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Effect of Psilocybin on the Positive Valence System in Treatment-resistant Depression

NCT06650800 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2025-08-20

No results posted yet for this study

Summary

The study hypothesis is that the antidepressant effect of psilocybin is mediated by a normalization of the functioning of the positive valence system. Depressive states, especially moderate to severe depressions that associate a certain level of anhedonia, produce an overvaluation of the cost of efforts and an infra-evaluation of the possible rewards derived from an action. Psilocybin would reduce anhedonia and the cost of efforts, facilitating the anticipation of reward. Thus, the antidepressant effect of psilocybin would be mediated by a greater anticipation of rewards (reduction of anhedonia) and a more optimistic estimation of the results of efforts (increase in motivation). Psilocybin-induced changes in the positive valence system will be observable on brain MRI images, particularly in the effort evaluation circuits: basolateral amygdala, dorsal anterior cingulate cortex, ventral pallidum, ventral striatum (VS), ventral tegmental area (VTA). The mesolimbic circuit (VS, VTA) is the anatomical substrate of anticipation of rewarding stimuli (food, sex, drugs). The amygdala also fulfills an associative function between environmental cues and rewarding stimuli. Structural and functional alterations in this circuit are associated with depressive symptoms such as anhedonia or distortions in the perception and memories of rewards. This hypothesis will be tested on a population of patients with moderate or severe depressive symptoms who meet the criteria for TRD.

Conditions

  • Depressive Disorder
  • Depressive Disorder, Treatment-Resistant
  • Hallucinogens
  • Reinforcement, Psychology

Interventions

DRUG

Psilocybin

Single-dose psilocybin administration: oral ingestion of one 25 mg capsule

OTHER

MRI

1.5 hour brain MRI before and after psilocybin administration

Sponsors & Collaborators

  • Centre Hospitalier Universitaire de Nīmes

    lead OTHER

Principal Investigators

  • Ismaël Conejero · CHU Nimes

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
25 Years
Max Age
60 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2024-11-19
Primary Completion
2025-03-26
Completion
2025-06-26

Countries

  • France

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06650800 on ClinicalTrials.gov