Impact of marijuana smoking on liver and sex hormones: Correlation with oxidative stress

Abstract: In recent years, there has been a dramatic increase in the number of marijuana users. Also, in the past two decades it was found that cannabinoids present in marijuana exert their biological effects via cannabinoids receptors CB1 and CB2. Such receptors act as crucial mediators in a variety of pathophysiological conditions including liver. This is because, a three-fold increase in CB1 receptors on isolated vascular endothelial cells was detected in cirrhotic human livers. Moreover, the liver plays a major role in the catabolism of the steroid hormones. Therefore, the aim of this study was to determine whether marijuana smoking can participates in liver damage and, therefore, in sex hormones abnormalities and/or oxidative stress, or not. In this study a group of marijuana smokers (n=90) with no history of liver diseases in addition to 25 of the healthy individuals with matched age and sex to that of the smoker group. In sera of marijuana smokers, the mean GGT activity was 86.6% higher than that of the control group and that of alkaline phosphatase (ALP) was 121.7% higher than that of the nonsmokers,group. In addition, the total bile acids, which were synthesized from cholesterol in the liver, as well as the acetyl cholinesterase (AChE) activity were 39.2% higher and 11.3% lower than those of the corresponding control values, respectively. However the mean nitric oxide level was dramatically increased in sera of marijuana smokers (210.8%), the C-reactive protein level was only 40 % higher in sera of marijuana smokers compared with those of the control group. Also, the mean SGPT activity was 19.4 % and that of bilirubin level was 39.1 % higher in sera of the smoker group than those of the healthy control group. With respect to the effect of the marijuana smoke on testosterone and its trophic pituitary hormone; luteinizing hormone, their levels were lowered by not less than 48.7% and 14.5% compared to those ofthe healthy control group, respectively. Moreover, the markers of the oxidative stress; namely glutathione (GSH),the total antioxidants capacity (TAC) and malondialdehyde (MDA), the first two were significantly reduced and the latter was elevated compared with those of the control group. Finally, negative correlations were found between testosterone and ALP, GGT and NO with a stronger negative correlation between the latter and testosterone. On the other hand, positive correlations were found between NO and both GGT and ALP with the strongest one between the latter and NO. Also, a positive correlation was found between GGT and ALP. These negative and positive correlations may lead one to conclude that marijuana smoke may participate in both liver and testicular damage via NO and its related radicals-dependent mechanisms