Will the exciting potential of NAC aka N-acetylcysteine on brain chemistry unlock a new generation of mental health medications?
NAC Supplement Mental Health
N-acetylcysteine (NAC) targets many pathways in mental health disorders. Current trends are trialing the use of NAC in disorders such as cocaine and smoking addiction, Alzheimer’s disease, compulsive and grooming disorder, depression, OCD, and bipolar disorder are on the rise. It’s clear to see why NAC has been gaining popularity, it’s found to be safe and tolerable in multiple studies across the board.
NAC Used for Over 30 Years
NAC has been used for over 30 years as an antidote in the treatment of Tylenol overdoses, as a mucus dissolver for chronic obstructive pulmonary disease (COPD) and as a kidney protective medication for kidneys injured through the use of contrast (a liquid used to highlight body structures on imaging such as a CT scan). Only recently have researchers been studying NAC supplement mental health benefits.
NAC Mechanism of Action in the Brain
Here, we are going to examine the possible mechanism of action of NAC in the treatment of mental health disorders. To keep it simple, we’re only going to discuss how NAC may work in the brain.
NAC, n-acetylcysteine is an early building block of an amino acid call cysteine. Cystine switches with glutamate (glutamate goes out of the cell while cystine goes in). When cystine goes inside the cell, it can become cysteine. This key step is needed to form the molecule glutathione.
Glutathione is an extremely vital antioxidant in the body and in the brain.
Glutamate is a chemical messenger that found to be imbalanced in many mental health disorders such as schizophrenia, addiction, OCD. Excessive activation of the glutamate receptor can cause damage to neurons in the brain.
NAC Lowers Glutamate Levels
NAC regulates this glutamate system and shows benefits in reversing the high levels of glutamate found outside the cells in the brain. This could help with behavioral deficits in schizophrenia.
In addition, NAC shows benefits in animal models of cocaine addiction.
NAC Modifies Glutamate Receptors
NAC also has the ability to change the activity of the glutamate receptor (N-methyl-d-aspartate receptor). Therefore, NAC has an indirect and direct therapeutic effect on glutamate.
NAC and Dopamine Release
NACmay also play a role in changing dopamine release.
In addition to contributing to the neurotransmitter reward and reinforcement behavioral actions, dopamine is thought to be a pro-oxidant which contributes to neurotoxicity. A pro-oxidant is something that causes oxidative stress. Dopamine imbalances are thought to be the pathology in schizophrenia and Parkinson’s disease. NACcan help regulate dopamine release via antioxidant effects of glutathione and cysteine.
Oxidative Stress in the Brain
Oxidative stress can occur in the brain through glutamatergic signaling and from neurotransmitter activity.
Neurons have an outer membrane that is necessary for it to transmit information. This outer membrane can be damaged by free radicals. More importantly, the brain produces lower levels of antioxidants compared to the rest of the body. Because of this, even a little amount of stress in the brain can have larger negative effects.
Thus, even a small imbalance in the levels of antioxidants and pro-oxidants can tip the “see-saw” and alter neuron function.
Imbalances in these antioxidants and pro-oxidants have been seen in attention deficit hyperactivity, bipolar disorder, autism, depression, and schizophrenia.
NAC is being extensively studied in cocaine addiction. In a 2-day study, participants who were abstaining from cocaine were given 2400mg NAC or placebo. The researchers found that there was a significant decrease in cravings, withdrawal symptoms and cocaine-use in the participants who were given the NAC.
NAC may reverse the imbalance of the glutamate system caused by long-term cocaine use.
A large review of the literature found that NAC may be better used to stop cravings and abstain from cocaine use after participants had already stopped using cocaine.
They found that NAC was not as helpful in the first step of stopping the addiction.
NAC for OCD
NAC has been studied for OCD and hair pulling disorders. After supplementation with NAC, symptoms of obsessive compulsive disorder decreased significantly.
Interestingly, researchers found that NAC may stop addictive behaviors that don’t stem from substance abuse. An 8-week study of twenty pathological gamblers showed that there was a significant reduction in gambling behavior when participants took 1800mg/kg of NAC. More studies are currently being conducted to examine NAC as a treatment for gambling.
In a 6-month study with 76 participants, participants who were treated with 1000mg of NAC twice a day in addition to bipolar treatment were found to have large decreases in symptoms of depression. Read more on NAC and depression.
NAC plays a role in many pathways that are implicated in neurodegenerative disorders such as Alzheimer’s disease.
Patients with late-stage Alzheimer’s disease were found to have significant improvement in their memory recall when treated with 50 mg/kg/day of NAC for six months. Similarly, other trials with NAC in patients with Alzheimer’s disease showed improvements in dementia and cognitive tests.
NAC may prevent and treat Alzheimer’s disease by protecting brain regions involved in memory such as the hippocampus which were found in mice studies.
NAC, n-acetylcysteineholds tremendous potential as a novel therapeutic option for a multitude of mental health disorders.
Although these studies are preliminary, the results are significant and give hope in finding better and improved therapy options in mental health disorders including depression, bipolar depression, substance addiction, compulsive disorders, schizophrenia, and Alzheimer’s disease. Future studies will be needed to explore NAC supplement mental health benefits.
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- Berk, Michael et al. The promise of N-acetylcysteine in neuropsychiatry. Trends in Pharmacological Sciences. 2013; 34(3): 167-177
- Dean O., et al. N-Acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J. Psychiatry Neurosci. 2011; 36: 78-86
- Echevarria, Marco et al. N-acetylcysteine for treating cocaine addiction – A systematic review. Psychiatry Research. 2017; 251: 197-203
- Shahidi, S et al. Influence of N-acetyl cysteine on beta-amyloid-induced Alzheimer’s disease in a rat model: A behavioral and electrophysiological study. Brain Research Bulletin. 2017; 131: 142-149.