Exploring the Effects of Cannabidiol on Psychological Health, Cognitive Function, Neural Health, and Natural Killer Cells

Cannabidiol (CBD), a non-psychotropic cannabis sativa derivative, is gaining attention as a potential promotor of neurological function and cognitive health and as a potential anti-inflammatory compound, although these claims lack evidence-based support from the scientific community. The purpose of this study was to determine whether 8 weeks of 2 doses, 40 mg (CB40) or 20 mg (CB20), of CBD containing beverages will improve psychological health, cognitive function, neural health as well as NK and NKT cell quantity and NK cell function when compared to a control vehicle beverage (CBDV) and a calorie-matched placebo beverage (PLAC) in a double-blind, randomized, placebo-controlled, 4 arm manner. It was hypothesized that participants consuming CBD will experience improvements in psychological health measured by the generalized anxiety disorder-7 (GAD-7) survey and piper fatigue scale (PFS), improvements in cognitive function measured by PROMIS Cognitive Function and Cognitive Abilities short forms and by the sustained attention to response task (SART), improvements in neural health measured by serum brain derived neurotrophic factor (BDNF), and improved immune function measured by increases in natural killer (NK) and NKT cell proportions of peripheral blood and increased NK cell cytotoxicity determined by measures of K562 human myelogenous leukemia cell viability following an 8-week CBD intervention.

A total of 102 healthy participants were recruited from the University of Northern Colorado and nearby communities and randomly assigned to one of four groups: CB40 (n = 25), CB20 (n = 28), CBDV (n = 24), PLAC (n = 25). Participants consumed their assigned beverage; (CB40; 50 mg/100mL L-Theanine, 2.4 mg/100mL Vitamin E, 42.3 mg/100mL Vitamin C), (CB20; 53 mg/100mL L-Theanine, 2.6 mg/100mL Vitamin E, 44.4 mg/100mL Vitamin C), (CBDV; 51 mg/100mL L-Theanine, 2.5 mg/100mL Vitamin E, 39.6 mg/100mL Vitamin C), or (PLAC; <10 mg/100mL L-Theanine, <LOQ mg/100mL Vitamin E, <LOQ mg/100mL Vitamin C) daily for 8 weeks. Participants completed measures of body size, body composition, psychological health and cognitive function, and a fasted peripheral blood draw at both pre- and post-intervention time points. Isolated serum was used to determine resting concentrations of BDNF, and heparinized whole blood was used to isolate NK and NKT cell proportions of peripheral blood mononuclear cells (PBMC) defined by CD56⁺/CD3^- and CD56⁺/CD3⁺, respectively. NK cell cytotoxic function was further defined by changes in K562 cell median fluorescence intensity and percent compared to control using flow cytometry following a 4-hour co-incubation of PBMC and K562 cells at a 40:1 effector:target (E:T) ratio, respectively. All data are presented as mean ± standard deviation with significance set to α = 0.05. A univariate analysis of variance (ANOVA) was run to assess homogeneity among groups for all outcome measures at the pre-intervention time point, and a 4 (group) x 2 (time) repeated measures ANOVA was used to identify significant interactions and main effects that occurred as a result of the intervention.

There were no significant differences between groups with respect to all study outcomes at the pre-intervention time point. There were significant main effects of time and group*time interactions for all plasma cannabinoid metabolite concentrations such that CB40 and CB20 groups experienced a 66.9 and 120.9 %, a 464 and 173 %, and 505 and 159 % increase in carboxy-CBD, 7-OH-CBD, and CBD concentrations, respectively, when compared to all other groups (p < 0.001). The CB40 group also experienced an 18 % increase in 6-OH-CBD concentrations when compared to CBDV and PLAC groups (p = 0.015). There were significant main effects of time for GAD-7, PFS, and Cognitive Abilities T scores such that overall, GAD-7 scores and PFS scores decreased by 15.55 % and 12.35 %, respectively, and Cognitive Abilities T scores increased by 4.68 % (p = 0.009) from pre- to post-intervention time points. While there were no significant group*time interactions in psychological health and cognitive function parameters between groups throughout the course of this investigation, a moderate effect size was detected with respect to the PROMIS Cognitive Abilities T scores F(3, 78) = 2.28, p = 0.086, ηp² = .08. There were no significant main effects of time or group*time interactions with respect to neural health defined by serum BDNF concentrations between groups throughout the course of this investigation; however, a moderate effect size was detected in treatment F(3, 78) = 2.69, p = 0.052, ηp² = .09, such that the CBDV group experienced a 12.21 % decrease in serum BDNF concentrations, and both CB40 and CB20 groups experienced a 19.22 % and 4.92 % increase in serum BDNF concentrations, respectively. Lastly, there were no significant main effects of time or group*time interactions with respect to NK and NKT cell population proportions, and there were no significant main effects of time or group*time interactions with respect to NK cell cytotoxic function throughout the course of this investigation. These results suggest that eight weeks of 40 mg of CBD or 20 mg of CBD containing beverages significantly increased cannabinoid metabolite concentrations. Additionally, a moderate effect size was detected with respect to measures of subjective cognitive function and serum BDNF concentrations; however, eight weeks of 40 mg of CBD or 20 mg of CBD containing beverages did not significantly improve psychological health, cognitive function measured by the SART, or NK and NKT cell quantity and NK cell function.