Adventrues in Neuroscience - Episode 1 - NACBy: The Cosmic LionIf you don't care about the science or my explanation, skip straight to the Conclusions section at the end for the concise summary and dosage recommendation!NAC, or N-acetylcysteine, can be found over the coutner at most GNC's and many health food stores. GNC sells the 600mg pills, fairly weak, it is ideal to seek the 1,000mg pills due to the high recommended dosages.
NAC is all at once a nooptropic (smart drug), a physical medicine, and a serious psychiatric tool
NAC is an acetylized version of the natural amino-acid cysteine that is a precursor to Glutamate, which effects the Glutamate system, which is responsible for learning, memory, motivation and cognition. It has a TON of medical application already. Additionally, recent studies show psychiatric effects on the glutmate, dopamaine and NMDA brain systems.
Bear with me here, this post is long but filled with goodies. I present you here with MY summary, Wiki + WedMD info, then at the end the NEW info regarding its new use in psychiatry (Including a CUSTOM dose recommendation!). I will also explain the relevance of each quote after its posted. Stay tuned.
New studies have shown that NAC "facilitates the release of dopamine" which has had profound psychiatric applications.
NAC has been used for various things for a while now, but only RECENTLY have larger doses been found to be EXTREMELY therapeutic psychologically so much so that it is now being WIDELY used by psychiatrists across the board.
NAC is being used by psychiatrists to treat previously untreatable patients suffering everything from mild to major depression & bi-polar, to schizophrenia. It is often MOST effective for people who are "stable" enough to not warrant pharma meds but that still in need something to get their life on track.
It also helps with addictions, including Cannabis.
A colleague of mine prescribes it to patients with PHENOMENAL results in going from unproductive to finally being "normal and motivated" again, even without weed!
So whats WIKI say about this stuff?
http://en.wikipedia.org/wiki/AcetylcysteineQuote:"Acetylcysteine, also known as N-acetylcysteine or N-acetyl-L-cysteine (abbreviated NAC), is a pharmaceutical drug and nutritional supplement used primarily as a mucolytic agent and in the management of paracetamol (acetaminophen) overdose."
IINNNTERESTING.... Lets get some clarity from WebMD:
Quote:"N-acetyl cysteine is used to counteract acetaminophen (Tylenol) and carbon monoxide poisoning. It is also used for chest pain (unstable angina), bile duct blockage in infants, amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease), Alzheimer’s disease, allergic reactions to the anti-seizure drug phenytoin (Dilantin), and an eye infection called keratoconjunctivitis. It is also used for reducing levels of a type of cholesterol called lipoprotein (a), homocysteine levels (a possible risk factor for heart disease) and the risk of heart attack and stroke in patients with serious kidney disease.
Some people use N-acetyl cysteine for chronic bronchitis, chronic obstructive pulmonary disease (COPD), hay fever, a lung condition called fibrosing alveolitis, head and neck cancer, and lung cancer. It is also used for treating some forms of epilepsy; ear infections; complications of kidney dialysis; chronic fatigue syndrome (CFS); an autoimmune disorder called Sjogren’s syndrome; preventing sports injury complications; radiation treatment; increasing immunity to flu and H1N1 (swine) flu; and for detoxifying heavy metals such as mercury, lead, and cadmium.
N-acetyl cysteine is also used for preventing alcoholic liver damage; for protecting against environmental pollutants including carbon monoxide, chloroform, urethanes and certain herbicides; for reducing toxicity of ifosfamide and doxorubicin, drugs that are used for cancer treatment; as a hangover remedy; for preventing kidney damage due to certain X-ray dyes; and for human immunodeficiency virus (HIV).
Healthcare providers give N-acetyl cysteine intravenously (by IV) for acetaminophen overdose, acrylonitrile poisoning, amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease), kidney failure in the presence of liver disease (hepatorenal syndrome), chest pain in combination with nitroglycerin, heart attack in combination with nitroglycerin and streptokinase, and for helping to prevent multi-organ failure leading to death."
AWESOME! How medicinal! But how does it effect the brain?Lets look a recent study, I'll even
BOLD the important parts for you:
"N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044191/Quote:Abstract:
"There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways.
This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research."
Sweet! So lets get to the good stuff:Quote:"Alterations in pro- and anti-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumour necrosis factor (TNF)–α, have been reported in populations with depression, and to a lesser extent, bipolar disorder and schizophrenia.16,17 These inflammatory cytokines are potential contributors to the underlying pathophysiology of these disorders. N-acetylcysteine has been shown to have anti-inflammatory properties (Fig. 1) that are linked to oxidative pathways, which may provide another potential mechanism of action in the benefits of NAC in psychiatry."
