61 replies to this topic

[pheanix997]

To reiterate, it's just frustrating that I could drink cup after cup of coffee and still feel sluggish - a little concerning actually, which is why I wanted to inquire into it. I think some of the reasons mentioned in this thread are spot on - I do probably suffer from adrenal fatigue and most likely have some problem with my sleep quality... 

[TheFountain]

 

 

 

It almost seems braggadocious when someone creates a thread about not being effected by a stimulant the way most are. 

 

What is the implication here? That you are strong for not being caffeine sensitive? For being able to handle 10 cups of coffee a day? That you're a 'winner' for this reason?

 

Why would this be the assumption? 

 

Have you considered there may be something wrong if you cannot feel the effect of caffeine? Not necessarily that it is a good thing?

 

When I was about 15 I smoked tons of weed, and never had any effect from it. I thought I was completely resistant to it. Then one day I suddenly felt really high. 

 

I cannot explain it, it just happened. Might have had to do with my sleeping habits at the time. Or any number of other variables. 

 

Point is don't brag about it like it's a good thing. Or like you're an amazing specimen for being able to tolerate that much caffeine. 

Um, the thread is about the disappointing reality of NOT being effected by caffeine. I could only hope that one day I could have a mid-day coffee at work and get a little jolt in mental alertness. I envy those who do.

 

 

Well, who doesn't wish they could enjoy the taste of coffee all day long without feeling completely wired? I find your preference for the stimulant effect of caffeine a little off center, as most with caffeine anxiety wish for the complete opposite.

 

Does theobromine effect you similarly, or shall I say not effect you similarly? 

 

It isn't all that bizarre when you consider that the person seeking the stimulation usually feels mentally sluggish, unfocused, and tired. Obviously nobody would want the bodily anxiety (heart palpitations, jitters) that many get from caffeine - so I hear what you're saying - but the mental alertness and "wakefulness" is something worth striving for. 

I've never taken theobromine, but I'll look into it . 

 

 

Have you considered re-arranging your sleep schedule to suit a more restful sleep period?

[Mr Matsubayashi]

I am affected by caffeine but i feel that i get tolerance to it extremely fast.

 

I have the following known genetic interactions with caffeine

 

rs5751876(T;T)

significantly higher anxiety levels after moderate caffeine consumption

 

gs159

CYP1A2 fast metabolizer Your CYP1A2 fast metabolizer status means that you are less stimulated by caffeine. Ciprofloxacin is also metabolized by CYP1A2, but is unclear if your genotype should influence its effect

 

rs762551(A;A)

Fast Caffeine Metabolizer. Like the majority of people, caffeine is broken down faster in your liver, so it has less effect on you. Supposedly this decreases heart attack risk, although other studies show caffeine is generally good for the heart. Caffeine will be less effective at preventing Breast Cancer, Alzheimer's Disease, and Parkinson's disease. Caffeine will not make your breasts smaller.

 

[pheanix997]

 

 

 

 

It almost seems braggadocious when someone creates a thread about not being effected by a stimulant the way most are. 

 

What is the implication here? That you are strong for not being caffeine sensitive? For being able to handle 10 cups of coffee a day? That you're a 'winner' for this reason?

 

Why would this be the assumption? 

 

Have you considered there may be something wrong if you cannot feel the effect of caffeine? Not necessarily that it is a good thing?

 

When I was about 15 I smoked tons of weed, and never had any effect from it. I thought I was completely resistant to it. Then one day I suddenly felt really high. 

 

I cannot explain it, it just happened. Might have had to do with my sleeping habits at the time. Or any number of other variables. 

 

Point is don't brag about it like it's a good thing. Or like you're an amazing specimen for being able to tolerate that much caffeine. 

Um, the thread is about the disappointing reality of NOT being effected by caffeine. I could only hope that one day I could have a mid-day coffee at work and get a little jolt in mental alertness. I envy those who do.

 

 

Well, who doesn't wish they could enjoy the taste of coffee all day long without feeling completely wired? I find your preference for the stimulant effect of caffeine a little off center, as most with caffeine anxiety wish for the complete opposite.

 

Does theobromine effect you similarly, or shall I say not effect you similarly? 

