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Aims: Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of med...

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... Daily cannabidiol doses vary from a few milligrams to grams per day, depending on the clinical indication. A systematic review of clinical studies reported dosing ranging from <1 mg/ kg/day to 50 mg/kg/day [78]. Some clinical studies observed biphasic and inverted U-shaped dose-response curves, influencing the dose administered [79,80]. ...
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Introduction: : In light of the widespread use of non-prescribed and prescribed cannabidiol, the use of cannabidiol with other medications is likely, and this may result in drug interactions. Areas covered: : We aimed to ascertain if clinical guidance could be provided on the dose range at which cannabidiol drug interactions are likely to occur with concurrently prescribed medicines. Literature searches were conducted in Embase, MEDLINE, and PubMed from database inception to January 2022 using Emtree and MeSH terms. Reference list screening yielded further studies. Using currently available data, likely drug interactions of which prescribers of cannabidiol need to be aware, at the doses likely to cause clinically significant interactions, and drug dosing changes that may be needed are highlighted. Expert opinion: : We have provided an overview of evidence-based pharmacokinetic predictions and general guidance about the dose range at which clinically relevant cannabidiol drug interactions are likely. For an individual patient, there are inherent limitations in providing clinical guidance due to gaps in specific drug dose-response data and knowledge of individual pharmacokinetic profiles, including different co-morbidities, and concurrent medicines. Clinician awareness of cannabinoid pharmacology, along with clinical and therapeutic drug monitoring are current best practice approaches to manage cannabinoid drug interactions.
... Previous systematic reviews investigated the dosage [26,27] and adverse effects [28] of CBD in clinical trials. Several systematic reviews focused on THC and CBD in humans [29][30][31][32], only THC in humans [33], cannabinoids in both humans and animals [34], or cannabis in animals only [35,36]. ...
Article
Background: Legislative changes have fueled the global availability of cannabis and cannabis-derived compounds, such as cannabidiol. Little is known about the effectiveness and safety of cannabidiol for treating health conditions other than seizure disorders. Objective: A systematic review of the literature was performed to investigate other health conditions, characteristics of the studied populations, and the effectiveness of cannabidiol in randomized clinical trials. Methods: Seven publication databases were searched from February to March 2021. The inclusion criteria for studies were: (1) utilized a randomized clinical trial design; (2) published in a peer-reviewed journal or thesis/dissertation; (3) published in English; (4) investigated either prescription (i.e., Epidiolex) or non-prescription CBD that was derived from the Cannabis sativa plant with < 3% ∆9-tetrahydrocannabinol; and (5) reported at least one outcome. This review excluded seizure-related disorders as several previous reviews have been done on this topic; it also excluded published protocols, other systematic reviews, or meta-analyses of randomized clinical trials that investigated cannabidiol. Independent reviewing, risk of bias assessment, and data abstraction were performed by two authors. Results: Fifty-eight studies from eight countries were included in this review. Twenty-seven studies (47%) were conducted in healthy populations, 14% were restricted to male individuals (n = 8), and 72% had sample sizes of fewer than 40 participants. Doses of cannabidiol used in these studies ranged from 400 µg to 6000 mg. The effect of cannabidiol on mental health was the most studied topic (53%), which focused mainly on anxiety, psychosis, schizophrenia, and substance use disorders. The remaining studies investigated neurological conditions (19%) and a myriad of other health conditions or outcomes. While cannabidiol appears to be anxiolytic, its effectiveness for other conditions was highly variable. Conclusions: This review highlights the inconsistencies of cannabidiol as a treatment for non-seizure-related health conditions or outcomes. Studies incorporating larger sample sizes in more diverse populations are encouraged. While cannabidiol was generally safe and well tolerated even in high doses among the included studies, clearer dosing guidelines and increased regulation of cannabidiol products are also needed.
... In type II DCs, DMF performed its therapeutic effect via inducing glutathione (GSH) depletion of DCs, followed by increasing the expression of antioxidant hemoxygenase-1 (HO-1) gene and impaired phosphorylation of STAT1 to ameliorate psoriasis and MS (Multiple Sclerosis) [76]. CBD (Cannabidiol), as a wide spectrum of antioxidant and anti-inflammatory modulators, is studied for application in preventing and treating redox imbalance and inflammation-associated diseases [130][131][132]. Indeed, CBD could be considered a potential anti-NETotic factor to inhibit NETosis formation by reducing NADPH oxidase and MPO expression [87]. ...