OK so people that are depressed, bi-polar or shitzo have an "unbalanced" cytokine system. They even believe this specific unbalance is the CAUSE of these disorders! The NAC shows anti-inflammatory properties that restore balance to the cytokine system thus restoring mental health.
Onward...
Lets take a look how NAC effects the Glutamate system:Quote:"In addition to the effects on oxidative balance, alterations in cysteine levels have also been shown to modulate neuro-transmitter pathways, including glutamate and dopamine (DA; Fig. 1).23,24 Cysteine assists in the regulation of neuronal intra- and extracellular exchange of glutamate through the cystine–glutamate antiporter. Whereas this antiporter is ubiquitous throughout all cell types, in the brain it is preferentially located on glial cells.25 The dimer, cystine, is taken up by astrocytes and exchanged for glutamate, which is released into the extracellular space. This free glutamate appears to stimulate inhibitory metabotropic glutamate receptors on glutamatergic nerve terminals and thereby reduce the synaptic release of glutamate.26 Given that relation, the amount of cysteine in the system as well as the feedback via GSH production by neurons may directly regulate the amount of glutamate present in the extracellular space. Furthermore, GSH itself has been shown to potentiate brain N-methyl-d-aspartate receptor response to glutamate in rats.27,28 Changes in the levels of neuronal GSH may not only alter available glutamate levels, but also have direct consequences on glutamatergic function."
WOW! Like me, I bet you missed some of the important stuff on the first read. Lets dissect it. Now THIS seems tricky... What is extra cellular space? "Extra cellular space (ECS) may be imagined as a system of interconnected channels demarcated by cellular membranes and filled with an ionic solution, primarily NaCl, along with macromolecules" in which "the ECS mediates intercellular communication and the transport of nutrients and metabolites"
OK so NAC causes Glutmate to enter this Extracellular Space (ECS). This glutamate in the ECS has the effect of inhibiting, or stopping, glutamate from being released in the synapse. This is significant because many patients suffer psychological issues from TOO MUCH glutamate in the synapse.
NAC modulates the Gluatmate system, with the glutamate system playing major factors in cognition, learning, memory and behavior.
ALRIGHT, wait, so wtf is this "N-methyl-d-aspartate recepor" it mentions??? This is none other then our popular NMDA receptor!
The NMDA receptor "is the predominant molecular device for controlling synaptic plasticity and memory function" in which "calcium flux through NMDARs is thought to be critical in synaptic plasticity, a cellular mechanism for learning and memory" which in turns leads to solutions to complex cognitive problems such as motivation.
So WHAT is going on here exactly? The NMDA receptor reacts GREAT to the NMDA compound (a synthetic compound) but only KIND OF reacts to glutamate (your barin's natural compound). The NAC increases the NMDA Receptor's ability to 'accept' glutamate thus leading to potential action of stimulating learning, memory and motivation.
WHAT NEXT?!?!
Lets take a look at NAC's effects on the Dopamine System. Quote:"In addition to modulating glutamate levels through the cystine–glutamate antiporter, NAC has also been shown to alter Dopamine (DA) release. Following amphetamine treatment to rat striatal slices, NAC has been shown to facilitate vesicular DA release at low doses in striatal neurons and inhibit release at millimolar concentrations.29 In monkeys, NAC has been shown to protect against reductions in DA transporter levels following repeated methamphetamine administration,30 suggesting one mechanism whereby increased DA release was facilitated in the previous study."
WOAH! So NAC makes Dopamine be released! Sweet deal! Lets take a closer look at dopamine... stimulants (ADD meds included) usually work by increasing amounts of dopamine in the brain. Dopamine, in some ways, can be considered a major 'thought' chemical. When someone is psychotic, they think too much and too extravagantly. Some of the most potent anti-psychotic drugs are dopamine-inhibiting agents which REMOVES dopamine from the brain (well from the synapses, but you know!)
OK so lets look at amphetamine users... the amphetamines stimulate TOO MUCH of a release of dopamine. This causes the tolerance, addiction and subsequent over-oxidation of emotional systems that leads to the long term personality disorders seen in amphetamine addicts. "Methamphetamine is not directly neurotoxic but its use is associated with an increased risk of Parkinson's disease due to the fact that uncontrolled dopamine release is neurotoxic.[5][21] Long-term dopamine upregulation occurring as a result of Methamphetamine abuse can cause neurotoxicity which is believed to be responsible for causing persisting cognitive deficits, such as memory, impaired attention and executive function"
So NAC "protects against reductions in Dopamine transporter levels following repeated methamphetamine use"!!! This means that it normalized your Dopamine system even if your amphetamine abuse is depleting it. Talk about neuroprotective!
NAC's action as a Dopamine modulator is likely the source of its effectiveness as a medication. It can increase dopamine in those that are 'down' or feel 'lack of energy' or 'no motivation' but it can also PREVENT too much dopamaine from being released in a toxic manner!
