Therapeutic Potential of Cannabinoids in Psychosis (original) (raw)
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Therapeutic Potential of Cannabinoids in Schizophrenia
Recent Patents on CNS Drug Discovery, 2014
Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia. The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana's psychoactive principle 9 -tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation. It has been suggested to be a pro-homeostatic and pleiotropic signalling system activated in a time-and tissue-specific manner during pathophysiological conditions. In the brain, activation of this system impacts the release of numerous neurotransmitters in various systems and cytokines from glial cells. Hence, the endocannabinoid system is strongly involved in neuropsychiatric disorders, such as schizophrenia. Therefore, adolescence use of Cannabis may alter the endocannabinoid signalling and pose a potential environmental risk to develop psychosis. Consistently, preclinical and clinical studies have found a dysregulation in the endocannabinoid system such as changed expression of CB1 and CB2 receptors or altered levels of AEA and 2-AG . Thus, due to the partial efficacy of actual antipsychotics, compounds which modulate this system may provide a novel therapeutic target for the treatment of schizophrenia. The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology. Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.
Cannabidiol as a potential treatment for psychosis
European Neuropsychopharmacology, 2013
Although cannabis use is associated with an increased risk of developing psychosis, the cannabis constituent cannabidiol (CBD) may have antipsychotic properties. This review concisely describes the role of the endocannabinoid system in the development of psychosis and provides an overview of currently available animal, human experimental, imaging, epidemiological and clinical studies that investigated the antipsychotic properties of CBD. In this targeted literature review we performed a search for English articles using Medline and EMBASE. Studies were selected if they described experiments with psychosis models, psychotic symptoms or psychotic disorders as outcome measure and involved the use of CBD as intervention. Evidence from several research domains suggests that CBD shows potential for antipsychotic treatment.
Review Endocannabinoids and Schizophrenia
2015
The endocannabinoids anandamide and 2-arachydonoylglycerol (2-AG) are lipids naturally derived from membrane precursors which bind cannabinoid receptors (CB 1 , CB 2). This endocannabinoid system is disturbed in schizophrenia. Indeed, there seems to be an association between schizophrenia and polymorphisms of the CB 1 receptor gene. Moreover, CB 1 receptors are found in higher density in the prefrontal cortex, hippocampus and basal ganglia of patients with schizophrenia. Similarly, anandamide levels are increased in the cerebrospinal fluid (CSF) and in the serum of schizophrenia patients, including during the prodromal state, suggesting that they may play a protective role in psychosis homeostasis. Future studies are needed to further explore the role of the endocannabinoid system in the pathophysiology of schizophrenia.
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
Translational psychiatry, 2012
Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest tha...
The endocannabinoid system and its role in schizophrenia: a narrative review
IP Innovative Publication Pvt. Ltd, 2017
Aim: To provide an overview of the currently understood structure and function of the endocannabinoid system and the putative relationships of endocannabinoid system dysfunction and schizophrenia. To delineate potential novel targets in the endocannabinoid system for therapeutic modulation. Methods Design: Narrative review of peer reviewed research articles and authorative texts. Study (and authorative text) selection and analysis: Several databases including PubMed, Science Direct and University of Dundee library were systematically searched for studies addressing the issues of: (a) an association between cannabis and schizophrenia; (b) an association between any component of the endocannabinoid system and schizophrenia; and (c) possible interventions in schizophrenia by modulating the endocannabinoid system were included. Authorative texts were manually located and information selected according to the same criteria. Results: This paper provides an overview of the currently known structure and function of the endocannabinoid system. Exogenously administered cannabinoids can produce a range of psychoactive effects including a psychosis with similar clinical features to acute schizophrenia. Additionally, cannabis may contribute to the development of schizophrenia in susceptible individuals. Changes are seen in the endocannabinoid system in schizophrenia and there are putative links between endocannabinoid system dysfunction and the disorder. Phytocannabinoids as well as commercially developed compounds acting on the endocannabinoid system have demonstrable antipsychotic effects. Conclusions: This review highlights the putative links between endocannabinoid system dysfunction and schizophrenia. Traditional antipsychotic agents have demonstrable effectiveness in treating schizophrenia and were developed in response to the dopamine hypothesis of schizophrenia. However, there remains considerable scope for improvements to be made in the management of this challenging disorder. Aberrant functioning of the endocannabinoid system could represent an exciting therapeutic target for the development of novel effective agents.
Schizophrenia Research and Treatment, 2011
Recent studies have found that cannabinoids may improve neuropsychological performance, ameliorate negative symptoms, and have antipsychotic properties for a subgroup of the schizophrenia population. These findings are in contrast to the longstanding history of adverse consequences of cannabis use, predominantly on the positive symptoms, and a balanced neurochemical basis for these opposing views is lacking. This paper details a review of the neurobiological substrates of schizophrenia and the neurochemical effects of cannabis use in the normal population, in both cortical (in particular prefrontal) and subcortical brain regions. The aim of this paper is to provide a holistic neurochemical framework in which to understand how cannabinoids may impair, or indeed, serve to ameliorate the positive and negative symptoms as well as cognitive impairment. Directions in which future research can proceed to resolve the discrepancies are briefly discussed.
