NAC is an antioxidant compound that has recently been reported to benefit depression and other mental health issues. But what does the latest science have to say about this compound, how it works, and its potential effects on health? Read on to learn more!
What is NAC?
The body uses N-acetyl cysteine (NAC) to make its own antioxidants. Medically, NAC is used to treat acetaminophen toxicity; it is almost 100% effective, as long as it’s given within the first eight hours after overdose [1, 2].
For all other purposes, NAC is an unapproved supplement. Preliminary evidence may look promising (and in some cases, very promising!), but future studies may find that NAC is actually ineffective for some of these purposes.
It’s important to talk to your doctor before adding NAC to your health strategies, as it may have unexpected interactions.
Snapshot
Proponents:
- Some preliminary evidence for benefits in depression
- May also help with obsessive-compulsive disorder symptoms, and addiction
- Promising early research in many mental health conditions
- Generally considered safe
CONs:
- Doesn’t taste good
- Can cause nausea
- May affect bleeding
- Many purported benefits remain unproven or inconclusive
Potential Mental Health Applications of NAC
NAC supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them, but don’t guarantee that they’re safe or effective.
None of the information in this post should ever be used to replace conventional medical care. Always speak with your doctor before trying any new supplements or other health strategies.
Possibly Effective For…
1) Depression
Some very early research has suggested that NAC may help people with depression by [3, 4]:
- Balancing brain glutamate levels
- Reducing inflammation
- Boosting the growth of new brain cells
According to one review of data from multiple individual studies (including data from 574 depression patients and healthy participants), NAC has been reported to potentially improve symptoms of depression and overall daily functioning within 3-6 months of use [5].
Additionally, it has been reported to improve mood in depression patients after 3-4 months [6, 4].
NAC may also balance mood by reducing oxidative stress in the brain. For example, one study of 76 depressed patients has reported that those who took NAC had higher brain antioxidant levels [7].
Insufficient Evidence For…
The following purported benefits are only supported by limited, small-scale clinical studies. In other words, there is currently insufficient evidence to conclusively support the use of NAC for any of the uses or applications listed below — and much more research will be needed before any of these potential applications can be confirmed and officially approved for medical use.
Remember to speak with a doctor before taking NAC, and never use it in place of something your doctor recommends or prescribes.
2) Bipolar Disorder and Mania
NAC is currently under scientific investigation for its potential to improve chronic health issues — such as heart disease and hormonal imbalances — in patients with bipolar disorder.
According to one preliminary small-scale study, NAC had an indirect effect on overall health, antioxidant status, and inflammation in 51% of bipolar patients with cardiovascular or hormonal issues [8].
In another study with 17 bipolar patients, NAC was reported to improve low mood and overall symptoms after 6 months of supplementation [9].
While the available scientific data so far only comes from small-scale studies, larger clinical studies are currently underway to investigate the potential benefits of NAC for bipolar disorder [10].
NAC has also been reported to improve mania symptoms after 6 months of supplementation, according to one small-scale, placebo-controlled study of 15 patients. The NAC group reported experiencing less severe mania symptoms, while the placebo group actually reported worsened symptoms over the course of the study [11].
3) Obsessive-Compulsive Disorder (OCD)
NAC may help with OCD by balancing glutamate and increasing antioxidants in the brain. In a study of 44 OCD patients, supplementing with NAC as an add-on to standard medications was reported to improve symptoms, even in patients with relatively severe cases [12].
According to one study of 48 OCD patients who previously didn’t respond to conventional pharmaceutical medications, NAC was reported to improve the symptoms after 3 months of supplementation, without significant rates of adverse side-effects [13].
Finally, one relatively large-scale review concluded that NAC may have significant future potential for treating obsessive-compulsive disorders, and that it appears to cause relatively few negative side-effects [14].
However, while some of these early findings seem promising, some other studies have reported not finding any significant or noticeable benefits of NAC supplementation in OCD patients — so the current evidence is still mixed [15].
4) Autism
According to some early research, NAC may have some future potential in treating some of the symptoms associated with autism.
For example, one preliminary small-scale study has reported that 3 months of supplementation with NAC helped reduce irritability in 33 children with autism [16].
In two other studies in a total of 80 autistic children, those who received NAC supplementation as an add-on to treatment with an antipsychotic (risperidone) for two months reported experiencing less irritability and hyperactivity [17, 18].
