N-acetylcysteine (NAC) is an over-the-counter supplement that may be used for several conditions. This molecule is a derivative of cysteine, which is an amino acid. In the hospital setting, it is used by the intravenous route for the treatment of acetaminophen overdose.1
NAC is also used in chronic obstructive pulmonary disease to break up mucous. It may also be beneficial in the prevention of contrast-induced nephropathy.2
During the last several years, there has been an interest in using acetylcysteine for other ailments.
This post will focus on the use of NAC for depression, anxiety, bipolar disorder, schizophrenia and the treatment of addiction.
Acetylcysteine has been studied for its ability to treat several types of addiction. A study conducted on 116 cannabis dependent adolescents and young adults found that those treated with 2.4 grams per day of NAC had a significantly higher incidence of negative urine cannabinoid tests as compared to the placebo group.3
This was a double-blind, randomized controlled trial lasting eight weeks. The NAC group also showed a more considerable decrease in self-reported days of cannabis use than the placebo group, but this was not statistically significant.
There is a possibility that NAC could increase cannabinoid elimination. This would increase the probability of the NAC group having a negative urine test.
More studies are needed to investigate the effects of NAC of cannabinoid metabolism.
Several controlled studies have shown NAC to be beneficial for treating cocaine addiction. The most extensive study showed positive effects only in a small subset of subjects that were abstinent at the beginning of the trial.
The studies for using NAC in other types of addiction, including gambling, were inconclusive.
The treatments currently available for anxiety disorder have limited effectiveness. Several studies suggest oxidative stress has a role in the development of anxiety. These findings have led to studies on the use of antioxidants in the treatment of anxiety.4
There has been a case study of a 17-year-old male with generalized anxiety disorder and social phobia who had failed cognitive behavioral therapy and several antidepressants but responded well to NAC.
Unfortunately, more studies are needed before NAC can be recommended as a treatment for anxiety.
Bipolar disorder is a mood disorder characterized by periods of depression alternating with periods of mania.
Symptoms of depression include:
- Feeling sad or hopeless.
- Loss of interest in pleasurable activities.
- Sleep disturbances – too much or too little sleep.
- Inappropriate guilt.
- Unexplained weight changes.
- Loss of energy or fatigue.
- Restlessness or lethargy.
Manic symptoms are as follows:
- Racing thoughts.
- Euphoria and increased self-confidence.
- Increased activity and agitation.
- Participation in risky behaviors.
- Poor decision making.
- Unusual talkativeness.
Bipolar disorder can be severe and may also present with psychotic features. Acetylcysteine has been shown to improve depressive symptoms in patients with bipolar disorder significantly.6
Unfortunately, this study was not able to show any significant difference in the frequency of new episodes of either depression or mania in the NAC group compared to the placebo group. More research is necessary to determine the role NAC may have in the treatment of bipolar disorder.
A randomized-controlled trial of 252 patients with major depressive disorder (MDD) showed NAC improved symptoms more effectively than placebo when added to the patient’s usual treatment regimen for a twelve-week period.7
There is also a case series of two patients who showed successful and sustained improvement of depressive symptoms when NAC was added to their antidepressant regimen.8
Other studies of NAC in the treatment of other disorders have found an improvement in mood and well-being.9
The current evidence suggests NAC may be a valuable treatment option either alone, or in combination with other agents for the treatment of mood disorders.
There have been positive results obtained when utilizing acetylcysteine for the treatment of schizophrenia.
One such study showed patients receiving NAC improved with regards to schizophrenia symptoms and akathesia.10
Other studies have also supported the use of NAC as a viable addition to schizophrenia treatment regimens.11
Although these results are promising, more studies with larger sample sizes are necessary to determine the true utility of NAC in the treatment of schizophrenia.
Mechanism of Action
The proposed mechanisms of action of NAC are too complicated for the scope of this post. This substance is thought to work as an antioxidant and anti-inflammatory. It is also thought to affect several neurotransmitters and mitochondrial function within cells.
Adverse Effects of Acetylcysteine
Acetylcysteine is generally well-tolerated. UpToDateTM lists the following adverse reactions to oral acetylcysteine:
- Chest tightness
- Rash (with or without fever)
- Nausea and Vomiting
- Hypersensitivity reaction
Less than 1%, post-marketing and/or case reports (important or life-threatening only):
Pregnancy and Breast-Feeding
Since acetylcysteine crosses the placenta, it should only be used in pregnancy when the benefits outweigh the risk. This may occur in the case of acetaminophen overdose.
It is not known whether NAC is excreted into breast milk. Based on pharmacokinetic data, acetylcysteine should be cleared from the body thirty hours after administration.
