Acetylcysteine - An OTC mucolitic with surpising bio-neurological benefits

[/navarone/]

Evening BlueADDs

Today my starting topic, of which I would glandly appreciate some indepth data from all fo you is about the potential uses of N-acetyl-L-cysteine which apart from being an OTC mucolitic, seems to have a wide range of medical and neurological benefits apart from being a good and specific antioxidants.

Despite the fact that most bluelighters might just precipitously react to this thread thinking "It's ajust a cold medicine Man!", I would like to post some very interestin data about its beneficial and probably neuroactive potentials of this common and simple aminoacid ester.

Starting from the information stated on Wikipedia, a few statements are worth to be highlighted:

• 
  Evidence that NAC and other antioxidants can exert beneficial effects on pancreatic b-cell function in diabetes was published in a 1999 study. The authors conclude that a sufficient supply of antioxidants (NAC, vitamin C plus vitamin E, or both) may prevent or delay b-cell dysfunction in diabetes by providing protection against glucose toxicity.

• 
  NAC has been shown to reduce cravings associated with chronic cocaine use in a study conducted at the Medical University of South Carolina.

• 
  An animal study indicates that acetylcysteine may decrease mortality associated with influenza.

• 
  There are claims that acetylcysteine taken together with vitamin C and B1 can be used to prevent and relieve symptoms of veisalgia (hangover following ethanol (alcohol) consumption). The claimed mechanism is through scavenging of acetaldehyde, a toxic intermediate in the metabolism of ethanol

• 
  Sulfur and sulfur-related amino acids are commonly depleted in autism. Glutathione, which largely depends on cysteine for its formation, is also frequently depleted in autism, and may contribute to the heavy metal burden commonly found in autistic patients.

• 
  Possible antidote for methylmercury poisoning. It produced an acceleration of urinary methyl-mercury excretion in mice

• It has been shown effective in Unverricht-Lundborg disease in an open trial in 4 patients. A marked decrease in myoclonus and some normalization of somatosensory evoked potentials with N -acetylcysteine treatment has been documented

• Small reduction of cell death in chemotherapy patients, due to reduction in oxidative stress. Reduced ROS and lipid peroxidation, and restored of antioxidant enzyme activities

Also it is widely used as an atidote for paracetamol overdose, an analgesic that me like many normally use.

The other appealing thing about this drug as a supplements is its ability to eliminate heavy metal deposits in the body (eg: mercury, lead, cadmium) from from certain fish ect. based diets both from the drugh itself and also thorugh through endogenous synthesis of glutathione.

To put a conclusion to my thread, I wanted to know if this drug does pass the blood bran barrier and possibly has some significant neurological effects apart from being an indeen good antioxidant and mucolitic supplement.

Any further information would be greatly apreaciated.
Cheers

-Nav

 

[MeDieViL]

To put a conclusion to my thread, I wanted to know if this drug does pass the blood bran barrier and possibly has some significant neurological effects apart from being an indeen good antioxidant and mucolitic supplement.

Any further information would be greatly apreaciated.
Cheers

-Nav

Apperantly it has been found effective for a number of psychological conditions:

http://www.springerlink.com/content/763746nj71604523/

Received: 15 October 2005 Accepted: 25 October 2005 Published online: 22 December 2005
Abstract
Rationale Dysfunction of glutamatergic neurotransmission has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD) and recent clinical reports suggest that some glutamate modulating agents are efficacious in the treatment of this disorder. N-acetylcysteine (NAC) is a readily available amino acid compound that is thought to attenuate glutamatergic neurotransmission. NAC may be useful in treating psychiatric disorders involving glutamatergic dysfunction such as OCD.
Objectives To examine the efficacy of augmentation with NAC in a patient with serotonin reuptake inhibitor (SRI)-refractory OCD.
Methods A patient with SRI-refractory OCD was treated with an off-label use of NAC augmentation of fluvoxamine over several weeks.
Results NAC augmentation of fluvoxamine resulted in a marked decrease in Yale-Brown Obsessive Compulsive Scale (Y-BBOCS) score and a clinically significant improvement in OCD symptoms.
Conclusions NAC augmentation was effective in treating SRI-refractory OCD in this single case. Further research is warranted to investigate the use of NAC and other glutamate modulating agents in the treatment of OCD.

N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial.
Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI.

