Evidence that schizophrenia has something to do with the endocannabinoid system (ECS) has been around for a long time, the increased prevalence of schizophrenia amongst people who take cannabis strongly implies this. However, the mechanisms for the causes and pathology of schizophrenia are still very poorly understood. One avenue for understanding this is to use the increasing knowledge of the endocannabinoid system to explore differences in the brains of schizophrenics and healthy individuals.
Previous studies have found that the inhibitory circuitry of the prefrontal cortex, an area of the brain that is essential for memory and cognition, is impaired in schizophrenic brains. The mechanisms of this circuit have been established and are endocannabinoid-mediated, using the endocannabinoid 2-AG to trigger a chain of signaling reactions.
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In the brains of schizophrenic individuals, the metabolism (breakdown) of 2-AG appears to be accelerated; and cannabinoid receptor type 1 (CB1R) binding is higher but producing less mRNA. These are vital clues as to the dysregulation of these important circuits that lead to schizophrenia.
It might not seem like much of a surprise to learn that the brains of mentally ill people are working differently to those of healthy people, but it is very important to establish this if effective treatments are to be developed.
In the schizophrenic brains studied here, a part of the brain called the dorsolateral prefrontal cortex (DLPFC) is altered. There are layers of neurons that work together to regulate working memory and these have been consistently found to be connecting differently. This is thought to be partially because of different concentrations of CB1R in the cell membranes, altering how signals pass through.
The significant differences in the number of endocannabinoid receptors, the concentrations of endocannabinoids, and the products of endocannabinoid signaling, suggest that the differences in DLPFC circuitry are at least in part due to ECS dysregulation. However, at this time it is unclear whether these differences are the brain compensating for the differences or the cause of them.
There are differences in the concentrations of endocannabinoids in the blood and cerebrospinal fluid of healthy and schizophrenic individuals, however, it has not been demonstrated why this is the case or what the implications are.
It is almost certain that the differences in endocannabinoid system in the brain of schizophrenics are at least part of the reason for the differences in brain functioning.
Because the endocannabinoid system can be easily disrupted by taking cannabis, which is full of cannabinoids that will bind to CB1R, it is easy to see how cannabis use might lead to schizophrenia. When cannabis is administered, the extra cannabinoids bind to and disrupt the signaling in the endocannabinoid system.
Some individuals appear to be more susceptible to more long-term disruption by cannabis, thought to be because the extra cannabinoids overwhelm the compensatory effects of 2-AG signaling. With consistent use, and especially in growing adolescent brains, the signaling pathways could be changed permanently, leading to schizophrenia.
The model of schizophrenia is being slowly expanded and built up. Schizophrenic brains show consistent differences in endocannabinoid signaling, which suggests that for at-risk individuals with genetic predispositions, avoiding cannabis would appear to be the right course of action, though further investigation is needed into CBD on its own. CBD vs THC effects on schizophrenia are the main reason there’s no definitive answer yet.