This review aims to present completed clinical trial data surrounding the medicinal benefits and potential side effects of the increasingly popular cannabidiol (CBD)-based drug products, specifically Epidiolex. The article is divided into two sections based on if the ailment being treated by this cannabinoid is classified as either physiological or neurological conditions. In addition to describing the current status, we also examined the different primary and secondary outcomes recorded for each study, which varies greatly depending on the funding source of the clinical trial. With the recent FDA-approval of Epidiolex, this review mainly focused on trials involving this specific formulation since it is the only CBD-based drug currently available to clinicians, although all other clinically trialed CBD(A) drugs were also examined. We hope this review will help guide future research and clinical trials by providing the various outcomes measured in a single review.

For nearly a century, Cannabis has been stigmatized and criminalized across the globe, but in recent years, there has been a growing interest in Cannabis due to the therapeutic potential of phytocannabinoids. With this emerging interest in Cannabis, concerns have arisen about the possible contaminations of hemp with pesticides, heavy metals, microbial pathogens, and carcinogenic compounds during the cultivation, manufacturing, and packaging processes. This is of particular concern for those turning to Cannabis for medicinal purposes, especially those with compromised immune systems. This review aims to provide types of contaminants and examples of Cannabis contamination using case studies that elucidate the medical consequences consumers risk when using adulterated Cannabis products. Thus, it is imperative to develop universal standards for cultivation and testing of products to protect those who consume Cannabis.

The opioid crisis is a pressing public health issue, exacerbated by the emergence of more potent synthetic opioids, particularly fentanyl and its analogs. While competitive antagonists exist, their efficacy against synthetic opioids is largely unknown. Furthermore, due to the short durations of action of current antagonists, renarcotization remains a concern. In this study, metabolic activity was characterized for fentanyl‐class opioids and common opioid antagonists using multiple in vitro systems, namely, cytochrome P450 (CYP) enzymes and hepatic spheroids, after which an in vitro ‐ in vivo correlation was applied to convert in vitro metabolic activity to predictive in vivo intrinsic clearance. For all substrates, intrinsic hepatic metabolism was higher than the composite of CYP activities, due to fundamental differences between whole cells and single enzymatic reactions. Of the CYP isozymes investigated, 3A4 yielded the highest absolute and relative metabolism across all substrates, with largely negligible contributions from 2D6 and 2C19. Comparative analysis highlighted elevated lipophilicity and diminished CYP3A4 activity as potential considerations for the development of more efficacious opioid antagonists. Finally, antagonists with a high degree of molecular similarity exhibited comparable clearance, providing a basis for structure‐metabolism relationships. Together, these results provide multiple screening criteria for early stage drug discovery involving opioid countermeasures.

Sodium fluoroacetate (1080) is a toxic metabolic poison with no known antidote. Its use is strictly regulated within the United States, but it is commonly used as a pesticide in Australia, Israel, Japan, Mexico, New Zealand, and South Korea. 1080 has been identified as a possible terrorist weapon, and exposure is extremely difficult to diagnose given its overlapping symptoms with other common diseases. An abandoned U.S. patent indicated that methylene blue (MB) could be used as a potential countermeasure to 1080 poisoning when combined with monosodium glutamate (MSG). In this study, MB was used as a stand‐alone treatment to determine if it is capable of rescuing cellular metabolism or decreasing 1080 lethality. Male Sprague‐Dawley rats were exposed to increasing concentrations of 1080 (0.5, 1.1, 2.1, 4.2, and 8.4 mg/kg) based on a LD50 logarithmic scale. A low dose of MB (11 mg/kg) was administered via intraperitoneal injection (i.p.) at 0.5 hr and 2 hr post‐exposure. Euthanasia occurred 24 hours post‐exposure and blood was collected from the descending aorta. Serum was separated after collection and stored at ‐80 °C. Bronchoalveolar lavage fluid (BALF) was also collected from the right lung using phosphate buffered saline (PBS) and then stored at ‐80 °C. Gas chromatography‐mass spectrometry (GCMS) was performed on serum samples to identify potential metabolic compounds of interest. From the GCMS data, L‐carnitine and methylmalonic acid (MMA) were proposed as potential markers of 1080 exposure. To quantitate circulating levels, an L‐carnitine colorimetric/fluorometric assay and a methylmalonic acid enzyme‐linked immunosorbent assay (ELISA) were performed. Based on previous data indicating cardiopulmonary effects of 1080, a high sensitivity rat cardiac troponin‐I ELISA was used to determine cardiac damage, and BALF was tested for the presence of protein and hemoglobin. The coenzyme‐A linked form of MMA is converted into succinyl‐CoA for use in the TCA cycle. MMA levels were relatively low and unchanged across all groups, except for rats receiving a 1.1 mg/kg dose of 1080. L‐carnitine is a compound involved in metabolism via the carnitine shuttle system, and is activated when ATP concentration decreases, allowing transport of fatty acid chains into the mitochondria to help replenish the ATP supply. Carnitine levels varied across the exposure concentrations in the groups treated with MB, but at the 2.1 mg/kg exposure dose, treatment with MB appeared to decrease the amount of circulation carnitine. Hemorrhagic pulmonary edema is a symptom of 1080 poisoning, and MB was able to significantly reduce the presence of hemoglobin in BALF for 0.5, 1.1, and 2.1 mg/kg groups. Treatment with MB was able to shift the LD50 curve of 1080 to 3.29 mg/kg from 2.18 mg/kg, giving a protective ratio of 1.53. MB was also able to increase the probability of survival of animals at the 8.4 mg/kg exposure dose. Overall, while MB has shown some promise as treatment for 1080, further testing is needed to determine how viable it is and identify...