A cannabinoid hypothesis of Schizophrenia Cognitive Impairments Due to Dysregulation of the Endogenous Cannabinoid System

Schizophrenia Very multifactorial  Gender differences  Neurostructural differences  Genetic predisposition Scientifically discovered dose-dependent correlation to THC Probably many subtypes

Supportive for the hypothesis Similarity between symptoms of productive psychoses in schizophrenia and the internal disturbances of perceptual functions of THC- intoxication The adverse reactions of cannabis also include acute anxiety attacks and acute paranoid psychosis

Mild/moderate cannabis intoxication symptoms drowsiness euphoria heightened sensory awareness altered time percept memory impairment depersonalization mood alteration

Dopaminergic system disturbance Classical view Supported by Parkisonian symptoms when lowered Several pathways CB-1 receptor

Today’s explanation Many neurotransmitters are affected  GABA  Serotonin  Glutamate  Acetylcholine  BALANCE

New findings on the topic Endogenous cannabinoids; anandamide and palmitylethanolamide were much higher in the CSF of schizophrenic patients than controls, but not in serum! Imbalance in endogenous cannabinoid signaling The anandamide is not increased in patients with schizophrenia treated with “typical” antipsychotics (D2- receptor), but in new antipsychotics Heavy cannabis abuse may lead to desensitization of brain CB 1 receptors, which may in turn facilitate psychoses and motor disturbances  schizophrenia.

Summary The correlation between schizophrenia and cannabinoids such as THC seem also to be multifactorial and complex. In the future we might explore the relationship further and understand the pathogenesis and potetial treatment benefits of THC on brain chemisty

Main sources; Cerebrospinal Anandamide Levels are Elevated in Acute Schizophrenia and are Inversely Correlated with Psychotic Symptoms Andrea Giuffrida 1,3,4, F Markus Leweke 2,3, Christoph W Gerth 2, Daniela Schreiber 1,2, Dagmar Koethe 2, Johannes Faulhaber 2, Joachim Klosterkötter 2 and Daniele Piomelli 1 Towards a Cannabinoid Hypothesis of Schizophrenia: Cognitive Impairments Due to Dysregulation of the Endogenous Cannabinoid System Hinderk M Emrich,, F.Markus Leweke, Udo Schneider Department of Clinical Psychiatry, Medizinische Hochschule Hannover, D Hannover, Germany Elevated endogenous cannabinoids in schizophrenia Leweke, F M. 1,4,6 ; Giuffrida, A 2,6 ; Wurster, U 3 ; Emrich, H M. 1 ; Piomelli, D 2,5