Long-Term, Self-Dosing CBD Users: Indications, Dosage, and Self-Perceptions on General Health/Symptoms and Drug Use

Introduction: Self-dosing of off-the-shelf cannabidiol (CBD) for a myriad of health conditions is common in the USA. These CBD products are often mislabeled, suggesting that much less or much more CBD is being consumed than indicated on the label. This study examined the relationship between long-term self-dosing of CBD and (a) indications and, when a verified concentration of CBD is being consumed, (b) the daily CBD dosage, (c) the impact on general health and symptoms, and (d) over-the-counter (OTC) and prescription (Rx) drug usage. Methods: US adults 18–75 years of age who had used unverified CBD products for >1 month were recruited to participate in this decentralized, observational, IRB-approved study and provided a concentration-verified CBD product of their choice from 15 different vendors for 4 weeks. Prior to receiving product, they were queried on their primary reason for use (PRfU), primary symptom for use (PSfU), general health score (GHS), symptom score (SS), OTC and Rx drug use, and daily CBD dose. Individuals were queried daily on OTC and Rx drug use and CBD dose and weekly on SS and GHS prior to (pre-CBD) and after (post-CBD) ingestion of CBD on that day. Results: The PRfU included chronic pain, mental health, general health and wellness, sleep disorders, the central nervous system, digestive health, and others, while the PSfU included anxiety, back and/or joint pain, sleep, inflammation, and others. The mean daily dose was normally distributed, with a mean, median, and range of 53.1, 40.8, 8–390 mg/day, respectively. For both GHS and SS, the post-CBD was significantly higher than the pre-CBD score for each category of PRfU. The GHS scores did not change over the study, but pre- and post-CBD SS improved over time, with pre-improving more than post-CBD SS. The percentage of individuals decreasing or completely stopping OTC drugs or Rx drugs over the 4 weeks was 31.2% and 19.2%, respectively, with those taking CBD for chronic pain, decreasing drug use the most. OTC and Rx drug usage decreased when the CBD dose was changed and when GHS and SS improved. Conclusion: Pain, mental health (primarily anxiety/stress), and sleep are the most common reasons for CBD use. Self-administration of CBD reduced OTC and Rx drug usage at daily doses less than those reported in controlled studies. CBD self-administration significantly improves self-perception of general health and decreases symptom severity, and as these improve, fewer OTC and Rx drugs are used

Randomized, Phase II Trial of Pemetrexed and Carboplatin with or without Enzastaurin versus Docetaxel and Carboplatin as First-Line Treatment of Patients with Stage IIIB/IV Non-small Cell Lung Cancer

Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-β) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer.Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP).Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia.There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin

The Effects of Long-Term Self-Dosing of Cannabidiol on Drowsiness, Testosterone Levels, and Liver Function

Introduction: Previous research indicated that cannabidiol (CBD) may result in low levels of male total testosterone (TT), elevations in liver tests (LTs), and daytime drowsiness (DD). We investigated the prevalences of TT and LT in a large adult sample self-administering CBD and determined the effect self-dosing of CBD has on the severity of DD. Methods: Adult participants (18–75 years of age) who self-dose CBD orally for a minimum of 30 days were recruited for this decentralized observational study from companies that offer CBD products. Participants were sent their usual CBD regimen. A clinical study platform was used on a phone app to obtain consent and collect study data. Data included demographic information, reasons for self-dosing, dosage, current medications and dosage, medical history, adverse effects, effects on DD, and efficacy. After 30 days, LT and TT were obtained and follow-up LT was offered to participants who demonstrated elevated values of alanine transaminase (ALT). Results: A total of 28,121 individuals were contacted, 1,475 met the criteria and were enrolled, and 1,061 (female: 65.2%, male: 34.8%) completed the study. Most of the participants used full-spectrum CBD oil or CBD isolate with the mean ± SD daily dose of CBD for all users of 55.4 ± 37.8 mg. CBD use was associated with a significant decrease in DD and a decrease in the prevalence of low TT in males >40 years of age. The prevalences of elevations in ALT and aspartate aminotransferase were not significantly different from those of the general adult population, and the prevalences of elevated levels of alkaline phosphatase and bilirubin were less than those of a healthy adult population. There was no relationship between LT and CBD dose. Conclusions: In this large-sample study, self-dosing CBD was not associated with an increased prevalence of elevation of LT or low levels of TT in men. Furthermore, CBD administration decreased DD and was associated with a lower prevalence of low testosterone levels in older men as compared to age-adjusted population norms

Reovirus-Induced Alterations in Gene Expression Related to Cell Cycle Regulation

Mammalian reovirus infection results in perturbation of host cell cycle progression. Since reovirus infection is known to activate cellular transcription factors, we investigated alterations in cell cycle-related gene expression following HEK293 cell infection by using the Affymetrix U95A microarray. Serotype 3 reovirus infection results in differential expression of 10 genes classified as encoding proteins that function at the G(1)-to-S transition, 11 genes classified as encoding proteins that function at G(2)-to-M transition, and 4 genes classified as encoding proteins that function at the mitotic spindle checkpoint. Serotype 1 reovirus infection results in differential expression of four genes classified as encoding proteins that function at the G(1)-to-S transition and three genes classified as encoding proteins that function at G(2)-to-M transition but does not alter any genes classified as encoding proteins that function at the mitotic spindle checkpoint. We have previously shown that serotype 3, but not serotype 1, reovirus infection induces a G(2)-to-M transition arrest resulting from an inhibition of cdc2 kinase activity. Of the differentially expressed genes encoding proteins regulating the G(2)-to-M transition, chk1, wee1, and GADD45 are known to inhibit cdc2 kinase activity. A hypothetical model describing serotype 3 reovirus-induced inhibition of cdc2 kinase is presented, and reovirus-induced perturbations of the G(1)-to-S, G(2)-to-M, and mitotic spindle checkpoints are discussed