21 replies to this topic

[Neuronic]

I have looked on several drug sites and cannot find any known interactions of Xyrem(GHB) and Deprenyl.
I want to start taking Deprenyl again because it seemed to make modafinil more effective. I just want to be sure it's safe to do.

[Neuronic]

Well while I am at it, let's add piracetam to the mix.
I got to thinking about how in the last year my narcolepsy feels much worse that it was and realized that it's been roughly a year since I stopped taking piracetam regularly. I took it for about 1 1/2 years because of it's ability to make caffeine more potent and it reduced my "need to sleep". Normally if I woke up in the morning with less than 8 hours of sleep I would do just about anything to go back to bed. But piracetam would make it "ok" to get up.

So I was thinking that maybe I should start back on it, but I want to be sure it would be fine combined with GHB, Deprenyl, and Modafinil.

[matter_of_time]

i have tried them both without trouble. But be warned, i have read in other forums it can cause some symptoms.
After i read this i never tried this combination.

[medievil]

I strongly advice against this combination as deprenyl could severely potentiate neurotoxic damage by GBL.

Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.).

A dose of 5mg of deprenyl a day can significantly lower your antioxidant enzymes (and rats arent humans, so its all gueswork) id say taking deprenyl itself is a bad idea if your into neuroprotective substances taking it with neurotoxic substances is stupid imo.

Edited by medievil, 09 August 2010 - 07:27 PM.

[Animal]

I strongly advice against this combination as deprenyl could severely potentiate neurotoxic damage by GBL.

Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.).

A dose of 5mg of deprenyl a day can significantly lower your antioxidant enzymes (and rats arent humans, so its all gueswork) id say taking deprenyl itself is a bad idea if your into neuroprotective substances taking it with neurotoxic substances is stupid imo.

Do you even understand the study you quoted? Deprenyl is neuroprotective in clinical doses, injecting 4mg/kg is an absurdly high dose and is not comparable at all to a human taking 5mg a day orally. Please try to correctly interpret a study before using it as evidence next time.

Edited by Animal, 09 August 2010 - 07:36 PM.

[medievil]

I strongly advice against this combination as deprenyl could severely potentiate neurotoxic damage by GBL.

Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.).

A dose of 5mg of deprenyl a day can significantly lower your antioxidant enzymes (and rats arent humans, so its all gueswork) id say taking deprenyl itself is a bad idea if your into neuroprotective substances taking it with neurotoxic substances is stupid imo.

Do you even understand the study you quoted? Deprenyl is neuroprotective in clinical doses, injecting 4mg/kg is an absurdly high dose and is not comparable at all to a human taking 5mg a day orally. Please try to correctly interpret a study before using it as evidence next time.

Rats arent tiny humans, those doses need to be converted to humans, someone here on the forum did the calculation allready, read this:

I did some math according to Dose translation from animal to human studies revisited

Here is how you do it: HED(mg/kg) = Animal dose (mg/kg) multiplied by (Animal Km / Human Km)
Where Animal Km is for instance 6 for rats and 37 for an adult human of 60 kg (Table 1 in the pdf).

So 0.5 mg/kg, which was too high for a rat would then be the following for a 60 kg adult:
0.5*(6/37)*60=4.86 mg, which would mean that 5 mg of Deprenyl per day is probably too high if taken for longevity!

And 0.25 mg/kg, which seemed to extend life in rats would give us
0.25*(6/37)*60=2.43 mg, which indicates that 2.5 actually seems to be more appropriate dosage for increasing lifespan in humans.

So according to my calculations (which I implore you all to double-check) a dose as low as 5 mg per day of Deprenyl might actually be harmful, at least in the long run. ~0.1-2.5 mg/day seems to be far superior health wise.
Of course one should bear in mind that these are studies on animals and not humans after all.

I haven't found any studies testing whether such a low dose actually has any therapeutic effects in humans (the lowest dosages tested I could find were 5 mg/day, I found one study where they tested 1.25 mg Zydis Selegiline and got results but that one has better bio-availibilty than regular Selegiline it seems so it doesn't really count in my mind). So whether such a low dose as 2.5 mg per day could give statistically significant effects in humans is still up in the air.