Talk about a SWEET neuro adaptogen!
So what implications does this have?Lets take a look:
Quote:OCD: Obsessive Compulsive Disorder
"At present, there is only 1 case report regarding the use of NAC in patients with OCD.38 This report showed notable benefits in an individual who was treatment-refractory.”
Quote:Bi-Polar Disorder
"A double-blind, randomized, placebo-controlled trial of NAC in 75 participants with bipolar disorder was conducted. This 6-month trial involved the addition of 2000 mg/d of NAC or placebo. Rating scores on the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Bipolar Depression Rating Scale showed large decreases in depressive symptoms (about 9 points on the MADRS between NAC and placebo groups at the end point).”
Quote:Schizophrenia
"A large-scale study investigating NAC as an adjunctive therapy for schizophrenia has been conducted,42 which employed a 1000 mg, bi-daily regimen (compared with placebo) in addition to existing medication over 6 months. In all, 140 participants took part in this double-blind, placebo-controlled, randomized trial. Improvements were seen in the negative symptoms, measured on the Positive and Negative Symptoms Scale. Furthermore, improvements in global function and improved abnormal movements, particularly akathisia, were also reported. These effect sizes were moderate, and improvements were lost 1 month after the discontinuation of treatment”
Quote:Marijuana Addiction
"A recent study by Gray and colleagues31 investigated the use of NAC (2400 mg/d) in an open-label study of 24 dependent marijuana users who reported an interest in reducing their use. Following treatment, users reported reductions in days/week of use and “number of hits.”
Quote:Nicotine Addiction
"In addition to the modulation of glutamate to reduce cravings and reward behaviours, NAC may have a role as an antioxidant in a disorder where oxidative stress is marked. There has been 1 placebo-controlled study (n = 29) investigating 2400 mg/day of NAC as a treatment for tobacco cessation.32 This study recorded participant ratings of use and cravings as well as biochemical measures to confirm reported use."
Quote:Cocaine Addiction
"In a small crossover study (n = 13), designed to determine tolerability and safety, participants (currently abstaining from cocaine use) were given 2400 mg of NAC or placebo over 2 days. The NAC group had a significant reduction in cravings, withdrawals and self-reported use compared with baseline, which was not seen in the placebo group.
Quote:Gambling Addiction
"In an open-label study involving 29 participants with a confirmed pathologic addiction to gambling, Grant and colleagues37 administered 1800 mg (titrated dose) of NAC over 8 weeks. A randomized trial of 13 responders was then conducted over the following 6 weeks (constant dose of 1800 mg/kg of NAC compared with placebo). During the open-label study, 16 participants experienced significant reductions in gambling behaviour.”
So, at last...
---IN CONCLUSION---NAC can be purchased over the counter, even at most GNC's. GNC sells the 600mg pills, fairly weak, it is ideal to seek the 1,000mg pills due to the high recommended dosages.
NAC shows vast potential as a nootropic due to its effects on Glutamate, NMDA and Dopamine systems.
NAC shows potential for helping in burnout feelings, ADD, mild depression, strong depression, bi-polar, OCD and schizophrenia.
NAC shows MUCH promise in treating addictions to Amphetamines, Marijuana, Nicotine, Cocaine and Gambling.
NAC can modulate glutamate, increasing it in the Extra-Cellular Space while decreasing it in the synapse. "Glutamate receptors are important for neural communication, memory formation, learning, and regulation" and too much or too little can cause problems in this area.
NAC made the NMDA receptor MORE SENSITIVE to glutamate thus allowing it to be more active. NMDA being "the predominant molecular device for controlling synaptic plasticity and memory function." With "synaptic plasticity [being] a cellular mechanism for learning and memory."
NAC facilitates the release of Dopamine. Indicating use for people with ADD, Motivation issues, 'lack of energy' issues and general 'slow thinking' issues. In fact, its NAC's action on Dopamine is probably the cause to a lot of its effects.
NAC modulates/prevents/slows down Dopamaine released from drugs like amphetamines. thus limiting the potential harm and unbalancing nature of amphetamines if NAC is taken WITH these drugs.
Final Dosage Recommendation:The daily dose based on studies: 2000-3000mg (2-3g) per DAY
A colleague of mine talked to the scientists THEMSELVES, the ones who did the study....
They recommend taking UP TO 6000-8000mg a day, without side effects.
NAC can lead to nausea so see how you react first.
ACTUAL DOSAGE RECOMMENDATION FROM PROFESSIONALS:
--2000mg-6000mg PER DAY-- Work your way up, make notice of any side effects/nausea.
Peace yall.
-Eternally Romping the Astral Savannahlands-