18 replies to this topic

[doctordog]

hi, i remember a study being posted on here about how doses of 600mg+(?) a day of NAC had proved to be unsafe due to their risk of causing PAH. i am interested in trying it for OCD and was wondering what dose would be advised? I've googled several OCD studies and most seem to use pretty mountainous amounts; this one, for example, (http://clinicaltrial...how/NCT00539513) had patients titrating up to 3000mg a day.

[numbered]

hi, i remember a study being posted on here about how doses of 600mg+(?) a day of NAC had proved to be unsafe due to their risk of causing PAH. i am interested in trying it for OCD and was wondering what dose would be advised? I've googled several OCD studies and most seem to use pretty mountainous amounts; this one, for example, (http://clinicaltrial...how/NCT00539513) had patients titrating up to 3000mg a day.

Why don't you start with a low dose and see how you feel and work it up from there? It has been discussed before but i am of the ones that feel that the danger from nac is exagerated.

[Cuil]

I have been taking about 6,000 mg a day for atleast 3 weeks with no problems so far. I started at 2 pills a day and worked my way up when I read more about it and realized that the more I took, the more progress I was making in repairing my nervous system. I am going to drop my dose soon to see if there are any noticable differences, but I have kept it high because I have been running my body through the ground with little sleep to get school work and side work done.

It definitely helped me with any ocd I had!

[VespeneGas]

I have been taking about 6,000 mg a day for atleast 3 weeks with no problems so far. I started at 2 pills a day and worked my way up when I read more about it and realized that the more I took, the more progress I was making in repairing my nervous system. I am going to drop my dose soon to see if there are any noticable differences, but I have kept it high because I have been running my body through the ground with little sleep to get school work and side work done.

It definitely helped me with any ocd I had!

6 grams per day? That sounds like too much unless you are under the guidance and supervision of a physician. What exactly are you taking NAC for? What is this repair to your nervous system that you speak of? I remember reading that NAC was neuroprotective, but neurotrophic? Do you have any studies handy to substantiate this use?

I'm not just playing the skeptic; if such evidence does exist, I would be thoroughly edified and consider upping my dose from 600mg e.o.d

[doctordog]

thanks for your replies. i've been e-mailing around and have found a psychiatrist who is willing to trial Memantine on me for OCD; the reason it was more difficult than I pictured is that the drug has just been released here for Alzheimers, and little is known about it's off-label use. i'm going to wait a couple of weeks before i begin so in the meantime i might still experiment with N-A-C. i'll maybe start with 250mg or so and work up from there.

[hamishm00]

6 grams per day is adventurous.

Lots of people on this forum take in excess of 1g a day, with zero complications.

[FunkOdyssey]

doctordog; give us some feedback on memantine after you've titrated up to a good dose and been there for awhile. Its one of my favorite drugs.

[Cuil]

I have been taking about 6,000 mg a day for atleast 3 weeks with no problems so far. I started at 2 pills a day and worked my way up when I read more about it and realized that the more I took, the more progress I was making in repairing my nervous system. I am going to drop my dose soon to see if there are any noticable differences, but I have kept it high because I have been running my body through the ground with little sleep to get school work and side work done.

It definitely helped me with any ocd I had!

6 grams per day? That sounds like too much unless you are under the guidance and supervision of a physician. What exactly are you taking NAC for? What is this repair to your nervous system that you speak of? I remember reading that NAC was neuroprotective, but neurotrophic? Do you have any studies handy to substantiate this use?

I'm not just playing the skeptic; if such evidence does exist, I would be thoroughly edified and consider upping my dose from 600mg e.o.d

I have't found any evidence of such high doses being neurotrophic. I have a theory that higher doses will accelerate the previously established effects (primarily returning dopamine transporter levels back to normal after taking amphetamine). In a cocaine addiction study, The subjects that recieved 3600 mg daily had better results than the the lower dosage groups. It seems to prevent some unwanted side effects of taking amphetamine to stay up all night doing school work. So basically, I have an idea that the higher the dose, the more dramatic effects it can have on stabalizing my nervous system and keeping it from getting fried, as well as making positive changes simultaniously.

