en Physiology Physiology پژوهشي Research <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b><span style="font-size:10.0pt">Introduction</span></b><span style="font-size:10.0pt">: Methamphetamine addiction is one of the most prevalent substance use disorders. Augmenting traditional drug treatments with non-pharmacological interventions can enhance treatment efficacy and sustainability. This study aims to investigate the impact of aerobic exercise and psilocybin on histopathological changes in the cerebral cortex of methamphetamine-induced rats.</span></span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b><span style="font-size:10.0pt">Material & Methods</span></b><span style="font-size:10.0pt">: This experimental research involved 30 female rats randomly allocated into five groups: control, methamphetamine, methamphetamine + aerobic exercise, methamphetamine + psilocybin, and methamphetamine + psilocybin + aerobic exercise. Rats received 15 mg of methamphetamine intraperitoneally every 12 hours for four days. Aerobic exercise was conducted on a treadmill with an 8-week program of escalating intensity, reaching a maximum running time of 30 minutes and speed of 25 m/min, with a 5% slope introduced in the fourth week. Psilocybin was administered intraperitoneally at a microdose of 0.025 mg/kg over 24 sessions. Histopathological changes were assessed using hematoxylin and eosin staining, and descriptive analysis with images was employed to interpret cortical brain tissue samples.</span></span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b><span style="font-size:10.0pt">Results</span></b><span style="font-size:10.0pt">: Histological examination revealed tissue and cellular disorganization, altered morphology of pyramidal neurons, and reduced microglial cell counts in methamphetamine-induced rats compared to controls. Endurance training, psilocybin supplementation, and their combination exhibited improvements in tissue and cellular alterations in the cerebral cortex of addicted rats.</span></span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b><span style="font-size:10.0pt">Conclusion</span></b><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">: &nbsp;</span></span></b><span style="font-size:10.0pt">This study demonstrates that exercise training and psilocybin administration in methamphetamine-exposed rats ameliorate cortical histopathology, with the combined intervention yielding the most significant effects. This synergistic effect may reduce the risk of relapse in methamphetamine users by positively modulating brain and central nervous system functions.</span></span></span><br> &nbsp; Methamphetamine, Aerobic Exercise, Psilocybin, cerebral Cortex, Rats 68 77 http://jbrms.medilam.ac.ir/browse.php?a_code=A-10-361-4&slc_lang=en&sid=1 Fariba Rasannezhad f.rasan@yahoo.com 10031947532846006893 10031947532846006893 No Department of Sport physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran Asieh Abbassi-Daloii abbasi.daloii@gmail.com 10031947532846006894 10031947532846006894 Yes Department of Sport physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran Seyyed Javad Ziaolhagh javadzia@gmail.com 10031947532846006895 10031947532846006895 No Department of Sport physiology, Shahrood Branch, Islamic Azad University, Shahrood, Iran Ahmad Abdi a.abdi58@gmail.com 10031947532846006896 10031947532846006896 No Department of Sport physiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran