User Tag List

Results 1 to 13 of 13
  1. #1
    Senior Member
    Join Date
    Sep 2011
    Posts
    202
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default What does NAC actually DO? How does it work for YOU?

    How do YOU take NAC? What effect has it had on your mood, dopamine function, etc.???

    And I have some questions...I've been taking NAC for two years now, at fairly nigh doses. I've taken anywhere from 1000-3600mg/day, and that includes taking Cerefolin NAC which is 600mg NAC along with b12 and methylfolate. I'm trying to understand whether I really need all this NAC at this point, and if it might be actually causing some negative effects at this dose.

    I originally used these doses after reading the Berk studies from Australia, showing that 2400mg of NAC was effective for bipolar depression, which is my primary condition. But can someone help me out and explain to me what NAC actually does? My understanding is that it supports glutamate/cysteine exchange, which somehow both enhances glutamate activity in certain circuits, but also attenuates glutamate hyperactivity/toxicity? Is that true? Is it this effect or the glutathiaone effect that dominates in bipolar depression.

    Also: why isn't it used for regular depression? I read through another thread here where Ex Dubio mentioned that it actually can HAMPER reward activity...given that I still struggle with anhedonia and motivation, is NAC actually harming me here? My mood has been overall pretty good the last three months due to intense exercise and DHEA and other stuff. I am also on heavy amounts of dopaminergics, including 600mg of bupropion, 0.5mg pramipexole, and 60mg vyvanse. How does the NAC fit into this? I am also taking Campral to help with "craving"...i am in AA for "addiction"-esque behaviors with respect to supplements and fucking with my meds. How would the high dose of NAC i'm on fit into THAT? I hear NAC is GOOD for OCD, right? But OCD is often a result of glutamate hyperactivity, so...? Anyway I'm confused, as you can see.

    What would you predict would be the effect if I went down from my 2400mg of NAC to 600mg. Would positive affect improve? Impulsivity, reward-related, motivation, dopamine function...etc.

    Really would value anyone's insights and please share your story of how YOU take NAC.

  2. #2
    Senior Member Tussmann's Avatar
    Join Date
    Sep 2010
    Posts
    899
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Quote Originally Posted by Satsumass View Post
    I am also on heavy amounts of dopaminergics, including 600mg of bupropion, 0.5mg pramipexole, and 60mg vyvanse. How does the NAC fit into this?
    WHAT?!? I have never heard of anyone prescribed 600 mg of buproprion, is this your own doing or your doctors?

    Sorry, but with the amount of drugs in your system I can't help but think 600-1200 mg of NAC is a blessing. Someone more educated on these matters needs to step in and address the other questions at hand.

  3. #3
    Senior Member
    Join Date
    Sep 2011
    Posts
    202
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    bupropion clinical trials tested it over 1000mg...i've taken it as high as 1050 with an anticonvulsant. 600mg has gotten me to wellness after an extended period of high dose PEA and emsam. i have a fucked up dopamine system, have issues with impulsivity and addiction...i need all the bupropion i can get.

  4. #4
    Senior Member kassem23's Avatar
    Join Date
    May 2010
    Location
    Dimension Unknown
    Posts
    2,246
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    How does N-acetylcysteine work? As gluathione precursor, of course. Why is that important?

    Here's a couple of great references:

    1. (PMID: 22033334) Link between glutahione and bipolar and schizophrenia.


    Redox-dysregulation represents a common pathogenic mechanism in schizophrenia (SZ) and bipolar disorder (BP). It may in part arise from a genetically compromised synthesis of glutathione (GSH), the major cellular antioxidant and redox-regulator. Allelic variants of the genes coding for the rate-limiting GSH synthesizing enzyme glutamate-cysteine-ligase modifier (GCLM) and/or catalytic (GCLC) subunit have been associated with SZ and BP. Using mice knockout (KO) for GCLM we have previously shown that impaired GSH synthesis is associated with morphological, functional and neurochemical anomalies similar to those in patients. Here we asked whether GSH deficit is also associated with SZ- and BP-relevant behavioral and cognitive anomalies. Accordingly, we subjected young adult GCLM-wildtype (WT), heterozygous and KO males to a battery of standard tests. Compared to WT, GCLM-KO mice displayed hyperlocomotion in the open field and forced swim test but normal activity in the home cage, suggesting that hyperlocomotion was selective to environmental novelty and mildly stressful situations. While spatial working memory and latent inhibition remained unaffected, KO mice showed a potentiated hyperlocomotor response to an acute amphetamine injection, impaired sensorymotor gating in the form of prepulse inhibition and altered social behavior compared to WT. These anomalies resemble important aspects of both SZ and the manic component of BP. As such our data support the notion that redox-dysregulation due to GSH deficit is implicated in both disorders. Moreover, our data propose the GCLM-KO mouse as a valuable model to study the behavioral and cognitive consequences of redox dysregulation in the context of psychiatric disease.
    2. (PMID: 18205981)

    Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attentiondeficithyperactivitydisorder. In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders. These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.
    3. (PMID: 18538422)

    There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in diverse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders.
    4. (PMID: 21118657) A great free full-text discussing the mechanism of action underlying N-acetylcysteine.

    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.




  5. Likes Josh liked this post
  6. #5
    Senior Member Josh's Avatar
    Join Date
    Jul 2004
    Location
    The most civil realm of HM ER II
    Posts
    4,301
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Nice post Kas!

    Are there any ways to increase CNS glutathione levels even further than can be achieved with c2.5g of the NAC alone?
    J
    Stop animal testing on dogs!

    Anti-vivisectionists are a more reliable model.


  7. #6
    Senior Member kassem23's Avatar
    Join Date
    May 2010
    Location
    Dimension Unknown
    Posts
    2,246
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Quote Originally Posted by Josh View Post
    Nice post Kas!
    Thank you.

    Quote Originally Posted by Josh View Post
    Are there any ways to increase CNS glutathione levels even further than can be achieved with c2.5g of the NAC alone?
    J
    - IV Glutahione every other week; caveats are obvious.
    - Vitamin C (recycling process)
    - Alpha-lipoic acid (recycling process)
    - Silymarin (indirect effects, as far as I can tell.)

    I am sure pharmaceutical companies are working on more advanced stuff.

  8. Thanks Josh thanked for this post
  9. #7
    Senior Member
    Join Date
    Jul 2009
    Posts
    1,726
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    what exactly was the MOA for NAC inducing brain fog, lethargy etc? I remember we discussed that back in the day, but have no clue where the thread is
    visit my nutrition & exercise science blog!
    SuppVersity @ SuppVersity.blogspot.com

    As ProfDrAndro, I am also one of the heads behind

    BodyRX Radio @ www.bodyRXRadio.com
    and a frequent guest at Carl Lenore's
    SuperHumanRadio @ www.superhumanradio.com

  10. #8
    Senior Member
    Join Date
    Jan 2012
    Posts
    192
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    NAC increases activity in the nucleus accumbens and so stimulates the rewarding system, acamprosate (Campral) does the opposite. I once proposed the theory that combination of both could arrest the rewarding system in a medium position and could be ideal for people with pathological impetus (OCD). I can imagine that this combination is an impetus killer for non-OCD people.

  11. #9
    Senior Member FunkOdyssey's Avatar
    Join Date
    Aug 2005
    Location
    Manchester, CT
    Posts
    4,172
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Quote Originally Posted by Olon View Post
    NAC increases activity in the nucleus accumbens and so stimulates the rewarding system, acamprosate (Campral) does the opposite. I once proposed the theory that combination of both could arrest the rewarding system in a medium position and could be ideal for people with pathological impetus (OCD). I can imagine that this combination is an impetus killer for non-OCD people.
    AFAIK NAC reduces glutamatergic activity in the nucleus accumbens and that is why it is effective for addictive and compulsive behaviors. From a study on NAC for trichotillomania:

    http://archpsyc.ama-assn.org/cgi/content/full/66/7/756
    Glutamatergic dysfunction has been implicated in the pathogenesis of obsessive-compulsive disorder,12-13 a disorder with phenomenologic and possible neurobiological links to trichotillomania.14-17Clinical studies18-20 support the possible efficacy of glutamatergic modulators, such as N-acetylcysteine, in the treatment of repetitive or compulsive disorders. N-acetylcysteine is a hepatoprotective antioxidant that is converted to cystine, a substrate for the glutamate-cystine antiporter. This antiporter allows for the uptake of cystine, which causes the reverse transport of glutamate into the extracellular space, which stimulates inhibitory metabotropic glutamate receptors and, thereby, reduces synaptic release of glutamate.13,
    I think this is related to the anhedonia and lack of motivation some have reported with NAC.
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