Maybe the above calculation is incorrect then i rest my case, but now it looks like that 5 mg of deprenyl a day can be harmfull and has a negative effect on the body's antioxidant enzyme's. Humans are also differend from rats so who knows what doses are harmfull and neuroprotective, i would avoid doses higher then 1 mg once a week to promote longevity. (personaly i avoid this substance).

Edited by medievil, 10 August 2010 - 02:23 AM.

[aLurker]

I strongly advice against this combination as deprenyl could severely potentiate neurotoxic damage by GBL.

Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.).

A dose of 5mg of deprenyl a day can significantly lower your antioxidant enzymes (and rats arent humans, so its all gueswork) id say taking deprenyl itself is a bad idea if your into neuroprotective substances taking it with neurotoxic substances is stupid imo.

Do you even understand the study you quoted? Deprenyl is neuroprotective in clinical doses, injecting 4mg/kg is an absurdly high dose and is not comparable at all to a human taking 5mg a day orally. Please try to correctly interpret a study before using it as evidence next time.

I'll just chime in here since I did the human dose equivalent calculations medievil quotes in the post above this one.

I have to agree with Animal here, although a source for the statement of Deprenyl being neuroprotective in clinical doses would be most appreciated since I'm taking Deprenyl right now.

About the calculations I did they really don't support your case medievil. They are based upon longevity studies in which I suppose oral doses were used. Even so, 4 mg/kg/inj. would give us a HED of ~38.9mg using the same math (4*(6/37)*60), a very high dose indeed, which was INJECTED. To repeat the obvious: an absurdly high dose directly injected to a rat is not at all comparable to a human taking 5mg a day orally!

To stay on topic, modafinil does affect dopamine and thus I'd think twice before using Deprenyl in conjunction with it. I have no idea about GHB and Deprenyl. Thismight be of interest, especially if you know Russian. Take care and let us know how everything works out.

[medievil]

Those doses were given 3 times a week, not every day and average lifespan rats started dying earlier when given a dose of 1.0 mg/kg 3 times a week.

While you are right those doses are injected, in average aged animals 1.0 mg/kg had a negative effect and this dose was only given 3 times a week.

Therefor i cant say your right here and i stand my case that combining deprenyl with GHB is playing with fire (and that taking deprenyl alone is something that needs to be avoided).

[chrono]

Maybe the above calculation is incorrect then i rest my case, but now it looks like that 5 mg of deprenyl a day can be harmfull and has a negative effect on the body's antioxidant enzyme's. Humans are also differend from rats so who knows what doses are harmfull and neuroprotective, i would avoid doses higher then 1 mg once a week to promote longevity. (personaly i avoid this substance).

There might be a case that 5mg/day in humans could be detrimental to lifespan. And 4mg/kg (~45mg for 70kg human) may cause a decrease in SOD, but lower dosages corresponding to ~5mg/day showed an increase in SOD, so I'm not sure why you're concluding that the putative lifespan-shortening effects at lower dosages are due to this.

As Animal said, there's a significant body of evidence showing that deprenyl is neuroprotective. I don't know much about the mechanisms of GHB or its neurotoxicity, so I can't say for sure, but it doesn't sound likely to potentiate damage based on the evidence you've cited so far.

Edited by chrono, 12 August 2010 - 05:54 AM.

[medievil]

The necessity of having a proper dose of (-)deprenyl (D) to prolong the life spans of rats explains discrepancies among different studies in the past.
Kitani K, Kanai S, Miyasaka K, Carrillo MC, Ivy GO.

