Cannabidiol Oil for Treatment-Resistant Major Depression

NCT07696871 | Recruiting Phase 1

• 4 other identifiers: CEP-UNISUL-8469525RBR-6n6wzsxU1111-1337-1000CAAE 88825025.3.0000.0261
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder is one of the leading causes of disability worldwide, and a substantial proportion of patients do not achieve adequate improvement with conventional antidepressant treatments. Cannabidiol (CBD), a non-intoxicating cannabinoid derived from Cannabis sativa, has shown potential anxiolytic, anti-inflammatory, and neurobiological effects that may be relevant for depressive disorders. The ANANDA trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy, safety, and tolerability of full-spectrum cannabidiol oil as an adjunctive treatment in adults with treatment-resistant major depressive disorder. A total of 120 participants will be randomly assigned to receive either full-spectrum cannabidiol oil or placebo for 12 weeks while maintaining stable antidepressant treatment. Clinical assessments of depressive symptoms, anxiety, sleep quality, perceived stress, and adverse effects will be performed at baseline, Week 4, and Week 12. Blood samples will be collected at baseline and after 12 weeks to investigate inflammatory and neuroendocrine biomarkers. The primary objective is to evaluate changes in depressive symptoms after 12 weeks of treatment. Secondary objectives include the assessment of anxiety, sleep quality, perceived stress, biological markers, safety, and tolerability. The findings of this study may contribute to the development of new therapeutic approaches for treatment-resistant depression and provide additional evidence regarding the clinical use of cannabidiol in psychiatric disorders.

Conditions

Treatment-resistant Depression (TRD); Major Depressive Disorder (MDD)

Keywords

Cannabidiol; Cannabinoids; Major Depressive Disorder; Treatment-Resistant Depression; Mood Disorders

Outcome Measures

Primary Outcomes (1)

• Change in Depressive Symptom Severity Assessed by the Hamilton Depression Rating Scale (HAM-17)

  Depressive symptoms will be assessed using the 17-item Hamilton Depression Rating Scale (HAM-17), a clinician-administered instrument that evaluates depressive symptom severity. HAM-17 assessments will be performed at baseline, Week 4, and Week 12. The primary endpoint is the change in HAM-17 total score from baseline to Week 12. Changes from baseline to Week 4 will be evaluated as an intermediate assessment.

  Baseline, Week 4, and Week 12

Secondary Outcomes (6)

• Change in Anxiety Symptoms Assessed by the Generalized Anxiety Disorder Scale (GAD-7)

  Baseline, Week 4, and Week 12

• Change in Insomnia Severity Assessed by the Insomnia Severity Index (ISI)

  Baseline, Week 4, and Week 12

• Change in Health-Related Quality of Life Assessed by the Short Form-36 Health Survey (SF-36)

  Baseline, Week 4, and Week 12

• Frequency and Severity of Adverse Effects Assessed by the UKU Side Effect Rating Scale

  Week 4 and Week 12

• Change in Inflammatory Biomarkers

  Baseline and Week 12

Study Arms (2)

CBD Full Spectrum 100 mg/mL

EXPERIMENTAL

Participants assigned to this arm will receive full-spectrum cannabidiol (CBD) oil containing 100 mg/mL of CBD administered sublingually for 12 weeks under double-blind conditions. The formulation contains cannabidiol and naturally occurring phytocannabinoids and terpenes derived from Cannabis sativa. Clinical assessments will be conducted at baseline, Week 4, and Week 12 to evaluate efficacy, safety, tolerability, and treatment adherence.

Drug: Full-spectrum CBD oil 100 mg/mL

Placebo (MCT oil)

PLACEBO COMPARATOR

Participants assigned to this arm will receive a placebo formulation consisting of medium-chain triglyceride (MCT) oil administered sublingually for 12 weeks under double-blind conditions. The placebo will be identical in appearance, color, viscosity, taste, and packaging to the active full-spectrum CBD oil to ensure maintenance of treatment blinding. Clinical assessments will be conducted at baseline, Week 4, and Week 12 to evaluate study outcomes, safety, tolerability, and adherence.

Drug: Placebo oil (MCT oil)

Interventions

Full-spectrum CBD oil 100 mg/mL DRUG

Full-spectrum Cannabis sativa extract containing cannabidiol (CBD) 100 mg/mL and tetrahydrocannabinol (THC) 3.33 mg/mL, administered sublingually for 12 weeks according to a structured dose titration schedule. Treatment will begin with low doses and may be gradually adjusted based on clinical response and tolerability, respecting predefined safety limits established in the study protocol.

CBD Full Spectrum 100 mg/mL

Placebo oil (MCT oil) DRUG

Placebo comparator consisting of medium-chain triglyceride (MCT) oil administered sublingually for 12 weeks according to the same dose titration schedule used in the experimental group. The placebo formulation is matched to the active intervention in appearance, color, viscosity, packaging, and administration conditions to maintain blinding throughout the study. Treatment adherence, tolerability, and adverse events will be monitored throughout the intervention period.

Placebo (MCT oil)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 69 years
• Diagnosis of Major Depressive Disorder (MDD)
• Persistent depressive symptoms despite ongoing antidepressant treatment
• Stable antidepressant treatment for at least four weeks before enrollment
• Residence in Brazil
• Ability to understand study procedures and comply with study requirements
• Provision of written informed consent

You may not qualify if:

• Current use of cannabis-derived products or cannabinoid-based medications
• Diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders
• Current substance use disorder, except nicotine or caffeine
• Pregnancy or breastfeeding
• Severe or unstable medical conditions that may interfere with study participation
• History of hypersensitivity or allergy to Cannabis sativa products or MCT oil
• Active suicidal ideation or significant suicide risk requiring immediate intervention
• Participation in another clinical trial within the previous 30 days
• Inability to comply with study procedures or follow-up assessments

Sponsors & Collaborators

• Federal University of Latin American Integration: collaborator
• Associação Cannabis Sem Fronteiras - ACSF: collaborator
• Universidade do Sul de Santa Catarina: lead

Study Sites (1)

Universidade do Sul de Santa Catarina - UNISUL

Tubarão, Santa Catarina, 88704900, Brazil

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Mood Disorders

Condition Hierarchy (Ancestors)

Depressive Disorder; Mental Disorders

Central Study Contacts

Rafael Mariano Bitencourt, PhD

CONTACT

+55 48 9 8833-6460; bitencourtrm@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants, investigators, healthcare providers, outcome assessors, and members of the research team responsible for participant follow-up and data analysis will remain blinded to treatment allocation throughout the study. The placebo formulation will be matched to the active intervention in appearance, color, packaging, and administration conditions to maintain blinding. Treatment allocation codes will be restricted to designated personnel not directly involved in participant assessments, clinical follow-up, or outcome evaluations and will only be accessed in cases of medical necessity or after completion of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study is designed as a multicenter, randomized, double-blind, placebo-controlled clinical trial with a parallel-group assignment. Participants will be randomly allocated in a 1:1 ratio to either the intervention group receiving full-spectrum cannabidiol (CBD) oil or the placebo group receiving a matched placebo formulation with similar organoleptic characteristics and administration conditions. Participants will remain in their assigned group throughout the 12-week intervention period, with no crossover between treatments. Clinical assessments will be conducted at baseline, Week 4, and Week 12, with additional remote follow-up visits performed throughout the study to monitor treatment adherence, tolerability, adverse events, and dose adjustments. Blood samples will be collected at baseline and after 12 weeks to evaluate inflammatory and neuroendocrine biomarkers associated with treatment response.

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 10, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 10, 2026

Record last verified: 2026-07

Locations

BR (1)