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Cannabidiol and Cocaine Craving/Dependence (CBD)

Primary Purpose

Substance Use Disorder, Cocaine Dependence, Withdrawal From Addictive Substance; Detoxification

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Cannabidiol
Sponsored by
Centre hospitalier de l'Université de Montréal (CHUM)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Substance Use Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  • DSM-5 criteria for current cocaine use disorder (moderate or severe).
  • Current cocaine use with last use during two weeks prior to admission to the study as confirmed by the Timeline Follow Back questionnaire.
  • Age between 18 and 65 years old (inclusive).
  • Women with diagnosed menopause (as confirmed by the study physician), under the age of 65, will be eligible for the study
  • Subject consents to inpatient detoxification at the CHUM.
  • Ability to give valid, informed consent.
  • Ability to speak and read French or English.

Exclusion criteria

  • Severe and/or unstable hepatic, neurologic (including diagnosis of seizures), cardiac (including arrhythmias) or renal disease), or any other severe or unstable medical condition that precludes safe participation in the study according to the study physician.
  • Patients who are already immunocompromised (e.g., patients with human immunodeficiency virus-1 who do not meet the following criteria: undetectable HIV virus (using modern assay) and CD4 count >350 cells/uL in the last 6 months prior to enrolment, patients on antiretroviral therapy; or other infectious organisms), exhibit malignancy and/or have autoimmune syndromes.
  • Hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
  • Severe psychiatric condition (history of schizophrenia, schizoaffective disorder or bipolar disorder); current acute psychosis, mania or severe suicidality based on the Mini International Neuropsychiatric Interview (MINI 7.0)).
  • Pregnancy or breastfeeding.
  • Inability (or unwillingness) of women of childbearing potential to use a medically acceptable form of contraception throughout study duration and for 3 months after dosing stops. A medically acceptable form of contraception is either: (1) contraceptive pill or intrauterine device or depot hormonal preparation (ring, injection, implant); and/or (2) a double barrier method of contraception such as diaphragm, sponge with spermicide and condom.
  • Couples planning to conceive within the next 12 months.
  • Men with history of fertility problems.
  • Another current severe substance use disorder or any substance use disorder that would require pharmacological treatment according to the addiction specialist except nicotine (e.g. benzodiazepine or opiate for alcohol or opioid use disorder).
  • Current treatment with medications that may interact with Cannabidiol (i.e., psychotropic medications such as benzodiazepines or anticonvulsants) or anticipation that the patient may need to initiate such treatment during the study.
  • Any serious medical condition or psychiatric illness that precludes the subject from signing the informed consent form.

Sites / Locations

  • Centre de recherche du Centre Hospitalier de l'Université de Montréal

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Cannabidiol

Placebo

Arm Description

Participants will receive CBD 800 mg for 92 consecutive days starting on Day 2 of a 10-day inpatient detoxification period followed by 12 weeks of outpatient follow-up

Participants will receive placebo for 92 consecutive days starting on Day 2 of a 10-day inpatient detoxification period followed by 12 weeks of outpatient follow-up

Outcomes

Primary Outcome Measures

Drug-cue induced craving
A 10-point visual analog scale (VAS) used to measure craving responses in the context of cocaine cue-induced craving during the laboratory session on Day 8 of detoxification
Number of days to relapse
The number of days to relapse will be determined as the number of days between detoxification discharge (Day 10) and the day of first cocaine use as determined by the first positive urine test for cocaine (the day prior to urine testing will be entered as the day of relapse) or the first day of cocaine use self-reported by participants (the earliest of both measures)

Secondary Outcome Measures

Stress-induced craving
A 10-point VAS used to measure craving responses in the context of stress-induced craving during the laboratory session on Day 8.
Cocaine use during the post-detoxification phase
The percentage of positive urine tests will be calculated - we will conservatively assign a 'positive' result to all visits for which the test result is not available for a given subject (including all visits after the subject's loss to follow-up and all scheduled 'intermediate' weekly visits to which the subject did not come or at which the test was not performed).

