Cannabinoids as a Treatment for Insomnia in Major Depression (CANMDD)

A Pilot, Double-Blind, Randomized, Placebo-Controlled Trial Evaluating the Efficacy and Safety of a Cannabis-Infused Oil For Treatment of Insomnia in Major Depression

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.

Study Overview

• Status: Completed
• Conditions: Depression; Sleep Disorder; Insomnia; Depressive Disorder, Major; Insomnia Chronic
• Intervention / Treatment: Drug: 25:1 CBD/THC; Drug: 5:1 CBD/THC; Other: Placebo

Detailed Description

The study will be a three-arm, randomized, double-blind, placebo-controlled trial. The study population will include 60 males and females, ages 19 and older, who report chronic problems with insomnia at least three times per week for at least three months and have a diagnosis of co-morbid MDD. Eligible participants will complete a urine screen for drugs of abuse including opioids, cannabis, benzodiazepines and amphetamines before treatment randomization. Participants with a positive screen for any of these drugs of abuse will be excluded from the study. If the drug screen is negative, the principal investigator will assess patient health history and perform a physical examination. All study participants must be able to fully understand the study procedures and must sign a research ethics board (REB)-approved informed consent before study entry. A neuropsychological battery will be used to assess cognitive function in the domains of attention, verbal memory, psychomotor functioning, and executive functioning at baseline and at the end of the 4-week treatment in order to examine possible cognitive benefits or side effects from the treatment. These cognitive domains were chosen because these domains are known to be negatively affected by chronic insomnia and by cannabis use. Patients will also complete a series of clinician-rated and self-reported questionnaires.

During the 4-week treatment period, participants will be instructed to start treatment with a single, dose of oil at bedtime. Each dose will have either 50 mg/ml CBD and 2 mg/ml THC (High CBD arm; MLP-001) or 10 mg/ml CBD and 2 mg/ml THC (Low CBD arm; MLP-002). Non-responding study participants will add 1 additional dose to their respective treatment after 2 weeks if a higher dosage is needed based on an Insomnia Severity Index (ISI) reduction of >8 points and tolerability (side effects). Responding participants will continue with 1 dose of their treatment after 2 weeks. This dose range is based on previous studies showing that the effective dosage of THC to improve sleep ranged, on average, between 5 and 15 mg daily.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L9C 0E3
      • St. Joseph's Healthcare Hamilton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. 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)
2. Diagnosis of MDD according to the Structured Clinical Interview for DSM-5 (SCID-5)
3. 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)
4. Participant must be willing and able to complete self-reported assessments, including having sufficient fluency in English
5. Participant must be willing to wear a wrist-worn actiwatch device
6. 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)

Exclusion Criteria

1. 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
2. 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
3. Current use of benzodiazepines or any other sleep aids
4. Positive screening for drugs of abuse including but not limited to opioids, cannabis, benzodiazepines, cocaine, and/or amphetamines (except prescribed stimulants for comorbid ADHD)
5. 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)
6. Presence of unstable medical conditions
7. 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
8. Allergy to cannabis or any components of the cannabis treatment (including terpenes)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High CBD [25:1]; 1 dose (1 mL) of HIGH CBD; 50 mg/ml CBD and 2 mg/ ml THC	Drug: 25:1 CBD/THC; 1 dose (1 mL) of HIGH CBD; 50 mg/ml CBD and 2 mg/ ml THC; Other Names: High CBD
Experimental: Low CBD [5:1]; 1 dose (1 mL) of LOW CBD; 10 mg/ml CBD and 2 mg/ ml THC	Drug: 5:1 CBD/THC; 1 dose (1 mL) of LOW CBD; 10 mg/ml CBD and 2 mg/ ml THC; Other Names: Low CBD
Placebo Comparator: Placebo; 1 dose (1 mL) of PLACEBO; No active ingredients	Other: Placebo; 1 dose (1 mL) of PLACEBO; No active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment compliance	Completion rate > 80% using descriptive statistics	through study completion, an average of 4 weeks
Sleep onset latency and wake after sleep onset	Change in time (minutes) as measured using actigraphy	through study completion, an average of 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-Reported Sleep Quality	A measure of self-reported sleep quality via questionnaires and sleep diaries	through study completion, an average of 4 weeks
Cognitive Functioning	Battery of cognitive function that cover cognitive domains associated with insomnia and cannabis use.	through study completion, an average of 4 weeks
Mean THC/CBD Dosing	Average THC and CBD dosage with the most optimal trade-off between efficacy and tolerability	through study completion, an average of 4 weeks
Health-Related Quality of Life (HRQoL)	Short questionnaire to evaluate five dimensions of Health-Related Quality of Life	through study completion, an average of 4 weeks
Healthcare Resource Utilization and Work Productivity	Short questionnaires to capture economic resource utilization and work productivity	through study completion, an average of 4 weeks

Collaborators and Investigators

• Sponsor: St. Joseph's Healthcare Hamilton
• Collaborators: McMaster University
• Investigators: Principal Investigator: Benicio N Frey, MD, MSc, PhD, St. Joseph's Healthcare Hamilton; Study Chair: Nirushi Kuhathasan, PhD, St. Joseph's Healthcare Hamilton

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2023
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Mental Health; Cognition; Major Depressive Disorder; Cannabis; Sleep Disorders; Chronic Insomnia
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mood Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Personal Satisfaction; Depression; Depressive Disorder, Major; Sleep Initiation and Maintenance Disorders; Marijuana Abuse; Sleep Wake Disorders; Psychological Well-Being; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: CANMDD001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No