This study evaluates the use of N-acetylcysteine in the treatment of alcohol and cocaine use disorders. Alcohol users will be split in two groups, one will receive the active N-acetylcysteine and the other placebo. The same division will occur with cocaine users. The effects of N-acetylcysteine in adherence, abstinence, psychiatric symptoms and stress biomarkers will be evaluated.

N-acetylcysteine acts replenishing the human body glutathione storages. Glutathione is an important antioxidant agent, and also modulates the N-methyl-D-aspartate (NMDA) glutamatergic receptor. Glutamate has been associated with the neuroadaptation related to substance use disorders, and thus it is considered a potential target for pharmacological interventions regarding these disorders. N-acetylcysteine also interacts with the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space.

N-acetylcysteine effects and its implications in the addiction disorders have been studied initially with animal models. Glutamate levels normalization through N-acetylcysteine reduced compulsive drug self-administration and drug-seeking behavior in mice. In addition, there are promising results also with human subjects, showing benefits for cocaine, alcohol and cannabis use disorders.

This study consists of a randomized, double-blind, placebo controlled trial with four arms: alcohol users divided into NAC vs Placebo and cocaine users divided into NAC vs Placebo.

Inclusion Criteria:

• Diagnostic of Alcohol or Cocaine Use Disorder
• Seven days of inpatient treatment in an addiction treatment specialized unit

Exclusion Criteria:

• Another Substance Use Disorder (exception: tobacco)
• Severe medical conditions (cardiac, renal or hepatic), that preclude subject participation
• History of asthma or convulsions medication use
• Recent use (<14 days) of any medication that could interfere with the study medication
• History of anaphylactic reactions with the study medication
• Suicide risk
• Inability to understand the informed consent form or to comply with the study requirements
• Any severe neuropsychiatric condition, not caused by the substance use, that requires specific medication treatments and could interfere with the study development, in the investigators opinion (for instance: dementia, schizophrenia or other psychoses, multiple sclerosis, severe depression, stroke, epilepsy, bipolar disorder)
• Failing to complete the screening procedures prior to the study first week