Clinical therapeutics
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With rising rates of cannabis use in the general population and an increasing number of US states legalizing both recreational and medical cannabis use, it is important to be informed about the adverse consequences of cannabinoids. This Commentary provides an overview of the psychiatric effects of plant-based and synthetic cannabinoids, differentiating acute effects from effects associated with persistent use. Cannabinoids produce multiphasic and dose-dependent effects on anxiety, mood, and perception, in addition to impairing cognition and psychomotor function. ⋯ Studies report long-term cannabis exposure has been linked to psychiatric disorders, such as anxiety, psychotic and mood disorders. Limitations to the existing evidence notwithstanding, the plausibility of a causal relationship between cannabinoid exposure and persistent negative psychiatric outcomes, and the potential for long-term brain changes by regular exposure, especially for adolescents, are sufficient to warrant discussions with clinicians and the public. Implications for clinicians who certify, prescribe, or care for patients receiving cannabinoids are discussed, and a case is made for further research to better understand the impact of legalization on public mental health.
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Epilepsy is a common neurologic disorder; it is estimated that ∼50million people are affected worldwide. About one third of those patients are drug resistant, defined as failure to stop all seizures despite adequate trials of at least 2 appropriate medications. ⋯ This review discusses the evidence supporting the anticonvulsant properties of cannabis in humans, focusing on cannabidiol. We begin by exploring the early and somewhat anecdotal evidence that was recently replaced by high-quality data from randomized controlled studies, which subsequently led to the US Food and Drug Administration approval of a purified cannabidiol extract for the treatment of 2 highly refractory pediatric epilepsy syndromes (Dravet and Lennox-Gastaut).
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Clinical therapeutics · Sep 2018
Altered Pharmacokinetics in Prolonged Infusions of Sedatives and Analgesics Among Adult Critically Ill Patients: A Systematic Review.
The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness. The critically ill population presents challenges when titrating infusions of sedatives and analgesics to maintain optimal sedation and pain levels. This systematic review examined the PK data in critically ill adult patients with prolonged infusions (>24 hours) of commonly used sedatives and analgesics to highlight possible altered PK parameters compared with noncritically ill patients. ⋯ These findings show a marked difference in many PK parameters from those reported for noncritically ill patients. Initiatives to improve the delivery of prolonged sedatives and analgesic infusions should be informed by PK parameters (Vdss, context-sensitive t1/2, and elimination t1/2) and data derived from critically ill patients.
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Cannabis sativa has a long history of use for medical purposes despite marijuana's addictive potential. The discovery of the endogenous cannabinoid system as a neuromodulatory system composed of receptors, endogenous ligands (endocannabinoids), and enzymes responsible for their synthesis and degradation, together with recent advancements in the elucidation of cannabinoid pharmacology, has renewed interest in medicines acting on the endocannabinoid system. ⋯ Because activation of cannabinoid receptors may induce central and peripheral beneficial effects, the newest synthetic cannabinoids having full agonistic activity and high potency at cannabinoid type 1 and type 2 receptors might have therapeutic potential too. However, case reports of acute and fatal intoxications are accumulating and revealing that this is not the case because adverse effects of the latest generation of synthetic cannabinoids far exceed the desired ones.
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Clinical therapeutics · Aug 2018
Randomized Controlled TrialThe Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.
Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. ⋯ The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals.