In the Journals

Endocannabinoid system appears abnormal in psychosis

Research published in JAMA Psychiatry revealed that measuring disturbance in the endocannabinoid system, or ECS, in the blood and cerebrospinal fluid may have potential as a biomarker for psychosis.

“The endogenous activity of the ECS is affected by exogenous cannabinoids, such as THC (delta-9-tetrahydrocannabinol), the main psychoactive components of cannabis, and cannabidiol (CBD),” Amedeo Minichino, MD, from the department of psychiatry, University of Oxford, and colleagues wrote. “The ECS may be an important system for understanding the factors associated with and effective treatments for psychosis.”

Minichino and colleagues conducted a systematic review using clinical databases and meta-analysis of relevant literature to examine the blood and cerebrospinal fluid (CSF) measures of the ECS in psychotic disorders. To determine the clinical relevance of ECS modifications, the researchers quantitatively synthesized the differences in blood and CSF markers of the ECS between patients and healthy controls, as well as the connection between these markers with symptom severity, stage of illness and treatment response.

Eighteen studies were included in the three individual meta-analyses.

In five studies, which involved 226 patients and 385 controls, the investigators observed significantly higher concentrations of anandamide in the CSF of patients than controls (standardized mean difference = 0.97; 95% CI, 0.67-1.26; I2 = 54.8%). In nine studies, which encompassed 344 patients and 411 controls, they also found significantly higher anandamide levels in blood in patients with psychosis compared with controls (SMD = 0.55; 95% CI, 0.05-1.04; I2 = 89.6%). Lastly, in three studies, which included 88 patients and 179 controls, they reported a significantly higher expression of type 1 cannabinoid receptors on peripheral immune cells in patients with psychosis compared with controls (SMD = 0.57; 95% CI, 0.31-0.84; I2 = 0%). The researchers reported a moderate to high level of heterogeneity in methods between studies.

“Serum anandamide levels and other blood markers of the ECS, such as the expression of cannabinoid receptors, have been associated with the severity of cognitive deficits in patients with schizophrenia,” Minichino and colleagues wrote. “These findings further support the hypothesis that the activation of the ECS in the periphery is clinically relevant for psychotic illnesses.”

In addition, the data also revealed a higher ECS tone at an early stage of illness in patients who were antipsychotic naïve or free, and elevated ECS tone had an inverse connection with symptom severity. This was normalized after successful treatment, according to the study.

“Understanding ECS activity in these disorders is relevant owing to the ongoing trials on exogenous cannabinoids as a therapeutic approach,” they researchers concluded.

David W. Volk, MD, PhD, and David A. Lewis, MD, from the department of psychiatry, University of Pittsburgh, wrote in an associated comment that these findings signal a need for “future studies that clearly establish the extent to which blood and/or CSF measures of endocannabinoids index endocannabinoid function in the brain, which would represent an important advance in developing new strategies for diagnosing and treating schizophrenia, and ongoing efforts to reduce cannabis use in populations at high risk for developing schizophrenia.” – by Savannah Demko

Disclosure: Minichino reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Volk reports grants from the NIH and other support from Veterans Integrated Service Network 4 Mental Illness Research Education and Clinical Center. Lewis reports grants from Merck and Pfizer.

Research published in JAMA Psychiatry revealed that measuring disturbance in the endocannabinoid system, or ECS, in the blood and cerebrospinal fluid may have potential as a biomarker for psychosis.

“The endogenous activity of the ECS is affected by exogenous cannabinoids, such as THC (delta-9-tetrahydrocannabinol), the main psychoactive components of cannabis, and cannabidiol (CBD),” Amedeo Minichino, MD, from the department of psychiatry, University of Oxford, and colleagues wrote. “The ECS may be an important system for understanding the factors associated with and effective treatments for psychosis.”

Minichino and colleagues conducted a systematic review using clinical databases and meta-analysis of relevant literature to examine the blood and cerebrospinal fluid (CSF) measures of the ECS in psychotic disorders. To determine the clinical relevance of ECS modifications, the researchers quantitatively synthesized the differences in blood and CSF markers of the ECS between patients and healthy controls, as well as the connection between these markers with symptom severity, stage of illness and treatment response.

Eighteen studies were included in the three individual meta-analyses.

In five studies, which involved 226 patients and 385 controls, the investigators observed significantly higher concentrations of anandamide in the CSF of patients than controls (standardized mean difference = 0.97; 95% CI, 0.67-1.26; I2 = 54.8%). In nine studies, which encompassed 344 patients and 411 controls, they also found significantly higher anandamide levels in blood in patients with psychosis compared with controls (SMD = 0.55; 95% CI, 0.05-1.04; I2 = 89.6%). Lastly, in three studies, which included 88 patients and 179 controls, they reported a significantly higher expression of type 1 cannabinoid receptors on peripheral immune cells in patients with psychosis compared with controls (SMD = 0.57; 95% CI, 0.31-0.84; I2 = 0%). The researchers reported a moderate to high level of heterogeneity in methods between studies.

“Serum anandamide levels and other blood markers of the ECS, such as the expression of cannabinoid receptors, have been associated with the severity of cognitive deficits in patients with schizophrenia,” Minichino and colleagues wrote. “These findings further support the hypothesis that the activation of the ECS in the periphery is clinically relevant for psychotic illnesses.”

In addition, the data also revealed a higher ECS tone at an early stage of illness in patients who were antipsychotic naïve or free, and elevated ECS tone had an inverse connection with symptom severity. This was normalized after successful treatment, according to the study.

“Understanding ECS activity in these disorders is relevant owing to the ongoing trials on exogenous cannabinoids as a therapeutic approach,” they researchers concluded.

David W. Volk, MD, PhD, and David A. Lewis, MD, from the department of psychiatry, University of Pittsburgh, wrote in an associated comment that these findings signal a need for “future studies that clearly establish the extent to which blood and/or CSF measures of endocannabinoids index endocannabinoid function in the brain, which would represent an important advance in developing new strategies for diagnosing and treating schizophrenia, and ongoing efforts to reduce cannabis use in populations at high risk for developing schizophrenia.” – by Savannah Demko

Disclosure: Minichino reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Volk reports grants from the NIH and other support from Veterans Integrated Service Network 4 Mental Illness Research Education and Clinical Center. Lewis reports grants from Merck and Pfizer.