Cannabinoids as a Treatment for Insomnia in Major Depression

Depression Clinical Trial

— CANMDD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05041647
• Other study ID #: CANMDD001
• Status: Recruiting
• Phase: Phase 2
• Start date: August 28, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: September 2023
• Source: St. Joseph's Healthcare Hamilton
• Contact: Abbey Schlatman
• Phone: (905) 522-1155
• Email: aschlatm[@]stjosham.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. Polysomnography data will also be 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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) 37

3. Diagnosis of Insomnia Disorder according to the Duke Structured Interview for Sleep Disorders 38 Patient Health Questionnaire (PHQ-9) 39 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)

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Insomnia
• Insomnia Chronic
• Parasomnias
• Sleep Disorder
• Sleep Initiation and Maintenance Disorders
• Sleep Wake Disorders

Intervention

Drug:
• 25:1 CBD/THC
1 dose (1 mL) of HIGH CBD 50 mg/ml CBD and 2 mg/ ml THC
• 5:1 CBD/THC
1 dose (1 mL) of LOW CBD 10 mg/ml CBD and 2 mg/ ml THC

Other:
• Placebo
1 dose (1 mL) of PLACEBO No active ingredients

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
St. Joseph's Healthcare Hamilton	McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Self-Reported Sleep Quality	A measure of self-reported sleep quality via questionnaires and sleep diaries	through study completion, an average of 4 weeks
Other	Cognitive Functioning	Battery of cognitive function that cover cognitive domains associated with insomnia and cannabis use.	through study completion, an average of 4 weeks
Other	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
Other	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
Other	Healthcare Resource Utilization and Work Productivity	Short questionnaires to capture economic resource utilization and work productivity	through study completion, an average of 4 weeks
Primary	Recruitment Rate	Rates > 80% using descriptive statistics	1 year, at the completion of the study
Primary	Retention Rate	Rates > 80% using descriptive statistics	1 year, at the completion of the study
Secondary	Sleep latency onset and wake after sleep onset	Change in time (minutes) as measured using actigraphy	through study completion, an average of 4 weeks
Secondary	Treatment compliance	Completion rate > 80% using descriptive statistics	through study completion, an average of 4 weeks