However, the available evidence is still mixed. For example, one study in 98 autistic children reported no benefits of NAC supplementation over the course of 6 months [19].
According to one other small-scale study in 31 children with autism, NAC supplementation was reported to increase levels of glutathione (a natural anti-oxidant compound), but had no larger effect on their overall social functioning over the course of the 12 weeks of treatment [20].
5) Schizophrenia
According to a few preliminary studies, NAC may help improve symptoms of schizophrenia and psychosis — possibly by balancing the brain’s levels of the neurotransmitter glutamate and fighting oxidative stress and inflammation.
In an early study of 58 patients with psychosis, 2g/day of NAC supplementation was reported to improve working memory and other cognitive processes (which are often disrupted in psychosis). Additionally, this study also reported that NAC supplementation reduced symptoms of mania and hallucinations, and improved responses to treatment with conventional antipsychotics, in another sample of 121 patients [21].
According to another study, NAC supplementation combined with conventional antipsychotics was reported to improve psychosis-symptoms in 42 schizophrenic patients. It also appeared to have an especially noticeable effect on emotional and motivational symptoms such as low mood and apathy. Overall, no major negative side-effects were reported by the patients [22].
6) Cognition
According to some very preliminary research, NAC supplementation may have some potential effects on cognition — especially in older populations suffering from age-related cognitive impairments or certain neurodegenerative diseases.
For example, combined treatment with NAC and several other anti-oxidant compounds has been reported to improve cognition in healthy older people with mild cognitive impairment (MCI) [23, 24]. However, it remains unclear from these results whether NAC itself was specifically responsible for these cognitive effects, or whether similar effects would be seen in younger populations.
Additionally, some preliminary research is underway to test the potential efficacy of NAC supplementation for treating some of the cognitive deficits involved in Alzheimer’s disease, Parkinson’s disease, and schizophrenia, as well as its potential to improve cognitive outcomes after surgical procedures involving the use of anesthesia [25].
7) Compulsive Behaviors
Some early studies have reported that NAC may help alleviate some compulsive behaviors associated with a variety of psychiatric conditions.
For example, NAC supplementation was reported to reduce compulsive skin-picking in a study of 66 children with excoriation disorder [26].
In another study of 42 children, NAC was also reported to reduce compulsive nail-biting behavior [27].
In one other study, NAC supplementation was reported to reduce compulsive hair-pulling behavior in 50 patients with trichotillomania [28].
8) Addiction
Based on a few early reports from studies of animal models of binge eating, some researchers have proposed that NAC may have some potential to help combat various types of addiction [29].
One large-scale review of data from 9 different studies (comprising a total of 165 addiction patients) reported that NAC may be potentially effective for treating cannabis and cocaine addictions. The authors of this study also suggest that NAC may be effective for other addictions, such as nicotine, methamphetamine, and pathological gambling, although the evidence for these applications is somewhat weaker and less clear [30].
Additionally, one study in combat veterans with PTSD-related substance addictions reported that combining NAC supplementation with traditional psychotherapy treatment may have helped reduce drug cravings, as well alleviate PTSD-related depression symptoms [31]. However, this treatment group is quite unique, and it’s unclear to what extent these findings might apply to other types of psychiatric patients or healthy human users.
While the specific biological mechanisms involved in these potential effects are not yet clear, some researchers have speculated that the cysteine contained in NAC supplements may help the brain better-regulate its levels of glutamate, a major neurotransmitter which is believed to play a critical role in the neural pathways involved in addiction [32, 33].
Amphetamines
NAC reportedly helped reduce craving in 23 people with methamphetamine addiction [34].
However, in another study, NAC combined with an opioid blocker (naltrexone) did not produce any benefits in 31 people with methamphetamine addiction [35].
Cocaine
When it comes to cocaine dependence, some researchers believe that NAC may help reduce craving and relapse. In one study of 111 people, NAC helped maintain abstinence from cocaine over 8 weeks [36].
NAC also reportedly helped reduce cocaine cravings in 15 people after just 3 days of supplementation [37].
While the potential underlying mechanisms are unknown, some preliminary evidence from a brain-imaging study in cocaine addicts reported that NAC supplementation was associated with reduced levels of glutamate in certain motivation- and reward-related regions of the brain, such as the anterior cingulate cortex (ACC) [38].
