ThePineapple - Journal Club #42: Mood, Arthritis, Pharmacology, Sepsis

Journal Club #42: Mood, Arthritis, Pharmacology, Sepsis

Week of 05-15-22

Sundays mean journal clubs at thepineapple. That means you can start the week with some freshly squeezed science. Here are four papers that might pique your interest. This week we have 2 clinical trials. One on the effects of cannabis and alcohol on mood and cognitive performance and another on the efficacy of using CBD as a treatment for osteoarthritis and psoriatic arthritis (spoiler alert, CBD did not mitigate pain). Then there is a review on the pharmacological effects of cannabidiol on transient receptor potential channels and a research paper on CD4+ T-Cell derived CB2 signaling in the context of sepsis.

Separate and combined effects of alcohol and cannabis on mood, subjective experience, cognition and psychomotor performance: A randomized trial. 

Wickens C, Wright M, Mann RE, Brands B, Di Ciano P, Stoduto G, Fares A, Matheson J, George TP, Rehm J, Shuper PA, Sproule B, Samohkvalov A, Huestis MA, Le Foll B.

Prog Neuropsychopharmacol Biol Psychiatry. 2022 May 9:110570. 

Co-use of alcohol and cannabis is associated with increased frequency and intensity of use and related problems. This study examined acute effects of alcohol and cannabis on mood, subjective experience, cognition, and psychomotor performance. Twenty-eight healthy cannabis users aged 19-29 years with recent history of binge drinking completed this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial. Participants received: placebo alcohol and placebo cannabis (<0.1% THC); alcohol (target breath alcohol content [BrAC] 80 mg/dL) and placebo cannabis; placebo alcohol and active cannabis (12.5% THC); and active alcohol and cannabis over four sessions. Profile of Mood States (POMS), Addiction Research Centre Inventory (ARCI), verbal free recall (VFR), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), and grooved pegboard (GPB) task were administered before and approximately 75 min after drinking alcohol (1 h after smoking cannabis ad libitum). Significant effects of condition were found for the POMS (Tension-Anxiety, Confusion) and ARCI (MBG, LSD, PCAG, Euphoria, Sedation), predominantly with greater increases emerging after cannabis or alcohol-cannabis combined relative to placebo. Significant effects were found for VFR (immediate total and delayed recall, percent retained), DSST (trials attempted, trials correct, reaction time), and GPB (non-dominant hand) predominantly with greater declines in performance after alcohol and alcohol-cannabis combined relative to placebo and/or cannabis. Cannabis appeared to affect mood and subjective experience, with minimal impact on cognitive performance. Alcohol appeared to impair cognitive and psychomotor performance, with minimal impact on mood and subjective experience. Acute effects of alcohol and cannabis combined were additive at most.

doi: 10.1016/j.pnpbp.2022.110570. Epub ahead of print. PMID: 35551928.

Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial. 

Vela J, Dreyer L, Petersen KK, Arendt-Nielsen L, Duch KS, Kristensen S. 

Pain. 2022 Jun 1;163(6):1206-1214. 

Cannabidiol (CBD) is increasingly used as analgesic medication although the recent International Association for the Study of Pain Presidential Task Force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. This trial examines CBD as add-on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized, double-blind, placebo-controlled design, patients received synthetic CBD 20 to 30 mg or placebo daily for 12 weeks. The primary outcome was pain intensity during the past 24 hours (0-100 mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale (PCS), and Health Assessment Questionnaire Disability Index. One hundred thirty-six patients were randomized, of which 129 were included in the primary analysis. Between-group difference in pain intensity at 12 weeks was 0.23 mm (95% confidence interval -9.41 to 9.90; P = 0.96). Twenty-two percent patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30 mm. We found neither clinically nor statistically significant effects of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared with placebo. In addition, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.

doi: 10.1097/j.pain.0000000000002466. Epub 2021 Aug 27. PMID: 34510141.

Pharmacological effects of cannabidiol by transient receptor potential channels. 

Etemad L, Karimi G, Alavi MS, Roohbakhsh A.

Life Sci. 2022 Jul 1;300:120582. 

Cannabidiol (CBD), as a major phytocannabinoid of Cannabis sativa, has emerged as a promising natural compound in the treatment of diseases. Its diverse pharmacological effects with limited side effects have promoted researchers to pursue new therapeutic applications. It has little affinity for classical cannabinoid receptors (CB1 and CB2). Considering this and its diverse pharmacological effects, it is logical to set up studies for finding its putative potential targets other than CB1 and CB2. A class of ion channels, namely transient potential channels (TRP), has been identified during two recent decades. More than 30 members of this family have been studied, so far. They mediate diverse physiological functions and are associated with various pathological conditions. Some have been recognized as key targets for natural compounds such as capsaicin, menthol, and CBD. Studies show that CBD has agonistic effects for TRPV1-4 and TRPA1 channels with antagonistic effects on the TRPM8 channel. In this article, we reviewed the recent findings considering the interaction of CBD with these channels. The review indicated that TRP channels mediate, at least in part, the effects of CBD on seizure, inflammation, cancer, pain, acne, and vasorelaxation. This highlights the role of TRP channels in CBD-mediated effects, and binding to these channels may justify part of its paradoxical effects in comparison to classical phytocannabinoids.

doi: 10.1016/j.lfs.2022.120582. Epub 2022 Apr 26. PMID: 35483477.

Activation of CD4+ T Cell-Derived Cannabinoid Receptor 2 Signaling Exacerbates Sepsis via Inhibiting IL-10.

Chen J, Wang F, Zhang S, Lin Q, Xu H, Zhu T, Peng L, Cen F, Li F, Wang Z, Feng CG, Yin Z, Liu Y, Zhang G. 

J Immunol. 2022 May 9:ji2101015. 

The cannabinoid receptor 2 (CB2) is a receptor mainly expressed in immune cells and believed to be immunosuppressive in infective or inflammatory models. However, its role in sepsis has not been fully elucidated. In this study, we delineate the function and mechanism of CB2 in the cecal ligation and puncture-induced septic model in mice. The activation of CB2 signaling with HU308 led to decreased survival rates and more severe lung injury in septic mice, and lower IL-10 levels in peritoneal lavage fluid were observed in the CB2 agonist group. The mice with conditional knockout of CB2-encoding gene CNR2 in CD4+ T cells (CD4 Cre CNR2fl/fl) improved survival, enhanced IL-10 production, and ameliorated pulmonary damage in the sepsis model after CB2 activation. In addition, double-knockout of the CNR2 gene (Lyz2 Cre CD4 Cre CNR2fl/fl) decreased the susceptibility to sepsis compared with Lyz2 Cre CNR2fl/fl mice. Mechanistically, the blockade of IL-10 with the anti-IL-10 Ab abolished its protection in CD4 Cre CNR2fl/fl mice. In accordance with the animal study, in vitro results revealed that the lack of CNR2 in CD4+ cells elevated IL-10 production, and CB2 activation inhibited CD4+ T cell-derived IL-10 production. Furthermore, in the clinical environment, septic patients expressed enhanced CB2 mRNA levels compared with healthy donors in PBMCs, and their CB2 expression was inversely correlated with IL-10. These results suggested that the activation of CD4+ T cell-derived CB2 increased susceptibility to sepsis through inhibiting IL-10 production.

doi: 10.4049/jimmunol.2101015. Epub ahead of print. PMID: 35534212.