Cannabis and psychosis/schizophrenia: human studies

Abstract

The association between cannabis use and psychosis has long been recognized. Recent advances in knowledge about cannabinoid receptor function have renewed interest in this association. Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative, and cognitive symptoms in some healthy individuals. Also clear is that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. The mechanisms by which cannabinoids produce transient psychotic symptoms, while unclear may involve dopamine, GABA, and glutamate neurotransmission. However, only a very small proportion of the general population exposed to cannabinoids develop a psychotic illness. It is likely that cannabis exposure is a "component cause" that interacts with other factors to "cause" schizophrenia or a psychotic disorder, but is neither necessary nor sufficient to do so alone. Nevertheless, in the absence of known causes of schizophrenia, the role of component causes remains important and warrants further study. Dose, duration of exposure, and the age of first exposure to cannabinoids may be important factors, and genetic factors that interact with cannabinoid exposure to moderate or amplify the risk of a psychotic disorder are beginning to be elucidated. The mechanisms by which exposure to cannabinoids increase the risk for developing a psychotic disorder are unknown. However, novel hypotheses including the role of cannabinoids on neurodevelopmental processes relevant to psychotic disorders are being studied.

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

“…Its use in youth increases the risk of developing psychosis, with an estimated odds ratio of 2.10-2.93 (Henquet et al, 2005;Moore et al, 2007), decreasing the age of schizophrenia onset (Sugranyes et al, 2009). The neurobiological mechanisms underlying this increased psychosis susceptibility are poorly understood (D'Souza et al, 2009;Gage et al, 2013). However, some studies have found that frequent cannabis exposure may downregulate AEA signalling in patients with schizophrenia, but not in healthy individuals (Leweke et al, 2007).…”

Alteration to hippocampal shape in cannabis users with and without schizophrenia

“…Cannabis use is highly comorbid with schizophrenia (Koskinen et al, 2010) and considered a component cause of the disorder (D'Souza et al, 2009;Murray et al, 2007). There is growing evidence that long-term or heavy cannabis use impacts upon brain structure and function, particularly in regions known to be affected in schizophrenia, such as the hippocampus (Ashtari et al, 2011;Lorenzetti et al, 2010;Solowij and Michie, 2007;Solowij et al, 2012).…”

Emergence of New Classes of Recreational Drugs—Synthetic Cannabinoids and Cathinones

“…16,24,25 In addition to the above immediate toxicities, there is concern over long-term SC use, as chronic use of marijuana has been associated with increased rates of schizophrenia and possible memory loss. 38,39 …”