 

It isn't all that bizarre when you consider that the person seeking the stimulation usually feels mentally sluggish, unfocused, and tired. Obviously nobody would want the bodily anxiety (heart palpitations, jitters) that many get from caffeine - so I hear what you're saying - but the mental alertness and "wakefulness" is something worth striving for. 

I've never taken theobromine, but I'll look into it . 

 

 

Have you considered re-arranging your sleep schedule to suit a more restful sleep period?

 

Although this is veering off the original topic . . .

 

I sleep at 10 PM and wake up at 7 AM... isn't that the optimal timeframe? Still I always wake up unrefreshed. I really don't know what it feels like to wake up and feel "on." I pretty much have a vague feeling of being hungover every morning. It takes a whole lot just to get my mind together and get going. 

 

 

 

 

It almost seems braggadocious when someone creates a thread about not being effected by a stimulant the way most are. 

 

What is the implication here? That you are strong for not being caffeine sensitive? For being able to handle 10 cups of coffee a day? That you're a 'winner' for this reason?

 

Why would this be the assumption? 

 

Have you considered there may be something wrong if you cannot feel the effect of caffeine? Not necessarily that it is a good thing?

 

When I was about 15 I smoked tons of weed, and never had any effect from it. I thought I was completely resistant to it. Then one day I suddenly felt really high. 

 

I cannot explain it, it just happened. Might have had to do with my sleeping habits at the time. Or any number of other variables. 

 

Point is don't brag about it like it's a good thing. Or like you're an amazing specimen for being able to tolerate that much caffeine. 

Um, the thread is about the disappointing reality of NOT being effected by caffeine. I could only hope that one day I could have a mid-day coffee at work and get a little jolt in mental alertness. I envy those who do.

 

 

Well, who doesn't wish they could enjoy the taste of coffee all day long without feeling completely wired? I find your preference for the stimulant effect of caffeine a little off center, as most with caffeine anxiety wish for the complete opposite.

 

Does theobromine effect you similarly, or shall I say not effect you similarly? 

 

It isn't all that bizarre when you consider that the person seeking the stimulation usually feels mentally sluggish, unfocused, and tired. Obviously nobody would want the bodily anxiety (heart palpitations, jitters) that many get from caffeine - so I hear what you're saying - but the mental alertness and "wakefulness" is something worth striving for. 

I've never taken theobromine, but I'll look into it . 

 

 

Have you considered re-arranging your sleep schedule to suit a more restful sleep period?

 

Although this is veering off the original topic . . .

 

I sleep at 10 PM and wake up at 7 AM... isn't that the optimal timeframe? Still I always wake up unrefreshed. I really don't know what it feels like to wake up and feel "on." I pretty much have a vague feeling of being hungover every morning. It takes a whole lot (time and will power) just to get my mind together and get going. 

[TheFountain]

 

 

 

 

 

It almost seems braggadocious when someone creates a thread about not being effected by a stimulant the way most are. 

 

What is the implication here? That you are strong for not being caffeine sensitive? For being able to handle 10 cups of coffee a day? That you're a 'winner' for this reason?

 

Why would this be the assumption? 

 

Have you considered there may be something wrong if you cannot feel the effect of caffeine? Not necessarily that it is a good thing?

 

When I was about 15 I smoked tons of weed, and never had any effect from it. I thought I was completely resistant to it. Then one day I suddenly felt really high. 

 

I cannot explain it, it just happened. Might have had to do with my sleeping habits at the time. Or any number of other variables. 

 

Point is don't brag about it like it's a good thing. Or like you're an amazing specimen for being able to tolerate that much caffeine. 

Um, the thread is about the disappointing reality of NOT being effected by caffeine. I could only hope that one day I could have a mid-day coffee at work and get a little jolt in mental alertness. I envy those who do.

 

 

Well, who doesn't wish they could enjoy the taste of coffee all day long without feeling completely wired? I find your preference for the stimulant effect of caffeine a little off center, as most with caffeine anxiety wish for the complete opposite.

 

Does theobromine effect you similarly, or shall I say not effect you similarly? 

 

It isn't all that bizarre when you consider that the person seeking the stimulation usually feels mentally sluggish, unfocused, and tired. Obviously nobody would want the bodily anxiety (heart palpitations, jitters) that many get from caffeine - so I hear what you're saying - but the mental alertness and "wakefulness" is something worth striving for. 