The endocannabinoid system and psychiatric disorders
Experimental Neurology, 2010
The present review summarizes the latest information on the role and the pharmacological modulation of the endocannabinoid system in mood disorders and its potential implication in psychotic disorders such as schizophrenia. Reduced functionality might be considered a predisposing factor for major depression, so boosting endocannabinoid tone might be a useful alternative therapeutic approach for depressive disorders. The picture regarding endocannabinoids and anxiety is more complicated since either too much or too little anandamide can lead to anxiety states. However, a small rise in its level in specific brain areas might be beneficial for the response to a stressful situation and therefore to tone down anxiety. This effect might be achieved with low doses of cannabinoid indirect agonists, such as blockers of the degradative pathway (i.e. FAAH) or re-uptake inhibitors. Moreover several lines of experimental and clinical evidence point to a dysregulation of the endocannabinoid system in schizophrenia. The high anandamide levels found in schizophrenic patients, negatively correlated with psychotic symptoms, point to a protective role, whereas the role of 2-arachidonoyl glycerol is still unclear. There is a potential for pharmacological manipulation of the endocannabinoid system as a novel approach for treating schizophrenia, although experimental findings are still controversial, often with different effects depending on the drug, the dose, the species and the model used for simulating positive or negative symptoms. Besides all these limitations, SR141716A and cannabidiol show the most constant antipsychotic properties in dopamine-and glutamate-based models of schizophrenia, with profiles similar to an atypical antipsychotic drug.
2010
Recent advances in knowledge about cannabinoid receptor function have renewed interest in the association between cannabis and psychosis. Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative and cognitive symptoms. Cannabinoids also produce some psychophysiological deficits also known to be present in schizophrenia. 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. Increasing evidence suggests that early and heavy cannabis exposure may increase the risk of developing a psychotic disorder such as schizophrenia. The relationship between cannabis exposure and schizophrenia fulfills some, but not all, of the usual criteria for causality. However, most people who use cannabis do not develop schizophrenia, and many people diagnosed with schizophrenia have never used cannabis. Therefore, it is likely that cannabis exposure is a "component cause" that interacts with other factors to "cause" schizophrenia or other psychotic disorder, but is neither necessary nor sufficient to do so alone. In the absence of known causes of schizophrenia, however, and the implications for public health policy should such a link be established the role of component causes such as cannabinoid exposure should remain a focus of further study. Finally, further work is necessary to identify the factors that underlie individual vulnerability to cannabinoid-related psychosis and to elucidate the biological mechanisms underlying this risk.
The Endocannabinoid System and its Role in Schizophrenia: A Systematic Review of the Literature
Revista Brasileira de Psiquiatria, 2012
Objective: Schizophrenia is a psychiatric disorder whose mechanisms have remained only partially elucidated. The current proposals regarding its biological basis, such as the dopaminergic hypothesis, do not fully explain the diversity of its symptoms, indicating that other processes may be involved. This paper aims to review evidence supporting the involvement of the endocannabinoid system (ECS), a neurotransmitter group that is the target of Cannabis sativa compounds, in this disorder. Methods: A systematic review of original papers, published in English, indexed in PubMed up to April, 2012. Results: Most studies employed genetics and histological, neuroimaging or neurochemical methods-either in vivo or post-mortem-to investigate whether components of the ECS are compromised in patients. Overall, the data show changes in cannabinoid receptors in certain brain regions as well as altered levels in endocannabinoid levels in cerebrospinal fluid and/or blood. Conclusions: Although a dysfunction of the ECS has been described, results are not entirely consistent across studies. Further data are warrant to better define a role of this system in schizophrenia.
Frontiers in Pharmacology, 2021
Cannabidiol (CBD), a principal phytocannabinoid constituent, has demonstrated antipsychotic properties in recent clinical trials. While it has also been suggested a promising candidate for the treatment of neurodegenerative disorders, it failed to demonstrate efficacy in cognitive impairments associated with schizophrenia as an add-on treatment (600 mg/day for 6 weeks) in 18 chronically ill patients co-treated with a variety of psychopharmacologic drugs. Here, we report on the results of parallel-group, active-controlled, mono-therapeutic, double-blind, randomized clinical trial (CBD-CT1; ClinicalTrials.gov identifier: NCT00628290) in 42 acute paranoid schizophrenic patients receiving either CBD (up to 800 mg/day) or amisulpride (AMI, up to 800 mg/day) for four weeks in an inpatient setting with neurocognition as a secondary objective. Twentynine patients (15 and 14 in the CBD and AMI group, respectively) completed two cognitive assessments at baseline and the end of the treatment p...