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

In a randomized controlled trial, 67 patients with major depressive disorder received either standard SSRI treatment, cognitive behavioral therapy (CBT), psilocybin therapy, or psilocybin combined with CBT. By week 10, all active treatment groups showed marked reductions in depression severity measured by the Hamilton Depression Rating Scale, with mean scores dropping to 2.84 in the CBT group, 3.24 in the psilocybin group, and 2.50 in the combined group. Serum oxytocin levels rose in all intervention groups, most in the combined treatment, although between-group differences were not significant. The findings suggest psilocybin, CBT, and their combination effectively improve depressive symptoms, with oxytocin possibly playing a neurobiological role.

Study at a glance

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 1st December 2024 to 30th 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.