Full Information

First Posted
September 22, 2015
Last Updated
October 21, 2020
Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
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1. Study Identification

Unique Protocol Identification Number
NCT02559167
Brief Title
Cannabidiol and Cocaine Craving/Dependence
Acronym
CBD
Official Title
Cannabidiol as a New Treatment for Cocaine Addiction
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
July 1, 2016 (Actual)
Primary Completion Date
August 16, 2019 (Actual)
Study Completion Date
August 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, the investigators seek to evaluate the effects of cannabidiol (CBD) on cocaine craving and relapse. Cocaine addiction is characterized by compulsive substance use and repetitive urges to consume the drug even after a sustained period of abstinence. While substance use remains the most obvious direct outcome of addiction, there is a growing interest in other core symptoms of this disorder. Craving has become a subject of great interest as it is a reliable intermediate phenotype of cocaine relapse and a distressing symptom of addiction associated with suffering. Indeed, even after a period of abstinence, cocaine-dependent individuals remain vulnerable to stress and other craving-inducing stimuli, which, in turn, lead to intense physiological responses and various negative feelings such as anger and sadness. Real-time daily monitoring of craving and drug use has shown that craving predicts cocaine relapse among cocaine-dependent individuals. In sum, working toward improving the treatment of craving could not only help prevent relapse, but also reduce patient distress on emotional, cognitive, and physiological levels. In the past decades, significant scientific efforts have been deployed toward the development of innovative strategies to beat cocaine addiction, but with partial success thus far. Psychosocial approaches have been widely used to help cocaine-dependent patients achieve better outcomes after drug cessation, but literature indicates that these strategies alone are at times insufficient to induce significant behavioural changes or a reduction in rates of drug consumption. Unlike other types of addiction, such as opioid and alcohol, no pharmacological treatment has yet been found to be truly effective in relieving cocaine-cessation symptoms like craving and anxiety or to prevent relapse. CBD is a natural cannabinoid with a favourable tolerability profile and discrete neurobiological actions that are linked to neural circuits closely involved in addiction disorders. Addiction to cocaine is characterized by alternating phases of intoxication and short abstinence, followed by recurrent drug-craving episodes which result in distress and relapse. Our hypothesis is that CBD a cannabinoid known for its broad spectrum properties is an interesting pharmacological contender to decrease cocaine craving and treat cocaine addiction. Previous studies conducted in animals and humans confirm that CBD is a very safe and tolerable medication.
Detailed Description
The investigators will carry out a double-blind, randomized, parallel-group, placebo-controlled trial to assess the effects of 92 days of CBD 400 mg (for the first 2 days starting on Day 2 of the study) or 800 mg (subjects who report side effects with the 800mg dose will be administered the CBD 400 mg dose for the remainder of the trial) or placebo on cocaine craving and cocaine use among 110 cocaine-dependent individuals. Phase I of the trial will assess the effects of CBD or placebo administration on cocaine craving in the context of a 10-day inpatient medical detoxification period. Phase II of the trial will be a 12-week post-detoxification outpatient follow-up period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Substance Use Disorder, Cocaine Dependence, Withdrawal From Addictive Substance; Detoxification