I've never taken theobromine, but I'll look into it . 

 

 

Have you considered re-arranging your sleep schedule to suit a more restful sleep period?

 

Although this is veering off the original topic . . .

 

I sleep at 10 PM and wake up at 7 AM... isn't that the optimal timeframe? Still I always wake up unrefreshed. I really don't know what it feels like to wake up and feel "on." I pretty much have a vague feeling of being hungover every morning. It takes a whole lot just to get my mind together and get going. 

 

 

 

 

It almost seems braggadocious when someone creates a thread about not being effected by a stimulant the way most are. 

 

What is the implication here? That you are strong for not being caffeine sensitive? For being able to handle 10 cups of coffee a day? That you're a 'winner' for this reason?

 

Why would this be the assumption? 

 

Have you considered there may be something wrong if you cannot feel the effect of caffeine? Not necessarily that it is a good thing?

 

When I was about 15 I smoked tons of weed, and never had any effect from it. I thought I was completely resistant to it. Then one day I suddenly felt really high. 

 

I cannot explain it, it just happened. Might have had to do with my sleeping habits at the time. Or any number of other variables. 

 

Point is don't brag about it like it's a good thing. Or like you're an amazing specimen for being able to tolerate that much caffeine. 

Um, the thread is about the disappointing reality of NOT being effected by caffeine. I could only hope that one day I could have a mid-day coffee at work and get a little jolt in mental alertness. I envy those who do.

 

 

Well, who doesn't wish they could enjoy the taste of coffee all day long without feeling completely wired? I find your preference for the stimulant effect of caffeine a little off center, as most with caffeine anxiety wish for the complete opposite.

 

Does theobromine effect you similarly, or shall I say not effect you similarly? 

 

It isn't all that bizarre when you consider that the person seeking the stimulation usually feels mentally sluggish, unfocused, and tired. Obviously nobody would want the bodily anxiety (heart palpitations, jitters) that many get from caffeine - so I hear what you're saying - but the mental alertness and "wakefulness" is something worth striving for. 

I've never taken theobromine, but I'll look into it . 

 

 

Have you considered re-arranging your sleep schedule to suit a more restful sleep period?

 

Although this is veering off the original topic . . .

 

I sleep at 10 PM and wake up at 7 AM... isn't that the optimal timeframe? Still I always wake up unrefreshed. I really don't know what it feels like to wake up and feel "on." I pretty much have a vague feeling of being hungover every morning. It takes a whole lot (time and will power) just to get my mind together and get going. 

 

Have you considered trying to get off the coffee for a couple weeks and use something else to energize you, like anti-oxidant supplements and adaptogenic herbs like ginseng? I recommend trying it out. It could be that you think you are unaffected by caffeine but your unconscious brains physiology knows better.

[Sciencyst]

I just wanted to point out that caffeine binds to adenosine-dopamine receptor heterodimers. These receptors act as D1/D2 (IIRC) receptors as well, so caffeine can be seen as a functional dopamine agonist.

[Raptor87]

It's not always the neurotransmittors man. Sometimes its just brainwiring, neurotic people are sensitive to caffeine. Some people aren't affected at all. Those who are not prone to high levels of stress/anxiety often don't get anything from caffeine. 

[Galaxyshock]

I just wanted to point out that caffeine binds to adenosine-dopamine receptor heterodimers. These receptors act as D1/D2 (IIRC) receptors as well, so caffeine can be seen as a functional dopamine agonist.

 

 

Good to know. Caffeine also somehow manages to subtitute for dopamine in reward learning:

 

