Please use this link to access this publication. Abstract Rationale Adaptive alteration of dopamine (DA) system in mesocorticolimbic circuits is an extremely intricate and dynamic process, which contributes to maintaining methamphetamine (METH)-related disorders. There are no approved pharmacotherapies for METH-related disorders. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, has received attention for its therapeutic potential in treating METH-related disorders. However, the major research obstacles of CBD are the yet to be clarified mechanisms behind its therapeutic potential. Recent evidence showed that DA system may be active target of CBD. CBD could be a promising dopaminergic medication for METH-related disorders. Objectives We investigated the...

Abstract Objective To estimate the timing of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]) onset, we conducted a post hoc analysis of GWPCARE6 (NCT02544763), a randomized, placebo-controlled, phase 3 trial in patients with drug-resistant epilepsy associated with tuberous sclerosis complex (TSC). Methods Patients received plant-derived pharmaceutical formulation of highly purified CBD (Epidiolex; 100 mg/ml oral solution) at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or placebo for 16 weeks (4-week titration, 12-week maintenance). Treatment started at 5 mg/kg/day for all groups and reached 25 mg/kg/day on Day 9 and 50 mg/kg/day on Day 29. Percentage change from baseline in TSC-associated seizure (countable focal or generalized) count was calculated...

Abstract Purpose Since the passage of the Agricultural Improvement Act of 2018, hand surgeons have increasingly encountered patients seeking counseling on over-the-counter, topical cannabidiol (CBD) for the treatment of pain. To this end, we designed a human clinical trial to investigate the therapeutic potential of CBD for the treatment of pain associated with thumb basal joint arthritis. Methods Following Food and Drug Administration and institutional approval, a phase 1 skin test was completed with 10 healthy participants monitored for 1 week after twice-daily application of 1 mL of topical CBD (6.2 mg/mL) with shea butter. After no adverse events were identified, we proceeded with a phase 2, double-blinded, randomized controlled trial....

Abstract Cannabidiol (CBD) has been suggested as a potential therapy for inflammatory and fibrotic diseases. Cannabidiol was demonstrated to reduce alcohol-induced liver inflammation and steatosis but its specific activity on the fibrotic process was not investigated. Herein, the antifibrotic effects of cannabidiol in the skin were analysed in vitro using NIH-3T3 fibroblasts and human dermal fibroblasts and in vivo using the bleomycin-induced model of skin fibrosis. In a second model, non-alcoholic liver fibrosis was induced in mice by CCl4 exposure. Cannabidiol was administered daily, intraperitoneally in mice challenged with bleomycin and orally in CCl4 mice, and skin and liver fibrosis and inflammation were assessed by immunochemistry. Cannabidiol inhibited collagen gene...

Please use this link to access this publication. Abstract Objective To evaluate the anti-inflammatory and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol (CBD). Design The cellular bioactivities of hemp extract and CBD were determined the inhibition of TNF-α and IL-1β in LPS-induced murine macrophage (RAW 264.7) cells by using ELISA while wound healing activity in human gingival fibroblast (HGF-1) cells was performed by a scratch test assay. The cytotoxicity was also concerned and evaluated by MTT assay. Results The hemp extract and CBD significantly decreased TNF-α release by up to 91.05 ± 2.91% and 50.78 ± 7.21% of LPS activity, respectively, in a dose-dependent manner, compared to 10 µg/mL hydrocortisone (61.67 ± 3.79%)....

Please use this link to access this publication. Abstract Women present increased susceptibility to anxiety- and stress-related disorders compared to men. A potentially promising pharmacological-based strategy to regulate abnormal aversive memories disrupts their reconsolidation stage after reactivation and destabilization. Male rodent findings indicate that cannabidiol (CBD), a relatively safe and effective treatment for several mental health conditions, can impair the reconsolidation of aversive memories. However, whether and how CBD influences it in females is still unknown. The present study addressed this question in contextually fear-conditioned female rats. We report that systemically administered CBD impaired their reconsolidation, reducing freezing expression for over a week. This action was restricted...

Please use this link to access this publication. Abstract Introduction: Cannabinoid hyperemesis syndrome (CHS) is characterized by intense nausea and vomiting brought on by the use of high-dose Δ9-tetrahydrocannabinol (THC), the main psychotropic compound in cannabis. Cannabidiol (CBD), a nonpsychotropic compound found in cannabis, has been shown to interfere with some acute aversive effects of THC. In this study, we evaluated if CBD would interfere with THC-induced nausea through a 5-HT1A receptor mechanism as it has been shown to interfere with nausea produced by lithium chloride (LiCl). Since CHS has been attributed to a dysregulated stress response, we also evaluated if CBD would interfere with THC-induced...

Abstract Candida albicans is a common fungal pathogen. Biofilm formation on various surfaces is an important determinant of C. albicans pathogenicity. Our previous results demonstrated the high potential of cannabidiol (CBD) to affect C. albicans biofilms. Based on these data, we investigated the possibility of incorporating CBD and/or triclosan (an antimicrobial agent that is widely utilized in dentistry) in a sustained-release varnish (SRV) (SRV-CBD, SRV-triclosan) to increase their pharmaceutical potential against C. albicans biofilm, as well as that of the mixture of the agents into SRV (SRV-CBD/triclosan). The study was conducted in a plastic model, on agar, and in an ex vivo tooth model. Our results demonstrated strong antibiofilm activity of...

Abstract The PINK1/Parkin pathway plays an important role in maintaining a healthy pool of mitochondria. Activation of this pathway can lead to apoptosis, mitophagy, or mitochondrial-derived vesicle formation, depending on the nature of mitochondrial damage. The signaling by which PINK/Parkin activation leads to these different mitochondrial outcomes remains understudied. Here we present evidence that cannabidiol (CBD) activates the PINK1-Parkin pathway in a unique manner. CBD stimulates PINK1-dependent Parkin mitochondrial recruitment similarly to other well-studied Parkin activators but with a distinctive shift in the temporal dynamics and mitochondrial fates. The mitochondrial permeability transition pore inhibitor cyclosporine A exclusively diminished the CBD-induced PINK1/Parkin activation and its associated mitochondrial effects. Unexpectedly, CBD treatment also...

Abstract Accumulating data from both human and animal studies suggest that cannabidiol (CBD) may be associated with improved cardiovascular function, markedly with regard to reduction in blood pressure and improved endothelial function. However, there is a lack of randomized studies to support these notions, especially in at-risk populations. The principal aim of this randomized, placebo-controlled, and crossover study is to examine the influence of chronic CBD administration on 24-h blood pressure in individuals with mild or moderate hypertension who are either untreated or receiving standard care therapy. The secondary aims of the study are to determine the safety and tolerability of 5 weeks of...