If NAC is consumed while breast feeding, breast milk should be pumped and discarded for thirty hours after ingestion.
NAC should not be used in pregnant women for depression, anxiety, bipolar disorder or the treatment of addiction.
There are no known drug interactions.
I became interested in N-Acetylcysteine after speaking to a child psychiatrist at the hospital where I practice. She had ordered it for one of her patients, and I was curious as to her reasoning for its use. She believed in NAC’s ability to improve several psychiatric symptoms in children with minimal risk. She sent me an article which detailed much of what I have covered in this post.
NAC has also been studied for use in Alzheimer’s disease, ADHD, autism, epilepsy, neuropathy, traumatic brain injury (TBI), and several impulse control disorders. It is essential to mention that more studies need to be done in all of these conditions before a recommendation can be made to use NAC.
I do believe it is worth trying NAC in patients who present with the disease states covered in this post. There is minimal risk, and the benefits could be significant. This is especially true in conditions such as anxiety disorder, where our treatment options are scarce and often ineffective.
Please feel free to contact me if you have any questions regarding acetylcysteine or any other medication or supplement. I would be happy to get an answer for you ASAP.
As always, have a great week, stay healthy, and stay safe!
Disclosure: This post may contain affiliate links, meaning, at no additional cost to you, I may earn a commission if you click on, or make a purchase through a third-party link.
- L. Green, K.J. Heard, K.M. Reynolds, D. Albert. Oral and intravenous acetylcysteine for treatment of acetaminophen toxicity: a systematic review and meta-analysis. West. J. Emerg. Med., 14 (3) (2013), pp. 218-226
- Quintavalle C, Donnarumma E, Fiore D, Briguori C, Condorelli G. Therapeutic strategies to prevent contrast-induced acute kidney injury. Current opinion in cardiology. 2013;28:676-82.
- K.M. Gray, M.J. Carpenter, N.L. Baker, S.M. DeSantis, E. Kryway, K.J. Hartwell, A.L. McRae-Clark, K.T. Brady A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am. J. Psychiatry, 169 (8) (2012), pp. 805-812
- Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11:851-76.
- Sansone RA, Sansone LA. Getting a Knack for NAC: N-Acetyl-Cysteine. Innovations in clinical neuroscience. 2011;8:10-4
- Berk, D.L. Copolov, O. Dean, K. Lu, S. Jeavons, I. Schapkaitz, M. Anderson-Hunt, A.I. Bush. N-acetyl cysteine for depressive symptoms in bipolar disorder – a double-blind randomized placebo-controlled trial. Biol. Psychiatry, 64 (6) (2008), pp. 468-475
- Berk, O. Dean, S.M. Cotton, S. Jeavons, M. Tanious, K. Kohlmann, K. Hewitt. The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. Clin. Psychiatry, 75 (2014), pp. 628-636
- A.F. Carvalho, D.S. Macedo, P. Goulia, T.N. Hyphantis. N-acetylcysteine augmentation to tranylcypromine in treatment-resistant major depression. Clin. Psychopharmacol., 33 (5) (2013)
- F.J. Martinez, J.A. De Andrade, K.J. Anstrom, T.E. King Jr., G. Raghu, Idiopathic Pulmonary Fibrosis Clinical Research Network Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. Engl. J. Med., 370 (22) (2014), p. 2093
- Berk, D. Copolov, O. Dean, K. Lu, S. Jeavons, I. Schapkaitz, M. Anderson-Hunt, F. Judd, F. Katz, P. Katz, S. Ording-Jespersen, J. Little, P. Conus, M. Cuenod, K.Q. Do, A.I. Bush. N-acetyl cysteine as a glutathione precursor for schizophrenia – a double-blind, randomized, placebo-controlled trial. Biol. Psychiatry, 64 (5) (2008), pp. 361-368
- Berk, A. Munib, O. Dean, G.S. Malhi, K. Kohlmann, I. Schapkaitz, S. Jeavons, F. Katz, M. Anderson-Hunt, P. Conus, B. Hanna, R. Otmar, F. Ng, D.L. Copolov, A.I. Bush. Qualitative methods in early-phase drug trials: broadening the scope of data and methods from an RCT of N-acetylcysteine in schizophrenia. Clin. Psychiatry, 72 (7) (2011), pp. 909-913
- Farokhnia, A. Azarkolah, F. Adinehfar, M.R. Khodaie-Ardakani, S.M. Hosseini, H. Yekehtaz, M. Tabrizi, F. Rezaei, B. Salehi, S.M. Sadeghi, M. Moghadam, F. Gharibi, O. Mirshafiee, S. Akhondzadeh. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin. Neuropharmacol., 36 (6) (2013), pp. 185-192