Can N-Acetyl-L-Cysteine (NAC) Treat Psychiatric Disorders?

What you need to know

• N-acetyl-L-cysteine (NAC) is a compound that may help treat various psychiatric disorders through its antioxidant, anti-inflammatory, and glutamate-modulating effects
• NAC shows the most promise for treating negative symptoms of schizophrenia, severe autism, depression, and obsessive-compulsive disorders
• Most studies on NAC have been small and short-term, so larger and longer trials are needed to better understand its potential benefits

How NAC may work in psychiatric disorders

N-acetyl-L-cysteine (NAC) is a compound that has several effects in the body and brain that may be helpful for treating psychiatric disorders:

1. Antioxidant effects: NAC helps produce glutathione, which is the main antioxidant in the brain. By reducing oxidative stress, NAC may protect brain cells from damage.

2. Anti-inflammatory effects: NAC can reduce levels of inflammatory molecules in the body and brain. Inflammation is thought to play a role in many psychiatric conditions.

3. Glutamate regulation: NAC helps regulate glutamate, an important brain chemical involved in mood, cognition, and behavior. Abnormal glutamate activity is linked to several psychiatric disorders.

4. Dopamine modulation: NAC may help regulate dopamine, another key brain chemical involved in motivation, pleasure, and movement.

5. Protection of mitochondria: NAC may help protect mitochondria, the energy-producing structures in cells, from damage. Mitochondrial dysfunction is associated with some psychiatric conditions.

6. Promoting neuroplasticity: There is some evidence NAC may promote the growth and reorganization of brain cells, which is important for learning and recovery.

Through these various mechanisms, NAC has the potential to address some of the underlying biology involved in psychiatric disorders. However, more research is still needed to fully understand how NAC works in the brain and which of these effects are most relevant for treating different conditions.

NAC for neurodevelopmental disorders

Autism spectrum disorder

NAC shows promise for treating some symptoms of autism spectrum disorder (ASD), particularly in more severe cases. A review of several small clinical trials found that NAC significantly improved irritability and hyperactivity symptoms in children with ASD compared to placebo. However, it did not show significant effects on social behaviors or repetitive behaviors.

The largest study to date, which included 102 children with ASD, did not find significant benefits of NAC over placebo. However, this study used a lower dose than most other trials. Overall, the evidence suggests NAC may help with some behavioral symptoms in more severe autism, but larger studies are still needed.

Tourette’s disorder

Only one small study has examined NAC for Tourette’s disorder, finding no significant benefit compared to placebo in children and adolescents. More research is needed before any conclusions can be drawn about NAC’s potential for this condition.

NAC for schizophrenia spectrum disorders

NAC shows promise for treating negative symptoms of schizophrenia, such as lack of motivation and reduced emotional expression. A review of several clinical trials found that NAC significantly improved negative symptoms compared to placebo after 24 weeks of treatment. However, it did not show benefits at earlier time points, suggesting NAC may take several months to have an effect.

NAC may work in schizophrenia by reducing oxidative stress and inflammation in the brain, as well as helping to normalize glutamate signaling. Brain imaging studies have found that NAC can alter brain glutamate levels and functional connectivity in people with schizophrenia.

For early psychosis and those at high risk for psychosis, the evidence for NAC is still limited. A few small studies have had mixed results, and larger trials are ongoing. NAC’s potential to prevent or delay the onset of psychosis is an important area for future research.

NAC for mood disorders

Bipolar disorder

The evidence for NAC in bipolar disorder is mixed. Early studies showed promising results for treating depressive symptoms, but later larger trials have not consistently replicated these findings. Some studies suggest NAC may have a delayed effect, taking several months to show benefits.

A review of clinical trials found no clear evidence that NAC is effective for bipolar depression overall. However, some researchers argue there may still be a benefit for certain patients, particularly those with higher levels of inflammation or oxidative stress. More research is needed to clarify if NAC could help a subset of people with bipolar disorder.

Major depressive disorder

For major depression, one large clinical trial found that NAC led to significant improvements in depression symptoms compared to placebo after 16 weeks. The benefits were most notable in people with more severe depression. However, other studies examining NAC for depressive symptoms have had mixed results.

Some evidence suggests NAC may be most helpful for people with depression who have high levels of inflammation or oxidative stress. However, more research is needed to confirm this and determine which patients are most likely to benefit from NAC.

NAC for anxiety and trauma-related disorders

Very little research has examined NAC for anxiety disorders specifically. One case report suggested it may be helpful when added to standard medication for generalized anxiety disorder, but controlled studies are lacking.

For post-traumatic stress disorder (PTSD), one small study found NAC reduced cravings in veterans with PTSD and substance use disorders. However, it did not significantly improve PTSD symptoms overall. Larger trials of NAC for PTSD are currently ongoing.

NAC for obsessive-compulsive and related disorders

NAC shows promise for treating obsessive-compulsive disorder (OCD) and related conditions:

• OCD: A review of clinical trials found NAC significantly reduced OCD symptoms compared to placebo. However, the effect was relatively small and may not be clinically meaningful for all patients.

• Trichotillomania (hair-pulling disorder): Two clinical trials have had mixed results, with one showing significant benefits of NAC and the other finding no effect. More research is needed.

• Excoriation (skin-picking) disorder: One clinical trial found NAC significantly reduced skin-picking symptoms compared to placebo.

• Onychophagia (nail-biting): One small study in children found no significant benefit of NAC for nail-biting.

Overall, NAC appears to have potential for treating OCD and related disorders, but more research is needed to determine its effectiveness for specific conditions and identify which patients are most likely to benefit.

NAC for substance use disorders

Many studies have examined NAC for various substance use disorders, but results have been largely disappointing:

• Alcohol use disorder: No clinical trials have directly examined NAC for alcohol addiction, though some studies of other conditions have found NAC may reduce alcohol consumption.

• Cannabis use disorder: Large clinical trials have not found significant benefits of NAC for cannabis addiction in adults, though there is some evidence it may help adolescents.

• Stimulant use disorders: Studies of NAC for cocaine and methamphetamine addiction have generally not found significant benefits over placebo.

• Nicotine addiction: Clinical trials have not found NAC to be effective for smoking cessation.

Some researchers have suggested NAC may be more helpful for preventing relapse in people who have already achieved abstinence, rather than for initial addiction treatment. However, more research is needed to confirm this.

NAC for cognitive disorders

NAC has shown some potential for improving cognition in various conditions:

• Traumatic brain injury: One study found NAC improved cognitive symptoms in military personnel with mild traumatic brain injury.

• Alzheimer’s disease: A small study found NAC improved some aspects of cognition in people with probable Alzheimer’s disease.

• Healthy older adults: Some studies have found NAC may improve certain cognitive functions in healthy older adults.

However, most of these studies have been small, and results have been mixed. Larger trials are needed to determine if NAC has meaningful cognitive benefits and for which conditions.

Conclusions

• NAC shows the most promise for treating negative symptoms of schizophrenia, irritability in severe autism, and obsessive-compulsive disorders
• Benefits of NAC may take several months to emerge in some conditions
• Most studies of NAC have been small and short-term, so larger and longer trials are needed
• More research is needed to determine optimal dosing, identify which patients are most likely to benefit, and understand NAC’s long-term effects