The Endocannabinoid System and its Role in Schizophrenia: A Systematic Review of the Literature

Ferretjans, Rodrigo; Moreira, Fabrício A.; Teixeira, Antônio Lúcio; Salgado, João Vinícius

doi:10.1016/j.rbp.2012.07.003

Cited by 29 publications

(26 citation statements)

References 46 publications

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“…Furthermore, these mice lack CB1 throughout development, and CB1 has a known role in axon guidance [66] Therefore, the effects on sleep may be attributable to aberrant developmental processes that emerge in the absence of the CB1 receptor. Nevertheless, long-term reduction in CB1 is associated with several neuropsychological disorders that are also associated with sleep disturbances including alcohol dependence [67] and schizophrenia [68], [69].…”

Section: Discussionmentioning

confidence: 99%

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep

et al. 2014

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Up-/down-state transitions are a form of network activity observed when sensory input into the cortex is diminished such as during non-REM sleep. Up-states emerge from coordinated signaling between glutamatergic and GABAergic synapses and are modulated by systems that affect the balance between inhibition and excitation. We hypothesized that the endocannabinoid (EC) system, a neuromodulatory system intrinsic to the cortical microcircuitry, is an important regulator of up-states and sleep. To test this hypothesis, up-states were recorded from layer V/VI pyramidal neurons in organotypic cultures of wild-type or CB1R knockout (KO) mouse prefrontal cortex. Activation of the cannabinoid 1 receptor (CB1) with exogenous agonists or by blocking metabolism of endocannabinoids, anandamide or 2-arachidonoyl glycerol, increased up-state amplitude and facilitated action potential discharge during up-states. The CB1 agonist also produced a layer II/III-selective reduction in synaptic GABAergic signaling that may underlie its effects on up-state amplitude and spiking. Application of CB1 antagonists revealed that an endogenous EC tone regulates up-state duration. Paradoxically, the duration of up-states in CB1 KO cultures was increased suggesting that chronic absence of EC signaling alters cortical activity. Consistent with increased cortical excitability, CB1 KO mice exhibited increased wakefulness as a result of reduced NREM sleep and NREM bout duration. Under baseline conditions, NREM delta (0.5–4 Hz) power was not different in CB1 KO mice, but during recovery from forced sleep deprivation, KO mice had reduced NREM delta power and increased sleep fragmentation. Overall, these findings demonstrate that the EC system actively regulates cortical up-states and important features of NREM sleep such as its duration and low frequency cortical oscillations.

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Section: Discussionmentioning

confidence: 99%

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep

et al. 2014

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“…In particular, reduced nicotinic α7 acetylcholine (nACh) receptor binding in the cingulate, hippocampus, and thalamus (for review, see Hajós and Rogers, 2010), reduced muscarinic M 1 and M 4 acetylcholine (mACh) receptor binding in the prefrontal cortex and hippocampus (for review, see Bymaster et al, 2002), reduced histamine H1 receptor binding in the frontal cortex (for review, see Ito, 2004), as well as increased or decreased endocannabinoid CB1 receptor binding in the prefrontal cortex and increased endocannabinoid CB1 receptor binding in the cingulate (for review, see Ferretjans et al, 2012) have been implicated in the pathophysiology of SZ.…”

Section: Other Neurotransmitter Systemsmentioning

confidence: 99%

Neurochemical dysfunction in treated and nontreated schizophrenia – a retrospective analysis of in vivo imaging studies

Nikolaus

Hautzel

Müller

2014

Reviews in the Neurosciences

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“…Studies have investigated the genetic relationship between schizophrenia and endocannabinoid system. The main findings point to CNR1 polymorphisms in this disorder, while these polymorphisms were not confirmed by other studies . Ho et al.…”

Section: Schizophrenia and Endocannabinoid Systemmentioning

confidence: 61%

Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains

et al. 2018

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Interest in the modulation of endocannabinoid signaling has increased since the discovery of receptors for compounds of Cannabis sativa. Endocannabinoids are crucial neuromodulators of many brain functions and changes in the ligands and their receptors have been associated with psychiatric disorders, such as schizophrenia. Genetic, neuroimaging, and behavioral studies have reinforced the role of endocannabinoids in the pathobiology of schizophrenia. However, molecular pathways and biological processes involved in cannabinoid effects are not totally understood. Additionally, the endocannabinoid signaling network with other non-cannabinoid targets, and the effects of phytocannabinoids increase the complexity to understand their role in schizophrenia and homeostasis conditions. Thus, proteomic studies can provide evidence about the involvement of cannabinoid receptors, as well as the metabolic and synthetic enzymes of the endocannabinoids in these disorders. Additionally, quantification of endocannabinoids in the blood serum or cerebrospinal fluid can be a useful approach to identify new biomarkers in schizophrenia, and lipidomic techniques can be used to quantify these compounds. Herein, the authors review proteomic and lipidomic studies that have been used for analysis of the endocannabinoid system in healthy and schizophrenia function. The findings may contribute to understand the involvement of endocannabinoids in the brain and in the neurobiological basis of schizophrenia.

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The Endocannabinoid System and its Role in Schizophrenia: A Systematic Review of the Literature

Abstract: 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.

Cited by 29 publications

References 46 publications

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep

Endocannabinoid Modulation of Cortical Up-States and NREM Sleep

Neurochemical dysfunction in treated and nontreated schizophrenia – a retrospective analysis of in vivo imaging studies

Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains

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