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Reactive oxygen species (ROS) at supraphysiological concentration have a determinate role in contributing to immuno-metabolic disorders in the epithelial immune microenvironment (EIME) of psoriatic lesions. With an exclusive focus on the gene-oxidative stress environment interaction in the EIME, a comprehensive strategy based on ROS-regulating nanomedicines is greatly anticipated to become the mainstay of anti-psoriasis treatment. This potential therapeutic modality could inhibit the acceleration of psoriasis via remodeling the redox equilibrium and reshaping the EIME. Herein, we present a marked overview of the current progress in the pathomechanisms of psoriasis, with particular concerns on the potential pathogenic role of ROS, which significantly dysregulates redox metabolism of keratinocytes (KCs) and skin-resident or -infiltrating cells. Meanwhile, the emergence of versatile nanomaterial-guided evolution for transdermal drug delivery has been attractive for the percutaneous administration of antipsoriatic therapies in recent years. We emphasize the underlying molecular mechanism of ROS-based nanoreactors for improved therapeutic outcomes against psoriasis and summarize up-to-date progress relating to the advantages and limitations of nanotherapeutic application for transdermal administration, as well as update an insight into potential future directions for nanotherapies in ROS-related skin diseases. Graphical Abstract
... The absence of such assessment leads to missing important information regarding cannabis exposure that could help determine physiological responses to cannabis, including the frequency, quantity, duration, recency, age of initiation, routes of and methods of administration, motives for use, tetrahydrocannabinol (THC) and cannabidiol (CBD) concentrations and ratios, potency, and source of cannabis products. Yet, assessing use characteristics is crucial for anticipating potential cardiovascular risks and planning treatment options for patients who use cannabis since the onset and course of the anticipated cardiovascular effects can vary based on the time, dose, and potency of exposure, as well as the route of administration, formulations, and concurrent drug use [9][10][11][12][13][14][19][20][21][22][23][24][25]. Moreover, substantial interindividual and intraindividual variations in use patterns and exposure make it difficult to anticipate or generalize effects based on a mere positive or negative use status. ...
... CBD dosage ranges for the treatment of anxiety disorders have been reported to be very ample and no standardized dosages currently exist. 27,28 Dosing for this study was individually adapted to each patient based on prior research examining the safety of CBD, considering the limited evidence available on clinical trials in psychiatric populations, 16,28-33 and following MacCallum and Russo's practical considerations; 34 therapy was started at a low dose between 5 and 20 mg per day, divided into two or three oral administrations per day. Afterwards, the dose was slowly increased until beneficial effects were observed in each patient without the appearance of side effects. ...
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Anxiety-related disorders are one of the most common mental health issues worldwide. Mexico has reported an increase in the prevalence of these ailments secondary to the confinement derived from the COVID-19 pandemic. Given the limitations of commonly used treatments for these disorders, a need arises to develop new pharmacological treatments for these patients. This paper has the primary objective of evaluating the efficacy and safety of cannabidiol isolate in drug compounding used as a personalized treatment in patients with anxiety disorders through the presentation of four clinical cases.
... Several systematic reviews indicated that daily doses of CBD were highly variable, for example, between <1 and 50 mg/kg/d and 150-600 mg/d. Thus, it was quite difficult to justify a suitable daily dose [24,[27][28][29]. In a recent phase 1 clinical study of CBD dry powder inhaler, the authors reported a C max of 18.78 ng/mL of CBD [30], and in general the lung drug concentration should be about 100-fold higher than the concentration in the plasma [31]. ...
Article
Cannabidiol (CBD) was formulated as a metered dose inhaler (CBD-MDI) and evaluated in vitro for its efficacy as an inhaled dosage form against inflammation caused by the SARS-CoV-2 virus, lipopolysaccharide (LPS) from Escherichia coli, silica particles, nicotine, and coal tar. A CBD-MDI formulation was prepared with 50 mg of CBD in 10 mL for a CBD dose of 250 μg/puff. The formulation ingredients included CBD, absolute ethanol as a cosolvent, and HFA-134a as the propellant. High aerosol performance of CBD-MDI was obtained with mass median aerodynamic diameter of 1.25 ± 0.01 μm, geometric standard deviation of 1.75 ± 0.00, emitted dose of 244.7 ± 2.1 μg, and fine particle dose of 122.0 ± 1.6 μg). The cytotoxicity and anti-inflammatory effectiveness of CBD-MDI were performed in alveolar macrophage (NR8383) and co-culture of alveolar macrophage (NR8383) and human lung adenocarcinoma (A549) cell line. CBD delivered from an MDI was safe on respiratory cells and did not trigger an immune response in alveolar macrophages. CBD-MDI effectively reduced the generation of cytokines in immune cells treated with viral antigen S-RBD, bacterial antigen LPS, silica particles, and coal tar. The efficacy of CBD-MDI was comparable to budesonide. Furthermore, the findings demonstrated that the use of CBD-MDI was more effective in treatment rather than prevention when inflammation was induced by either a viral or bacterial stimulant.
