An Observational Study of the Application of a Topical Cannabinoid Gel on Sensitive Dry Skin.

Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus, erythema and excoriation. While AD has a multifactorial etiology, neuro-signaling pathways are now recognized to play an essential role in the pathogenesis of AD, particularly pruritus. Neuromodulators, such as topical naltrexone, are being utilized in AD treatment. Another class of neuromodulator, Palmitoylethanolamide (PEA), has demonstrated effectiveness in the treatment of itch, excoriation and erythema in AD patients. Phytocannabinoids including cannabidiol (CBD) are becoming increasingly accessible to the public and continue to be advertised for their efficacy to treat inflammatory skin disorders such as eczema. However, no human studies have been conducted to support the claim. Therefore, this study aimed to explore the effects of CBD in individuals with self-reported eczema. Twenty individuals consented to participate and 16 completed a 28-item online questionnaire assessing subjects’ disease severity using Patient Oriented Eczema Measure (POEM) and psychosocial burden of their disease through the emotional domain of Quality of Life Hand Eczema Questionnaire (QOLHEQ). Findings demonstrated a significant reduction in the mean score of POEM from baseline (mean ±SE: 16±1.35) and at a two weeks interval (8.25 ±1.80), P<0.0007. Similar reduction was seen in emotional domain of QOLHEQ from a mean score of 20.9±2.06 to 8.375 ±1.609 at 2 week-interval, P<0.004. 67% of subjects reported a decrease in itch and 50% perceived an improvement in their eczema by more than 60%. This observational study shed light on the potential clinical utility of topical CBD in the treatment of atopic dermatitis. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5464.

A randomized, double-blind, placebo-controlled, repeated-dose pilot study of the safety, tolerability, and preliminary effects of a cannabidiol (CBD)- and cannabigerol (CBG)-based beverage powder to support recovery from delayed onset muscle soreness (DOMS).

BACKGROUND: Cannabinoid-containing products are marketed to athletes as promoting recovery, in spite of a lack of data on their safety and effects. This randomized, double-blind, placebo-controlled, repeated-dose pilot study tested the safety, tolerability, and preliminary effects on recovery of a formulation containing cannabidiol (CBD; 35 mg), cannabigerol (CBG; 50 mg), beta caryophyllene (BCP; 25 mg), branched-chain amino acids (BCAAs; 3.8 g), and magnesium citrate (420 mg). METHODS: Exercise-trained individuals (N = 40) underwent an experimental induction of delayed onset muscle soreness (DOMS) and completed follow-up visits 24-, 48-, and 72-hours post-DOMS. Participants were randomized to active or placebo formulation, and consumed the formulation twice per day for 3.5 days. RESULTS: There was one adverse event (AE) in the active group (diarrhea) and two AEs in placebo (dry mouth; eye rash/swollen eye). There was 100% self-reported compliance with formulation consumption across the two groups. For the primary outcome of interest, the estimate of effect for ratings of average soreness/discomfort 72 hours post-DOMS between active and placebo groups was -1.33 (85% confidence interval = -2.55, -0.10), suggesting moderate evidence of a treatment difference. The estimate of effect for the outcome of ratings of interference of soreness, discomfort, or stiffness on daily activities at work or home 48 hours post-DOMS was -1.82 (95% confidence interval = -3.64, -0.01), indicating a treatment difference of potential clinical importance. There was no significant effect between active and placebo groups on objective measures of recovery, sleep quality, or mood disturbance. CONCLUSIONS: The tested formulation reduced interference of DOMS on daily activities, demonstrating its improvement on a functional aspect of recovery.

Anti-inflammatory Effect of Cannabidiol and Palmitoylethanolamide Containing Topical Formulation on Skin in a 12- O -Tetradecanoylphorbol-13-Acetate-Induced Dermatitis Model in Mice.