[doctordog]

doctordog; give us some feedback on memantine after you've titrated up to a good dose and been there for awhile. Its one of my favorite drugs.

hey - the psych I contacted was still a little skeptical, given he hadn't heard of the drug, and recommended I try clomipramine first, though I said I'm over TCA/SSRI cognitive side-effects. do you have any studies on Memantine & OCD I could point him to, just to seal the deal?

also, do you mind summarizing your experience on it? did it help anxiety / obsessive thoughts? i'm busy tapering off Nardil, and while I appreciate not feeling like a narcoleptic zombie all day, I can already feel my OCD coming back with a vengeance :(

[krillin]

In addition to redox signalling disruption, thiols in large doses will also give you the risk of aortic rupture. I really can't understand people's attachment to this stuff when whey protein is widely available as a safe source of cysteine that won't defeat the body's safety mechanisms.

Cystine example
Cysteamine example

[yoyo]

In addition to redox signalling disruption, thiols in large doses will also give you the risk of aortic rupture. I really can't understand people's attachment to this stuff when whey protein is widely available as a safe source of cysteine that won't defeat the body's safety mechanisms.

Cystine example
Cysteamine example

i think the glutamate modulating properties are the big attraction

[Cuil]

In addition to redox signalling disruption, thiols in large doses will also give you the risk of aortic rupture. I really can't understand people's attachment to this stuff when whey protein is widely available as a safe source of cysteine that won't defeat the body's safety mechanisms.

Cystine example
Cysteamine example

i think the glutamate modulating properties are the big attraction

Yep, thats what I got it for. It really does help with those areas of functioning. Not to mention some people don't like whey protien.

[FunkOdyssey]

doctordog; give us some feedback on memantine after you've titrated up to a good dose and been there for awhile. Its one of my favorite drugs.

hey - the psych I contacted was still a little skeptical, given he hadn't heard of the drug, and recommended I try clomipramine first, though I said I'm over TCA/SSRI cognitive side-effects. do you have any studies on Memantine & OCD I could point him to, just to seal the deal?

These studies are small and not properly double-blinded and placebo-controlled, however there seems to be enough preliminary evidence to convince any open-minded psychiatrist to give it a try, especially considering its safety and tolerability. A couple of them do not have abstracts -- hopefully you can obtain the full-text.

Psychopharmacol Bull. 2009;42(1):81-93.
Differential Efficacy of Memantine for Obsessive-Compulsive Disorder vs. Generalized Anxiety Disorder: An Open-Label Trial.
Feusner JD, Kerwin L, Saxena S, Bystritsky A.

Department of Psychiatry and Biobehavioral Sciences University of California, Los Angeles David Geffen School of Medicine at UCLA Los Angeles, CA, USA.

Objective: A substantial proportion of patients with obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) do not respond to, or are intolerant of, standard treatments. Additional treatment strategies are therefore necessary. Excessive action of the excitatory neurotransmitter glutamate may play a role in the pathophysiology of OCD and possibly GAD. Memantine blocks the excitatory action of glutamate at the N-methyl- D-aspartate (NMDA) receptor under pathological conditions. The objective of this study was to compare the efficacy and safety of memantine in OCD and GAD, and to probe relative effects on OCD and anxiety symptoms. Method:Ten OCD and 7 GAD subjects received 12 weeks of open-label memantine 10 mg twice daily, as either monotherapy or augmentation of their existing medication. Primary outcome measures were the Yale-Brown Obsessive Compulsive Scale ( YBOCS) for the OCD group, the Hamilton Anxiety Rating Scale (HARS) for the GAD group, and the Clinical Global Impression-Improvement Scale (CGII) for both groups. Results: The OCD group experienced a significant mean 40.6% reduction in YBOCS scores at endpoint (t = 4.75, p < 0.001). Three of 10 of OCD subjects were classified as responders, although 7 of 10 experienced a >/= 45% reduction in YBOCS scores. The GAD group experienced a mean 22.4% reduction in HARS scores (t = 3.56, p = 0.012). None of the GAD subjects were responders, and none experienced a >/= 50% reduction in HARS scores. Memantine was well tolerated, and there were no serious adverse effects. Conclusions: These results suggest that memantine may have preferential efficacy in the treatment of OCD versus GAD. These preliminary findings warrant larger, placebo-controlled studies in OCD.