... Despite the promising hepatoprotective effects of CBD observed in experimental models of CLDs, all available clinical studies on humans evaluating the therapeutic effect of CBD on liver-metabolism disorders, such as diabetes, did not confirm any therapeutic benefits of CBD (Table 2) [35,36]. A phase II randomized controlled trial comparing daily CBD (200/400/800 mg) intake for 8 weeks with a placebo in people with steatosis (n = 25) did not show a significant reduction in the hepatic fat accumulation, total serum cholesterol, or total serum triglycerides compared with the placebo group, even at a high dose (800 mg) [36,122]. In another pilot clinical trial, where CBD (100 mg) was administrated twice daily, alone or in combination with THCV (5 mg) (total doses: CBD: 200 mg; THCV: 10 mg) in diabetic patients, no significant changes in the direct hepatic triglyceride levels, total serum cholesterol, or total serum triglycerides emerged. ...
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Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.
... Cannabidiol (CBD) is an active compound found in the cannabis plant (FDA, 2020a) and is most commonly promoted online as a remedy for anxiety and physical pain (Tran & Kavuluru, 2020). It also has promising potential for anti-inflammatory effects and has shown positive results in treating schizophrenia and social anxiety disorder (Burstein, 2015;Millar et al., 2019). CBD is a cannabinoid system modulator (Darkovska-Serafimovska et al., 2018) and differs from delta-9-tetrahydrocannabinol (THC) in that it does not produce intoxication (Burstein, 2015). ...
... Because of the wide dosage variance in unregulated CBD products, it is difficult to research and predict the effects. In a review of clinical studies, the therapeutic window appears to be wide, but phase III trials have not been conducted to provide conclusive evidence (Millar et al., 2019). ...
... In a survey of 878 fibromyalgia patients, the reported average dose of CBD was 16-27 mg/day, although 1/3 did not know the daily amount of CBD used [43]. Millar et al. investigated doses of CBD administered as an oral solution, capsule, or sublingual spray in various clinical populations with 35 included studies, with most studies reporting doses ranging from ˂1 to 20 mg/kg/ day [47]. Most higher doses were used in neurological conditions (e.g., Dravet Syndrome), with higher doses typically unaffordable for off-label use. ...
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Purpose of Review This review will address the many uncertainties surrounding the medical use of cannabidiol (CBD). We will begin with an overview of the legal and commercial environment, examine recent preclinical and clinical evidence on CBD, explore questions concerning CBD raised by healthcare professionals and patients, investigate dosing regimens and methods of administration, and address current challenges in the accumulation of sound evidence. Recent Findings CBD has potential for relief of symptoms of pain, sleep, and mood disturbance in rheumatology patients, but sound clinical evidence is lacking. CBD is safe when accessed from a regulated source, whereas wellness products are less reliable regarding content and contaminants. Dosing for symptom relief has not yet been established. Summary As many rheumatology patients are trying CBD as a self-management strategy, the healthcare community must urgently accrue sound evidence for effect.
... CBD dominant products can be used at higher concentrations than THC products because they produce fewer adverse effects. Doses of CBD between 1 and 50 mg/kg/ day improve psychotic symptoms, seizures, and anxiety [29]. An average CBD dose of 15 mg/kg/day showed positive significant reductions of seizure while CBD between 150 and 600 mg/day produced therapeutic effects in social anxiety disorder and insomnia. ...
Chapter
Cannabis medicines are in demand from the public for treating a range of diseases and symptoms; however, clinicians are reluctant to prescribe these products because of limited evidence and prescribing information. To generate this evidence , quality clinical trials of cannabis medicines must be undertaken, yet their design is a complex, often uncharted territory, and involves the cooperation and sharing of knowledge of multiple stakeholders. Before designing a clinical trial, researchers require a clear understanding of the potential therapeutic benefit cannabis medicines may have, the form and formulation of the product, and the dose to be investigated. Researchers must also be aware of the applicable pharmaceutical regulations in the country or jurisdiction where the research is to be undertaken, as well as manufacturing or licensing regulations that may be imposed at the source of the cannabis product. Importantly, collaborations with industry are a key to the successful outcome of cannabis medicines clinical trials. Without funding and sponsorship of clinical trials, the ability to generate quality data will be limited and the evidence for cannabis medicines to be registered as therapeutics lacking. Collaborations between researchers, industry, and regulators, working together in sharing knowledge, are therefore critical to generate high quality cannabis medicines research.