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.
In recent years, there has been an increased availability of cannabis products in Europe, despite strict regulations. Numerous manufacturers of niche products promote cannabidiol (CBD) and Cannabis ...sativa (C. sativa) as ingredients, often in ambiguous ways leading to consumer confusion. The aim of this study was to analyze a diverse range of foods, food supplements, health related products and other consumer products (e.g. vapes) associated with C. sativa/CBD in order to determine whether the declared and promised ingredients are present in the products and how these comply to current legal regulations. We have established a HPLC-UV method to quantify the most important cannabinoids, namely the legally important THC and THCA, and the CBD/CBDA. All of the 35 analyzed products met the legally required limit for THC/THCA. A total of 27 of the samples explicitly listed CBD contents. In 33% of the samples, the analyzed value matched the content given on the label, 26% exceeded the declared CBD content, while 41% contained lower amounts. CBD products with an unclear or not defined CBD content, were mostly below the limit of detection (LoD). Products promising “full spectrum C. sativa extracts” were further screened by GC-MS method to detect additional naturally-occurring cannabinoids, to verify the use of C. sativa plant material/extracts as the source of CBD. No further cannabinoids could be detected in one out of eight products claiming the use of C. sativa extracts.
This study shows, that this niche market is still a constantly evolving product sector, depending on the type and origin of the products, there may be significant discrepancies between the marketing and the actual ingredients contained, making the market less transparent for consumers.
•An HPLC-UV method was established to quantify THC, THCA, CBD, and CBDA.•C. sativa related products were analyzed and relevant cannabinoids quantified.•Comparison of declared and analyzed CBD contents showed larger discrepancies.•“Full spectrum” products were verified using an additional GC-MS approach.
Cannabidiol (CBD) is considered a non‐psychoactive, antioxidant, and anti‐inflammatory compound derived from the Cannabis sativa plant. There are various reports on the versatile function of CBD, ...including ameliorating chronic inflammation and fibrosis formation in several tissue types. However, only a hand full of studies have proposed or provided a molecular justification for the beneficial properties of this Phyto‐compound. This review focused on the anti‐inflammation and anti‐fibrotic effects of CBD based on modulating the associated chemokines/cytokines and receptor‐mediated pathways. We also highlighted the regulatory impact of CBD on reactive oxygen species (ROS) producing‐NADPH oxidase (Nox), and ROS scavenging‐superoxide dismutase (SOD) enzymes. Although CBD has a low affinity to Cannabinoid receptors 1 and 2 (CB1 and CB2), we reported on the activation of these receptors by other CBD analogs, and CBD on non‐CBD receptors. CBD downregulates pro‐inflammatory and pro‐fibrotic chemokines/cytokines by acting as direct or indirect agonists of Adenosine A2A/equilibrative nucleoside transporter receptors, Peroxisome proliferator‐activated receptor gamma, and Transient receptor potential vanilloid receptors or channels, and as an antagonist of GPR55 receptors. CBD also caused the reduction and enhancement of the ROS producing, Nox and ROS‐scavenging, SOD enzyme activities, respectively. This review thus recommends the continued study of CBD's molecular mechanism in treating established and emerging inflammatory and fibrosis‐related diseases.
Knowledge about the therapeutic potential of medical cannabis has greatly improved over the past decade, with an ever-increasing range of developments in human clinical applications. A growing body ...of scientific evidence supports the use of medical cannabis products for some therapeutic indications, whilst for others, the evidence base remains disputed. For this narrative review, we incorporate areas where the current evidence base is substantial, such as intractable childhood epilepsy and multiple sclerosis, as well as areas where the evidence is still controversial, such as PTSD and anxiety.
We provide a high-level summary of current developments using findings from recent major reviews, as well as real world evidence (RWE), including global database registries and other patient reported outcomes (PROs). On the one hand, our strongest empirical data supports the use of cannabis-based medicinal products (CBMPs) for conditions with relatively small patient numbers. Yet on the other hand, the conditions, where the highest patient numbers present, often have debatable clinical evidence but good RWE, incorporating PROs of 1000s of patients.
