NAC - An Overview
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NAC (N-Acetyl-Cystine) is a powerful antioxidant supplement with many benefits for the body and brain.
In fact, it may have the most wide-ranging positive effects of any nootropic on the market. According to research, it could potentially help with:
- Depression & mood
- Learning & memory
- Overall brain health
Hospitals around the world use it to reverse acetaminophen (Tylenol) overdose. In fact, it is so important, the World Health Organization considers it one of their “essential medicines.”
Many people have started using NAC supplements for mental health issues. For some, NAC can help treat things like anxiety, OCD, or depression. Others take NAC supplements as brain-boosting nootropics.
Of all the nootropics, NAC has one of the widest varieties of benefits it can confer to those who take it.
There are DOZENS of positives that people report while taking this nootropic, and many of them are backed by extensive research.
In fact, 300 human clinical trials have been done in the past 10 years, which is pretty incredible for a supplement.
Even better, there are very few reported side effects. NAC is very well tolerated for most people. It is also inexpensive and available over the counter.
NAC supplements work through the body’s glutamate system.
What Does NAC Do?
NAC for Anxiety
NAC is rapidly gaining popularity as an anti-anxiety supplement.
Anxiety is often caused by overstimulation.
The most powerful excitatory transmitter in the brain is glutamate and levels get too high, it may trigger anxious or panicked feelings.
Luckily, NAC inhibits the flow of glutamate.
Anxiety and stress can also cause oxidation, damaging your cells and creating dangerous free radicals in your system.
NAC’s powerful antioxidant effect can protect your nerves from these harmful effects.
By increasing glutathione production, NAC can clean up the oxidative damage caused by too much stress.
Because NAC’s action on the glutamate system is unique among anxiety treatments, it may be able to help in cases where other methods don’t.
A 2017 Brazilian trial found a link between NAC and lower anxiety in patients suffering from OCD.
This double-blind, placebo-controlled 16-week study saw lower self-reported anxiety in those that had been treated with NAC.1Costa DLC, et al Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder, J Clin Psychiatry. 2017
One recent animal study from 2019 suggests that NAC may be an effective general anxiety/stress treatment.
Researchers exposed zebrafish to “unpredictable chronic stress” for several days, then were either given NAC or a placebo.
For the fish that received NAC, they found it “reversed the anxiety-like behavior and oxidative damage.” We look forward to seeing more trials like this with human participants.2Mocelin R, et al N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish, Mol Neurobiol. 2019
NAC for Depression
Currently, researchers are examining the role that glutamate and NMDA receptors may play in depression. Due to its action on this system, NAC may be a new way to deal with this condition.
Two studies show cessation in depressive symptoms after supplementing with NAC for 3-4 months.3Berk M, et al The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial, J Clin Psychiatry. 2014 4Hasebe K, eta. Adjunctive N-acetylcysteine in depression: exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor, Acta Neuropsychiatr. 2017
A meta-analysis of NAC and depression saw that there was a clear correlation between the two. This overview looked at placebo-controlled trials using N-acetylcysteine for depressive symptoms across 5 studies.
The researchers concluded that “administration of N-acetylcysteine ameliorates depressive symptoms, improves functionality, and shows good tolerability.”
In other words, it’s an effective and safe depression treatment.5Fernandes BS. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis, J Clin Psychiatry. 2016
Another study looked at 75 bipolar sufferers who were already taking medication for their condition.
They found that patients given NAC scored better on mood tests than those just taking medication. The effects faded after NAC was discontinued.6Berk M, et al N-acetyl cysteine for depressive symptoms in bipolar disorder–a double-blind randomized placebo-controlled trial, Biol Psychiatry. 2008
NAC for Addiction
NAC supplementation shows real potential as an addiction treatment. It’s impressive the wide range of addictions that NAC may be useful for.
This may be due to NAC’s ability to rebalance the glutamate system, which is often implicated in addiction.
Many researchers theorize that the glutaminergic system may play a large role in compulsive behaviors of all stripes.
Of all the psychological issues that NAC may treat, addiction has the most clinical research behind it.
Two studies have investigated the effects of NAC in young people with cannabis dependence.
They found that even after a few weeks, NAC helped curb their cravings.