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
79 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cannabidiol
Arm Type
Active Comparator
Arm Description
Participants will receive CBD 800 mg for 92 consecutive days starting on Day 2 of a 10-day inpatient detoxification period followed by 12 weeks of outpatient follow-up
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo for 92 consecutive days starting on Day 2 of a 10-day inpatient detoxification period followed by 12 weeks of outpatient follow-up
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Other Intervention Name(s)
CBD
Intervention Description
The investigators will carry out a double-blind, randomized, controlled trial comparing the effects of 92 days of 400 (only for the first 2 Days starting on the Day 2 of the study) or 800 mg CBD (subjects who report side effects with the 800mg dose will be administered the CBD 400 mg dose for the remainder of the trial) vs. placebo administration on cocaine craving and relapse in 110 cocaine-dependent subjects.
Primary Outcome Measure Information:
Title
Drug-cue induced craving
Description
A 10-point visual analog scale (VAS) used to measure craving responses in the context of cocaine cue-induced craving during the laboratory session on Day 8 of detoxification
Time Frame
Day 8
Title
Number of days to relapse
Description
The number of days to relapse will be determined as the number of days between detoxification discharge (Day 10) and the day of first cocaine use as determined by the first positive urine test for cocaine (the day prior to urine testing will be entered as the day of relapse) or the first day of cocaine use self-reported by participants (the earliest of both measures)
Time Frame
Day 10 to 92
Secondary Outcome Measure Information:
Title
Stress-induced craving
Description
A 10-point VAS used to measure craving responses in the context of stress-induced craving during the laboratory session on Day 8.
Time Frame
Day 8
Title
Cocaine use during the post-detoxification phase
Description
The percentage of positive urine tests will be calculated - we will conservatively assign a 'positive' result to all visits for which the test result is not available for a given subject (including all visits after the subject's loss to follow-up and all scheduled 'intermediate' weekly visits to which the subject did not come or at which the test was not performed).
Time Frame
Day 10 to 92
Other Pre-specified Outcome Measures:
Title
Detailed cocaine craving
Description
Assessed using the Cocaine Craving Questionnaire: CCQ-Brief.
Time Frame
Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Title
Subjective cocaine craving
Description
A 10-point VAS used to measure cocaine craving.
Time Frame
Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Title
Cocaine withdrawal symptoms
Description
Assessed using the Cocaine Selective Severity Assessment: CSSA. The CSSA enquires about 18 symptoms commonly reported in the literature as being associated with early cocaine abstinence; items are rated on a scale of 0-7.
Time Frame
Day 1, Day 3, Day 5, Day 7, Day 9, Week 4, Week 8, Week 12
Title
Anxiety
Description
Using the Beck Anxiety Inventory (BAI). 21-item self-report scale that measures the severity of anxiety in adults. The BAI total score is the sum of the ratings given by the examinee for the 21 symptoms. Each symptom is rated on a 4-point scale ranging from 0 to 3. The maximum score is 63 points.
Time Frame
Day 2, Day 9, Week4, and Week 12
Title
Subjective anxiety
Description
A 10-point VAS used to measure anxiety.
Time Frame
Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Title
Positive and negative affect
Description
Positive and Negative Affect Schedule: PANAS is a 10 positive and 10 negative affects rated on a scale from 1 to 5.
Time Frame
Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Title
Blood pressure
Description
Blood pressure during the laboratory session and daily during detoxification.
Time Frame
Day 1 to 10, Week 4, Week 12
Title
Heart rate
Description
Heart rate during the laboratory session and daily during detoxification.
Time Frame
Day 1 to 10, Week 4, Week 12
Title
Self-report cocaine use during the post-detoxification phase
Description
Total number of self-reported days of cocaine use using the Time Line Follow-Back (TLFB).
Time Frame
Day 10 to 92
Title
Sustained abstinence
Description
Defined as three weeks without self-reported cocaine use (using the TLFB) or positive urine test
Time Frame
Day 10 to 92
Title
Addiction severity
Description
Using the Addiction Severity Index: ASI-Lite questionnaire. The ASI-Lite is a semi structured interview tool to assess potential problem areas in substance-abusing patients: medical status, employment and support, drug use, alcohol use, legal status, family/social status, and psychiatric status.
Time Frame
Day 2 and Day 92
Title
Sleeping pills used during phase 1 (detoxification)
Description
Doses of Benadryl or trazodone administered during detoxification.
Time Frame
Day 1 to 10
Title
Depressive symptoms
Description
Beck's Depression Inventory second edition: BDI-II. The BDI-II is a 21-item self-report instrument for measuring the severity of depression in adults.
Time Frame
Day 2, Day 9, Week4 and Week 12
Title
Number of psychosocial intervention sessions (outpatient phase)
Description
Number of attended group therapy sessions during the outpatient phase.