National Institute for Longevity Sciences, Morioka-cho, Obu-shi, Aichi, Japan. kitani@nils.go.jp
Abstract
(-)Deprenyl (D) has been shown to be effective in prolonging life span in experimental animals, although, there are some discrepancies in its effect on the life span the even within the same species (rats). The present study aims to clarify the reason for these discrepancies. Male F344/DuCrj rats began receiving subcutaneous (s.c.) injections of D at the age of 18 months. Doses used were 0.25, 0.50, and 1.0 mg/kg/injection (inj.), three times a week. Average life spans of animals were significantly longer in male rats given 0.25 and 0.5 mg/kg/inj.; however, rats given a 1.0 mg/kg dose began dying earlier than control rats, leading to an inverse U-shaped dose-efficacy relationship, a hormesis. Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.). Our results clearly indicate that a proper dose of D within a certain dose range can significantly increase the life span of rats, but that a greater dose becomes less effective and may actually adversely affect the life span of rats. A similar hormetic response for its effect on antioxidant enzyme activities and the parallel between the two different effects of D suggest a possible causal relationship between these two effects of D. The presence of this effective dose range of D may explain previously reported discrepancies in the effect of D on the life span of animals.

There's not much info in this abstract about the 1mg/kg doses but the rats began dying earlier so i assumed there was the same detrimental effect on the body's antioxidant enzyme's as 4mg/kg in the old rats. Calculated to humans 1mg/kg is 9mg and that dose is not given everyday but 3 times a week.

9mg 3 times a day is pretty damn close to 5mg a day.

Forgive me if i made a mistake here, but thats how i see it. The human study showing increased mortality is also worrysome imo, ive seen a few sites debunk that study but how trustworthy are they if they have a financial intrest in promoting deprenyl as a life extending substance?

Also chrono congrats for becoming a moderator on the site

Forgive me for bringing up the "dangers" of deprenyl the whole time, i just felt there's still enough room for discussion left before it should be accepted as a neuroprotectant by the whole forum.

Edited by medievil, 12 August 2010 - 10:42 AM.

[Animal]

9mg 3 times a day is pretty damn close to 5mg a day.

Look up the bioavailabilty of deprenyl when administered orally, 5mg/day taken orally is still in no way comparable to 9mg injected 3 times a week.

[medievil]

9mg 3 times a day is pretty damn close to 5mg a day.

Look up the bioavailabilty of deprenyl when administered orally, 5mg/day taken orally is still in no way comparable to 9mg injected 3 times a week.

Hmm, seems like you have a point there, i should have factored in the bioavailabilty.

[chrono]

There's not much info in this abstract about the 1mg/kg doses but the rats began dying earlier so i assumed there was the same detrimental effect on the body's antioxidant enzyme's as 4mg/kg in the old rats.

Right, but in this same abstract, it's showing that 0.25-2mg/kg has a positive effect on antioxidants, so I'm unable to see how that's possible. I'm imagining that the modulation of lifespan is through a different mechanism. I could be wrong, but I don't think this data suggests it.

[medievil]

There's not much info in this abstract about the 1mg/kg doses but the rats began dying earlier so i assumed there was the same detrimental effect on the body's antioxidant enzyme's as 4mg/kg in the old rats.

Right, but in this same abstract, it's showing that 0.25-2mg/kg has a positive effect on antioxidants, so I'm unable to see how that's possible. I'm imagining that the modulation of lifespan is through a different mechanism. I could be wrong, but I don't think this data suggests it.

The present study aims to clarify the reason for these discrepancies. Male F344/DuCrj rats began receiving subcutaneous (s.c.) injections of D at the age of 18 months. Doses used were 0.25, 0.50, and 1.0 mg/kg/injection (inj.), three times a week. Average life spans of animals were significantly longer in male rats given 0.25 and 0.5 mg/kg/inj.; however, rats given a 1.0 mg/kg dose began dying earlier than control rats, leading to an inverse U-shaped dose-efficacy relationship, a hormesis.

Old (27-month-old) rats given different doses of D for 1 month showed a typical hormetic response for antioxidant enzyme activities, indicating a significant increase in superoxide dismutase (SOD) and catalase (CAT) activities in brain dopaminergic regions with four lower doses (0.25 to 2 mg/kg/inj., 3 times a week), but a significantly negative response with the highest dose (4 mg/kg/inj.).

I assumed here that the increase in SOD and CAT at 1mg/kg only occured in the old rats, and that in the rats when started at a young age it decreased lifespan (probably by decreasing those enzyme's). They didnt do the same antioxidant enzyme test in the young animals.

