The solution to both understanding and solving psychosis is perhaps more simple than previously thought. At least this may account for some psychoses.
Reinforcement learning occurs with opioid neurotransmission. The purpose is to learning desires and aversions. Desires are learned when Mu-Opioid receptors bind simultaneously with a heteromeric D1 or other type receptor that would cause NMDA receptor to be more sensitive and enhance learning. On the other hand, there is Kappa-Opioid receptors which reduce NMDA receptor activity and cause dysphoria and dissociative effects.
Hyperactivity of D2 receptors are related to psychosis. Kappa-Opioid stimulation potentiates the D2 receptor’s effects. Hypoactivity of NMDA receptors is also implicated in psychosis, and even drugs that block NMDA receptors very effectively cause psychosis. Dynorphin is the body’s natural Kappa-Opioid neurotransmitter. Dynorphin releases during stress and is to help us learn to avoid stress. Mu-Opioid and Kappa-Opioid receptors have opposite effects on dopamine release, where Mu-Opioid receptors cause dopamine release and Kappa-Opioid receptors inhibit dopamine release. This blocking of dopamine prevents us from learning to habituate bad things while the dopamine release effects of Mu-Opioid receptors causes enhanced reinforcement and habituation. Kappa-Opioid and Mu-Opioid receptors also connect together which probably means that Mu and Kappa block each other’s effects when activated, which would mean reducing Kappa-Opioid activity is rewarding as it’s known that Mu-Opioid stimulation is rewarding, and when it is no longer being reduced we should expect this occurrence to feel rewarding, thus promoting the learning of avoidance and aversion of negative experiences.
This is where it gets interesting. Mu-Opioid agonists have shown to be antipsychotic. This gives some evidence that dynorphin may cause many psychotic symptoms, as these drugs would inhibit dynorphin’s effects. Mu-Opioid receptor modulation is implicated in socialization. This is particularly interesting due to Karl Marx’s concept that religion is the opium of the masses. Religion is a hyper social environment where everyone agrees upon some set of ideas, generally dogmatically, and maybe because of the opioid benefits of the shared ideas and agreement. To question the dogma is to remove the anti-suffering agent, to inflict suffering. Those with schizophrenia were shown to have lower friendships than any other mental disorder, and there is a correlation to level of friendships and level of psychosis.
Why Does It Occur?
My theory is that problems and stressful situations activate psychotic effects. Creativity is enhanced as to increase one’s ability to resolve the stress via problem solving. When the problem is unsolved for longer periods of time, creativity continues to enhance. If the problem is unsolvable, or if the creative state is not conducive to solving the problem then you are left with a feedback loop that will result in the typical manifestations of psychosis as the individual becomes evermore creative and stressed.
Those who have the DRD4 7 repeat polymorphism tend to be at risk for psychosis (linked below) because they are more exploratory than other people. Exploration is tends to be a less safe strategy than dogmatically following the herd of humans because of many reasons. Exploratory paths have not yet undergone the trial and error process. Error is risky and those who lack this gene will also tend to not feel comfortable around the risk takers. This breeds isolation.
Exploration also means you will deviate from the herd and your ability to empathize will be reduced. Empathy is often thought to be some sort of ability that humans have, but I suspect this is not the case. We tend to empathize with those who are more homogenous with ourselves. Empathy in this sense does not mean love or concern but the ability to understand the state of mind that other’s have. Empathy for foreigners is reduced, empathy for the homeless is even more reduced. We often struggle to understand other animal species. Basically no human can empathize with a mollusk. When we try to construct a perspective and theory of mind for what mollusks experience, we are left with a void. Does this mean we all have a disorder of empathy? A mollusk is a very simple creature so our empathy should be at its’ highest state when attempting to understand a mollusk’s perspective of it were based on a capacity to understand differences in psychology. If empathy were based on a skill of understanding other minds then we should expect that humans are far harder to understand than a mollusk simply due to the human’s complexity.
So I propose a new hypothesis: We may have evolved to become more homogenous for the sake of a structured and stable society, while those with the DRD4 7R gene as well as other similar genes may tend to cause individuals to leave the herd and benefit the species with their discoveries and creativity. This causes these individuals to be much more likely to be rejected and thus at much higher risk to psychosis.
To read more about this, check out my Xenotypy Theory, where you can find tons of journal articles linked to every claim to make my case. Including the link between DRD4 7r and schizophrenia.
