Research On Niacinamide / Nicotinamide And Benzodiazepines

haidut

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I have been mentioning in many of my posts that there is quite a bit of research (mostly Russian) claiming that niacinamide (and to a lesser degree niacin) act like true benzodiazepine drugs. This comparison was my motivation for combining the caffeine with niacinamide. Here are some studies that discuss this connection:

http://www.nature.com/nature/journal/v2 ... 563a0.html

"...We describe here the isolation and benzodiazepine-like actions of nicotinamide, a compound which might exert these actions in the brain physiologically."

http://www.ncbi.nlm.nih.gov/pubmed/2931304

"...The data suggest that the mechanisms of the anticonvulsant action of nicotinamide are mediated via the GABA-benzodiazepine receptor complex"

http://www.ncbi.nlm.nih.gov/pubmed/6090200

"...Psychopharmacological methods were used to study and compare the effects of diazepam and ligands of benzodiazepine receptors (inosin, nicotinamide and their structural analogs NMF and AzN) in animal experiments. It was found that they possess demonstrable sedative, anticonvulsant, antiaggressive and myorelaxant properties, inhibit the conditioned avoidance reflex in a shuttle-box and the conditioned reflex with positive (drinking) reinforcement in a T-maze. The structural analogs of nicotinamide, NMF and AzN, were found to occupy the intermediate position between diazepam and endogenous ligands of benzodiazepine receptors from the standpoint of pharmacological activity."

http://www.ncbi.nlm.nih.gov/pubmed/6141825

"...Experiments on mice and rats were made to study the nootropic and anxiolytic properties of endogenous ligands of benzodiazepine receptors of nicotinamide and inosin and of their new structural analogs--NMF and AZN. They were shown to have overt antihypoxic and anxiolytic effects. NMF and AZN given in 10-fold lower doses than endogenous benzodiazepine ligands appeared more active than these compounds and almost similar to diazepam as regards the activity."

http://www.ncbi.nlm.nih.gov/pubmed/6314203

"...nicotinamide and harmane alkaloids have been proposed as ligands at the benzodiazepine receptor..."

http://www.ncbi.nlm.nih.gov/pubmed/6217985

"...When given in a dose of 1000 mg/kg nicotinamide prevented clonico-tonic convulsions and mortality, and considerably raised the latent period of convulsions and the lifespan of the animals intoxicated with thiosemicarbazide and strychnine."

http://www.ncbi.nlm.nih.gov/pubmed/6216928

"...Nicotinamide (250-500 mg/kg) increased the latent period of seizures without affecting the intensity of seizures or lethality. Nicotinamide (1000 mg/kg) prevented the development of clonico-tonic attacks and lethality. The antiseizure effects of nicotinamide depended on the time of its injection. Phenazepam (1.4 mg/kg) abolished seizures and in a dose of 0.1-0.7 mg/kg protected the animals from death and considerably relieved seizure manifestations."

http://www.ncbi.nlm.nih.gov/pubmed/6264499

"...Nicotinamide (NAM, 1000 mg/kg), inosine (INS, 1000 mg/kg), hypoxanthine (HXT, 500 mg/kg), putative endogenous ligands of the benzodiazepine receptor, and nicotinic acid (NA, 500 mg/kg) diminished DL-kynurenine-(DL-K, 50 micrograms ICV) induced seizures in C57BL/6 adult male mice and only prolonged the latency of pentylenetetrazol (PTZ, 500 micrograms iCV) seizures. It is suggested that if NAM, INS and HXT are of functional importance in the central nervous system, they can act as antagonists of endogenous brain kynurenine. NA and NAM are suggested to be functional feedback inhibitory regulators of the kynurenine pathway of metabolism of tryptophan."

