Cannabinoids as a Treatment for Insomnia in Major Depression

NCT05041647 | Completed Phase 2 DMC

• 1 other identifier: CANMDD001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This single-site study is a pilot, three-armed, double-blinded, placebo-controlled randomized controlled trial (RCT) that will determine the feasibility of a definitive RCT investigating the use of cannabis oil as a treatment for insomnia in individuals with MDD. The study will also determine whether standard THC with higher CBD vs lower CBD has a differential impact on insomnia. The study will also analyze other important objective parameters of sleep including total sleep time and sleep efficiency from actigraphy data. Optional polysomnography data may also be collected and analyzed. In addition, standardized, validated instruments will be used to collect data on severity of depressive symptoms, cognitive functioning biological rhythm disruption, daytime sleepiness, health-related quality of life (HRQoL), healthcare resource utilization, work productivity and activity impairment, as well as other side effects, in order to better understand the potential impact of the use of cannabis oil on these important health outcomes.

Conditions

Insomnia Chronic; Sleep Disorder; Depression; Insomnia; Depressive Disorder, Major

Keywords

Mental Health; Cognition; Sleep Disorders; Major Depressive Disorder; Chronic Insomnia; Cannabis

Outcome Measures

Primary Outcomes (2)

• Recruitment Rate

  Rates \> 80% using descriptive statistics

  1 year, at the completion of the study

• Retention Rate

  Rates \> 80% using descriptive statistics

  1 year, at the completion of the study

Secondary Outcomes (2)

• Sleep onset latency and wake after sleep onset

  through study completion, an average of 4 weeks

• Treatment compliance

  through study completion, an average of 4 weeks

Other Outcomes (5)

• Self-Reported Sleep Quality

  through study completion, an average of 4 weeks

• Cognitive Functioning

  through study completion, an average of 4 weeks

• Mean THC/CBD Dosing

  through study completion, an average of 4 weeks

Study Arms (3)

High CBD [25:1]

EXPERIMENTAL

* 1 dose (1 mL) of HIGH CBD * 50 mg/ml CBD and 2 mg/ ml THC

Drug: 25:1 CBD/THC

Low CBD [5:1]

EXPERIMENTAL

* 1 dose (1 mL) of LOW CBD * 10 mg/ml CBD and 2 mg/ ml THC

Drug: 5:1 CBD/THC

Placebo

PLACEBO COMPARATOR

* 1 dose (1 mL) of PLACEBO * No active ingredients

Other: Placebo

Interventions

25:1 CBD/THC DRUG

* 1 dose (1 mL) of HIGH CBD * 50 mg/ml CBD and 2 mg/ ml THC

Also known as: High CBD

High CBD [25:1]

5:1 CBD/THC DRUG

* 1 dose (1 mL) of LOW CBD * 10 mg/ml CBD and 2 mg/ ml THC

Also known as: Low CBD

Low CBD [5:1]

Placebo OTHER

* 1 dose (1 mL) of PLACEBO * No active ingredients

Placebo

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19 or above (A minimal age of 19 was chosen in order to align with the cannabis legalization rules of the Province of Ontario, where the research participants will be recruited from: https://www.ontario.ca/page/cannabis-legalization#section-1)
• Diagnosis of MDD according to the Structured Clinical Interview for DSM-5 (SCID-5)
• Diagnosis of Insomnia Disorder according to the Duke Structured Interview for Sleep Disorders Patient Health Questionnaire (PHQ-9) score of \<10, indicating severity of mild-to-no depression (This criterion is important because a proper diagnosis of current co-morbid insomnia disorder cannot be accurately ascertained during acute major depressive episodes)
• Participant must be willing and able to complete self-reported assessments, including having sufficient fluency in English
• Participant must be willing to wear a wrist-worn actiwatch device
• Participants may be using psychotropic medications for treatment of depression, except benzodiazepines or any other sleep aids, as long as the dosage remains the same from a minimum of 2 months prior to study enrolment until the end of the study (This criterion is important because many individuals with MDD use antidepressant agents and this criterion would make the results more generalizable and useful in real life clinical practice)

You may not qualify if:

• Lifetime diagnosis of Schizophrenia, Bipolar Disorder or any other psychotic disorder, as well as current or recent (last 6 months) Alcohol or Substance Use Disorder according to the SCID-5
• Individuals with current diagnosis of Generalized Anxiety Disorder, Panic Disorder, Obsessive-Compulsive Disorder, Post-Traumatic Stress Disorder or Eating Disorder will be excluded because these psychiatric disorders are associated with sleep disturbance; however, because of the high rates of co-morbid psychiatric conditions in MDD lifetime/past diagnosis will be allowed in order for the results to be generalizable and useful in real life clinical practice
• Current use of benzodiazepines or any other sleep aids
• Positive screening for drugs of abuse including but not limited to opioids, cannabis, benzodiazepines, cocaine, and/or amphetamines (except prescribed stimulants for comorbid ADHD)
• Presence of any sleep disorder other than insomnia that is considered the primary diagnosis, determined by the Duke Structured Interview for Sleep Disorders (e.g. Sleep Apnea, Limb Movement Disorder, or Circadian Rhythm Disorders)
• Presence of unstable medical conditions
• Pregnancy or breastfeeding (female participants will need to agree to use an acceptable contraceptive method during the study because of potential unknown teratogenic effects of cannabinoids
• Allergy to cannabis or any components of the cannabis treatment (including terpenes)

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• McMaster University: collaborator

Study Sites (1)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L9C 0E3, Canada

Location

Related Publications (4)

• Broyd SJ, van Hell HH, Beale C, Yucel M, Solowij N. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. Biol Psychiatry. 2016 Apr 1;79(7):557-67. doi: 10.1016/j.biopsych.2015.12.002. Epub 2015 Dec 8.

  PMID: 26858214 BACKGROUND

• Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 2017 Apr;19(4):23. doi: 10.1007/s11920-017-0775-9.

  PMID: 28349316 BACKGROUND

• Gates PJ, Albertella L, Copeland J. The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Med Rev. 2014 Dec;18(6):477-87. doi: 10.1016/j.smrv.2014.02.005. Epub 2014 Mar 7.

  PMID: 24726015 BACKGROUND

• Kuhathasan N, Dufort A, MacKillop J, Gottschalk R, Minuzzi L, Frey BN. The use of cannabinoids for sleep: A critical review on clinical trials. Exp Clin Psychopharmacol. 2019 Aug;27(4):383-401. doi: 10.1037/pha0000285. Epub 2019 May 23.

  PMID: 31120284 BACKGROUND

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Depressive Disorder, Major; Sleep Wake Disorders; Depression; Psychological Well-Being; Marijuana Abuse

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Nervous System Diseases; Mental Disorders; Depressive Disorder; Mood Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Personal Satisfaction; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Benicio N Frey, MD, MSc, PhD

  St. Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

• Nirushi Kuhathasan, PhD

  St. Joseph's Healthcare Hamilton

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study participants will be randomly assigned in a 1:1:1 manner to one of the three treatment arms using a computer-generated, permuted-block randomization schedule. Randomization will be stratified by sex. All of the treating physicians who will be also administering the clinical questionnaires, the trained research assistants conducting cognitive testing, as well as any other trial staff, will be blinded to the subjects' status until the end of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioural Neurosciences, Prinicipal Investigator

Model Details: The study will be a pilot, three-arm, randomized, double-blind, placebo-controlled trial.

Study Record Dates

• First Submitted: July 14, 2021
• First Posted: September 13, 2021
• Study Start: August 28, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)