PMID: 19204653

J Clin Psychopharmacol. 2009 Feb;29(1):51-5.
Memantine augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial.
Aboujaoude E, Barry JJ, Gamel N.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. eaboujaoude@stanford.edu

BACKGROUND: Data from the fields of genetics, neuroimaging, and animal studies, along with case reports and small clinical trials, point to a role for glutamatergic dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). We report on the first open-label study to test the hypothesis that memantine, a noncompetitive glutamate antagonist, will result in a clinically meaningful reduction in OCD symptoms in adults with treatment-resistant OCD. METHODS: We recruited 15 adult subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18 or higher, who had failed to respond to treatment with a serotonin reuptake inhibitor (SRI), given at an adequate and stable dose for at least 12 weeks. The duration of memantine treatment was 12 weeks, and the dose was gradually increased to a target of 20 mg/d. Response was defined as a 25% or greater reduction in the Y-BOCS score at study end and a Clinical Global Impression-Improvement scale rating of "much" or "very much" improved. RESULTS: Data from 14 subjects were analyzable. Mean baseline Y-BOCS score was 27.4 (SD, 5.0). Subjects had failed an average of 2.8 (SD, 1.8) SRI trials; 6 subjects had failed augmentation with atypical antipsychotics. At study end, 6 subjects (42.9%) were responders, and response was achieved by EOW4. Responders had significantly lower baseline Y-BOCS scores (2-tailed t tests, P < 0.05, t = 2.2) and had failed fewer SRIs (P <or= 0.05, t = 2.2). Side effects to memantine were mild and transient, and no subject withdrew from the study for an adverse event. SUMMARY: In this open-label augmentation trial of memantine in treatment-resistant OCD, almost half the subjects had a meaningful improvement in symptoms. Our study was limited by its small size, presence of comorbidities, and lack of control. Large double-blind placebo-controlled trials are needed to further test our findings.

PMID: 19142108

Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):1173-5. Epub 2006 May 30.
Memantine augmentation for refractory obsessive-compulsive disorder.
Pasquini M, Biondi M.

Department of Psychiatric Science and Psychological Medicine, University La Sapienza of Rome, Italy. maxpasquini@tiscalinet.it

Glutamatergic hyperactivity hypothesis in obsessive-compulsive disorder (OCD) has been proposed but not tested. Memantine is an uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist. We report two cases of refractory obsessive-compulsive disorder treated with an augmentation of memantine at 15 mg/day. The first case did not benefit from such treatment, while the second showed immediate and substantial improvement. Contrasting results, reflecting different subtypes of OCD, are discussed. We hypothesized that in certain OCD subtypes an agent that enhances memory for actions may promote a reduction in orbitofrontal activation.

PMID: 16730870

Am J Psychiatry. 2009 Feb;166(2):237.
Memantine as an augmenting agent for severe pediatric OCD.
Hezel DM, Beattie K, Stewart SE.

PMID: 19188297

Am J Psychiatry. 2005 Nov;162(11):2191-2.
Memantine for treatment-resistant OCD.
Poyurovsky M, Weizman R, Weizman A, Koran L.

PMID: 16263867

Edited by FunkOdyssey, 13 April 2009 - 04:56 PM.

[krillin]

NAC's disruption of redox signalling also impairs healing and eliminates a benefit of angiotensin receptor blockers.

Crit Care. 2009 Apr 9;13(2):R55.
Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity.
Yang R, Miki K, He X, Killeen ME, Fink MP.

ABSTRACT: INTRODUCTION: Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in the US and Europe. Massive hepatocyte necrosis is the predominant feature of APAP-induced acute liver injury (ALI). Liver regeneration is a vital process for survival after a toxic insult, it occurs at a relative late time point after the injurious phase. Currently N-acetylcysteine (NAC), a glutathione precursor, is the antidote for acetaminophen overdose. However, NAC is effective only for patients who present within hours of an acute overdose, and is less effective for late-presenting patients. It is possible that in delayed patients, previously reduced endogenous glutathione (GSH) level has restored, prolonged treatment with NAC might be toxic and impairs liver regeneration. Therefore, we hypothesize that prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP. METHODS: ALI was induced in C57BL/6 male mice by a single dose of APAP (350 mg/kg) intraperitoneal injection. Following 2 hrs of APAP challenge, the mice were given 100 mg/kg NAC dissolved in 0.6 mL saline, or saline treatment every 12 hours for a total of 72 hours. RESULTS: 72 hrs after APAP challenge, compared to saline treatment, NAC treatment significantly increased serum transaminases (ALT/AST), induced evident hepatocytes vacuolation in the periportal area and delayed liver regeneration seen in histopathology. This detrimental effect was associated with reduced hepatic NF-kappaB DNA binding and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration. CONCLUSIONS: Prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP.

