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Human & Experimental Toxicology Human & Experimental Toxicology http://het.sagepub.com/ Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students Mona EL−Gohary and Manal A Eid Hum Exp Toxicol 2004 23: 149 DOI: 10.1191/0960327104ht426oa The online version of this article can be found at: http://het.sagepub.com/content/23/3/149 Published by: http://www.sagepublications.com Additional services and information for Human & Experimental Toxicology can be found at: Email Alerts: http://het.sagepub.com/cgi/alerts Subscriptions: http://het.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav Citations: http://het.sagepub.com/content/23/3/149.refs.html >> Version of Record - Mar 1, 2004 What is This? Downloaded from het.sagepub.com at UCSF LIBRARY & CKM on September 26, 2014 Human & Experimental Toxicology (2004) 23: 149 ]/156 www.hetjournal.com Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students Mona EL-Gohary*,1 and Manal A Eid2 1Department of Forensic Medicine and Toxicology, Faculty of Medicine, Tanta University, Medical College of Georgia, Augusta, Georgia USA; 2Department of Clinical Pathology, Faculty of Medicine, Tanta University, Medical College of Georgia, Augusta, Georgia USA The discovery of cannabinoid receptors in the immune lymphocytes, T and B lymphocytes and natural killer system and a family of endogenous ligands of these (NK) cells in bhang users as compared to controls receptors provides a basis for understanding the cellular (P B/0.05). Moreover, the fatty acid amide hydrolase and molecular mechanisms of cannabis-induced immu- (FAAH) showed significant decrease in bhang users as notoxicity. The present study was conducted on 90 compared to controls and in subgroup 2 as compared to nonsmoker males of high school and university students subgroup 1 (P B/0.05), indicating that the decrease in living in Tanta city of matched age and socioeconomic FAAH protein level is closely related to the duration of lifestyle. They were divided into a control group (30 bhang use. Positive correlations were found between males) and a bhang user group (60 males), which used FAAH level and the absolute number of mononuclear bhang by eating its sweet juice after boiling with a little cells (T, B lymphocytes and NK cells) among bhang user water and drying in an oven, ‘fola’. The bhang group was subgroups. The present study is the first study to report divided equally into two subgroups: subgroup 1 used on the effect of bhang on complement proteins and bhang for 6 /24 months (average 199/1.2) and subgroup 2 ] immunoglobulins in humans. Our study revealed that used bhang for 24 /36 months (average 319/1.7). The immunotoxic effects] of using bhang appeared in the form bhang-induced immunotoxicity could be attributed to of a significant decrease in serum immunoglobulins (IgG decrease in FAAH protein. Human & Experimental and IgM), and C3 and C4 complement protein concentra- Toxicology (2004) 23, 149 ]/156 tions (P B/0.05). In addition, our results demonstrated a significant decrease in the absolute number of function- ally different subsets of peripheral blood mononuclear Key words: bhang; fatty acid amide hydrolase; immunotoxicity Introduction Illicit use of bhang is a major drug problem in both present in a sticky, golden yellow resin produced by the adolescent and adult population of many mod- glandular hairs located mainly on the flowers and ern societies. Despite its current legal status, the use leaves of the plant.2 of bhang became very popular in Egypt and invaded The toxic effect of tetrahydrocannabinoid (THC), all sectors of the society, especially university the primary psychoactive substance of cannabis, on students, manual workers and youth. There is a immune cells has been extensively studied and 3 public concern about its widespread use and contradictory results have been revealed. dangers to society.1 Bhang is the dried mature Interestingly, cannabinoids are being suggested as leaves, and flower stems of the Cannabis sativa important in the regulation of the immune system plant, the Indian hemp plant, which grows in most and probably important during the evolution of the 4 parts of the world. The psychoactive substances are animal immune and central nervous systems. In addition, data obtained through cell culture studies using various immune cell populations *Correspondence: Mona EL-Gohary, Department of Forensic Medicine and Toxicology, Faculty of Medicine, Tanta University, extracted from animals and humans, together with Medical College of Georgia, Augusta, Georgia USA those obtained using animal models of infection, are E-mail: [email protected] consistent with the proposition that THC alters Received 16 September 2003; revised 23 December 2003; immune cell function and can exert deleteri- accepted 29 December 2003 ous effects on resistance to infection in humans. Ó Arnold 2004 10.1191/0960327104ht426oa Downloaded from het.sagepub.com at UCSF LIBRARY & CKM on September 26, 2014 Effect of cannabinoid