Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · May 2019
ReviewPositive and Negative Effects of Cannabis and Cannabinoids on Health.
Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short- and long-term side effects, including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia, and mood disorders. ⋯ The current article presents a contemporary review on the adverse effects, safety, and the therapeutic potential of cannabis and cannabinoid-based drugs. Given the growing popularity in the use of cannabinoid-based drugs for both recreational and medical purposes and their potential harmful effects, there is a need for further investigation in this field.
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Clin. Pharmacol. Ther. · May 2019
Randomized Controlled TrialPharmacokinetics and Pharmacodynamics of the BACE1 Inhibitor Verubecestat (MK-8931) in Healthy Japanese Adults: A Randomized, Placebo-Controlled Study.
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of β-amyloid (Aβ) peptides and is considered a potential treatment target for Alzheimer's disease (AD). To support Japan's participation in the global clinical development program, we characterized the safety, pharmacokinetics (PKs), and pharmacodynamics of the BACE1 inhibitor verubecestat (MK-8931) in 24 healthy Japanese adults in a two-part, single-center, randomized, placebo-controlled phase I trial (protocol MK-8931-007) and compared the results with historical data from non-Japanese subjects. ⋯ Verubecestat also reduced mean cerebrospinal fluid concentrations of the Aβ proteins Aβ40, Aβ42, and soluble β fragment of amyloid precursor protein; the level of reduction was comparable between Japanese and non-Japanese subjects. These results support the continued global development of verubecestat as a potential disease-modifying agent for Japanese and non-Japanese subjects who are at risk for developing AD.
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Clin. Pharmacol. Ther. · May 2019
ReviewCalcitonin Gene-Related Peptide Antagonists in the Treatment of Episodic Migraine.
Migraine is a prevalent, disabling neurological disorder involving the trigeminovascular system. Previous treatments were either originally intended for other conditions and/or associated with intolerable adverse effects (AEs). ⋯ The CGRP antagonists (gepants and monoclonal antibodies) are the first treatments created specifically for migraine, modulating pain signaling pathways and alleviating migraine attacks and recurrences. With their efficacy in several clinical trials and relatively fewer AEs, the CGRP antagonists show great promise for use in episodic migraine.