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Misc (aminos) L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiaz

xapken

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Stumbled onto this. Lysine potentiates diazepam and appears to be GABAergic (?).

Source: http://www.springerlink.com/content/g5245284836123x8/

Our earlier observations showed that l-lysine enhanced the activity of diazepam against seizures induced by pentylenetetrazol (PTZ), and increased the affinity of benzodiazepine receptor binding in a manner additive to that caused by gamma-aminobutyric acid (GABA). The present paper provides additional evidence to show thatl-lysine has central nervous system depressant-like characteristics.

l-lysine enhanced [3H]flunitrazepam (FTZ) binding in brain membranes was dose-dependent and stimulated by chloride, bromide and iodide, but not fluoride. Enhancement of [3H]FTZ binding byl-lysine at a fixed concentration was increased by GABA but inhibited by pentobarbital between 10–7 to 10–3M. While GABA enhancement of [3H]FTZ binding was inhibited by the GABA mimetics imidazole acetic acid and tetrahydroisoxazol pyridinol, the enhancement by pentobarbital andl-lysine of [3H]FTZ binding was dose-dependently increased by these two GABA mimetics. The above results suggest that l-lysine and pentobarbital acted at the same site of the GABA/benzodiazepine receptor complex which was different from the GABA binding site.

The benzodiazepine receptor antagonist imidazodiazepine Ro15-1788 blocked the antiseizure activity of diazepam against PTZ. Similar to pentobarbital, the anti-PTZ effect of l-lysine was not blocked by Ro15-1788. Picrotoxinin and the GABA, receptor antagonist bicuculline partially inhibitedl-lysine''s enhancement of [3H]FTZ binding with the IC50s of 2 mgrM and 0.1 mgrM, respectively. The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding byl-lysine. This article shows the basic amino acidl-lysine to have a central nervous system depressant characteristics with an anti-PTZ seizure activity and an enhancement of [3H]FTZ binding similar to that of barbiturates but different from GABA.

edit: clean up
 
pretty cool, I take lysine supplements to prevent cold sores lol gross >.< would taking those supplements lower tolerance or enhance the effect of diazepam if one already has tolerance?
 
I just wanted to post a link to a great discussion that includes many article abstracts regarding L-Lysine and its mood altering properties. I'm interested in hearing from people who have attempted using L-Lysine as a supplement and what their experiences were/are. I've just started taking the supplement (2.5g/day) today with the goal of reducing my Xanax use (currently 1.5mg/day).

http://www.mindandmuscle.net/forum/10168-benefits-l-lysine-reducing-stress-anxiety

Am J Clin Nutr. 1983 Jan;37(1):93-8.
Lysine-carnitine conversion in normal and undernourished adult men-suggestion of a nonpeptidyl pathway.
Khan-Siddiqui L, Bamji MS.

Administration of 5 g L-lysine orally to normal adults produced a significant increase in plasma carnitine levels within 6 h followed by a further rise by 48 h. Levels remained high up to 72 h. Similar changes in plasma carnitine were not observed if blood was sampled without lysine load or after administering a load of other amino acids such as tryptophan or threonine. Maximum excretion of carnitine per g creatinine was observed in 24 to 48 h collection after lysine load. Two subjects showed an early peak in 3-h and 6-h collections, respectively. Undernourished subjects failed to demonstrate similar change. After rehabilitation the undernourished subjects behaved as did the well-nourished subjects. These observations suggest that there may be a rapid in vivo conversion of orally administered lysine to carnitine in humans. Conversion of lysine to carnitine may be impaired in malnutrition.

Publication Types:
* Clinical Trial
* Controlled Clinical Trial
PMID: 6401379 [PubMed - indexed for MEDLINE]





Neurochem Res. 1995 Aug;20(8):931-7.
L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor.
Chang YF, Gao XM.
Department of Biochemistry University of Maryland Dental School, Baltimore 21201, USA.

Our earlier observations showed that L-lysine enhanced the activity of diazepam against seizures induced by pentylenetetrazol (PTZ), and increased the affinity of benzodiazepine receptor binding in a manner additive to that caused by gamma-aminobutyric acid (GABA). The present paper provides additional evidence to show that L-lysine has central nervous system depressant-like characteristics. L-lysine enhanced [3H]flunitrazepam (FTZ) binding in brain membranes was dose-dependent and stimulated by chloride, bromide and iodide, but not fluoride. Enhancement of [3H]FTZ binding by L-lysine at a fixed concentration was increased by GABA but inhibited by pentobarbital between 10(-7) to 10(-3)M. While GABA enhancement of [3H]FTZ binding was inhibited by the GABA mimetics imidazole acetic acid and tetrahydroisoxazol pyridinol, the enhancement by pentobarbital and L-lysine of [3H]FTZ binding was dose-dependently increased by these two GABA mimetics. The above results suggest that L-lysine and pentobarbital acted at the same site of the GABA/benzodiazepine receptor complex which was different from the GABA binding site. The benzodiazepine receptor antagonist imidazodiazepine Ro15-1788 blocked the antiseizure activity of diazepam against PTZ. Similar to pentobarbital, the anti-PTZ effect of L-lysine was not blocked by Ro15-1788. Picrotoxinin and the GABA, receptor antagonist bicuculline partially inhibited L-lysine's enhancement of [3H]FTZ binding with the IC50s of 2 microM and 0.1 microM, respectively. The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding by L-lysine. This article shows the basic amino acid L-lysine to have a central nervous system depressant characteristics with an anti-PTZ seizure activity and an enhancement of [3H]FTZ binding similar to that of barbiturates but different from GABA.

