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Background: The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD. Methods: Participants (n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system. Results: Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims. Conclusion: Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition.
RESUMEN
CONTEXT: Lipotoxicity (increased tissue fat content) has been implicated in the development of muscle insulin resistance and type 2 diabetes mellitus (T2DM). OBJECTIVE: The aim was to study the effect of pioglitazone on intramyocellular fat metabolism. RESEARCH DESIGN: Twenty-four T2DM subjects (glycosylated hemoglobin = 8.3 +/- 0.4%) participated in three similar study protocols before and after 4 months of 45 mg/d pioglitazone treatment: 1) 3-h euglycemic insulin (80 mU/m(2) . min) clamp with measurement of intramyocellular fat with proton nuclear magnetic resonance; 2) vastus lateralis muscle biopsy for measurement of LC-FACoAs 60 min before start of the insulin clamp; and 3) muscle biopsy for measurement of diacylglycerol 60 min before start of the insulin clamp. RESULTS: In all three protocols, pioglitazone similarly reduced (all P < 0.05) the glycosylated hemoglobin (Delta = 0.8-1.2%), fasting plasma glucose (39-76 mg/dl), fasting free fatty acid (132-236 mumol/liter), and increased insulin-stimulated glucose disposal (by 25-56%). Intramyocellular fat (protocol I) declined from 1.5 to 0.9% (P < 0.05) and correlated with the increase in glucose disposal rate (r = 0.65; P < 0.05). Long chain-fatty acyl-coenzyme A decreased from 12.5 to 8.1 nmol/g (P < 0.05) and correlated with the increase in disposal rate (r = 0.76; P < 0.05). Pioglitazone therapy had no effect on muscle diacylglycerol content. CONCLUSIONS: Pioglitazone improves insulin resistance in T2DM in association with mobilization of fat and toxic lipid metabolites out of muscle.