  12. Likes physicus007 liked this post
  13. #10
    Senior Member
    Join Date
    Sep 2011
    Posts
    202
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    I am on the combination of acamprosate and NAC...i guess the last three months I've been feeling reasonably better, but that was from a fairly bad state. My doctor put me on acamprosate for addictive/compulsive behaviors, mostly the "craving" for screwing with my meds and piling on a ton of supplements in my body, and spending hours doing supplement research etc. Mental mastubatory things basically. I think it may have helped a little bit, but i'm also doing daily AA meetings. I'm still slipping despite all of this though, i started researching drugs the other morning and was about to order ketamine online (this is a big no no)...i've been going to AA for 6 months now and I slipped up last week and screwewd with my meds (non-sobriety as defined by me and my sponsor) so yeah, i'm not sure how well this acamprosate and NAC combo is doing. I'm also on paxil which has helped some of the obsessive thinking and compulsive behavior.

    Funny though, the obsessive and mind spinning thoughts, when my mood is good, thats where I feel a lot of my creativity and ideas come from, so I kinda miss it when things are quieter as a result of the paxil. But i don't miss driving around the city essentially in the same circle for an hour every day in traffic with absolutely zero reason to...that kinda behavior has decreased. I still can't stop going to the vitamin store though...hopefully today things will change as i'm meeting with an integrative MD for the first time and will have someone who can tell me exactly what I can/cannot take in terms of supplements.

    Anyway back to original question, I guess i'ma leo struggling with general drive and motivation issues...do acamprosate and NAC work in opposition on that dimension? I certainly don't want any more anhedonia, the SSRIs are already bad for that. Anyway whole point of this thread was trying to figure out what to do with my NAC dose. Should I push it up to 3600mg as used in some of the studies...will that help my addictive behavior and drive? Or should I take it down to 600mg...how will those changes affect mood (i'm bipolar 2) hedonia, drive, addiction, etc....

  14. #11
    Senior Member
    Join Date
    Jan 2012
    Posts
    192
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Quote Originally Posted by FunkOdyssey View Post
    AFAIK NAC reduces glutamatergic activity in the nucleus accumbens and that is why it is effective for addictive and compulsive behaviors.
    In the nucleus accumbens with high doses of NAC the effect of mGlu5-receptors prevail over mGlu2, and so in this brain area one has increased glutamate release.
    http://www.ncbi.nlm.nih.gov/pubmed/22137594

  15. #12
    Senior Member FunkOdyssey's Avatar
    Join Date
    Aug 2005
    Location
    Manchester, CT
    Posts
    4,172
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Quote Originally Posted by Olon View Post
    In the nucleus accumbens with high doses of NAC the effect of mGlu5-receptors prevail over mGlu2, and so in this brain area one has increased glutamate release.
    http://www.ncbi.nlm.nih.gov/pubmed/22137594
    That would mean that "high dose" NAC would be pro-addictive than wouldn't it? I'm not certain what high vs low dose translates to in humans, but from clinical studies on OCD and addiction, I think it's safe to assume typical doses of NAC (600-2400mg) fall into the low dose category that inhibits nucleus accumbens synaptic glutamate release.
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

  16. #13
    Senior Member
    Join Date
    Jan 2012
    Posts
    192
    Mentioned
    0 Post(s)
    Tagged
    0 Thread(s)

    Default

    Both stimulation (NAC) and inhibition (acamprosate) do the job, in the first case the drug is not necessary, in the second case it is futile.

Thread Information

Users Browsing this Thread

There are currently 1 users browsing this thread. (0 members and 1 guests)

Similar Threads

  1. What do you work on most at the gym?
    By Scout200 in forum General Training and Bodybuilding
    Replies: 19
    Last Post: December 29th, 2012, 01:04 AM
  2. Did this work?
    By KeepOnKpnOn in forum Neuroscience/Nootropics
    Replies: 14
    Last Post: December 6th, 2008, 01:56 AM
  3. speed work and rep work in the same wo
    By ManuelW in forum General Training and Bodybuilding
    Replies: 15
    Last Post: October 18th, 2007, 01:15 AM
  4. Does this work?
    By john2006 in forum M&M Lounge
    Replies: 4
    Last Post: February 13th, 2007, 10:04 PM
  5. I work for the gov't now, so...
    By stabmaster in forum M&M Lounge
    Replies: 5
    Last Post: December 3rd, 2004, 05:14 AM

Bookmarks

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •