N-Acetylcysteine and Mental Health

N-acetylcysteine (NAC) is a form of the amino acid cysteine that is often used as a nutritional supplement. Cysteine is considered a conditionally essential amino acid. In certain situations, it may be essential for an individual to cover their needs for cysteine by consuming it in the diet. Cysteine is used by the body in building proteins and is an important precursor for producing the antioxidant glutathione.

The Biochemical Benefits of NAC

As a treatment, NAC has a number of effects. It acts as a precursor to glutathione production, one of the body’s main protective antioxidants. It also acts as an antioxidant itself, helping to reduce the body’s free radical burden. Beyond antioxidant benefits, it can help to reduce inflammation, a key component often present in a number of mental health conditions.

Other effects of NAC relevant for mental health concerns include its effects on neurotransmitters. Glutamate is an excitatory neurotransmitter that has been implicated in numerous mental health conditions, from depression to schizophrenia. Excess glutamate activity is so toxic for cells that it can excite them to death. NAC is effective at modulating glutamate and protecting brain cells from this so-called “excitotoxicity” (Raghu 2021).

Based on these effects, it’s not surprising that research has started exploring the effects of NAC supplementation on mental health. Benefits for a number of different conditions appear likely, from bipolar disorder and depression, to obsessive-compulsive disorder and schizophrenia.

NAC and Bipolar Disorder

Bipolar disorder is a life-long condition where individuals struggle with both manic and depressive episodes. While medications can help to reduce symptoms, they often come with concerning side effects. Additionally, standard medications are not a cure, and patients may struggle with residual symptoms. As such, treatments that help to reduce bipolar symptoms further with minimal side effects can be quite useful for bipolar disorder treatment.

NAC appears to be just such a treatment. The first study on NAC for bipolar disorder was in 2008 (Berk 2008). The study lasted for six months, which is important, since the effects of NAC appear to have a relatively slow onset. It included 75 patients struggling with bipolar disorder. Over the course of the study, depression symptoms decreased by 60% with NAC as compared to an increase in 7% with placebo.

While the research overall is somewhat mixed, the latest review from 2023 still found that NAC was recommended as an adjunctive treatment for bipolar disorder (Xu 2023).

NAC, Depression and Suicide

The main study available on NAC and major depressive disorder found that NAC had modest benefits. The study didn’t find a significant difference from NAC and placebo on standard depression scales, but overall functioning and clinical impressions were significantly better with NAC supplementation (Berk 2014).

It’s also worth noting that a small study of patients who intentionally overdosed on medications found that NAC appeared beneficial (Hans 2022). In patients who received a bolus dose of NAC in the emergency room, suicidality and severe depressive symptoms after one week were significantly lower than patients who received standard care without NAC. The author’s suggest that further studies should continue to explore the potential anti-suicidal effects of acute NAC supplementation.

NAC and Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a condition with a common reputation for being difficult to treat. While medications have been shown to be helpful, many patients don’t respond or only have marginal improvements.

The latest data indicates that NAC may have a place as an adjunctive therapy (Kishi 2022). For a more complete discussion, you can read our recent, in-depth articlein-depth article exploring NAC and OCD treatment.

NAC and Schizophrenia

Similar to bipolar disorder, schizophrenia is typically a lifelong illness with significant negative effects on an individual’s quality of life. While medications may reduce symptoms, helping individuals to lead a more functional life, they often leave residual symptoms and have concerning side effects.

The first study published on NAC for schizophrenia found that NAC reduced overall symptoms over the course of six months (Berk 2008). Glutathione levels are known to be low in patients with schizophrenia, so NAC, as a precursor to glutathione, was hypothesized to potentially help through increasing glutathione levels.

The largest meta-analysis to date found that NAC had a medium-sized effect for lowering total symptom scores in schizophrenia (Kishi 2023). Worth noting is that this effect size is larger than what was shown by a recent meta-analysis for antipsychotic medication (Leucht 2022).

Takeaway

NAC has a number of interesting biochemical effects that are relevant for mental health. From antioxidant and anti-inflammatory activity to direct neurotransmitter effects, NAC helps support brain function. In cases of bipolar disorder, OCD and schizophrenia, NAC may help to lower symptoms. NAC may also be useful for reducing acute suicidal ideation.