Cannabis
People addicted to cannabis who try to quit often revert to alcohol abuse (i.e. to “compensate” for the loss of their preferred substance). According to one study of 302 people addicted to cannabis, NAC supplementation was reported to reduce alcohol consumption by up to 30% in those trying to quit [39].
In another study of 116 marijuana-dependent teenagers, NAC supplementation was associated with relatively lower overall rates of marijuana and alcohol consumption [40].
Preliminary findings such as these may suggest that NAC could be a comparatively safe “add-on” treatment to help reduce substance abuse in certain addicted populations. However, the current evidence is still mixed: for example, in another study, NAC appeared to have no significant or noticeable effects on cannabis addiction in adults [41].
Additional clinical studies of the potential role in NAC in treating or managing substance use during marijuana cessation are ongoing, and will hopefully clarify and extend some of these preliminary findings further [42].
Nicotine
One study in 100 smokers and non-smokers reported that smokers tend to have significantly higher brain levels of glutamate compared to people who don’t smoke [43].
Because some other preliminary research has suggested that NAC may potentially counteract elevated glutamate levels, some researchers have investigated whether NAC supplementation may have some potential in treating nicotine addiction by targeting glutamate levels and activity [32, 38, 44, 33].
In one small-scale study of 16 chronic smokers, NAC supplementation was reported to help maintain abstinence and reduce cigarette cravings. Brain-imaging of these patients suggests that NAC may achieve these effects by “re-structuring” the brain’s reward pathways, even after just 4 days of NAC supplementation [45].
In another small-scale, placebo-controlled study of 35 chronic smokers, 3 months of NAC supplementation was reported to reduce the total number of cigarettes these patients smoked. By the end of the study, almost half of the NAC-treated group of smokers reported having quit smoking entirely, compared to only 1/5th of the patients who received an inactive placebo treatment instead [46].
Finally, according to one other short-term study, just 3.5 days of NAC supplementation was reported to partially alleviate nicotine withdrawal symptoms in a small group of chronic smokers who were trying to quit. While many of the smokers in this study ended up relapsing and smoking again, those who received NAC supplementation reported that their first cigarette after temporarily quitting was noticeably less enjoyable than usual, suggesting a potential effect on NAC on the “pleasurable” or “rewarding” effects of cigarettes [44].
While these early reports seem promising, all of the available studies so far have only used very small samples of nicotine users — and much larger-scale, long-term studies will be needed to confirm these initial findings.
Pathological Gambling
According to one early, small-scale study, 8 weeks of NAC supplementation was reported to reduce gambling behaviors in 27 patients with compulsive gambling disorders [47].
NAC supplementation has also been reported to increase the effectiveness of psychotherapy in a 3-month study of 28 pathological gamblers who were also chronic smokers [48].
9) Lupus & (Comorbid) ADHD
One of the biological signs of lupus is dysfunctional T-cells, an important component of the immune system. Some researchers have speculated that stimulating glutathione production by supplementing with NAC may have some potential benefits on “re-balancing” T-cell levels in patients with lupus.
According to one early trial in 36 lupus patients, 2.4 – 4.8g/day of NAC supplements for 3 months was reported to partially alleviate lupus symptoms. The study authors also observed significantly reduced mTOR activity in the treated patients, which may imply a direct role of the glutathione pathway in mediating these therapeutic effects [49].
Interestingly, people with lupus have been reported to have increased rates of ADHD, suggesting that these two conditions may be linked by some common mechanisms. In line with this possible connection, one study in 100 lupus patients with ADHD reported that NAC supplementation (at 5g/day) was associated with reduced ADHD symptoms (such as impulsivity and various cognitive impairments) [50].
Takeaway
N-acetyl cysteine (NAC) is a common supplemental form of the amino acid cysteine. The human body uses it to produce antioxidants, and emergency responders and doctors use it to prevent acetaminophen poisoning.
Recent human studies have uncovered a number of potentially applications for NAC in mental health. The best evidence comes from a series of trials in which NAC improved symptoms of depression. Other promising (but early and insufficient) evidence suggests that NAC may help with bipolar disorder, OCD, autism, schizophrenia, and addiction.
Further Reading
- What is NAC? Side Effects, Dosage, Mechanism, Reviews
- 29+ Health Benefits & Uses of NAC (N-Acetyl Cysteine)
