Background Current arthritis treatments often have side-effects attributable to active compounds as well as route of administration. Cannabidiol (CBD) attenuates inflammation and pain without side-effects, but CBD is hydrophobic and has poor oral bioavailability. Topical drug application avoids gastrointestinal administration, first pass metabolism, providing more constant plasma levels. Methods This study examined efficacy of transdermal CBD for reduction in inflammation and pain, assessing any adverse effects in a rat complete Freund’s adjuvant-induced monoarthritic knee joint model. CBD gels (0.6, 3.1, 6.2 or 62.3 mg/day) were applied for 4 consecutive days after arthritis induction. Joint circumference and immune cell invasion in histological sections were measured to indicate level of inflammation. Paw withdrawal latency (PWL) in response to noxious heat stimulation determined nociceptive sensitization, and exploratory behaviour ascertained animal’s activity level. Results Measurement of plasma CBD concentration provided by transdermal absorption revealed linearity with 0.6–6.2 mg/day doses. Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner. PWL recovered to near baseline level. Immunohistochemical analysis of spinal cord (CGRP, OX42) and dorsal root ganglia (TNFα) revealed dose-dependent reductions of pro-inflammatory biomarkers. Results showed 6.2 and 62 mg/day were effective doses. Exploratory behaviour was not altered by CBD indicating limited effect on higher brain function. Conclusions These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects.

Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa, has received attention for therapeutic potential in treating neurologic and psychiatric disorders. Recently, CBD has also been explored for potential in treating drug addiction. Substance use disorders are chronically relapsing conditions and relapse risk persists for multiple reasons including craving induced by drug contexts, susceptibility to stress, elevated anxiety, and impaired impulse control. Here, we evaluated the "anti-relapse" potential of a transdermal CBD preparation in animal models of drug seeking, anxiety and impulsivity. Rats with alcohol or cocaine self-administration histories received transdermal CBD at 24 h intervals for 7 days and were tested for context and stress-induced reinstatement, as well as experimental anxiety on the elevated plus maze. Effects on impulsive behavior were established using a delay-discounting task following recovery from a 7-day dependence-inducing alcohol intoxication regimen. CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history. The results provide proof of principle supporting potential of CBD in relapse prevention along two dimensions: beneficial actions across several vulnerability states and long-lasting effects with only brief treatment. The findings also inform the ongoing medical marijuana debate concerning medical benefits of non-psychoactive cannabinoids and their promise for development and use as therapeutics.

Carbon nanotube (CNT) membranes were employed as the active element of a switchable transdermal drug delivery device that can facilitate more effective treatments of drug abuse and addiction. Due to the dramatically fast flow through CNT cores, high charge density, and small pore dimensions, highly efficient electrophoretic pumping through functionalized CNT membrane was achieved. These membranes were integrated with a nicotine formulation to obtain switchable transdermal nicotine delivery rates on human skin (in vitro) and are consistent with a Fickian diffusion in series model. The transdermal nicotine delivery device was able to successfully switch between high (1.3 AE 0.65 μmol∕hr-cm 2 ) and low (0.33 AE 0.22 μmol∕hr-cm 2 ) fluxes that coincide with therapeutic demand levels for nicotine cessation treatment. These highly energy efficient programmable devices with minimal skin irritation and no skin barrier disruption would open an avenue for single application long-wear patches for therapies that require variable or programmable delivery rates.electroosmosis | electrophoresis | smoking cessation | medical device

The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.

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This study evaluated the effects of dietary vitamin A and E on the in vitro capacity of blood mononuclear leukocytes from calves to produce nitric oxide. Calves fed milk replacer received 100 IU/d of vitamin E as RRR-alpha-tocopherol or RRR-alpha-tocopheryl acetate and 0, 1700, 34,000, or 68,000 IU of vitamin A as retinyl acetate. Leukocytes from calves produced greater amounts of nitric oxide relative to leukocytes from adult cattle. The greater production of nitric oxide by calf leukocytes may be typical of the immature neonatal immune system. Nitric oxide production by calves fed RRR-alpha-tocopherol and either 1700 or 34,000 IU of vitamin A was less than that of calves in other groups and was more typical of production by leukocytes from cows. Our data suggest that optimal amounts of dietary vitamins A and E prompt the maturation of this response toward one that is more typical of adult cattle. Leukocytes from 1-wk-old calves produced less nitric oxide and were less responsive to stimuli than were leukocytes from older calves, a possible consequence of suppressive factors that were present in the ingested colostrum or in the circulation at birth.

The purpose of this study was to quantify the in-vitro human skin transdermal flux of Delta8-tetrahydrocannabinol (Delta8-THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of Delta8-THC and CBD. Tissue concentrations of Delta8-THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for Delta8-THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates.

Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p = 0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/d). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p < 0.05), while IP CBD resulted in a 50.6% (p < 0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.