The discord between PROs and the respective strength of the evidence from randomised controlled trials (RCTs) highlights the urgent need for further research. The scientific literature examining the efficacy of medical cannabis for many conditions is still developing, whilst large numbers of patients globally have been successfully using medical cannabis to treat a broad range of conditions. We conclude on the importance of systematically developing RWE databases to supplement RCTs and to bridge the current evidence gaps.
•Improved knowledge about cannabis based medicinal products (CBMPs) is widening the range of human clinical applications.•Some of the conditions for which CBMPs are used are well established by now, while other areas remain controversial.•The strongest empirical data supports the use of CBMPs for conditions with relatively small patient numbers.•The conditions with the highest patient numbers often have debatable clinical evidence but good Real World Evidence (RWE).•Discords between RWE and the strength of evidence from randomised controlled trials (RCTs) highlight the need for further research.
Cannabinoids in dermatologic surgery Kong, Ha Eun; Pollack, Brian P.; Blalock, Travis W.
Journal of the American Academy of Dermatology,
December 2021, 2021-12-00, 20211201, Volume:
85, Issue:
6
Journal Article
Peer reviewed
Though known as a medicinal herb for centuries, the recent legalization of cannabinoids across many states has ushered in a new era where cannabinoids have become a popular treatment option among ...clinicians and patients alike. Cannabinoids have demonstrated efficacy in wound healing, reducing inflammation, ameliorating pain, and have shown potential as an antitumor agent. As a result, cannabinoids have been rapidly woven into the fabric of modern medicine. However, the utility of cannabinoids in dermatologic surgery has not been explored to date. In this article, we review the current literature to discuss the potential impact of cannabinoid use in dermatologic surgery.
The social push for the therapeutic use of cannabis extracts has increased significantly over recent years. Cannabis is being used for treatment for conditions such as epilepsy, cancer and pain ...management. There are a range of medicinal cannabis products available, but the use of cannabis resin obtained by super critical fluid extraction, often diluted in oil, is becoming increasingly more prominent. Much of the research on cannabis has focused on plant biomass or the final therapeutic product with a concerning lack of information on the intermediate resin. This study aims to bridge the gap between current methods of analysis for biomass and the final therapeutic product by describing a fully developed and validated ultra-high-performance-liquid-chromatography method with diode array detection (UHPLC-DAD) for the qualification and quantification of the cannabinoids CBDA, CBD, CBN, THC, CBC and THCA, in medicinal cannabis biomass and resin obtained by super-critical fluid extraction (SFE). The method was validated for specificity, linearity, limit of detection (LOD), limit of quantitation (LOQ), precision, accuracy, robustness, spike recovery and stability in accordance with the Validation of Analytical Procedures: Text and Methodology Q2 to meet the requirements of the International Council for Harmonisation (ICH), Therapeutic Goods Authority (TGA) and the Food and Drug Administration (FDA) test method validation regulations.
•A UHPLC-UV method for cannabinoids in plant and resin has been validated.•Method surpasses the requirements of the ICH and FDA regulations for an API.•Simple extraction process improves current methods removing hazardous chemicals.•Method is ideal for sample analysis in a GMP environment.•Low cost and superior reproducibility make PDA ideal for routine analysis.
Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These ...pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America's (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.
A novel approach for rapid (15s) detection and quantification of predominant cannabinoids in hemp was developed using Fourier-transformed near-infrared spectroscopy (FT-NIR), enabling real-time and ...field-based applications. Hemp samples (n = 91) were obtained from certified online vendors, the OARDC Weed Lab, and a local Ohio farm. Reference data of major cannabinoids content were determined by uHPLC-MS/MS. Spectral data were collected by a miniaturized, battery-operated FT-NIR instrument, and combined with the reference data to generate partial least squares regression (PLSR) models. uHPLC-MS/MS analysis showed two samples had over 0.36% of Δ9-tetrahydrocannabinol (Δ9-THC), and 64% (32 out of 50) of online-bought hemp samples were not in compliance with their total cannabidiol (CBD) content declaration. PLSR prediction models showed excellent correlation (Rpre = 0.91–0.95) and a low standard error of prediction (SEP = 0.02–0.61%). This method could be used as an alternative to traditional methods for in-situ assessment of hemp quality.