Situations that should cause psychosis would be loss of a loved one, loss of a social group, rejection from society, social isolation, or loss of any significant source of anti-dynorphin and/or Mu-Opioid and Delta-Opioid promoting agents. Holistic treatment of psychosis should include reinstatement of anti-dynorphin and/or Mu-Opioid and Delta-Opioid promoting agents. Social acceptance through the development of new social groups and relationships with people who understand that the symptoms of the psychotic patients is temporary and also understand that simply thinking novel thoughts can lead to rejection should help individuals in psychosis. Shifting culture and bringing awareness of the nature of psychosis from this perspective are necessary and an ethical obligation for professionals who’s job is to correct psychotic disorders.
Nicotine may help treat schizophrenia because of its unique modulation of the opioid system, seemingly towards both Mu-Opioid and Kappa-Opioid binding neurotransmitters. This study noted that nicotine use causes Mu-Opioid receptors to upregulate while Kappa-Opioid receptors downregulate. This may mean that nicotine causes the release of all types of opioid neurotransmitters as part of its effects. This balanced effect may prove more useful than pure Mu-Opioid agonists, which will tend to upregulate dynorphin activity over time with continued use and thus psychotic induction upon cessation or between doses. This article explores and challenges the self-medication hypothesis of relationship between nicotine and schizophrenia. In that study linked, it states that 50% of all cigarettes are consumed by schizophrenics. We’ve also seen patterns of large monetary influences such as drug companies trying to suppress that their antidepressants increased suicidality. And we know the tobacco industry would surely die if schizophrenia was a common outcome for those who are in the top 50th percentile of product consumers.
Using nicotine to treat psychotic symptoms may prove problematic though. 80% or more schizophrenics tend to use nicotine. This number seems abnormally high. It is known that nicotine binds to acetylcholine receptors, which drugs such as scopolamine and diphenhydramine block. These acetylcholine blocking drugs produce all symptoms of psychosis, hallucinations, delusions, perceptual problems, confusion, dissociation, memory problems, attention issues, mood problems and thought disorders. It could easily be the case that, much like how opioid medications slowly increase pain sensitivity with long-term use and tolerance, nicotine similarly increases psychotic proneness with long-term use.
Psychotomimetic neurotransmitter, Dynorphin, is necessary for nicotine withdrawal induced reinstatement of drug seeking. This means that nicotine withdrawal symptoms caused by Dynorphin could be the main cause of psychosis here.
To see my full write up, check here.
I suspect that in some cases where lingering psychosis occurs in someone due to loss of loved ones or identity problems such as shame that psilocybin may prove useful. Psilocybin has been known to treat PTSD and addiction, both of which are mediated in part by opioid neurotransmission, and so it dosing may help in the case of psychosis as well. The idea would be that psychosis is a result of trauma as well as conditioned thinking and psychedelics reverse conditioned learning and open the mind again. This method of treatment likely won’t work if the psychotic patient is currently in a traumatic environment. For example if the patient is severely dependent on parents who initially caused the trauma. Typically psychotic patients are seen as highly dependent and incapable of independent living, and so this may trap many of the patients in the environments which are actually perpetuating their stress and sickness. Psilocybin may only erase whatever shred of previous pre-trauma hope they had and reform their mind towards their current situation.
But for those who have achieved independent living and only suffer the psychosis as a residual effect of their previous environmental conditions, psilocybin may prove liberating, a way to update the mind to the new environment and move past old traumas.
Another issues is that psilocybin may cause non-intoxicated people to judge and worry about the intoxicated individual’s mental status which can be isolating and traumatic. Being diagnosed as schizophrenic alone would be traumatic but imagine that you are diagnosed by unprofessional friends and family whom treat you like a witch in Salam, an other. If the person on psilocybin acts out of line with cultural norms while intoxicated, the judgments of anyone who sees may linger long after the drug has worn off. The intoxicated individual may even be aware of this and become quickly traumatized and self-isolate. The onlookers may assume the intoxicated individual has lost their mind, which causes them to objectify and become cold and non-empathetic towards the intoxicated individual. It is dehumanization. Then if the intoxicated person were to react to this dehumanization they would sink further into the problem as onlookers would label this behavior as crazy as well.
To use psilocybin for psychosis we would need to form a healthy relationship with the patient and not stigmatize them during or after the experience.
To further understand how psychosis can manifest from rejection, please read my other works:
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