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Case Report: Cannabidiol-Induced Skin Rash: A Case Series and Key Recommendations

Abstract Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four women who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new...
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Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis

Abstract Rationale Delta-9-tetrahydrocannabinol (THC), an active component of cannabis, can cause anxiety in some users during intoxication. Cannabidiol (CBD), another constituent of cannabis, has anxiolytic properties suggesting that cannabis products containing CBD in addition to THC may produce less anxiety than THC-only products. Findings to date around this issue have been inconclusive and could conceivably depend on moderating factors such as baseline anxiety levels in users. Objective The present study examined whether anxiety following single doses of vaporised THC, CBD and THC/CBD might be explained by state and trait anxiety levels at baseline. Methods A placebo-controlled, randomised, within-subjects study including 26 healthy recreational cannabis...
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Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function

Abstract Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m2) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different...
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Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms: an open label study

Abstract In recent years there has been growing interest in the potential benefits of CBD-rich cannabis treatment for children with ASD. Several open label studies and one double-blind placebo-controlled study have reported that CBD-rich cannabis is safe and potentially effective in reducing disruptive behaviors and improving social communication. However, previous studies have mostly based their conclusions on parental reports without the use of standardized clinical assessments. Here, we conducted an open label study to examine the efficacy of 6 months of CBD-rich cannabis treatment in children and adolescents with ASD. Longitudinal changes in social communication abilities and restricted and repetitive behaviors (RRB) were quantified...
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Extracellular vesicles of cannabis with high CBD content induce anticancer signaling in human hepatocellular carcinoma

Abstract Plant-derived extracellular vesicles (EVs) have been the topic of interest in recent years due to their proven therapeutic properties. Intact or manipulated plant EVs have shown antioxidant, anti-inflammatory, and anti-cancerous activities as a result of containing bioactive metabolites and other endogenous molecules. Less is known about the EV efficacy with high levels of bioactive secondary metabolites derived from medicinal or non-edible plants. Numerous data suggest the functionality of Cannabis sativa extract and its phytocannabinoids in cancer treatment. Here, two chemotypes of cannabis with different levels of D-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) were selected. EVs were isolated from each chemotype via differential ultracentrifugation. HPLC analysis was illustrative of...
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Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue

Abstract Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective and antitumor effects. Although oral CBD consumption in humans affords beneficial effects in epileptic and inflammatory states, its pharmacokinetics and subsequent uptake into tissue are largely unknown. This study investigated plasma pharmacokinetics and accumulation of CBD in gastrocnemius muscle, liver and adipose tissue in adult rats following oral gavage. CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group. Pharmacokinetics were assessed on day 1 and day 28 in the...
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New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts

Abstract COVID-19 is caused by the SARS-CoV-2 virus, which enters target cells via interactions with ACE2 and TMPRSS2. Here, we show AKT serine/threonine kinase-dependent epigenetic control of ACE2 and TMPRSS2 expression by high-cannabidiol (CBD) cannabis extracts and their individual components. CBD alone and extracts #1, #5, #7, and #129 downregulated ACE2 and TMPRSS2 in lung fibroblast WI-38 cells through AKT-mediated inhibition. miR-200c-3p and let-7a-5p were two contributing miRNAs in CBD-mediated suppression of ACE2 and TMPRSS2. CBD and terpene PTWT2.2 profoundly inhibited ACE2 and TMPRSS2 expression, both individually and in combination. Extracts #1, #5, #7, and #169 suppressed COX2 expression and remarkably attenuated TNFα/IFNγ-triggered induction...
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Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies

Abstract Objective To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020. Study selection Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for...
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α-Glucosidase inhibitory activity of cannabidiol, tetrahydrocannabinol and standardized cannabinoid extracts from Cannabis sativa

Abstract Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of −7.5 and −6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in...
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Cannabinoids in Late Life Parkinson’s Disease and Dementia: Biological Pathways and Clinical Challenges

Abstract The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of...
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