The Mental Health Research Institute of Victoria, Parkville, Australia.
BACKGROUND: Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and refractory to treatment. N-acetyl cysteine (NAC) increases brain glutathione in rodents. This study was conducted to evaluate the safety and effectiveness of oral NAC (1 g orally twice daily [b.i.d.]) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period. METHODS: A randomized, multicenter, double-blind, placebo-controlled study. The primary readout was change from baseline on the Positive and Negative Symptoms Scale (PANSS) and its components. Secondary readouts included the Clinical Global Impression (CGI) Severity and Improvement scales, as well as general functioning and extrapyramidal rating scales. Changes following a 4-week treatment discontinuation were evaluated. One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were randomized; 84 completed treatment. RESULTS: Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [-5.97 (-10.44, -1.51), p = .009], PANSS negative [mean difference -1.83 (95% confidence interval: -3.33, -.32), p = .018], and PANSS general [-2.79 (-5.38, -.20), p = .035], CGI-Severity (CGI-S) [-.26 (-.44, -.08), p = .004], and CGI-Improvement (CGI-I) [-.22 (-.41, -.03), p = .025] scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia (p = .022). Effect sizes at end point were consistent with moderate benefits. CONCLUSIONS: These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.

N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial.
Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI.

The Mental Health Research Institute of Victoria, Victoria, Australia.
Comment in:

Biol Psychiatry. 2008 Nov 1;64(9):e1.
BACKGROUND: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorder are complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder. METHODS: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n = 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning. RESULTS: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: -8.05 [-13.16, -2.95], p = .002) and most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p = .968) and no significant between-group differences in adverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts. CONCLUSIONS: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder.

Nail-biting stuff? The effect of N-acetyl cysteine on nail-biting.
Berk M, Jeavons S, Dean OM, Dodd S, Moss K, Gama CS, Malhi GS.

Department of Clinical and Biomedical Sciences, University of Melbourne, Australia. [email protected]
N-acetyl cysteine (NAC) is a widely available nutraceutical with a variety of actions. As a precursor of cysteine and glutathione, it has antioxidant properties that may impact on mood and contribute to an effect on impulsivity and obsessive behaviour. Via its additional effect on glutamate via the cystine-glutamate exchange system, NAC has been shown to mediate impulsivity in preclinical models of addiction, reduce craving, and cue extinction. Further, by boosting glutathione, NAC acts as a potent antioxidant and has been shown in two positive, large-scale randomized placebo-controlled trials to affect negative symptoms in schizophrenia and depression in bipolar disorder. We describe three cases in which its actions specifically on nail-biting and associated anxiety may offer a potential treatment. The spontaneous findings are reported as part of an ongoing treatment trial examining the utility of NAC in bipolar disorder. Its actions, if robustly replicated, also point to potential treatment targets in glutathione or glutamate pathways in the brain.

N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study.
This study, the first to our knowledge that examines the efficacy of a glutamatergic agent in the treatment of trichotillomania, found that N-acetylcysteine demonstrated statistically significant reductions in trichotillomania [obsessive hair pulling] symptoms. No adverse events occurred in the N-acetylcysteine group, and N-acetylcysteine was well tolerated.

 

[^Xayo]

I once had a bad cold and for making my cough "Smoother" I used N-Acetylcysteine. Turned out that after one dose of this (400mg I recall) I had to throw up for 2 days and was in a kind of delirious fog. Ofcourse it could've been cold symptoms but the cold was a rather slight one so I don't think it suddenly turned into a 2 day hyperthermia puking delirium.

 

[hamhurricane]

I have taken NAC daily for about a year, it is dirt cheap in bulk - although the crystalline material has odd dynamics in that it cannot be packed into a capsule like piracetam or carnitine - it simply flows out - so it must be scooped into a capsule rather than packed in with a downward motion. It's amazing the way different crystalline powder behave. Taking a 00 capsule half filled with carnitine and half with NAC seems to be good at preventing a wide variety of oxidative stress related ailments, add some ALA to the mix and your pretty well covered.

 

[/navarone/]

Also I wanted to add that coming from a ,editerrenean location, where fish consumption is rather abboundant, tuna especially, NAC has a good potential in depleting heeavy metal acumulation in the body probably through its sulphur containing stucture that contributres to its chelating activity especially when it gets converted in glutathione.

Medeivel, thanks a lot for the scientific documentation, that really helped..
Your investigational skills have improved a lot in the last years.
God job!

 

[23536]

It's probably really good for you but it won't get you high.

As for BBB permeability: I believe it's actively transported.

 

[alfaromeo1979]

I have tried NAC, as well as memantine, for a condition called Trichotillomania (a disorder that lies on the OCD spectrum). Even though memantine was potently effective, the side effects were intolerable. To my pleasant surprise, NAC was even more effective than memantine in diminishing my OCD symptoms. No side effects were noted from the NAC, and I'm sure my liver was thankful for it as well. Had to stop due to prohibitive cost and lack of availability. Would definitely do again, highly recommended.

 

[MeDieViL]

Also I wanted to add that coming from a ,editerrenean location, where fish consumption is rather abboundant, tuna especially, NAC has a good potential in depleting heeavy metal acumulation in the body probably through its sulphur containing stucture that contributres to its chelating activity especially when it gets converted in glutathione.

