Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jun 2015
Assessing the public health impacts of legalizing recreational cannabis use in the USA.
A major challenge in assessing the public health impact of legalizing cannabis use in Colorado and Washington State is the absence of any experience with legal cannabis markets. The Netherlands created a de facto legalized cannabis market for recreational use, but policy analysts disagree about how it has affected rates of cannabis use. ⋯ Given experience with more liberal alcohol policies, the legalization of recreational cannabis use is likely to increase use among current users. It is also likely that legalization will increase the number of new users among young adults but it remains uncertain how many may be recruited, within what time frame, among which groups within the population, and how many of these new users will become regular users.
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This issue of Clinical Pharmacology & Therapeutics focuses on cannabinoids. Our understanding of these interesting endogenous and synthetic compounds, and their role in the cannabinoid system, has evolved dramatically, in part because of the acquisition of new research tools. ⋯ Novel cannabinoid drugs are emerging for medicinal use (e.g., dronabinol, nabiximols) and as illicit drugs (e.g., Spice, K2) perpetuating the perception that cannabinoid drugs can be a friend or foe. This special issue will cover these various aspects of cannabinoid pharmacology and therapeutics ranging from basic chemistry, pharmacokinetics, pharmacodynamics, and clinical trial results, to policy and education efforts in this area.
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Clin. Pharmacol. Ther. · May 2015
ReviewBruton's tyrosine kinase inhibitors in B-cell non-Hodgkin's lymphomas.
The B-cell receptor pathway (BCR) is aberrantly activated in select B-cell malignancies. This knowledge has allowed for the development of inhibitors of different crucial steps of this pathway. Bruton's tyrosine kinase (BTK) is a key component of BCR signaling and functions as an important regulator of multiple cell functions including differentiation, proliferation, and survival in various B-cell malignancies. ⋯ Given the high response rates, tolerability, and acceptable toxicities, ibrutinib was recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed mantle cell lymphoma and chronic lymphocytic leukemia. It is also currently being evaluated in combination with chemotherapy and as frontline therapy in B-cell NHL. This review summarizes the preclinical and clinical development of ibrutinib in the treatment of B-cell NHL.
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Clin. Pharmacol. Ther. · May 2015
ReviewTargeting Bruton's tyrosine kinase with ibrutinib in B-cell malignancies.
The B-cell receptor signaling pathway, which is critical to the development and maturation of normal B-cells, is emerging as an attractive therapeutic target in B-cell malignancies. Ibrutinib is a potent irreversible inhibitor of Bruton's tyrosine kinase (Btk), a key kinase important for signal transduction in the B-cell receptor (BCR) pathway. ⋯ Ongoing clinical studies have also demonstrated great potency of ibrutinib in treating other types of non-Hodgkin's lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM). Combination of ibrutinib with chemoimmunotherapy and other promising novel agents in B-cell malignancy therapy has also been under clinical investigation.