PMID: 8587651 [PubMed - indexed for MEDLINE]

Biomed Res. 2007 Apr;28(2):85-90.
Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans.Smriga M, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y.
Institute of Life Sciences, Ajimoto Co. Inc, 1-1 Suzuki-cho, 210-8681 Kawasaki-ku, Kawasaki-shi, Japan. [email protected]

Dietary supplementation with an essential amino acid L-lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. A combination of L-lysine and L-arginine has been documented to normalize hormonal stress responses in humans with high trait anxiety. The present study was carried out in one hundred eight healthy Japanese adults. The aim of study was to find out whether a week-long oral treatment with L-lysine (2.64 g per day) and L-arginine (2.64 g per day) reduces trait and stress-induced state anxiety and basal levels of stress hormones. We confirmed that, without regard to gender, the amino acid treatment significantly reduced both trait anxiety and state anxiety induced by cognitive stress battery. In addition, we found that the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects. These results of this double-blind, placebo controlled and randomized study confirm the previous findings in humans and animals and point to a combination of L-lysine and L-arginine as a potentially useful dietary intervention in otherwise healthy humans with high subjective levels of mental stress and anxiety.

PMID: 17510493 [PubMed - indexed for MEDLINE]
 
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I just wanted to post a link to a great discussion that includes many article abstracts regarding L-Lysine and its mood altering properties. I'm interested in hearing from people who have attempted using L-Lysine as a supplement and what their experiences were/are. I've just started taking the supplement (2.5g/day) today with the goal of reducing my Xanax use (currently 1.5mg/day).

How is it going for you? I find 500mg l-lysine (usually taken once or twice a day) gives me noticeable effects. A friend with a high benzo dependence tried it and was amazed at how much it potentiated his benzos and allowed him to reduce his dose.
 
I'm kind fo skeptical how effective L-lysine would be if you're eating a good high-protein. It seems to me all these amino acids would have trouble making it past the blood-brain barrier and would be mostly distributed to the periphery.

But that study showing it decreases cortisol is pretty solid. I wtill think it'd be better for your daily nutrient uptake (and wallet) if instead of supplementing with lysine, eat proteinacous fods. Beans, legumes, lean meats, milk / soya milk, eggs, cheese, seeds.

There's 2g of L-lysine in 100g of chicken - just make yourself a sandwich and throw a few dark leafy greens on it if you want a lysine supplement. Don't like chicken? Bean salad is the way to go, or maybe curried legumes of some sort.

You'll save tons of money and gain a wide spectrum of amino acids & nutrients this way. Everyone feels better after a good meal.
 
Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana.Ghosh S, Smriga M, Vuvor F, Suri D, Mohammed H, Armah SM, Scrimshaw NS.

Nevin Scrimshaw International Nutrition Foundation, Boston, MA 02111, USA. [email protected]

BACKGROUND: Lysine affects diarrhea and anxiety via effects on serotonin receptors, enhanced intestinal repair, and sodium chloride-dependent opioid peptide transport.

OBJECTIVE: The objective was to investigate the effects of lysine supplementation on morbidity, growth, and anxiety in children and adults of peri-urban areas of Accra, Ghana.

DESIGN: In a double-blind randomized trial, the effect of lysine supplementation (1 g lysine/d) compared with that of placebo was examined in 2 groups of men, women, and children (n = 271). Primary outcomes included diarrheal and respiratory morbidity, growth, and anxiety and complement C3, C-reactive protein, serum cortisol, transferrin, and ferritin values. Independent-sample t tests, odds ratios, generalized estimating equations, 4-parameter sinusoid regression, and generalized linear models were used.

RESULTS: 30% of men, 50% of women, and 15% of children were at risk of lysine inadequacy. Supplementation in children reduced diarrheal episodes [19 lysine, 35 placebo; odds ratio (OR): 0.52; 95% CI: 0.29, 0.92; P = 0.046] and the total number of days ill (21 lysine, 47 placebo; OR: 0.44; 95% CI: 0.26, 0.74; P = 0.034). Mean days ill per child per week (0.058 ± 0.039 lysine, 0.132 ± 0.063 placebo; P = 0.017) were negatively associated with weight gain with control for baseline weight and study group (P = 0.04). Men had fewer coryza episodes (23 lysine, 39 placebo; OR: 0.60; 95% CI: 0.36, 1.01; P = 0.05), total number of days ill (lysine: 130; placebo: 266; OR: 0.51; 95% CI: 0.28, 0.93; P = 0.03), and mean days ill per person per week (lysine: 0.21 ± 0.23; placebo: 0.41 ± 0.35; P = 0.04). Serum ferritin (P = 0.045) and C-reactive protein (P = 0.018) decreased in lysine-supplemented women but increased in placebo-supplemented women.

