The in vitro effect of delta-9-tetrahydrocannabinol and cannabidiol on whole blood viscosity, elasticity and membrane integrity

Abstract

Background The main biological activities of cannabis are due to the presence of several compounds known as cannabinoids. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are two of the main cannabinoids. Studies have shown that the effects of THC can be modulated by CBD. Objective This study aims to look at the effect of different concentrations of THC and CBD separately and in combination, on blood viscosity, elasticity and membrane integrity. Methods Blood samples were collected from twenty-four healthy adult non-smokers. Blood viscosity and elasticity were determined using the Vilastic Scientific Bioprofiler for different concentrations (0, 2.5, 25, 50 and 100 ng/ml) of CBD and THC respectively, as well as in extracts with combinations of CBD and THC in 4:1 and 1:1 ratios respectively. Repeated measures analysis of variance (ANOVA) was used to determine the difference between the means of the groups. Results Blood viscosity increased significantly with increasing concentrations of both THC and CBD from 25 ng/ml up to 100 ng/ml ranging from 6.45 ± 0.36 mPa·s to 11.60 ± 1.12 mPa·s for THC and ranging from 5.46 ± 0.24 mPa·s to 9.91 ± 1.10 mPa·s for CBD respectively, being more pronounced in the extracts at 21.33 ± 2.17 mPa·s for the 4THC:1CBD extract and 21.76 ± 1.88 mPa·s for the 1THC:1CBD extract. There was no significant increase in elasticity for THC and CBD separately. However, a significant increase in elasticity was observed in the extracts. THC and CBD affected red cell morphology resulting in complete disintegration at the highest concentrations. Conclusions THC and CBD increased red blood cell viscosity and elasticity separately and in combination. They also adversely affected membrane integrity.

Effects of cannabinoids on ligand-gated ion channels

“…From this aspect, it appears that alone or the combination of two mechanisms can describe the lipophilic actions of cannabinoids ( Oz, 2006 ; Oz et al, 2014 ; Ghovanloo and Ruben, 2021 ). First, cannabinoids, like other lipophilic molecules, partition into the lipid bilayer and alter the biophysical properties of the membrane by reducing membrane electrical resistance ( Bach et al, 1976 ), increasing membrane fluidity ( Hillard et al, 1985 ; Mavromoustakos et al, 2001 ; Dainese et al, 2012 ), changing membrane order ( Bloom et al, 1997 ), increasing membrane stiffness ( Ghovanloo et al, 2021 ; Ghovanloo and Ruben, 2021 ), increasing membrane elasticity ( Medeiros et al, 2017 ; James et al, 2022 ), and changing physicochemical and structural properties of bilayer membranes ( Makriyannis et al, 1990 ; Yang et al, 1992 ; Ambrosi et al, 2005 ; Tiburu et al, 2007 ; Tian et al, 2011 ). Secondly, cannabinoids can bind directly to transmembrane domains of ion channels embedded in the cell membrane ( Xiong et al, 2011a ; Xiong et al, 2012b ; Lu et al, 2018 ; Ghovanloo et al, 2021 ).…”

Cannabidiol (CBD) Upregulates Vitamin D3 Receptors (VDRs) Expression That Modulates Cytokines (TNF-α, IL-6), Tissue Elasticity, Cellular Senescence, and Mitochondrial ATP Generation in Human and Rodent Cell Lines

“…Another in vitro experiment reported that CBD extract in combination with THC significantly increased the elasticity of blood cells ie, RBC morphology and membrane integrity. 2 Moreover, clinical trial data had shown that topical application of CBD-enriched ointment without THC significantly improved skin elasticity. 23 Our results showed that CBD significantly improved elasticity in rat cardiomyoblast cell line (H9C2) at various concentrations.…”

“…One of the clinical trial data reported that CBD increased red blood cell viscosity and elasticity. 2 CBD has potent anti-inflammatory, 3 immunomodulatory, and analgesic effects through activating cannabinoid-1 and − 2 (CB1 and CB2) receptors. CBD treatment also reduced the production of cytokines in an animal model of chronic asthma, inflammatory lung diseases, etc.…”