Increased Pulmonary Function Following Administration of a CBD‐Containing Compound NCMB‐1 in Fibrotic Lungs of African Green Monkeys.

Abstract

The endocannabinoid system is a neuromodulatory system that is conserved among vertebrate species. Cannabidiol (CBD) is a modulator of cannabinoid (CB) receptor action both in the central nervous system and in the periphery. CB receptors are involved in inflammatory responses in peripheral organs, including lung tissue. CBD administration has been shown to reduce airway inflammation and fibrosis in vitro and in experimentally induced rodent models of asthma through modulation of the immune system. However, little is understood regarding the relationship between pulmonary disease and CBD modulation of general CB receptors in vivo. The African Green Monkey (Chlorocebus aethiops sabaeus; AGM) has bronchiolar tissue and tracheal branching remarkably similar to that in human lungs, therefore making it a translational model for the study of CBD treatment on pulmonary fibrosis‐related lung dysfunction. We hypothesize that administration of NCMB‐1, a hemp extract with CBD, will increase the tidal volume, inspiratory flow rate, and respiration rate of animals with previously induced pulmonary fibrosis. Baseline tidal volume, inspiration flow rate, and respiration rate of 16 male AGM with induced lung fibrosis were measured. Animals were divided into a vehicle and 3 treatment groups: 50 μL of undiluted, 5X dilution, and 25X dilution NCMB‐1 administered orally twice daily via banana sections for two weeks. Compared to control (n=4, 206.6 ± 36.4 mL), 5X NCMB‐1 treated animals increased tidal volume (n=4, 484.0 ± 54.6 mL; p<0.05) from baseline at two weeks of treatment. Inspiratory flow rate also increased in 5X treated animals (n=4, 412.0 ± 49.9 mL/s; p<0.05) compared to control (n=4, 212.3 ± 50.7 mL/s) after two weeks of administration. Respiration rates increased from baseline in 1X treated animals (n=4, 33.0 ± 4.5 breaths/min) and 5X treated animals (n=4, 30.8 ± 3.9 breaths/min) compared to control (n=4, 28.5 ± 4.1 breaths/min; p<0.05). Treatment with 25X dilution of NCMB‐1 did not alter pulmonary function at either one or two weeks of treatment compared to vehicle treated animals. Thus, administration of 5X diluted NCMB‐1 to AGM with induced pulmonary fibrosis increased tidal volume, inspiratory flow rate, and respiration rate from compared to vehicle treated AGM. These results indicate CBD as a potential modulator of CB receptors improving pulmonary function and suggest a potential for therapeutic value of CBD in the treatment of restrictive pulmonary disease. Future directions include identification of active CBD compounds within the extract responsible for changes in airway resistance, expression of specific pulmonary genes involved in reduction of inflammation, and immunohistochemistry of CB receptors in the hypothalamus of AGM with induced pulmonary fibrosis. CBD crossing the blood brain barrier in animals treated with NCMB‐1 may cause up or downregulation of CB1 and/or CB2 receptors that could positively impact lung function.Support or Funding InformationFunding provided by Primates Plus, LLC.