n-acetylcysteine + naltrexone

A combination of N-acetylcysteine (NAC), a glutamate modulator with antioxidant properties, and naltrexone, an opioid antagonist. This combination has been studied for its potential in treating substance use disorders, particularly methamphetamine and alcohol dependence, by targeting complementary mechanisms - regulating glutamatergic tone (NAC) and blocking opioid receptor activity which influences dopaminergic pathways (naltrexone). **Pharmacological Properties** N-acetylcysteine is a glutamate modulator that helps regulate glutamatergic receptors and has antioxidant properties through glutathione replenishment. It's well-known for its clinical efficacy as a mucolytic agent and for treating acetaminophen overdose. Naltrexone is an opioid antagonist that blocks the euphoric and sedative effects of opioids by binding to opioid receptors. It's FDA-approved for treating both opioid use disorder (OUD) and alcohol use disorder (AUD). **Clinical Research** A 2010 double-blind, placebo-controlled study examined the efficacy of NAC plus naltrexone for methamphetamine dependence over 8 weeks. The study included 31 subjects and failed to demonstrate statistically significant differences from placebo on primary and secondary outcomes, but the small sample size limited statistical power. A more recent clinical trial is investigating the combination of NAC and high-dose naltrexone (150 mg) for alcohol dependence over 12 weeks, comparing the combination to high-dose naltrexone alone and high-dose naltrexone to low-dose naltrexone (50 mg) alone. **Safety Profile** NAC is generally considered safe and well-tolerated, with mild side effects in 1-5% of cases. Naltrexone's common side effects include nausea, sleepiness, headache, dizziness, vomiting, decreased appetite, painful joints, muscle cramps, cold symptoms, trouble sleeping, and toothache. Serious side effects may include severe injection site reactions, liver damage, allergic reactions, pneumonia, and depressed mood. Naltrexone is contraindicated in patients receiving opioid analgesics, those dependent on opioids or in acute opioid withdrawal, individuals who fail the naloxone challenge test or have a positive urine screen for opioids, and those with a history of sensitivity to naltrexone.

Other names

NAC plus naltrexone