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•A novel designed handheld FT-NIR sensor allowed for the rapid screening of cannabinoid content in hemp.•From 50 online-bought hemp samples, 32 samples were not in compliance with their total CBD content declaration.•A rotating sample stage was engineered in the novel sensor to enable spatial averaging over a variety of angles for heterogeneous plant samples while the spectral acquisition.•Alternative method to time-consuming traditional testing for in-situ assessment of hemp quality.
•Many patients (37%) utilized emergency healthcare services (EHS) after cannabidiol (CBD) initiation.•There were no significant differences in discontinuation rates between age groups.•Close ...monitoring should occur within the first 4 months to optimize treatment.
This study evaluated prescription cannabidiol (CBD) outcomes during the first 12 months of therapy.
A single-center, prospective cohort study was performed including patients prescribed CBD from January 2019 - April 2020, excluding clinical trial patients and those using external specialty pharmacy services. The primary outcome wasepilepsy-related emergency healthcare service (EHS) use within 12 months of initation. Secondary outcomes included prescription CBD discontinuation rate and reason and concomitant anti-seizure medication (ASM) use. A multiple logistic regression model evaluated the odds of EHS use, adjusting for initial concomitant ASM count, age, and insurance type.
The 136 patients included were 85% white, 50% female, and 68% pediatric. EHS utilization occurred in 37% (n = 50) of patients; 29 patients (21%, n = 20 pediatric, n = 9 adult) had at least one emergency department (ED) visit, 9 patients (7%) had two or more; 30 patients (22%, n = 22 pediatric, n = 8 adult) had at least one hospitalizaion. Median time to first ED and hospitalization was 69 (IQR 31–196) and 104 (IQR 38–179) days, respectively. Prescription CBD was discontinued in 31 patients (23%, n = 18 pediatric, n = 13 adult), due to major side effects (n = 12, 39%), common side effects (n = 11, 36%), and unsatisfactory response (n = 11, 36%). There was no significant change in concomitant ASM use.
Despite potential benefits of prescription CBD, many patients utilize EHSs in the first 12 months of treatment with minimal changes in concomitant ASM use.
The majority of states have fully legalized the use of medical cannabis (MC), and nearly all other states allow limited access to cannabidiol (CBD), a non-intoxicating constituent of cannabis often ...touted for a range of therapeutic indications. Further, the Agricultural Improvement Act of 2018 legalized hemp-derived products in all 50 states; typically high in CBD, these products are derived from cannabis varieties containing ≤0.3% delta-9-tetrahydrocannabinol (THC) by weight. The recent "green rush" has resulted in a striking increase in cannabis use among patients and consumers who often use a wide variety of novel product types, each with a unique blend of cannabinoid constituents. Importantly, however, several cannabinoids have the potential to cause drug-drug interactions (DDI) with other medications, primarily due to their involvement with the hepatic cytochrome P450 (CYP450) system. This article examines the potential for individual cannabinoids, particularly CBD, to interact with the hepatic metabolic system, which is concerning given its involvement in the metabolism of commonly-prescribed medications. CBD and other cannabinoids are metabolized extensively by the CYP450 system, and also inhibit many of these enzymes, potentially leading to variable serum levels of other medications, as well as variable levels of cannabinoids when other medications modify the system. As access and interest in cannabinoid-based products continues to increase, critical questions remain unanswered regarding their safety. The complex relationship between cannabinoids and the hepatic metabolic system, including common potential DDI resulting from cannabinoid exposure, are explored along with the clinical significance of these potential interactions and monitoring or mitigation strategies.
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