N-acetylcysteine, also known as Acetylcysteine and NAC, is a medication that is used to treat paracetamol (acetaminophen) overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders, such as pneumonia and bronchitis.

[22] When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body.

[23] Research suggests that the rate of liver toxicity is approximately 3% when acetylcysteine is administered within 10 hours of overdose.

[25] However, 3% to 6% of people given intravenous acetylcysteine show a severe, anaphylaxis-like allergic reaction, which may include extreme breathing difficulty (due to bronchospasm), a decrease in blood pressure, rash, angioedema, and sometimes also nausea and vomiting.

Several studies have found this anaphylaxis-like reaction to occur more often in people given intravenous acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic.

This therapeutic effect is achieved through the cleavage of disulfide bonds[31] within mucoproteins (strongly cross-linked mucins),[32] thereby decreasing the mucus viscosity and facilitating its clearance from the respiratory tract.

This mechanism is particularly beneficial in conditions characterized by excessive or thickened mucus,[33] such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, rhinitis or sinusitis.

[23] Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, stomatitis, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction.

[46] Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.

The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitro and in vivo.

[47] In humans, much lower dosages (600 mg per day) have been observed to counteract some age-related decline in the hypoxic ventilatory response as tested by inducing prolonged hypoxia.

[58] The oral bioavailability of acetylcysteine is relatively low due to extensive first-pass metabolism in the gut wall and liver.

[medical citation needed] Acetylcysteine is the N-acetyl derivative of the amino acid L-cysteine, and is a precursor in the formation of the antioxidant glutathione in the body.

Pure acetylcysteine is in a solid state at room temperature, appearing as a white crystalline powder or granules.

[69] While many antioxidants have been researched to treat a large number of diseases by reducing the negative effect of oxidative stress, acetylcysteine is one of the few that has yielded promising results, and is currently already approved for the treatment of paracetamol overdose.

[70] N-acetylcysteine has been widely believed to prevent adverse effects of long term Ketamine use on the bladder and kidneys, and there is growing body of evidence to support this.

[92] Based upon limited evidence, NAC appears to normalize glutamate neurotransmission in the nucleus accumbens and other brain structures, in part by upregulating the expression of excitatory amino acid transporter 2 (EAAT2), a.k.a.

[83] NAC has been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.

Nonetheless, meta-analytic evidence shows that add-on N-acetylcysteine was more effective than placebo only in reducing depression scales scores (low quality evidence), without positive effects on response and remission outcomes, limiting its possible role in clinical practice to date.

[100][101] A combination of guanfacine and N-acetylcysteine has been found to lift the "brain fog" of eight patients with long COVID, according to researchers, but the results are inconclusive and have not been confirmed by other studies.

[102] A combination of glycine and N-acetylcysteine is suspected to have potential to safely replenish depleted glutathione levels in COVID-19 patients.