Cannabidiol or CBD Oil: Help, Hope, and Hype for Psychiatric and Neurologic Conditions.

OBJECTIVE: This article presents proven, promising, and potential therapeutic uses for cannabidiol (CBD) in the treatment of psychiatric and neurologic conditions and diseases. It presents popular, but scientifically unproven health and therapeutic claims of CBD supporting the beneficial homeostatic effects of the intrinsic or endogenous cannabinoid system. It includes a review of cannabinoid pharmacology; it compares properties and the legal status of CBD and THC (delta 9-tetrahydrocannabinol) as well as the hemp and marijuana varieties of Cannabis, and it reviews the historic 2018 U.S. Food and Drug Administration approval of Epidiolex, an oral solution of cannabidiol for two rare treatment-resistant childhood epilepsies, as the first Cannabis-derived drug. METHOD: We reviewed literature on cannabidiol, CBD, the endocannabinoid neuropharmacology system, and hemp and marijuana varieties of Cannabis sativa. RESULTS: The proven and promising medical uses and deficiencies of unproven health claims for CBD, legal implications for Cannabis-derived drugs, and comparisons of CBD and THC and hemp and marijuana are summarized objectively with pertinent references. CONCLUSION: CBD and CBD and THC combinations have potential to provide safe, effective therapy for several psychiatric and neurologic conditions and diseases. However, such achievement will require a uniform standard of CBD purity and strength, and corroboration from adequately large and rigorously controlled clinical research studies.

Mean Kinetic Temperature for Controlled Room Temperature Drug Storage: Official Definitions and Example Calculations.

Mean kinetic temperature, a thermodynamically calculated average temperature that is used to determine whether or not the controlled room temperature drug storage limit has been maintained to ensure drug stability, first became official in the Ninth Supplement of the United States Pharmacopeia-National Formulary on November 15, 1993. The calculations involved may appear lengthy, and their mathematic solutions are presented in this article. Also included is a short history on the development of the Arrhenius equation, which is the basis for "mean kinetic temperature," and the accomplishments of Dr. Svante August Arrhenius.

Does Your Drug Expertise Include Clinical Pharmaceutics?

Whose job is it to protect patients from harm from drug instabilities and incompatibilities and other aspects of clinical pharmaceutics? Pharmacists are better educated via multiple required general and organic chemistry prerequisite and professional curricula medicinal chemistry and pharmaceutics courses. Therefore, no healthcare professional other than pharmacists are nicknamed drug experts or are better formally educated to master drug chemistry in the bottle (i.e., injection stability and compatibility/incompatibility clinical pharmaceutics) as a prerequisite for drug administration to cause safe and effective drug chemistry in the body (i.e., clinical pharmacokinetics and pharmacology). To be a patient's last chance for safe and effective drug therapy requires terminal control by pharmacists over identification, retrieval, preparation, labeling, and counseling or instruction of drug therapy.

Atrial Fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human adult left atrial appendages.

Atrial Fibrillation (AF), the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS) have identified that the single nucleotide polymorphisms (SNPs) most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

United States Parmacopeia Chapter <797> timeline: 1989 to 2013.

This article features a tabular chronology of events deemed relevant to the creation and revision of United States Pharmacopeia General Chapter <797> Pharmaceutical Compounding--Sterile Preparations, which premiered in 2004.

Weighted gene coexpression network analysis of human left atrial tissue identifies gene modules associated with atrial fibrillation.

BACKGROUND: Genetic mechanisms of atrial fibrillation (AF) remain incompletely understood. Previous differential expression studies in AF were limited by small sample size and provided limited understanding of global gene networks, prompting the need for larger-scale, network-based analyses. METHODS AND RESULTS: Left atrial tissues from Cleveland Clinic patients who underwent cardiac surgery were assayed using Illumina Human HT-12 mRNA microarrays. The data set included 3 groups based on cardiovascular comorbidities: mitral valve (MV) disease without coronary artery disease (n=64), coronary artery disease without MV disease (n=57), and lone AF (n=35). Weighted gene coexpression network analysis was performed in the MV group to detect modules of correlated genes. Module preservation was assessed in the other 2 groups. Module eigengenes were regressed on AF severity or atrial rhythm at surgery. Modules whose eigengenes correlated with either AF phenotype were analyzed for gene content. A total of 14 modules were detected in the MV group; all were preserved in the other 2 groups. One module (124 genes) was associated with AF severity and atrial rhythm across all groups. Its top hub gene, RCAN1, is implicated in calcineurin-dependent signaling and cardiac hypertrophy. Another module (679 genes) was associated with atrial rhythm in the MV and coronary artery disease groups. It was enriched with cell signaling genes and contained cardiovascular developmental genes including TBX5. CONCLUSIONS: Our network-based approach found 2 modules strongly associated with AF. Further analysis of these modules may yield insight into AF pathogenesis by providing novel targets for functional studies.

The ps in therapeutics.

The decline of ps (pharmaceutical sciences) content and emphasis, especially pharmaceutics in pharmacy education, has been followed by pharmacy practice journals since the final BS to PharmD degree transition of 1990-2000. The particular deficit of drug compatibility, compounding, packaging, reactivity, solubility, stability and storage instruction, and information was a major impetus for the 1996 premier of the International journal of pharmaceutical compounding and the 2011 introduction of the Science and technology for the hospital pharmacist electronic newsletter. The four ps examples provided in this article to corroborate the introduction to Vol. 1, No. 2 of the Science and technology for the hospital pharmacist, which featured Dr. Richard Penna's prudent reflection that biological, chemical, and physical ps facts and knowledge are vital to patient care.

Maillard reactions in pharmaceutical formulations and human health.

