Up close: CBD in psychosis

by Duncan Fisher

September 16, 2022 - 3 min read

One of the strange properties of cannabis is that the demonstrated psychotogenic effects of delta-9 tetrahydrocannabinol (THC) can be ameliorated by cannabidiol (CBD). With THC exposure, neuroanatomic alterations occur across regions that are high in cannabinoid receptors (i.e., hippocampus, prefrontal cortex, amygdala, cerebellum), varying by dose and by age of onset. While THC exacerbates these, CBD protects from them. Evidence is that CBD may ameliorate psychotic symptoms overall, with a superior side-effect profile than established antipsychotics, both in patients with schizophrenia and in sufferers of psychosis induced by long-term use of THC. 

The endocannabinoid system, part of the mammalian cell-signaling network alters, via the cannabinoid neural receptors CB1 and CB2, levels of AEA and 2-AG, and is able to control the function of other receptors, like N-methyl-D-aspartate (NMDA), that are associated with psychosis and other symptoms of schizophrenia. Injection of the CB1 receptor agonist oleamide, for example, has no influence on psychotic short- and long-term memory-related disturbances in mice, or on hyperlocomotion, provoked by an acute injection of MK-801, but these effects were attenuated by AM 251, a CB1 receptor antagonist. As well, in mononuclear cells obtained from subjects suffering from schizophrenia, selective alterations of DNA methylation at the promoter of CB1 have been observed in schizophrenic patients, with no changes in any other disorder. Regulation of CB1 was confirmed in a well-validated animal model of schizophrenia, where, in the prefrontal cortex, a significant increase in CB1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter was shown. CB1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. Possibly because of this, ventral hippocampal overexpression of cannabinoid receptor interacting protein 1 has been shown to produce a schizophrenia-like phenotype in rats. As well, embryonic exposure to methylazoxymethanol in rats leads to schizophrenia-related changes in CB1 mRNA expression late in development. CBD may finally exert its antipsychotic effect finally through decreased glial reactivity. 


THC-induced psychosis

Experimental studies reveal that cannabis can induce acute psychosis which lasts beyond the period of intoxication and persists as long as a month. Exposure to cannabis in adolescence is associated with an increased risk for later psychotic disorder in adulthood. This association is consistent and dose-dependant. Cannabinoids are not necessary or sufficient to cause a long-term psychotic disorder by themselves. Meta-analyses show that people who develop psychosis experience onset of symptoms about 2-3 years earlier if they are cannabis users, however. This effect is not observed with alcohol or other substances. Present cannabis abuse or dependence increases the risk of transition into psychosis in those already at very high risk. About a third of patients with first-episode psychosis are cannabis users.  Discontinuation of cannabis use in psychosis treatment reduces the risk of relapse into psychosis. People with psychosis who continue to use cannabis finally present more severe positive symptoms and poorer levels of functioning. 

CBD does show an ability to counteract psychotic symptoms and cognitive impairment associated with cannabis use. In addition, CBD may lower the risk for developing psychosis related to cannabis use. These opposing effects are probably the result of abnormal salience attribution, mediated in the striatum, hippocampus and prefrontal cortex, where there is differential activation under the influence of THC and CBD. THC reduces fronto-striatal connectivity, and CBD enhances it. Conversely, mediotemporal-prefrontal connectivity is enhanced by THC and reduced by CBD. 


Classical schizophrenia

CBD augmentation does not always associate with improvement in symptom scores in stable antipsychotic-treated outpatients with schizophrenia, though generally across trials it tends to, where it is also well tolerated. CBD’s role in psychosis appears to be complex, and not a simple extension of its typical effects. Emerging evidence suggests that polymorphisms of several genes related to dopamine metabolism (COMT, DAT1, and AKT1) may moderate the effects of cannabinoid agonists in laboratory studies. Cannabinoid agonists do induce dopamine release, but the magnitude of this release by itself does not appear proportional to the variety or magnitude of its psychotropic effect. 



DiolPure products contain PureForm CBD™ transformed from aromatic terpenes for pharmaceutical-grade purity. PureForm CBD™ is bioidentical to CBD extracted from hemp and cannabis, but free of any residual cannabinoids like THC or impurities or chemicals that can associate with traditional plant-derived production processes. 


The foregoing is a report on trends and developments in cannabinoid industry research. No product description herein is intended as a recommendation for diagnosis, treatment, cure or prevention of any disease or syndrome. 

 





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