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Brain Research Dec 2020Studies investigating alterations of the endocannabinoid system (ECS) in Alzheimer's disease (AD) in humans have reported inconsistent findings so far. We performed a...
Studies investigating alterations of the endocannabinoid system (ECS) in Alzheimer's disease (AD) in humans have reported inconsistent findings so far. We performed a systematic review of studies examining alterations of the ECS specifically within humans with AD or mild cognitive impairment (MCI), including neuroimaging studies, studies of serum and cerebrospinal fluid biomarkers, and post-mortem studies. We attempted to identify reported changes in the expression and activity of: cannabinoid receptors 1 and 2; anandamide (AEA); 2-arachidonoylglycerol (2-AG); monoacylglycerol lipase (MAGL); fatty acid amide hydrolase (FAAH); and transient receptor potential cation channel V1 (TRPV1). Twenty-two studies were identified for inclusion. Mixed findings were reported for most aspects of the ECS in AD, making it difficult to identify a particular profile of ECS alterations characterising AD. The included studies tended to be small, methodologically heterogeneous, and frequently did not control for important potential confounders, such as pathological progression of AD. Eight studies correlated ECS alterations with neuropsychometric performance measures, though studies infrequently examined behavioural and neuropsychiatric correlates. PROSPERO database identifier: CRD42018096249.
Topics: Alzheimer Disease; Amidohydrolases; Arachidonic Acids; Cognitive Dysfunction; Endocannabinoids; Humans; Monoacylglycerol Lipases; Polyunsaturated Alkamides; Receptors, Cannabinoid
PubMed: 32980333
DOI: 10.1016/j.brainres.2020.147135 -
Clinical Pharmacology and Therapeutics Oct 2019The HIV type-1 nonnucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV type-1 infection. Efavirenz is predominantly metabolized into...
The HIV type-1 nonnucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV type-1 infection. Efavirenz is predominantly metabolized into inactive metabolites by cytochrome P450 (CYP)2B6, and patients with certain CYP2B6 genetic variants may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. We summarize the evidence from the literature and provide therapeutic recommendations for efavirenz prescribing based on CYP2B6 genotypes.
Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Cytochrome P-450 CYP2B6; HIV Infections; HIV-1; Humans; Pharmacogenetics; Pharmacogenomic Testing; Practice Guidelines as Topic
PubMed: 31006110
DOI: 10.1002/cpt.1477