CONCLUSION: Lysine supplementation reduced diarrheal morbidity in children and respiratory morbidity in men in Ghana.

PMID: 20720257

How is it going for you? I find 500mg l-lysine (usually taken once or twice a day) gives me noticeable effects. A friend with a high benzo dependence tried it and was amazed at how much it potentiated his benzos and allowed him to reduce his dose.

It has only been about three days and I have already reduced my Xanax dose down by .5mg.

Started using on Thursday:
8/23 - 2.5g Lysine + 1.5mg Xanax (.5 in XR form)
8/24 - 3g Lysine + 1.5mg Xanax (.5 in XR form)
8/25 - 3g Lysine + 1mg Xanax (.5 in XR form)
8/26 - today - So far I feel very good today. I actually feel much better than I do most mornings (more energy and focus for example). I did notice a slight reduction in my sleep along with the Xanax reduction dose, but no increases in anxiety or panic. I took 1g Lysine when waking up and have yet to take any Xanax.

It is still very early in my experiment and I will keep you all updated.
 
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Awesome to hear Gyrospeck :).

I'm kind fo skeptical how effective L-lysine would be if you're eating a good high-protein. It seems to me all these amino acids would have trouble making it past the blood-brain barrier and would be mostly distributed to the periphery.

Why not try it? I find taking a l-lysine supplement to have way more noticeable effects than eating lysine-containing food. I feel very different if I take 500mg of lysine as a supplement compared to eating 100g of chicken, which should supposedly have 4x the lysine. Although I do enjoy chicken, but I think that's more because it's delicious, since I am not a fan of other high-lysine foods like lentils or chickpeas
barf.gif
. I can only speculate as to why the supplement seems to provide more noticeable effects, maybe taking it in food slows the absorption and keeps the lysine busy doing other things?
 
It has only been about three days and I have already reduced my Xanax dose down by .5mg.

Started using on Thursday:
8/23 - 2.5g Lysine + 1.5mg Xanax (.5 in XR form)
8/24 - 3g Lysine + 1.5mg Xanax (.5 in XR form)
8/25 - 3g Lysine + 1mg Xanax (.5 in XR form)
8/26 - today - So far I feel very good today. I actually feel much better than I do most mornings (more energy and focus for example). I did notice a slight reduction in my sleep along with the Xanax reduction dose, but no increases in anxiety or panic. I took 1g Lysine when waking up and have yet to take any Xanax.

It is still very early in my experiment and I will keep you all updated.

I'm skeptical. You have more focus and energy because you lowered your benzo dose.
 
I have to vouch for l-lysine.

I have a horrible benzo tolerance - at one point 2mg of Xanax would get me where I needed - now its 5mg.

I've taken 1000mg l-lysine split twice in the day, morning and 1-2 hours before I take a benzo I have, and it's definitely enhanced. I even felt slight benzo like feelings the first time I took it, possibly as it was already reacting to leftover benzos in my system. I was shocked by it.

I know opiates and benzos are dangerous but it's a common mix I use as I know my limos - and I have to cut my benzo dose in at least half or I feel especially sedated, to what seems a frightening, forcing my self awake so I don't die state.

Strange one indeed.
 
I become skeptical about one's understanding of amino acids, peptides, and proteins when one doesn't understand protein rate limiting ratios and how consuming an amino acid with a slew of other amino acids is not the same as consuming amino acids individually. Of course, I'm a nerd and I find this stuff utterly fascinating!

I just started l-lysine about a week ago, mostly for it's connection with serotonin. It's the only amino acid that mildly upsets my stomach. If the upset stomach doesn't end I may have to give up on the lysine. :(

It's been well over a year Gyrospeck (bump)...are you still taking lysine??
 
Hmmm, this is actually quite fascinating. Might be worth a shot for me although I'm leery of anything GABAergic since I'm actually tapering off my Valium. That said, I don't really think it will cause any real harm and if it poses problems I'll just stop it but anything that can get me off of Valium faster without increased consequences would be quite welcome.
 
It would make sense to me that taking a supplement would be more effective than just eating the stuff since there's no metabolism and much less unwanted material, eating 100g of chicken for the 2g of lysine that's present as protein that has to be broken down won't work nearly as well as just eating the lysine supplement.

The problem with these reports is that people with anxiety problems are more susceptible to placebo effect.

I think it may have some benefit, but I doubt it's particularly strong, and most of these studies are looking at people who are deficient.
 
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