http://www.ncbi.nlm.nih.gov/pubmed/6457475

"...In experiments on cats it was shown that nicotinamide injected intravenously in a dose of 300 to 500 mg per kg body weight depressed singular epileptic foci and groups of foci with synchronized activity induced in the animals' brain cortex by application of strychnine (0.1 ml of 3% solution). The vitamin was also effective, though to a lesser degree, in depressing foci induced by application of penicillin (2% solution). Pyridoxal-5-phosphate (Pyr-5-Ph) injected intravenously in a dose of 10 mg/kg depressed singular foci and groups of foci with synchronized activity induced by application of 2% solution of penicillin, but was less effective in depressing strychnine-induced foci. Combined application of both drugs even in lower doses (nicotinamide, 200 mg/kg; Pyr-5-Ph, 5 mg/kg) resulted in depression of groups of epileptic foci induced by combined application of strychnine and penicillin. Mechanisms of the effects discovered are discussed. A question on possible use of combined nicotinamide and pyridoxal-5-phosphate in the treatment of epilepsy is raised."

http://www.ncbi.nlm.nih.gov/pubmed/2869801

"...The interaction of nicotinamide and its electron structural analogs (NMF and AzN compounds) with central benzodiazepine receptor antagonist Ro 15-1788 and GABA-ergic system antagonist bicuculline were studied in a conflicting situation test. NMF and AzN behaved as the agonists of GABA-benzodiazepine receptor complex. Like in diazepam, the anxiolytic effects of benzodiazepines and nicotinamide was prevented by bicuculline and Ro 15-1788."

http://www.ncbi.nlm.nih.gov/pubmed/9229848

"...Chronic administration of phenazepam and nicotinamide results in the change of coupling in GABA-benzodiazepine receptor complex."

http://www.ncbi.nlm.nih.gov/pubmed/14577176

"...Our study suggests that nicotinamide and especially GABA play an important role in improving the functioning of brain GABA-benzodiazepine complex impaired in diabetes through specific ligand-mediated mechanism and can be useful in the management of diabetes-associated brain failures."

http://www.ncbi.nlm.nih.gov/pubmed/6452183

"...In an epileptic focus produced by application of 5-10% acetylcholine and 0.5% proserine, injection of nicotinamide leads at first to the disappearance of after-effect discharge and then of spike potential. It is concluded that nicotinamide has an antiepileptic activity."

The last excerpt above is quite important. In addition to supporting the beneficial effects of niacinamide, it also supports the view that choline is excitotoxic (it causes seizures according to the study). So anticholinergic drugs like cyproheptadine would be protective.
Overall, the message I think is clear - niacinamide would be a very good substitute for people using any of the benzo drugs and for other at risk of seizures (e.g. eclampsia, pre-eclampsia, menstrual-cycle related seizures due to progesterone deficiencies, etc).
 
J

j.

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If Niacinamide is like benzodiazepines, wouldn't both be good or both be bad?

Are the good effects of niacinamide proof that benzodiazepines are good? Are the bad effects of benzodiazepines proof that niacinamide is bad?
 
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aguilaroja

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j. said:
If Niacinamide is like benzodiazepines, wouldn't both be good or both be bad?

I think the general point here is that there is "constructive inhibition" where the GABAergic and other "systems" prevent brain overstimulation or "excitotoxicity". "Inhibition" is selectively useful at every level so that harmonious stimulation can flow.

"Sedative, anticonvulsant, antiaggressive and myorelaxant" properties are useful in context. It is closer to the ideal to have these functions without the known dangers and drawbacks of the benzodiazepines. Haidut seems to propose that niacinamide effects might substitute for benzodiazepines. Niacinamide is very safe compared to benzodiazepines. William Kaufman, among others, had people using a few grams daily for decades, to good ends.

It's not uncommon in pharmacology to name a "receptor" after a drug. That may be a little misleading. It may be more useful to think of the restorative function and the change at the cell interface which enables the function. But we collect evidence with the literature we have :^}
 
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My experience with niacinamide @ 100g was massive anxiety relief that lasted for hours. I felt so calm and just wanted to sit still and not move a muscle. Similar to a benzo. It did make me feel lazy and unmotivated for that day. After about 5 hours I felt like I had some kind of rebound effect where anxiety was much worse and it continued for a few days. It felt almost like a blood sugar crash. Maybe if I had of taken a few other doses over the course of the day?
 
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jyb

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J

j.

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embs2001 said:
It felt almost like a blood sugar crash.

Since niacinamide increases use of glucose, maybe it WAS a blood sugar crash?
 
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Sorry, yes 100mg.

