm skeptical, merely because there's a whole lot of junk science regarding cannabis. Also, this study does not quite show what you said: it shows increased binding affinity of the receptor, but the expression/density of the receptor was unaffected. Also, the dosage was fairly high, corresponding to a few bowls a day, every day, for weeks. Actually, far more since this was injected, and you don't absorb nearly 100 percent of the THC in smoke . Fortunately, even at this dose, the study conveniently provides an antidote: inhibiting mTOR prevented the alterations to the receptor.
 

Terma

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I think 5-ht2a is overly villified, both in mainstream and this forum (no thanks to excessive faith in correlations). It may be essential for REM sleep (which I did not realize until recently) and an important part of the human experience.

Yes it does increase cortisol and stress hormones, but that just means it's not supposed to be activated chronically, only during important moments, and that its activation of downstream stress hormones should be compensated by pro-GABA and other neurotransmitters and substances. Also some of the stress hormones it promotes (such as possibly vasopressin) may be temporally important. All that article says to me is that Mary-J is not the best substance to do this on its own, or you shouldn't get high 24/7.

I have yet to see proof either way that 5-ht2a is dispensible. The reason is that it's plausible it may excite neurons in localization and patterns that is not reproducible using other neurotransmitters or substances. We won't know for awhile. Serotonin is a massively complex network.

(Also in other articles and discussions its effects get conflated with 5-ht2c a lot, though that does not apply to this article... apparently?)
(And that said I think the postsynaptic 5-ht1 receptors which get all the good press are way overrated; this comment is limited to 5-ht2a)
 

Ideonaut

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Makes some sense in explaining the psychedelic properties of cannabis. Producing some of the symptoms of schizophrenia and psychosis (temporarily) seems to be an effect of most psychedelic drugs. I'm still undecided whether experiencing that "loopiness" could be beneficial when trying to improve or evaluate oneself under a different light. I feel I become a little too "sane," or trapped in my patterns and behaviors, when I go too long without using some kind of psychoactive substance, psychedelic or otherwise. However, I definitely notice those "self-evaluative" benefits are replaced by legitimate mental illness symptoms with chronic use of marijuana.

Perhaps the exacerbation of schizophrenic neurochemistry can help people oblivious to their psychological condition (or those who know them) recognize that they have schizophrenia in the first place. I'm not convinced it would actually trigger the condition.
Tho I understand what you mean by "I feel I become a little too "sane," or trapped in my patterns and behaviors, when I go too long without using some kind of psychoactive substance" I feel that there is no such thing as too much sanity. A high level of sanity would include being creative and aware enough not to be overly patterned. I like my natural mind just fine--it is plenty creative and doesn't need to be jolted by drugs. There are plenty of other things that can "jolt" one more healthily, like learning new things and travel.
 

raysputin

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Tho I understand what you mean by "I feel I become a little too "sane," or trapped in my patterns and behaviors, when I go too long without using some kind of psychoactive substance" I feel that there is no such thing as too much sanity. A high level of sanity would include being creative and aware enough not to be overly patterned. I like my natural mind just fine--it is plenty creative and doesn't need to be jolted by drugs. There are plenty of other things that can "jolt" one more healthily, like learning new things and travel.
I would have to agree here. I think there’s a push, whether found in films or literature or media in general, that in order to be quirky or different or creative a person has to have had experience with drugs. One of the most intelligent and creative people I know has never done drugs and has a somewhat encyclopedic understanding of world history, politics, culture, science. He is much more interesting to be around than any stoner friends I have.
 

anqele

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Marijuana will be legalized here soon. No matter how mild the weed there has been paranoia after smoking always. No schizophrenia whatsoever, just paranoia. Is there a way I can enjoy Canadian pot without paranoia?
 

managing

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Marijuana will be legalized here soon. No matter how mild the weed there has been paranoia after smoking always. No schizophrenia whatsoever, just paranoia. Is there a way I can enjoy Canadian pot without paranoia?
I always experienced paranoia from smoking. I haven't smoked it in ~20 years. However, I've had edibles recently. Mints and gummies. Low dose (5-10mg, THC, no CBD). And I've enjoyed that quite a bit, without any paranoia. Its a much less intense experience. But in many ways even more "fun" than what I did when I was young. My wife never really smoked it, but has enjoyed the edibles too.

Especially if (other people) are new to it, I'd recommend starting with low dose edibles.
 

anqele

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I always experienced paranoia from smoking. I haven't smoked it in ~20 years. However, I've had edibles recently. Mints and gummies. Low dose (5-10mg, THC, no CBD). And I've enjoyed that quite a bit, without any paranoia. Its a much less intense experience. But in many ways even more "fun" than what I did when I was young. My wife never really smoked it, but has enjoyed the edibles too.

Especially if (other people) are new to it, I'd recommend starting with low dose edibles.

Thank you. Never had edibles so will try that in the very low dose.
Curious, why only TCH and no CBD emphasized?

Thanks again!
 
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