But anyway animal appears to have given a good argument.

[Neuronic]

Ok, so it looks like there is some controversy about taking deprenyl along with the Xyrem. So what about piracetam?

[aLurker]

Deprenyl works great with Piracetam. No interactions there. Matter of fact I'm using this combination right now with good results, as do others.

[medievil]

Piracetam with GHB or with deprenyl?

I agree that low deprenyl doses are probably safe, without factoring in the bioavailability everything was WAY to close for me to promote deprenyl as a neuroprotectant or consider it safe (especially because of interspecies differences i wouldnt be comfortable with taking doses that are damn close to potential harmfull doses).

GHB is neurotoxic due to a excitoxic mechanism, it has been said before that piracetam could potentially potentiate such damage, but then again its also a antioxidant (wich show some protection in excitoxiticy) and i think i even saw a study that is protected against excitoxiticy but i'm not sure and could be wrong.

Either way, low doses once and awhile probably arent harmfull, even if any of those potentiate toxiticy (i dont think they would).

[Neuronic]

Actually I was asking about piracetam and GHB. Well I have taken about 7,200mg of piracetam today, 2400mg every 2-3 hours and I must say I feel much less debilitatingly sleepy.
I was wanting to find out how GHB would improve my symptoms before adding/trying something else, but it's been making me so much of a zombie since I started I have to do something or my job will be in trouble.

[xswerve]

GHB is neurotoxic due to a excitoxic mechanism...

Are you serious? Man you are so off it's not even funny! GHB is close to a miracle drug especially for narcolepsy! The FDA criminalized for Big Pharma since it is an all natural compound, they couldn't patent it until it was given the Schedule 1 status.

http://www.ncbi.nlm....pubmed/17105951

http://www.ceri.com/

[Thorsten3]

GHB is neurotoxic due to a excitoxic mechanism...

Are you serious? Man you are so off it's not even funny! GHB is close to a miracle drug especially for narcolepsy! The FDA criminalized for Big Pharma since it is an all natural compound, they couldn't patent it until it was given the Schedule 1 status.

http://www.ncbi.nlm....pubmed/17105951

http://www.ceri.com/

You need to do some more learning son. You honestly think that something that feels that euphoric is neuroprotective and healthy for your brain? It's pretty naive to believe you have found the magic bullet but sadly you're mistaken. What goes up, usually comes back down again.

GHB is neurotoxic in lesser, stimulating doses. Basically the higher you get the more neurotoxic it is. The more sedating the dose the more neuroprotective it is AGAINST the neurotoxic damage (as per the study you posted).

Do a google search and type in GHB neurotoxicity.

Also, GHB is neurotoxic via glutamanergic pathways (much like alcohol) when the drug wears off.

Edited by HyperHydrosis, 04 June 2011 - 06:30 AM.

[Raptor87]

It´s from wiki but here it goes.

In multiple studies, GHB has been found to impair spatial and working learning and memory in rats with chronic administration.[58][59][60][61] These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.[58]

Pedraza et al. (2009) found that repeated administration of GHB to rats for 15 days drastically reduced the number of neurons and non-neuronal cells in the CA1 region of the hippocampus and in the prefrontal cortex. With doses of 10 mg/kg of GHB, they were decreased by 61% in the CA1 region and 32% in the prefrontal cortex, and with 100 mg/kg, they were decreased by 38% and 9%, respectively. It is interesting to note that GHB has biphasic effects on neuronal loss, with lower doses (10 mg/kg) producing the most neurotoxicity, and higher doses (100 mg/kg) producing less.

Pretreatment with NCS-382, a GHB receptor antagonist, prevents both learning/memory deficits and neuronal loss in GHB-treated animals, suggesting that GHB's neurotoxic actions are mediated via activation of the GHB receptor.[61] In addition, the neurotoxicity appears to be caused by oxidative stress.

GHB has neuroprotective properties and has been found to protect cells from hypoxia.[42]

This is something I did not know?

Also I´ve read somewhere that ghb offers neuroprotection through hibernation.

[Nootr]

IS it true that GHB and GBL oxidate the nervous system and kill neurons?