N-acetylcysteine for the Treatment of Cannabis Dependence: Working Mechanisms

Study Overview
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Brief Summary
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This study investigates the effects of repeated NAC administration on glutamate concentrations in the anterior cingulate cortex (ACC), on neurocognitive functioning, and on neuro-inflammatory parameters in adult cannabis-dependent individuals.

Official Title
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N-acetylcysteine for the Treatment of Cannabis Dependence: Working Mechanisms

Conditions
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Cannabis Use Disorder, Cannabis Dependence

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: Placebo Oral Tablet
* Other: Magnetic Resonance Imaging
* Other: Neurocognitive measures
* Other: Neuro-inflammatory measures


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current DSM-IV diagnosis of cannabis dependence, >1 week detoxified and abstinent; Able to provide written informed consent and to comply with study procedures. Dutch speaking (Dutch as primary language). Exclusion Criteria: Currently dependent on any substance other than cannabis, alcohol or nicotine; History of any major internal disease (including diabetes, cardiovascular disease, lung disease, liver or kidney disease); An active or any history of neurological disorder, including but not limited to seizure disorder, epilepsy, stroke, neurological disease, cognitive impairment, head trauma with prolonged loss of consciousness (>10 minutes), or migraine headaches; An active or a history of a psychiatric disorder including, but not limited to, depression, schizophrenia, bipolar disorder, anxiety, or other psychiatric disorders; Asthma; Known hypersensitivity or allergy to n-acetylcysteine, or receiving chronic therapy with medication that could interact adversely with n-acetylcysteine within 30 days prior to randomization (i.e., nitroglycerin, ACE inhibitors or antihypertensive drugs, anti-coagulants); Exclusion criteria for MRI: having metal in the body and/or having claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: RCT
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine<br> | Drug: N-acetylcysteine<br>* 1200 mg/day, twice daily, N-acetylcysteine<br>Other: Magnetic Resonance Imaging<br> <br> Other: Neurocognitive measures<br> <br> Other: Neuro-inflammatory measures<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo Oral Tablet<br>* twice daily, placebo<br>Other: Magnetic Resonance Imaging<br> <br> Other: Neurocognitive measures<br> <br> Other: Neuro-inflammatory measures<br> <br> |
| Active Comparator: Healthy controls<br> | Other: Magnetic Resonance Imaging<br> <br> Other: Neurocognitive measures<br> <br> Other: Neuro-inflammatory measures<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain glutamate concentrations | Glutamate concentrations in the anterior cingulate cortex (ACC) | at study end (2 weeks after study start) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor impulsivity | Stop Signal Reaction Time (SSRT) on the Stop Signal Task | at study end (2 weeks after study start) | 
| Cognitive impulsivity | Indifference point measured by a Monetary Delayed Discounting Task | at study end (2 weeks after study start) | 
| Attentional Bias | Difference in response time for incongruent-congruent stimuli on a Stroop task | at study end (2 weeks after study start) | 
| Neuro-inflammation | Concentration of interleukin in blood | at study end (2 weeks after study start) |