PMID: 19358737

Kulak Burun Bogaz Ihtis Derg. 2007;17(1):22-5.
Does topical N-acetylcysteine application after myringotomy cause severe otorrhea?
Sanli A, Eken M, Evren C, Ateş G, Paksoy M.
Department of Otolaryngology, Dr. Lütfi Kirdar Training and Research Hospital, Istanbul, Turkey.

OBJECTIVES: The effect of topical N-acetylcysteine (NAC) application was investigated on the healing of acute experimental tympanic membrane perforations. MATERIALS AND METHODS: Twenty guinea pigs were used in this study. Under intraperitoneal ketamine anesthesia, incisional myringotomies were performed in the posterosuperior quadrant of the tympanic membranes with a straight otologic hook. The diameter of the perforations was approximately 2 mm. Perforations in both ears were treated with freshly prepared sponges soaked in either 0.1 ml 0.9% NaCl solution (10 control animals) or 0.6 mg/0.1 ml NAC (10 animals) for three consecutive days. All the tympanic membranes were examined by otomicroscopy on the third, fifth, seventh, and ninth days. RESULTS: In the control group, all the perforations were completely closed at the end of nine days. During the same period, only 40% of the perforations were completely closed in the NAC group. The remaining ears exhibited otorrhea by the third day. CONCLUSION: N-acetylcysteine may cause severe otorrhea in the healing process of tympanic membrane perforations. Further studies including histopathological examinations are required to elucidate this condition.

PMID: 17483607

Antioxid Redox Signal. 2008 Dec;10(12):1999-2008.
N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.
Matsuhisa S, Otani H, Okazaki T, Yamashita K, Akita Y, Sato D, Moriguchi A, Iwasaka T.
The Second Department of Internal Medicine, Division of Cardiology, Kansai Medical University, Moriguchi City, Japan.

Oxidative stress mediated by activation of angiotensin II type-1 receptor (AT(1)R) plays a crucial role in the progression of heart failure. We investigated the effect of N-acetylcysteine (NAC) and an AT(1)R blocker on oxidative stress and left ventricular (LV) remodeling in BIO14.6 cardiomyopathy hamsters. The cardiomyopathy hamsters were treated with NAC or the AT(1)R blocker losartan for 20 weeks. Although NAC and losartan inhibited oxidative stress and upregulation of iNOS in the cardiomyopathy hamster heart, only losartan inhibited LV chamber dilation, myocardial fibrosis, and LV dysfunction in the cardiomyopathy hamster. Co-treatment with NAC abolished the protective effect of losartan against LV remodeling associated with inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt and eNOS activation. An iNOS inhibitor 1400W or a nonselective NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) exacerbated LV remodeling in the cardiomyopathy hamster. However, L-NAME but not 1400W abrogated losartan-mediated inhibition of LV remodeling. These results suggest that redox-sensitive upregulation of iNOS plays a crucial role in preventing LV remodeling in the BIO14.6 cardiomyopathy hamster. Losartan inhibits LV remodeling by switching the cardioprotective mechanism from iNOS- to eNOS-dependence, but NAC abolishes the protective effect of losartan by inhibiting redox-sensitive activation of PI3K/Akt and eNOS in the cardiomyopathy hamster.

PMID: 18665799

[doctordog]

*BUMP*

few more memantine questions:

a) i've heard that stimulants can increase central focus, but at the expense of more peripheral creative sensations. i'm not sure of the relationship between memantine and more traditional stimulants, but can anyone describe what kind of cognitive effects (+, -, or neutral) it had on them w/r/t creativity, word recall etc.?

b) is memantine viable as a long-term therapy, or does it poop out pretty quickly?

c) for those suffering from (post-SSRI) apathy, anhedonia, etc., did memantine go anyway towards reversing those sensations?

thanks for your time

[Cuil]

Those studies that claim that NAC is very dangerous for long term supplementation does concern me, but I would like to know more about several variables, such as how would long term NAC affect someone who takes stimulants or other chemicals that can suppress liver function?

[nancyd]

deleted

Edited by nancyd, 20 April 2009 - 09:48 PM.

[bgwithadd]

There is a study saying that NAC could help with neurotoxicity but their reasoning was a little wonky. Basically equating dopamine level with less neurotoxicity, which is bad logic.

It seems likely the reason meth has mega neurotoxicity is largely due to increasing NAC a great deal. I believe its metabolites are neurotoxic, too. So, added with the pulmonary arterial hypertension I'd say the safest dose is most probably zero. It seems most of the amino acids really should not be taken in too high of doses, or in many cases at all.

[lemon_]

nac bad long term --- what else is good ?