The adolescents taking NAC were more likely to reduce or stop cannabis use during the evaluation period.7Kevin M. Gray, et al N-Acetylcysteine (NAC) in Young Marijuana Users: An Open-Label Pilot Study, Am J Addict 2010 8Gray KM, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents, Am J Psychiatry. 2012
NAC can reduce cravings for harder stuff as well. It is effective at treating cocaine addictions according to three separate studies.
One even shows that NAC reduces glutamate at a faster rate in cocaine abusers than non-addicts. This indicates NAC may naturally act as an “equalizer” in the brain.9LaRowe SD, et al Is cocaine desire reduced by N-acetylcysteine?, Am J Psychiatry. 2007 10LaRowe SD, et al A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence, Am J Addict. 2013 11Schmaal L, et al N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study, Neuropsychopharmacology. 2012
There is preliminary evidence NAC may help with methamphetamine addiction. More studies will be needed to draw a definitive conclusion, though12Mousavi SG, et al The efficacy of N-acetylcysteine in the treatment of methamphetamine dependence: a double-blind controlled, crossover study, Arch Iran Med. 2015
One meta-analysis looked at several individual studies regarding cocaine, nicotine, methamphetamine, marijuana, and gambling addictions.
All of these studies saw an across-the-board reduction in addictive behavior after NAC was administered for a few months.13Asevedo E, et al Systematic review of N-acetylcysteine in the treatment of addictions, Braz J Psychiatry. 2014
Another meta-analysis claims that NAC may be most useful as an “anti-relapse agent” for those trying to stay clean.14Rachel L. Tomko, et al N-acetylcysteine: A potential treatment for substance use disorders, Curr Psychiatr. 2018
Researchers have also studied N-acetylcysteine as a treatment for trichotillomania.
Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss.
It’s a surprisingly common compulsion, especially among younger people. They found that “NAC demonstrated statistically significant reductions in trichotillomania symptoms” after 12 weeks.
They indicate that “modulation of the glutamate system may prove to be useful in the control of a range of compulsive behaviors.”15Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study, Arch Gen Psychiatry. 2009
Two studies on compulsive gambling seem to back this claim up.
These studies suggest that the combination of NAC and psychotherapy is more effective than just psychotherapy for this addiction.16Grant JE, Kim SW, Odlaug BL.. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study, Biol Psychiatry. 2007 17Grant JE, et al. A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers, J Clin Psychiatry. 2014
Two separate studies indicate NAC can help with compulsions in children as well as adults.
These studies looked at skin picking and nail-biting. They found that the children who took NAC decreased these behaviors compared to the placebo.18Ghanizadeh A, Derakhshan N, Berk M.N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial, Antiinflamm Antiallergy Agents Med Chem. 2013 19Grant JE, et al N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial, JAMA Psychiatry. 2016 v
All-in-all, NAC is one of the promising new treatments for addiction and compulsive behavior.
It’s fascinating just how many different types of addiction it may help with. We look forward to seeing larger studies on this subject in the future.
Does NAC Help With Hangovers?
There is some circumstantial evidence that NAC can prevent or lessen hangovers. If you plan on letting loose this weekend, NAC could help combat the Sunday morning blues (to an extent.)
Hangovers have many unpleasant symptoms, but most of them are caused by acetaldehyde toxicity.
Acetaldehyde is a compound that is formed when your liver breaks down alcohol.
Acetaldehyde is far more toxic than alcohol, by as much at 30x. If you build up too much of this compound in your body, it can cause wreak havoc.
And, although many symptoms of a hangover will pass soon enough, this toxin can ultimately damage your liver, which is no laughing matter.
Luckily, your body can break down acetaldehyde and turn it into harmless acetic acid. It does this with the antioxidant glutathione.
As we mentioned above, NAC is a precursor to glutathione. This means supplementing NAC before you drink should increase your available glutathione, which will, in turn, break down acetaldehyde quicker.
Theoretically, this should reduce the severity and length of your hangover, as well as protect your liver.
So, does it work? Well, while there are no human trials, there is one animal study that suggests this may be the case.
Researchers induced alcohol poisoning in rats, then measured them for signs of liver damage.
