3.1. Sex Difference
By analyzing CBD plasma concentrations at the first measurement timepoint, after 2.5 weeks of CBD consumption, it was observed that CBD concentrations were higher in men than in women. As time progressed, and after repeated higher doses at the next timepoint (after 5 weeks), the concentration of CBD was higher in women than in men. Broadly consistent with these observations, in their rat study, Child and Tallon found that after 28 days of taking CBD, CThe results of our study show that after stopping CBD intake and a two-week washout, CBD concentrations in female subjects remained significantly higher. More females than males tested positive for circulating CBD after the washout and 2.5 weeks of consuming the placebo capsules. Five weeks after taking the placebo, no men tested positively. In all subjects, at all examined timepoints, the presence of 7-COOH-CBD metabolites was significantly higher in women compared to men. Differences in concentration in favor of women may be due to their higher fat content compared to men. Due to its high lipophilicity, CBD disperses more readily in a lipophilic environment and is subsequently partly deposited, which affects cumulative concentration and slows elimination. According to Review by Millar et al. [Knaub et al. reported that healthy female volunteers may achieve higher CBD concentrations than healthy male volunteers, depending on the CBD formulation ingested [A statistical correlation was observed with the percentage of body fat in the subjects. After 5 weeks of CBD ingestion, male individuals had a negative correlation, while females after washout had a positive correlation. According to the results of our study, the values of body fat percentage of female subjects were significantly higher compared to men, while at the same time, the percentages of muscle tissue and water were significantly lower. This likely explains the difference in the higher plasma CBD concentrations achieved at the later measurement timepoints. The findings of the study by Child and Tallon, which was carried out on rats (groups of six males and six females) over the course of 28 days, demonstrated that CBD accumulated in the tissues that were examined, including fat, muscle, and the liver, with a suggestion that higher values were found in adipose tissue and in female rats [There has been a lot of research in recent years on the pharmacokinetics and pharmacodynamics of CBD and the differences between the sexes, but the studies were either acute, did not involve many subjects of either sex, or were not conducted on humans [Our findings revealed that the presence of CBD in the plasma was evident in female participants 50 days after the last intake of CBD preparations. The difference in fat tissue between men and women is likely the reason for such findings. The fat tissue content of our study participants differed significantly in favor of women. It was 74% higher. Child and Tallon’s research on rats of both sexes, showed significant changes in concentrations related to the time of the measurements [In our previous study [