Time Frame
Day 10 to 92
Title
Compliance to CBD
Description
Assessed by measuring CBD remaining in bottle weekly during post-detoxification visits and weekly journal entries by patient.
Time Frame
Day 10 to 92
Title
Completion rate
Description
Assessed by determining if participants is still in the study at week 12.
Time Frame
Day 10 to 92
Title
Potential biological substrates of CBD's impact on cocaine craving and relapse - cortisol
Description
Assessed by measuring cortisol levels
Time Frame
Day 2, Day 8 and Week 4
Title
Potential biological substrates of CBD's impact on cocaine craving and relapse - anandamide
Description
Assessed by measuring anandamide (AEA) levels
Time Frame
Day 2, Day 8 and Week 4
Title
CBD plasma levels
Description
CBD plasma levels.
Time Frame
Day 8, Day 9, Week 4 and Week 12
Title
Inflammatory markers - leukocytes
Description
Assessed by evaluating modulation of the activation status of the immune cells (circulating leukocytes) in their sera at defined time points.
Time Frame
Day 2, Day 8, Week 4 and Week 12
Title
Inflammatory markers - inflammatory proteins
Description
Assessed by evaluating modulation of the presence of inflammatory proteins in their sera at defined time points.
Time Frame
Day 2, Day 8, Week 4 and Week 12
Title
Cognition
Description
Memory, attention, impulsivity and decision-making will be assessed using a CANTAB battery.
Time Frame
Day 1, Day 7, Week 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria DSM-5 criteria for current cocaine use disorder (moderate or severe). Current cocaine use with last use during two weeks prior to admission to the study as confirmed by the Timeline Follow Back questionnaire. Age between 18 and 65 years old (inclusive). Women with diagnosed menopause (as confirmed by the study physician), under the age of 65, will be eligible for the study Subject consents to inpatient detoxification at the CHUM. Ability to give valid, informed consent. Ability to speak and read French or English. Exclusion criteria Severe and/or unstable hepatic, neurologic (including diagnosis of seizures), cardiac (including arrhythmias) or renal disease), or any other severe or unstable medical condition that precludes safe participation in the study according to the study physician. Patients who are already immunocompromised (e.g., patients with human immunodeficiency virus-1 who do not meet the following criteria: undetectable HIV virus (using modern assay) and CD4 count >350 cells/uL in the last 6 months prior to enrolment, patients on antiretroviral therapy; or other infectious organisms), exhibit malignancy and/or have autoimmune syndromes. Hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products. Severe psychiatric condition (history of schizophrenia, schizoaffective disorder or bipolar disorder); current acute psychosis, mania or severe suicidality based on the Mini International Neuropsychiatric Interview (MINI 7.0)). Pregnancy or breastfeeding. Inability (or unwillingness) of women of childbearing potential to use a medically acceptable form of contraception throughout study duration and for 3 months after dosing stops. A medically acceptable form of contraception is either: (1) contraceptive pill or intrauterine device or depot hormonal preparation (ring, injection, implant); and/or (2) a double barrier method of contraception such as diaphragm, sponge with spermicide and condom. Couples planning to conceive within the next 12 months. Men with history of fertility problems. Another current severe substance use disorder or any substance use disorder that would require pharmacological treatment according to the addiction specialist except nicotine (e.g. benzodiazepine or opiate for alcohol or opioid use disorder). Current treatment with medications that may interact with Cannabidiol (i.e., psychotropic medications such as benzodiazepines or anticonvulsants) or anticipation that the patient may need to initiate such treatment during the study. Any serious medical condition or psychiatric illness that precludes the subject from signing the informed consent form.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Didier Jutras-Aswad, MD,MS,FRCPC
Organizational Affiliation
Centre de Recherche du CHUM / Université de Montréal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre de recherche du Centre Hospitalier de l'Université de Montréal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 0A9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35135986
Citation
Mongeau-Perusse V, Rizkallah E, Morissette F, Brissette S, Bruneau J, Dubreucq S, Gazil G, Trepanier A, Jutras-Aswad D. Cannabidiol Effect on Anxiety Symptoms and Stress Response in Individuals With Cocaine Use Disorder: Exploratory Results From a Randomized Controlled Trial. J Addict Med. 2022 Sep-Oct 01;16(5):521-526. doi: 10.1097/ADM.0000000000000959. Epub 2022 Feb 8.
Results Reference
derived
PubMed Identifier
33464660
Citation
Mongeau-Perusse V, Brissette S, Bruneau J, Conrod P, Dubreucq S, Gazil G, Stip E, Jutras-Aswad D. Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: a randomized placebo-controlled trial. Addiction. 2021 Sep;116(9):2431-2442. doi: 10.1111/add.15417. Epub 2021 Feb 9.
Results Reference
derived

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Cannabidiol and Cocaine Craving/Dependence

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