Yea I don't think im quite recovered from low carb days it was likely connected to blood sugar. 4 months of peat eating and im still sensitive to fruit juice and too much sugar. Also low blood sugar if i go to long without eating.

I miss before paleo when I could tolerate infinite amounts of carbs. Hopefully ill have that feeling back eventualy.
 
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Mittir

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embs2001 said:
Sorry, yes 100mg.

Yea I don't think im quite recovered from low carb days it was likely connected to blood sugar. 4 months of peat eating and im still sensitive to fruit juice and too much sugar. Also low blood sugar if i go to long without eating.

That seems like a problem of liver glycogen storage. I have noticed i can go longer hours
(10-12 hours) without eating since i started niacinamide. RP recommends Niacinamide with
some carbohydrate as free fatty acids decreases ,the use of sugar increases.
I have read here many had headache like symptoms from high dose niacinamide.
I started at low dose, 50 mg for a week and then slowly increased and now
i take 100 mg 2-3 times a day with meal. When i tried to increase the dose quickly
i was having delayed sleep problem. I believe my liver function has improved
since Niacinamide lowered damaging PUFA release. RP thinks lowering
FFA is a key in restoring health. Aspirin and frequent meals also lower PUFA release.
 
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haidut

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jyb said:
j. said:

I can't access the study. What was the protocol? I can only read that it's a total of 2,500mg daily.


embs2001 said:
My experience with niacinamide @ 100g was massive anxiety relief that lasted for hours.

100mg or 100g? If its 100g, that's a lot of capsules...


Here is the full study:
http://www.orthomolecular.org/library/j ... 2-p104.pdf

I read it long time ago. I think the patient started with lower dosages - 500mg twice a day and then raised the dosage to 2.000mg-2500mg. His long term dosage was 500mg in the morning, 500mg at lunch and 1,000mg at night.
 
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chelle86

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haidut said:
The last excerpt above is quite important. In addition to supporting the beneficial effects of niacinamide, it also supports the view that choline is excitotoxic (it causes seizures according to the study). So anticholinergic drugs like cyproheptadine would be protective.
Overall, the message I think is clear - niacinamide would be a very good substitute for people using any of the benzo drugs and for other at risk of seizures (e.g. eclampsia, pre-eclampsia, menstrual-cycle related seizures due to progesterone deficiencies, etc).

I have found that using niacinamide, aspirin, and increased progest-e together have seemed to aid in stopping my daughter's seizures (petite mal) at their onset and kept what normally turns into a day with at least one grand mal into a day where everything calms down and life can go on as 'normal'. The increase in estrogen with her monthly cycle is clear, and the inflammation due to not only the estrogen surges, but her diet as well have been greatly helped by the anti-inflammatory nature/estrogen squashing abilities of the above mentioned.
 
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Situationlive

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Sorry, yes 100mg.

Yea I don't think im quite recovered from low carb days it was likely connected to blood sugar. 4 months of peat eating and im still sensitive to fruit juice and too much sugar. Also low blood sugar if i go to long without eating.

I miss before paleo when I could tolerate infinite amounts of carbs. Hopefully ill have that feeling back eventualy.

Hi I saw your post and was wondering if you could share an update of how your health is now. You posted this back in 2014, and Im currently attempting to bounce back from all my low-carb days and have sensitivities to the sugar and fruit juice.

Would love to hear what you are doing now?
 
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Hi I saw your post and was wondering if you could share an update of how your health is now. You posted this back in 2014, and Im currently attempting to bounce back from all my low-carb days and have sensitivities to the sugar and fruit juice.

Would love to hear what you are doing now?
I would not go crazy with the sugar right away. Stick to moderate amounts of starches and low fructose fruits like berries. After a while you can try some more fruit and sugar if you want, but if you don't react well, don't keep doing it. Make small changes slowly.
 

tomisonbottom

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Sorry, yes 100mg.

Yea I don't think im quite recovered from low carb days it was likely connected to blood sugar. 4 months of peat eating and im still sensitive to fruit juice and too much sugar. Also low blood sugar if i go to long without eating.

I miss before paleo when I could tolerate infinite amounts of carbs. Hopefully ill have that feeling back eventualy.

what happens when you have "too much sugar or fruit juice"?
 
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