Dataset Information

Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders.

ABSTRACT: Neuropsychiatric disorders, such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder, and neurodevelopmental disorders such as autism spectrum disorder, are associated with significant illness burden. Accumulating evidence supports an association between these disorders and inflammation. Consequently, anti-inflammatory agents, such as the cyclooxygenase-2 inhibitors, represent a novel avenue to prevent and treat neuropsychiatric illness. In this paper, we first review the role of inflammation in psychiatric pathophysiology including inflammatory cytokines' influence on neurotransmitters, the hypothalamic-pituitary-adrenal axis, and microglial mechanisms. We then discuss how cyclooxygenase-2-inhibitors influence these pathways with potential therapeutic benefit, with a focus on celecoxib, due to its superior safety profile. A search was conducted in PubMed, Embase, and PsychINFO databases, in addition to Clinicaltrials.gov and the Stanley Medical Research Institute trial registries. The results were presented as a narrative review. Currently available outcomes for randomized controlled trials up to November 2017 are also discussed. The evidence reviewed here suggests cyclooxygenase-2 inhibitors, and in particular celecoxib, may indeed assist in treating the symptoms of neuropsychiatric disorders; however, further studies are required to assess appropriate illness stage-related indication.

SUBMITTER: Sethi R

PROVIDER: S-EPMC6738329 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders.

Sethi Rickinder R Gómez-Coronado Nieves N Walker Adam J AJ Robertson Oliver D'Arcy OD Agustini Bruno B Berk Michael M Dodd Seetal S

Frontiers in psychiatry 20190904

Neuropsychiatric disorders, such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder, and neurodevelopmental disorders such as autism spectrum disorder, are associated with significant illness burden. Accumulating evidence supports an association between these disorders and inflammation. Consequently, anti-inflammatory agents, such as the cyclooxygenase-2 inhibitors, represent a novel avenue to prevent and treat neuropsychiatric illness. In this paper, we first review t ...[more]

PMID: 31551825

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Project description:To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. ?(9) -Tetrahydrocannabinol (?(9) -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and ?(9) -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of ?(9) -THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the ?3 and ?1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:?(9) -THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Dataset Information

Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders.

Publications

Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders.

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