INTRODUCTION: The non-intoxicating plant-derived cannabinoid, cannabidiol (CBD), has demonstrated therapeutic potential in a number of clinical conditions. Most successful clinical trials have used relatively high (≥300 mg) oral doses of CBD. Relatively few studies have investigated the efficacy of lower (<300 mg) oral doses, typical of those available in over-the-counter CBD products. METHODS: We present a protocol for a randomised, double-blind, placebo-controlled, parallel-group clinical trial investigating the effects of a low oral dose (150 mg) of CBD on acute psychosocial stress, situational anxiety, motion sickness and cybersickness in healthy individuals. Participants (n=74) will receive 150 mg of CBD or a matched placebo 90 min before completing three virtual reality (VR) challenges (tasks) designed to induce transient stress and motion sickness: (a) a 15 min 'Public Speaking' task; (b) a 5 min 'Walk the Plank' task (above a sheer drop); and (c) a 5 min 'Rollercoaster Ride' task. The primary outcomes will be self-reported stress and nausea measured on 100 mm Visual Analogue Scales. Secondary outcomes will include salivary cortisol concentrations, skin conductance, heart rate and vomiting episodes (if any). Statistical analyses will test the hypothesis that CBD reduces nausea and attenuates subjective, endocrine and physiological responses to stress compared with placebo. This study will indicate whether low-dose oral CBD has positive effects in reducing acute psychosocial stress, situational anxiety, motion sickness and cybersickness. ETHICS AND DISSEMINATION: The University of Sydney Human Research Ethics Committee has granted approval (2023/307, version 1.6, 16 February 2024). Study findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12623000872639).
- MeSH
- dvojitá slepá metoda MeSH
- kanabidiol * terapeutické užití MeSH
- kinetózy * farmakoterapie MeSH
- lidé MeSH
- nauzea farmakoterapie MeSH
- psychický stres MeSH
- randomizované kontrolované studie jako téma MeSH
- úzkost farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
- Geografické názvy
- Austrálie MeSH
Cannabidiol (CBD) is the second most abundant component of the plant Cannabis sativa. Currently, CBD is approved for Lennox-Gastaut and Dravet syndrome and newly for tuberous sclerosis complex. However, based on the available data, CBD migth have a broad spectrum of potential therapeutic uses. Therefore, the aim of this review was to summarize the evidence on the effects of CBD on pain and inflammation of various causes. PubMed and Web of Science databases were searched until January 2023. The medical keyword term "cannabidiol" was combined with "pain", "arthritis", and "inflammation". Based on the initial search for these terms, 9, 5, and 5 relevant publications have been selected. Based on the available data, it is not possible to draw a clear conclusion about the effect of CBD to releave pain, because each study used a different route of administration or treatment regimen. The studies also differed in etiopathogenesis of pain (chronic, neuropathic, and possibly inflammatory pain), and in general included only small number of subjects. In case of anti-inflammatory qualities of CBD, its effect on the intestinal system is negligible. On the other hand, positive treatment results were observed in all publications dealing with the effect of CBD on arthritis.
- MeSH
- artritida * MeSH
- bolest farmakoterapie etiologie MeSH
- epilepsie myoklonické * farmakoterapie MeSH
- kanabidiol * terapeutické užití MeSH
- lidé MeSH
- zánět farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The use of cannabinoids (substances contained specifically in hemp plants) for therapeutic purposes has received increased attention in recent years. Presently, attention is paid to two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). With respect to the psychotropic effects and dependence potential of THC (though it is very mild), its use is associated with certain restrictions, and thus the therapeutic properties of CBD are frequently emphasized because there are no limitations associated with the risk of dependence. Therefore, this review covers the main pharmacodynamic and pharmacokinetic features of CBD (including characteristics of endocannabinoidome) with respect to its possible beneficial effects on selected diseases in clinical practice. A substantial part of the text deals with the main effects of CBD on aging, including Alzheimer's disease and related underlying mechanisms.
Cannabinoids, a class of compounds derived from Cannabis sativa L., have recently become more widely accessible for public consumption in the form of diverse cannabis products, in parallel with weakening the measures that so far restricted their availability. The US Food and Drug Administration has approved several cannabis-derived drugs for management of various diseases as well as chemotherapy-induced nausea and vomiting. Besides the attenuation of adverse effects of chemotherapy, numerous reports about cannabinoid-mediated anticancer effects further motivate cancer patients to support their therapy with such products. Here we present a set of preclinical data with human cell culture models, suggesting that cannabidiol and cannabis extracts may effectively counteract the anticancer effects of the clinically widely used standard-of-care platinum-based drugs. We show that even low concentrations of cannabinoids reduced the toxicity of cisplatin, oxaliplatin, and carboplatin, an effect which was accompanied by decreased platinum adduct formation and a set of commonly used molecular markers. Mechanistically, our results excluded the possibility that the observed enhanced survival of cancer cells was mediated transcriptionally. Instead, trace metal analyses strongly indicate an inhibitory impact of cannabinoids on intracellular platinum accumulation, thereby implicating changes in cellular transport and/or retention of these drugs as the likely cause of the observed biological effects. Our study raises the possibility that the desirable effect of counteracting adverse effects of chemotherapy might, at least for some cannabinoids, reflect impaired cellular availability, and consequently attenuation of the anticancer effects of platinum drugs. DATA AVAILABILITY: All data supporting the conclusions are available in the article and supplementary files. Raw data are available upon request from the corresponding author.
Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is gaining popularity as a supportive therapy during cancer treatment, often in combination with standard-of-care cancer chemotherapeutics. However, CBD is a biologically active substance that modulates various cellular targets, thereby possibly resulting in unpredictable outcomes, especially in combinations with other medications and therapeutic modalities. In this review, we summarize the current knowledge of CBD interactions with selected anticancer chemotherapeutics, discuss the emerging mechanistic basis for the observed biological effects, and highlight both the potential benefits and risks of such combined treatments. Apart from the experimental and preclinical results, we also indicate the planned or ongoing clinical trials aiming to evaluate the impact of CBD combinations in oncology. The results of these and future trials are essential to provide better guidance for oncologists to judge the benefit-versus-risk ratio of these exciting treatment strategies. We hope that our present overview of this rapidly advancing field of biomedicine will inspire more preclinical and clinical studies to further our understanding of the underlying biology and optimize the benefits for cancer patients.
- MeSH
- antitumorózní látky * farmakologie terapeutické užití MeSH
- Cannabis * MeSH
- kanabidiol * farmakologie terapeutické užití MeSH
- kanabinoidy * terapeutické užití MeSH
- lékové interakce MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Disulfiram (DSF), an established alcohol-aversion drug, is a candidate for repurposing in cancer treatment. DSF's antitumor activity is supported by preclinical studies, case reports, and small clinical trials; however, ongoing clinical trials of advanced-stage cancer patients encounter variable results. Here, we show that one reason for the inconsistent clinical effects of DSF may reflect interference by other drugs. Using a high-throughput screening and automated microscopy, we identify cannabidiol, an abundant component of the marijuana plant used by cancer patients to mitigate side effects of chemotherapy, as a likely cause of resistance to DSF. Mechanistically, in cancer cells, cannabidiol triggers the expression of metallothioneins providing protective effects by binding heavy metal-based substances including the bis-diethyldithiocarbamate-copper complex (CuET). CuET is the documented anticancer metabolite of DSF, and we show here that the CuET's anticancer toxicity is effectively neutralized by metallothioneins. Overall, this work highlights an example of undesirable interference between cancer therapy and the concomitant usage of marijuana products. In contrast, we report that insufficiency of metallothioneins sensitizes cancer cells toward CuET, suggesting a potential predictive biomarker for DSF repurposing in oncology.
Cannabidiol (CBD), a non-psychotropic cannabinoid produced by the genus Cannabis, is a phytoceutical that activates the endocannabinoid system (ECS) through binding to CB1 and CB2 receptors. The ECS is involved in cellular homeostasis and regulates metabolic processes in virtually all mammalian tissues. Published studies on CBD focus, inter alia, on its use in prophylaxis and as an anti-inflammatory agent. Here the authors present a critical assessment of the effects of CBD on inflammatory periodontal diseases caused by bacterial virulence factors, and evaluate critically the possible benefits and drawbacks of CBD use in dentistry. Particular attention is paid to the interaction of CBD with microbially colonized oral tissues, the inflammatory response in relation to the immune response, and the destruction/regeneration of hard and soft tissues of the periodontium.
- MeSH
- analgetika MeSH
- kanabidiol * metabolismus farmakologie terapeutické užití MeSH
- kanabinoidy * MeSH
- lidé MeSH
- nemoci parodontu * farmakoterapie MeSH
- receptor kanabinoidní CB1 MeSH
- savci metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
V léčbě epilepsie dospělých lze farmakoterapií kontrolovat záchvaty u 70-80 % pacientů. Novinky lze rozdělit na oblast taktiky léčby, na možnost využít nové léčivé přípravky a případně (precizní) individualizovanou léčbu vzácných geneticky podmíněných epilepsií pomocí tzv. "orphan drugs". Novinky v taktice spočívají v systematickém a pokud možno rychlém otestování vhodných léčivých přípravků v dostatečných dávkách pomocí krátkodobého a dlouhodobého plánu. Ke změně u nás došlo v oblasti záchranné "rescue" medikace registrací bukálního midazolamu. V posledních letech byly v ČR na trh uvedeny nové léčivé přípravky pro přídatnou léčbu fokálních záchvatů (perampanel, brivaracetam), případně i generalizovaných tonicko-klonických záchvatů (perampanel), některé byly registrované jako "orphan drug" (kanabidiol) pro vzácné epilepsie, další byly registrované a jejich uvedení na trh u nás lze do budoucna očekávat (cenobamát).
In adults, 70-80 % of patients with epilepsy can be seizure free with pharmacological treatment. Novel approaches have been adopted in treatment strategies, new drugs have been introduced to the market and individualized precision therapy with a use of "orphan drugs" have been successfully used in few well characterized genetically determined epilepsies. In the treatment strategy, a short - and a long-term plan should be established to test systematically for the efficacy of different drugs. Buccal midazolam has been registered as a "rescue medication ". New drugs have been introduced recently for add-on therapy of focal seizures (perampanel, brivaracetam) or generalized tonic-clonic seizures (perampanel), some has been registered as an "orphan drug"(cannabidiol) for rare epilepsies, some has been registered (cenobamate) and their introduction to the market in the Czech Republic is expected in the future.
- Klíčová slova
- brivaracetam,
- MeSH
- AMPA receptory terapeutické užití MeSH
- antikonvulziva terapeutické užití MeSH
- epilepsie * farmakoterapie MeSH
- genetické nemoci vrozené farmakoterapie MeSH
- kanabidiol terapeutické užití MeSH
- léčivé přípravky MeSH
- léková rezistence MeSH
- lidé MeSH
- pyridony terapeutické užití MeSH
- pyrrolidinony terapeutické užití MeSH
- výroba orphan drugs MeSH
- záchvaty farmakoterapie MeSH
- Check Tag
- lidé MeSH