The rats that had been given NAC showed significantly less liver toxicity than the rats that had not.20Resat Ozaras, et al. N-acetylcysteine attenuates alcohol-induced oxidative stress in he rat, World J Gastroenterol. 2003
Based on what we know about NAC, there is no reason to think it SHOULDN’T help with hangovers at least somewhat.
Many people swear by it, claiming it significantly reduces their discomfort the morning after.
That said, there are no magic bullets out there, and NAC can only help up to a point.
It may help take the edge off a few drinks, but it won’t save you from a bender. As always, moderation is the main factor when it comes to preventing hangovers.
NAC For OCD
There is plenty of evidence that NAC is effective at reducing addictive behaviors, so it comes as no surprise that it can help treat OCD as well.
Obsessive-compulsive disorder shares many of the same hallmarks as addiction. Researchers believe they may arise from the same biological roots.
Several studies conclude that NAC can be useful alongside traditional therapy for this condition.
NAC is well tolerated and has very few interactions with other medications, making it an ideal supplement.21Smith L, Tracy DK, Giaroli G. What Future Role Might N-Acetyl-Cysteine Have in the Treatment of Obsessive Compulsive and Grooming Disorders?: A Systematic Review, J Clin Psychopharmacol. 2016 22Afshar H, et al. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial, J Clin Psychopharmacol. 2012 23APaydary K, et al. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder: randomized, double-blind, placebo-controlled trial, J Clin Pharm Ther. 2016
There is some evidence that NAC may be helpful for weight loss. This could be due to multiple factors.
First, it may stop overconsumption. As we mentioned above, NAC can help curb addictive behavior.
This includes overeating. For those with a tendency to indulge, NAC may help reduce those cravings. One preliminary study on rats found that “administration of NAC resulted in significant reductions of binge eating.”
While human trials are needed to draw a firm conclusion, this is a promising start.24Hurley MM, et al. N-acetylcysteine decreases binge eating in a rodent model, Int J Obes (Lond). 2016
Secondly, NAC may keep your body from storing fat.
Another rat study, this one from 2016, indicates this could be the case. By the end, the rats that had taken the NAC dose weighed less than their counterparts.
They concluded that “NAC supplementation inhibited the increase of fat mass and the development of obesity.” The treated rats also showed fewer markers of inflammation.25Ma Y, Gao M, Liu D. N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders, Pharm Res. 2016
How NAC Works In The Brain
When it enters the body, NAC replenishes your glutathione stores.
Glutathione is one of the most critical antioxidants in the body.
It is very effective at fighting inflammation and clearing out free radicals from the body.
This anti-oxidant effect can have wide-ranging benefits for mental and physical health.
NAC also binds to NMDA and AMPA receptors in the brain and modulates glutamate production.
Glutamate is a critical neurotransmitter that handles many cognitive functions.
It is the most abundant excitatory transmitter in your brain and plays a principal role in neural activation.
Proper glutamate levels are vital for learning, memory, neuroplasticity, and long-term brain health.26Y. Zhou, N. C. Danbolt. Glutamate as a neurotransmitter in the healthy brain, J Neural Transm. 2014
But, too much glutamate can overstimulate your neurons, leading to cell toxicity and death.
Fortunately, it seems NAC can regulate the amount of glutamate in your brain and keep your neurons operating effectively.
NAC Potential Side Effects
Side effects with NAC are very rare.
However, high amounts may cause nausea, vomiting, diarrhea and constipation.
We strive to bring you the most up to date, research-based information about NAC and other nootropics.
Something we missed? Do you use NAC? Share your thoughts and experiences in the comments below.
About the author:
Erik Levi is a co-founder of HolisticNootropics.com and a certified holistic nutritional therapy practitioner.
As an NTP Erik takes a nutrition first approach to health. He has worked with many different people to help them use nutrition to optimize their quality of life.
Erik believes that mental health is a physiological process and cognitive enhancement is not something that can be achieved by just taking some pills with good Amazon reviews.
Instead, true cognitive enhancement comes with the right balance of nutrients, movement, and gratitude. Erik continues to stay up to date with the most current nootropic and holistic health research and promises to deliver the best solutions possible.
You can check out his personal health blog/podcast/YouTube Channel all under the name Holistic A-Hole.