Medeivel, thanks a lot for the scientific documentation, that really helped..
Your investigational skills have improved a lot in the last years.
God job!

Cheers mate, i suspect it can be of benefit for tolerance too since it slows down glutaminergic firing, paradoxically by increasing glutamate and activating 2 mglur autoreceptors causing a netto anti glutaminergic effect.

 

[23536]

Had to stop due to prohibitive cost and lack of availability. Would definitely do again, highly recommended.

If you're in the US, check pharmacies for liver products. I'm staring at one right now that has 300 mg NALC per pill.

Thanks for teaching me a new word!

 

[StaySedated]

this stuff is in the muscle building powder supplement i use.

i didn't know it had so many uses.

 

[Torabora]

nice post next time I will add some ACC to my suplement mix when taking drugs ^^

 

[SugarTorch]

Actions of acetylcysteine of NMDA receptors

Hi Nav, hope you don't mind that I'm a greenlighter. As you summarized, acetylcysteine seems to have neuroprotective/antioxidant effects cerebrally and can prevent neuronal damage from free radicals and peroxides. As MeDieVil pointed out, n-alc crosses the BBB and contributes to synthesis of extracellular glutathione, which is a physiologic NMDA-receptor agonist. People who suffer from schizophrenia, autism, Alzheimer's disease & perhaps even bipolar disorder seem to have less active (or a smaller number of ) NMDA receptors than "normal" folks. So those receptors are involved with sensory perception and appropriate interpretation and integration of sensory information, as well as cognitive function and memory. In other words, schizophrenics may hallucinate because their sensory visual or auditory input is being mismanaged by their NMDA receptors. When you ask, "what neuronal action could n-alc have?" I assume you're referring to psychoactive properties or effects on mood, thought, etc. If you feel your NMDAs are depressed then you might feel "enhanced" or "better" with n-alc. However, most noticeable effects seem to result from NMDA receptor antagonism , as in ketamine, PCP, ethanol and DXM intoxication. The "dissociative" and anaesthetic effects of those drugs has to do with their NMDA receptor blockade.

Therapeutic dose for IV n-alc (Acetadote) is 30 mg/kg "over 21 hours" per Acetadote package info. You can take 15 mg/kg IV in first hour. 100 mg/kg produced overdosage in lab animals. Overdose caused neuronal death exhibited by "ataxia, hypoactivity and cyanosis." Also of note is that IV n-alc caused anaphylaxis in up to 20% of human test subjects, especially asthmatics, and that risk of anaphylaxis increased with IV rather than oral usage.
In conclusion, I think that it would be really great to have more NMDA receptors, and I would like to grow some, or find a drug that caused them to proliferate. Now, that would be cool.

 

[atara]

It also, unfortunately, has terrible oral bioavailability.

http://www.youtube.com/watch?v=3n0ZWS_ygHg

I wonder if a sublingual formulation would be effective? It's tough to get a hundred milligrams of anything through the epithelium, though...

 

[DJHENRU]

been eating so much garlic lately. I would eat it more, but I worry about disturbing others with the smell.

 

[/navarone/]

^Stop trollin, especially on ADD.

 

[/navarone/]

BTW what is the reason behind the poor oral bioavailability of acetylcysteine?
Gastric hydrolysis? Enzymatic brakedown in the digestie tract?

Would there be ways to increase oral bioavailability instead of sticking it up your ass?
Pharmacies sell a lot of injectable acetylcysteine vials at slightly higher prices (by dose) but I've been away from needls for a long time and don't quite feel like shooting up again, especially a non truly psychoactive 'drug'.

 

[/navarone/]

BTW can anyone whats the rectal bioavailability for L-acetyl-cysteine?
I tired plunging a concentrated solution of it a few days ago and for some reason when I farted there was a high sulphur like smell. This gave me the doubt that some enzymes in the rectum brake down cysteine releasing probably hydrogen sulphide.

 

[DJHENRU]

not trollin

 

[atara]

BTW what is the reason behind the poor oral bioavailability of acetylcysteine?
Gastric hydrolysis? Enzymatic brakedown in the digestie tract?

I'd assume some combination of the two. Between stomach acid and serine protease it's not likely that it'll stick around!

Regardless, the oral bioavailability of N-acetylcysteine is 6-10%. I don't know any of the effective doses for the effects people are claiming. It's possible that inhalation may be a viable route, though its boiling point is 371 C, which is kind of, high. I'm not sure about sublingual; it should be possible up to 50 mg, or several doses through the day.

Insufflation is probably effective and fsm knows there are people who have snorted grams/day of cocaine for years on end but it will mess up your nose.

 

[MeDieViL]

What about just taking higher oral doses? I'm not sure i see the big problem with a low bioavailable, 10% is enough to get proper doses by taking it oral.