Investigation of the relationship between Gastrointestinal System (GIS) hormones and aggression and craving in patients with cannabis use disorder

INTRODUCTION AND OBJECTIVE: Substance abuse appears as a bio-psycho-social problem worldwide. The most common illegal substance is marijuana and its synthetic derivatives. Cannabis abstinence has been recently described and aggression and craving are among the most common withdrawal symptoms. Control of aggression and craving plays a key role in both detoxification and maintenance of addiction treatments. Ghrelin, leptin, adiponectin and resistin, known as gastrointestinal hormones (GIS), are among the new research topics in relation to the regulation of appetite as well as some psychiatric diseases and addictions. In this study, the relationship between aggression and craving and GIS hormones during abstinence in patients with cannabis use disorder will be examined. The aim of this study is to add a different dimension to addiction treatment by showing the relationship between GIS hormones and aggression and craving. MATERIAL AND METHOD: This study included 45 healthy volunteers and 56 patients who were hospitalized for treatment at Alcohol and Substance Abuse Treatment Center (AMATEM) Clinic between September 2018 and March 2020 and were diagnosed as "Cannabis Use Disorder" according to DSM-5 criteria. The scales that will be applied to the patients and healthy volunteers included in the study; Addiction Profile Index (API), Buss Perry AgressionQuestionaire (BPAQ), Drug Craving Scale (DCS) (only for patients), State-Trait Anxiety Inventory (STAI-1 ve 2). In addition, PSAP (Point-Subtraction-Aggression-Paradigm) computer application was used to evaluate aggression. After a week, the patients were again administered DCS, BPAQ, STAI-1, STAI-2 and The Overt Aggression Scale (OAS). RESULTS: When the hormone levels of patients and controls were compared on day 0, blood levels of ghrelin, leptin and adiponectin were significantly lower in patients. A positive correlation was found between leptin and response/provocation in PSAP in all participants. It has been shown that there is a significant increase in ghrelin levels and a significant decrease in resistin levels after computer game (PSAP) induced aggression in patients. When the anxiety scores of the patients were compared on days 0 and 7, STAI-1 scores decreased, whereas STAI-2 scores decreased significantly. When the aggression levels of the patients on days 0 and 7 were compared, it was found that the anger subscale of the BPAQ scale decreased significantly. It was found that the craving scores of the patients decreased on day 7 compared to day 0, and the levels of adiponectin, leptin and resistin increased significantly on day 7, but no significant correlation was found between craving scores and hormone levels. CONCLUSION: In patients with cannabis use disorder, ghrelin, leptin and adiponectin levels were found to be significantly lower than healthy controls. Although chronic cannabinoid use is effective on ghrelin, leptin and adiponectin hormones, it is not clear which mechanism this effect is. The aggression and anxiety scores of cannabinoid addicts are higher than healthy volunteers. Unlike the control group, the significant increase in ghrelin levels after the game inducing aggression suggests that cannabinoids affect ghrelin signaling and change the hormonal response to the induction of aggression in the patient group. A negative correlation was found between anxiety scores and ghrelin levels. These findings (the higher aggression and anxiety scores in the patient group compared to the control group. no correlation between aggression scores and ghrelin levels, a correlation between anxiety scores and ghrelin levels) suggest that the role of ghrelin in aggression may be due to anxiety regulation in cannabinoid addicts. The correlation between leptin levels and continued behavior of earning points despite provocation in PSAP suggests that leptin may have a role in regulating motivation. In cannabinoid addicts, anxiety, aggression and craving scores were found to decrease during one-week abstinence. A significant increase in leptin, ghrelin and resistin levels was detected after one-week abstinence. We think that these hormones have a complex and dynamic relationship with anxiety, aggression and craving. However, no correlation was found between craving and hormone levels. In order to understand the relationship between craving, aggression and GIS hormones, we think that the repetition of study data and longer sample clinical studies with larger sample are needed.