The relationship between Agouti related protein and leptin in patients with methamphetamine use disorder

Abstract Background Appetite regulation involves a complex interplay between peripheral signals and central hypothalamic neuropeptides. Two key hormones in this mechanism are leptin, an adipocyte-derived hormone that suppresses food intake, and Agouti-Related Protein (AgRP), a potent orexigenic neuropeptide produced in the hypothalamic arcuate nucleus. Methamphetamine (METH), a widely abused psychostimulant, is known to alter metabolic rate and suppress appetite, often resulting in weight loss. However, the impact of methamphetamine use on leptin and AgRP levels remains underexplored. Investigating these hormonal changes may provide insights into the neuroendocrine basis of disordered eating behaviors associated with substance use. Objective This study aimed to assess the relationship between plasma leptin and AgRP concentrations in individuals with methamphetamine use disorder compared to healthy controls, and to evaluate their association with body mass index (BMI), addiction severity, and disordered eating attitudes. Methods A comparative cross-sectional observational study was conducted, including 20 adult males (Case group) who met the DSM-5 criteria for methamphetamine use disorder and 20 healthy drug- free males (Control group), matched with the patients for the socio-demographic data. Inclusion criteria limited participants to those with normal BMI to eliminate confounding from body weight. The patient`s recruitment was from the Psychiatry and Addiction Management Hospital of Cairo University, Faculty of Medicine (Kasr Al Ainy), while the healthy controls were recruited from the workers in Cairo University Hospitals. Structured Clinical Interview for DSM-5 (SCID-5), Addiction Severity Index (ASI), Eating Attitudes Test (EAT-26) were applied. A sample of blood was taken from both groups to measure the leptin and AgRP levels. Statistical analysis was performed using SPSS v22. Results Plasma leptin levels were significantly higher in the case group (14.11 ± 0.85 ng/ml) compared to control group (6.43 ± 1.38 ng/ml), ( p ≤ 0.001). Plasma AgRP levels were significantly lower in case group (19.3 ± 1.56 pg/ml) compared to control group (24.95 ± 1.91 pg/ml), ( p ≤ 0.001).BMI did not differ significantly between groups (22.08 ± 1.11 vs. 21.64 ± 0.97 kg/m 2 , p = 0.18), as per study design. Eating disorder symptoms (EAT-26) were significantly more prevalent among methamphetamine users (mean score 22.95 ± 6.29, 75% had scores > 20) versus controls (13.6 ± 5.21, 20% affected), ( p ≤ 0.001).AgRP levels had statistically significant negative correlation with leptin ( r = –0.757, p < 0.001) and positive correlation with BMI ( r = 0.587, p = 0.007) in the case group. Leptin levels were negatively correlated with BMI in methamphetamine users ( r = –0.822, p < 0.001).No significant correlations between eating Attitudes test scores and hormonal levels in both groups. Conclusion Methamphetamine use is associated with a significant dysregulation in appetite-related hormones, characterized by elevated leptin and reduced AgRP concentrations, even in individuals with normal BMI. Moreover, Methamphetamine use disorder is associated with abnormal eating behaviors. This reflects the neurobehavioral impact of methamphetamine use on appetite, food control, and body image perception.