Clinical trial NCT02559167: Cannabidiol and Cocaine Craving/Dependence
Official title: Cannabidiol as a New Treatment for Cocaine Addiction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Substance Use Disorder
Cocaine Dependence
Withdrawal From Addictive Substance; Detoxification
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
First posted: 2015-09-24
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Drug-cue induced craving
timeFrame: Day 8
measure: Number of days to relapse
timeFrame: Day 10 to 92
Secondary outcomes:
measure: Stress-induced craving
timeFrame: Day 8
measure: Cocaine use during the post-detoxification phase
timeFrame: Day 10 to 92
Other outcomes:
measure: Detailed cocaine craving
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
measure: Subjective cocaine craving
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
measure: Cocaine withdrawal symptoms
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 9, Week 4, Week 8, Week 12
measure: Anxiety
timeFrame: Day 2, Day 9, Week4, and Week 12
measure: Subjective anxiety
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
measure: Positive and negative affect
timeFrame: Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
measure: Blood pressure
timeFrame: Day 1 to 10, Week 4, Week 12
measure: Heart rate
timeFrame: Day 1 to 10, Week 4, Week 12
measure: Self-report cocaine use during the post-detoxification phase
timeFrame: Day 10 to 92
measure: Sustained abstinence
timeFrame: Day 10 to 92
measure: Addiction severity
timeFrame: Day 2 and Day 92
measure: Sleeping pills used during phase 1 (detoxification)
timeFrame: Day 1 to 10
measure: Depressive symptoms
timeFrame: Day 2, Day 9, Week4 and Week 12
measure: Number of psychosocial intervention sessions (outpatient phase)
timeFrame: Day 10 to 92
measure: Compliance to CBD
timeFrame: Day 10 to 92
measure: Completion rate
timeFrame: Day 10 to 92
measure: Potential biological substrates of CBD's impact on cocaine craving and relapse - cortisol
timeFrame: Day 2, Day 8 and Week 4
measure: Potential biological substrates of CBD's impact on cocaine craving and relapse - anandamide
timeFrame: Day 2, Day 8 and Week 4
measure: CBD plasma levels
timeFrame: Day 8, Day 9, Week 4 and Week 12
measure: Inflammatory markers - leukocytes
timeFrame: Day 2, Day 8, Week 4 and Week 12
measure: Inflammatory markers - inflammatory proteins
timeFrame: Day 2, Day 8, Week 4 and Week 12
measure: Cognition
timeFrame: Day 1, Day 7, Week 6
Locations:
city: Montreal
country: Canada
facility: Centre de recherche du Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Centre de Recherche du CHUM / Université de Montréal
name: Didier Jutras-Aswad, MD,MS,FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.