Cannabidiol and Cocaine Craving/Dependence

Cocaine Dependence Clinical Trial

— CBD  

Official title:

Cannabidiol as a New Treatment for Cocaine Addiction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02559167
• Other study ID #: 14.183
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2016
• Est. completion date: August 16, 2019

Study information

• Verified date: January 2020
• Source: Centre hospitalier de l'Université de Montréal (CHUM)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: August 16, 2019
• Est. primary completion date: August 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cocaine Dependence
• Cocaine-Related Disorders
• Substance Use Disorder
• Substance-Related Disorders
• Withdrawal From Addictive Substance; Detoxification

Intervention

Drug:
• Cannabidiol
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.

Locations

Country	Name	City	State
Canada	Centre de recherche du Centre Hospitalier de l'Université de Montréal	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre hospitalier de l'Université de Montréal (CHUM)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Detailed cocaine craving	Assessed using the Cocaine Craving Questionnaire: CCQ-Brief.	Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Other	Subjective cocaine craving	A 10-point VAS used to measure cocaine craving.	Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Other	Cocaine withdrawal symptoms	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.	Day 1, Day 3, Day 5, Day 7, Day 9, Week 4, Week 8, Week 12
Other	Anxiety	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.	Day 2, Day 9, Week4, and Week 12
Other	Subjective anxiety	A 10-point VAS used to measure anxiety.	Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Other	Positive and negative affect	Positive and Negative Affect Schedule: PANAS is a 10 positive and 10 negative affects rated on a scale from 1 to 5.	Day 1, Day 3, Day 5, Day 7, Day 9, Week 1, Week 3, Week 5, Week 7, Week 9, Week11
Other	Blood pressure	Blood pressure during the laboratory session and daily during detoxification.	Day 1 to 10, Week 4, Week 12
Other	Heart rate	Heart rate during the laboratory session and daily during detoxification.	Day 1 to 10, Week 4, Week 12
Other	Self-report cocaine use during the post-detoxification phase	Total number of self-reported days of cocaine use using the Time Line Follow-Back (TLFB).	Day 10 to 92
Other	Sustained abstinence	Defined as three weeks without self-reported cocaine use (using the TLFB) or positive urine test	Day 10 to 92
Other	Addiction severity	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.	Day 2 and Day 92
Other	Sleeping pills used during phase 1 (detoxification)	Doses of Benadryl or trazodone administered during detoxification.	Day 1 to 10
Other	Depressive symptoms	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.	Day 2, Day 9, Week4 and Week 12
Other	Number of psychosocial intervention sessions (outpatient phase)	Number of attended group therapy sessions during the outpatient phase.	Day 10 to 92
Other	Compliance to CBD	Assessed by measuring CBD remaining in bottle weekly during post-detoxification visits and weekly journal entries by patient.	Day 10 to 92
Other	Completion rate	Assessed by determining if participants is still in the study at week 12.	Day 10 to 92
Other	Potential biological substrates of CBD's impact on cocaine craving and relapse - cortisol	Assessed by measuring cortisol levels	Day 2, Day 8 and Week 4
Other	Potential biological substrates of CBD's impact on cocaine craving and relapse - anandamide	Assessed by measuring anandamide (AEA) levels	Day 2, Day 8 and Week 4
Other	CBD plasma levels	CBD plasma levels.	Day 8, Day 9, Week 4 and Week 12
Other	Inflammatory markers - leukocytes	Assessed by evaluating modulation of the activation status of the immune cells (circulating leukocytes) in their sera at defined time points.	Day 2, Day 8, Week 4 and Week 12
Other	Inflammatory markers - inflammatory proteins	Assessed by evaluating modulation of the presence of inflammatory proteins in their sera at defined time points.	Day 2, Day 8, Week 4 and Week 12
Other	Cognition	Memory, attention, impulsivity and decision-making will be assessed using a CANTAB battery.	Day 1, Day 7, Week 6
Primary	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	Day 8
Primary	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)	Day 10 to 92
Secondary	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.	Day 8
Secondary	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).	Day 10 to 92