This article reviews pharmaceutical and health implications of the nonenzymatic Maillard reaction, also referred to as browning or N-glycation. The spontaneous Maillard reaction between reducing sugars and amines was first reported by French scientist Louis Maillard in 1912; the Maillard reaction may also occur with other drugs. Hemoglobin A1c and chemically complex colored products that follow initial dextrose and amino acids adducts in parenteral nutrition solutions are the advanced maillard products most familiar to pharmacists.

Calcium and phosphate compatibility in low-osmolarity parenteral nutrition admixtures intended for peripheral vein administration.

BACKGROUND: Precipitation of calcium (Ca) and phosphate (P) salts can lead to potentially lethal outcomes, especially in low-osmolarity parenteral nutrition (LO-PN) formulations. Three concentrations of amino acids (AA) and 2 concentrations of calcium gluconate and sodium phosphate injections on the compatibility of Ca and P in LO-PN admixtures were studied. METHODS: Final AA concentrations of 1%, 2%, or 3% (n = 3) and 5% glucose (G) were prepared with either 2.5 or 5 mmol/L (5 or 10 mEq) of Ca (n = 2) and 15 or 30 mmol/L of P (n = 2) for a total of 12 base (3 x 2 x 2) formulations. Triplicate bags of each were analyzed for subvisible micro-precipitates using the light obscuration (or extinction) method for particle counts per milliliter (PC) in the size range of 1.8-50 mum at 7 time intervals over 48 hours stored at 30 degrees C +/- 0.2 degrees C. Visual evaluation was performed using a high-intensity lamp against a black background for detection of macro-precipitates. The pH of all 36 admixtures was measured at 0 and 48 hours. Any precipitated material was isolated and characterized by polarized light microscopy and infrared spectroscopy. RESULTS: Of the 12 base LO-PN formulations tested, those containing 1% and 2% AA with 5 mmol/L of Ca and 30 mmol/L of P showed significant increases in PC, and some resulted in visible dibasic calcium phosphate precipitation. Analyses of variance based on concentrations of AA, Ca, P, and time were highly significant independent variables for increases in the PC of potentially embolic particles, that is, sizes >5 mum (P < .0001). The lowest concentrations of Ca and P, 2.5 and 15 mmol/L, respectively, had significantly lower PC (P < .05) for all sizes compared with the other Ca and P combinations. CONCLUSIONS: LO-PN admixtures (AA

Drug incompatibility chemistry.

PURPOSE: The chemical interactions that cause drug incompatibility in solutions, with emphasis on the acid-base and ionized-nonionized forms of organic, weak, electrolyte drugs, are examined. SUMMARY: When the dilution or mixing of the salt or ionized forms of organic drugs results in precipitation, the most likely cause is formation of the nonionized drug forms. More than 90% of drugs are organic, weak electrolytes, especially those compounded, manufactured, or reconstituted as injections in predominantly ionized or salt forms. Acid-base reactions are the most common causes of drug incompatibility as precipitation of nonionized drug forms. Precipitation is likely when oppositely charged, organic drug ions that contain aromatic rings are combined in relatively strong concentrations. Salts of polyvalent anions and cations are generally less soluble than salts in which both ions are monovalent or in which one ion is monovalent and its opposite ion is polyvalent. The most clinically important potential precipitates among these ions are dibasic and monohydrogen calcium phosphate. CONCLUSION: Incompatibility of drug and nutrient injections is clinically hazardous. Knowledge of products' chemical facts, organic acid-base equilibria in relation to ionization and nonionization and aqueous solubility, and ranges of pH and ingredient strength from United States Pharmacopeia monographs and product labeling is the foundation of expertise in drug incompatibility. Precipitation in injectable drug solutions should be suspected, particularly when oppositely charged drug salts are mixed in relatively strong concentrations and when pH values of dilutions create more than 1% of nonionized drug forms.

The NAPLEX: evolution, purpose, scope, and educational implications.

Since 2004, passing the North American Pharmacist Licensure Examination (NAPLEX) has been a requirement for earning initial pharmacy licensure in all 50 United States. The creation and evolution from 1952-2005 of the particular pharmacy competency testing areas and quantities of questions are described for the former paper-and-pencil National Association of Boards of Pharmacy Licensure Examination (NABPLEX) and the current candidate-specific computer adaptive NAPLEX pharmacy licensure examinations. A 40% increase in the weighting of NAPLEX Blueprint Area 2 in May 2005, compared to that in the preceding 1997-2005 Blueprint, has implications for candidates' NAPLEX performance and associated curricular content and instruction. New pharmacy graduates' scores on the NAPLEX are neither intended nor validated to serve as a criterion for assessing or judging the quality or effectiveness of pharmacy curricula and instruction. The newest cycle of NAPLEX Blueprint revision, a continual process to ensure representation of nationwide contemporary practice, began in early 2008. It may take up to 2 years, including surveying several thousand national pharmacists, to complete.

Basics of compounding: United States pharmacapeia general chapter 797 pharmaceutical compounding-sterile preparations, part 10: first revision: the main changes, events, and rationale.

From 2005 to 2007, the United States Pharmacopeia's Sterile Compounding Committee revolutionized sterile preparation practices with a thorough revision to a monumental standard. By revising United States Pharmacopeia General Chapter 797, they defined safe procedures for compounded sterile preparations in profound detail. From proper hygiene to air quality control, the revised Chapter 797 aims to reduce complications related to treatment with compounded sterile preparations, offers invaluable information to those involved in the compounding process, and establishes standards to improve the quality of the compounding process. The vast intellect, innovative review process, and dedicated research incorporated into this revision have assisted those involved with compounding pharmacy around the world.