COMBINATION OF PSILOCYBIN AND COGNITIVE BEHAVIORAL THERAPY IMPROVES OXYTOCIN LEVELS AND DEPRESSIVE SYMPTOMS IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER

Abstract

Background: Major depressive disorder is a prevalent psychological condition that is characterized by sustained low mood, dysfunction and biological dysregulation. Depression can be treated with cognitive behavioral therapy, and newer studies indicate that psilocybin-based therapy may improve depressive symptoms when used under supervised psychological support. Oxytocin, a neuropeptide that plays a role in stress, emotions and bonding, may help us understand treatment effects.

Objective: To evaluate the effect of psilocybin therapy, cognitive behavioral therapy, and combined psilocybin assisted cognitive behavioral therapy on depressive symptoms and serum oxytocin levels among patients with major depressive disorder.

Methods: This randomized controlled trial was carried out at the Psychiatry Department of Hayatabad Medical Complex and Khyber Medical University, Peshawar from 1^st December 2024 to 30^th July 2025­­. Sixty-seven patients with major depressive disorder were included and randomly distributed into four groups: ‘SSRI treatment, CBT, psilocybin therapy, and psilocybin combined with CBT’. Hamilton Depression Rating Scale was used to measure the severity of depression at baseline, week 6 and week 10. Serum oxytocin levels were also evaluated. Data was analyzed using SPSS 25. Repeated-measures ANOVA, Bonferroni post hoc comparisons were applied.

Results: The control group showed minimal change in HAM-D scores, while marked reductions were observed in all active intervention groups. By week 10, mean HAM-D scores decreased to 2.84 ± 2.01 in the CBT group, 3.24 ± 1.56 in the psilocybin group, and 2.50 ± 1.51 in the psilocybin assisted CBT group. Repeated-measures ANOVA showed a significant effect of time on HAM-D scores and a significant time × group interaction (p<0.001). Serum oxytocin levels increased in CBT, psilocybin, and combined treatment groups, with the greatest rise being observed in the psilocybin assisted CBT. Between-group differences in oxytocin were ‘not significant’ (p=0.649), but significant rises were observed within all intervention groups.

Conclusion: Patients treated with psilocybin, CBT, or their combined approach showed significant improvement in depressive symptoms. Serum oxytocin levels increased most significantly in the combined treatment group, suggesting a possible neurobiological role of oxytocin in treatment response.