ingestion on immune system M EL-Gohary and MA Eid 150 However, few controlled epidemiological and im- CB1 and CB2, thus, cells from marijuana users munological studies have been undertaken to corre- express higher levels of cannabinoid receptors.14 late the immunosuppressive effects of marijuana Endocannabinoids, the endogenous ligands of smoke on the incidence of infections or viral disease cannabinoid receptors, bind to both CB1 and CB2 in humans.5 Although THC was found to allow receptors, thus mimicking some of the psychotropic 15 cancer and opportunistic infections to spread more and analgesic effects of THC. easily, the National Toxicology Program failed to Anandamide (N-arachidonoylethanolamine, 3 support this notion.6 AEA) and 2-arachidonoylglycerol (2-AG) are the Evidence of cannabis-induced immunotoxicity in main endocannabinoids described to date. Much human has been reviewed. Recent reports indicate like the exogenous cannabinoids, AEA and 2-AG that THC alters host defences to bacterial, proto- bind and activate the CB receptors and induce 16 zoan, and viral infection in marijuana smokers. The cannabinoid behavioural effects. This effect is decrease in host resistance may be a consequence of weak and transient, because of its rapid catabolism the toxic action of cannabinoids on the functionality by the hydrolyzing enzyme fatty acid amide hydro- of macrophages, T lymphocytes, and natural killer lase (FAAH). cells (NK) which indicate that marijuana use pre- Recently, there have been reports on the associa- tion between decreased concentrations of FAAH, the sents a potential risk of decreased resistance to endocannabinoids degrading enzyme, in peripheral infections in humans.7,8 lymphocytes and immunotoxicity induced by can- The exact mechanism of cannabis-induced im- nabis use.17 This finding seemed of interest, because munotoxicity is still being investigated and no the cellular and molecular mechanisms of cannabis- conclusive data have been recorded. It has been induced immunotoxicity remain largely unknown. found that THC alters cytokine production and/or The aim of this study was to investigate the effect release resulting in increase in the susceptibility to of bhang on the immune system. Therefore, several viral, fungal, parasitic and extracellular pathogens.9 subsets of peripheral blood mononuclear cells i.e., T, It has been also shown that THC has an ‘antigen- B lymphocytes and NK cells, have been analysed in specific’ effect on the immune function of macro- addition to immunoglobulin and complement pro- phage cells. This means that THC can alter the teins (C3 & C4). We were also interested in investi- immune response differently for different types of gating the molecular pathway that might mediate antigens, but the mechanism or signalling pathway the immunotoxic effects of bhang, therefore the level is still not clearly known. One ‘immune signalling of FAAH enzyme, and the hydrolyzing enzyme of pathway’ from the receptor to action in the cell is the cannabinoid ligands were examined. believed to be the inhibition of adenylate cyclase; another chemical signalling pathway is the release of nitrous oxide.10 Recently, it has been reported that the pharmacological effect of THC is regulated Subjects and methods through specific receptors known as cannabinoid The study included 90 noncigarette smokers, of high receptors. Two types of cannabinoid receptors have school and university students, living in Tanta city. been identified, namely CB1 and CB2. CB1 receptors They were divided as follows: have been detected in the central nervous system 1 Bhang user group: The subjects of this group (where they are responsible for the characteristic including 60 males who used bhang by boiling it effects of cannabis, including catalepsy, depression with sugar and a little water. The juice was then left of motor activity, analgesia and feelings of relaxation to dry in an oven before eating. Its street name is and well being) and in peripheral neurons (where ‘fola’. This way of using bhang is more popular in their activation produces suppression in neurotrans- Upper Egypt; however it has begun to spread all over mitter release in the heart, bladder, intestine and vas the country. The amount of bhang consumed by deferens). CB2 receptors have only been detected each individual ranged from 1.5 to 3 g/day with a outside the central nervous system, mainly in cells mean value of 2.29/0.23 g. They were not using any of the immune system, presumably mediating can- other substances of abuse. They were divided 11 ] 13 nabinoid-induced immunotoxic effects. equally into two subgroups according to the dura- The physiological effect of cannabinoids’ binding tion of bhang use as follows: upon their receptors has been researched through Subgroup 1: This subgroup included individuals both animal and human studies. However, the who had used bhang for 6]/24 months (average 199/ results are mixed. Recent studies suggest that 1.2).
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