BACKGROUND: Chronic inflammatory skin disorders, such as atopic dermatitis, have significant disease burden worldwide. Although efficacious, the adverse effect profile of topical corticosteroids limits long-term use. As an alternative, cannabinoids have been shown to have anti-inflammatory therapeutic effects. OBJECTIVE: The aim of this study was to assess the effects of a topical cannabinoid product using dermatitis mouse model. METHODS: Thirty-five mice were randomized into treatment groups. 12- O -tetradecanoylphorbol-13-acetate was used as an irritant on 1 ear with the contralateral ear serving as a control. Ear edema was calipered. The test product containing 0.9% cannabidiol and palmitoylethanolamide was compared with a potent topical corticosteroid. RESULTS: Treatment with topical cannabinoid formulation reduced ear edema by 51.27% at 24 hours' and 65.69% at 48 hours' postapplication. Alternatively, mometasone reduced ear edema by 89.82% at 24 hours and 98.25% at 48 hours. Natural reduction (control) in ear edema was 26.32% at 24 hours and 44.21% at 48 hours. Both test groups resulted in significantly decreased edema when compared with baseline ( P < 0.05), as well as compared with the negative control group ( P < 0.05). CONCLUSIONS: Significant reduction in ear edema, a marker for localized cutaneous inflammation, could be attributed to anti-inflammatory properties of cannabinoids. Although effects were less robust than topical corticosteroid use, cannabinoid formulations have therapeutic promise for dermatitis.

Serum Markers of Bone Turnover Following Controlled Administration of Two Medical Cannabis Products in Healthy Adults.

Introduction: Cannabidiol (CBD) has been shown to maintain bone integrity in pre-clinical models, but little is known about the effects of delta-9-tetrahydrocannabinol (THC) on bone turnover. In this study we explored the effects of two oral medical cannabis products on normal bone homeostasis through evaluation of markers of bone resorption (carboxyl-terminal collagen crosslinks, CTx) and bone formation (procollagen type 1 N-terminal propeptide, P1NP; alkaline phosphatase, ALP). Methods: This study is an analysis of secondary data from two Phase 1 double-blind, placebo-controlled trials of Spectrum Yellow (0.9 mg THC, 20 mg CBD/mL of oil) and Spectrum Red (2.5 mg THC, 0.3 mg CBD/softgel). Healthy participants (n=38 men, 45 women) were randomized to receive 5-20 mg THC (CBD levels varied as a function of administered product) or placebo daily (BID) for 7 days. Bone markers were assessed at baseline, upon completion of product administration (day 8), and after a 5-day washout (day 13). Results: All bone markers were significantly higher in men at baseline (p≤0.008). For CTx, there was a significant day×group interaction (F=3.23, p=0.04); CTx levels were significantly lower in participants treated with Spectrum Red (b=-164.28; 95% confidence interval [CI], -328 to -0.29; p=0.04) and marginally lower in participants treated with Spectrum Yellow (b=-157.31; 95% CI, -323 to 8.68; p=0.06) versus placebo on day 8. For P1NP and ALP, there were no significant differences between treatments across study days. Bone marker values outside the reference range (RR) were observed; CTx > RR (n=71) was predominantly (85.9%) observed in male participants, whereas P1NP > RR (n=100) was more evenly distributed between sexes (53.0% in men). These were not considered clinically significant and did not differ between treatment groups. Conclusions: These are the first interventional human data on the effect of cannabinoids on biomarkers of bone turnover. Short-term treatment with CBD- or THC-dominant medical cannabis products resulted in attenuation of a marker of bone resorption. Although the attenuation was not clinically significant, this finding may be indicative of protective properties of cannabinoids in bone. Further research over longer dosing durations in individuals exhibiting bone-specific conditions (e.g., osteoporosis) is warranted. ClinicalTrials.gov IDs: ACTRN12619001723178 and ACTRN12619001450101.

Involvement of Sensory Regions in Affective Experience: A Meta-Analysis.

A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area, and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory, and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.