Studies of mutant mice lacking dopamine in dopaminergic neurons (but retaining it in noradrenergic neurons) show that brain dopamine is not absolutely necessary for food-rewarded instrumental learning. If given caffeine to arouse them, dopamine-deficient mice can learn to choose the correct arm of a T-maze for food reward (Robinson et al., 2005). This implicates dopamine in the motivational arousal that is lacking in dopamine-deficient mice that are not treated with caffeine, and indicates that dopamine is not essential to – though it normally contributes greatly to – the rewarding effects of food. It is interesting to note, however, that caffeine – required if the mutant mice are to behave at all without dopamine – also restores the feeding response that is lost after neurotoxic lesions of dopamine neurons in adult animals (Stricker et al., 1977). The mechanism of the caffeine effects is not fully understood, but caffeine affects the same medium-sized spiny striatal neurons that are the normal neuronal targets of dopaminergic fibers of the nigro-striatal and meso-limbic dopamine systems. It acts there as a phosphodiesterase inhibitor that increases intracellular cyclic AMP (Greengard, 1976) and as an adenosine receptor antagonist (Snyder et al., 1981). Moreover, the adenosine receptors that are blocked by caffeine normally form heteromers with dopamine receptors and affect the intracellular response to the effects of dopamine at those receptors (Ferre et al., 1997; Schiffmann et al., 2007). The complex interactions of dopamine and adenosine receptors in the striatum raises the possibility that caffeine enables learning in dopamine-deficient mice by substituting for dopamine in a shared or overlapping intracellular signaling cascade.

→ source (external link)

[specs143]

I have narcolepsy and cataplexy (not extreme cataplexy, just blurrier vision and shaky knees at times). The effects of caffeine cause overstimulation in my brain, thus I feel more tired upon consumption. I am also more "up and down", when taking caffeine. I used to drink Red Bull to fall asleep at night. Now I am on Xyrem and do not need any added stimulation from caffeinated beverages. You look into Cataplexy, I used to be perplexed myself about my body "ignoring caffeine".

[FW900]

I have narcolepsy and cataplexy (not extreme cataplexy, just blurrier vision and shaky knees at times). The effects of caffeine cause overstimulation in my brain, thus I feel more tired upon consumption. I am also more "up and down", when taking caffeine. I used to drink Red Bull to fall asleep at night. Now I am on Xyrem and do not need any added stimulation from caffeinated beverages. You look into Cataplexy, I used to be perplexed myself about my body "ignoring caffeine".

 

First of all, welcome to Longecity. I'm sorry to "call you out" , but your theory is incorrect. If it caused an overstimulation, you would be awake for a period of time.

 

As I pointed out earlier, the reason caffeine does not affect people with narcolepsy is due to the fact that people with narcolepsy are theorized to have much less Orexin (Hypocretin) neurons. Caffeine acts as an adenosine receptor antagonist. Caffeine, binds to the adenosine receptor, which prevents the usual action of adenosine inhibiting Orexin production, which in turn promotes sleep. People with narcolepsy are theorized to have a low number of Orexin neurons to begin, so the effects of caffeine, especially in terms of warding off sleep, are greatly diminished.

 

Another reason you possibly benefited from taking caffeine before you sleep is that some with Narcolepsy have an excess of REM sleep. Caffeine lessens REM sleep, which is another reason you thought it may have been beneficial.

[specs143]

[quote name="FW900" post="663008" timestamp="1400335677"]

[quote name="specs143" post="662981" timestamp=
 
First of all, welcome to Longecity. I'm sorry to "call you out" , but your theory is incorrect. If it caused an overstimulation, you would be awake for a period of time.
 
As I pointed out earlier, the reason caffeine does not affect people with narcolepsy is due to the fact that people with narcolepsy are theorized to have much less Orexin (Hypocretin) neurons. Caffeine acts as an adenosine receptor antagonist. Caffeine, binds to the adenosine receptor, which prevents the usual action of adenosine inhibiting Orexin production, which in turn promotes sleep. People with narcolepsy are theorized to have a low number of Orexin neurons to begin, so the effects of caffeine, especially in terms of warding off sleep, are greatly diminished.
 
Another reason you possibly benefited from taking caffeine before you sleep is that some with Narcolepsy have an excess of REM sleep. Caffeine lessens REM sleep, which is another reason you thought it may have been beneficial.[/quote]

Well, that makes sense. I appreciate the scientific explanation. I apologize for being incorrect on my theory, however, I do stand by the fact that the underlying cause of this is discussion is potentially due to Narcolepsy and Cataplexy (which yes, means that there is a low number of Orexin neurons). It is worth investigating if extreme fatigue is present and not combated by caffeine. Thanks!

Edited by specs143, 17 May 2014 - 02:57 PM.

[NeuroNootropic]

 

I have narcolepsy and cataplexy (not extreme cataplexy, just blurrier vision and shaky knees at times). The effects of caffeine cause overstimulation in my brain, thus I feel more tired upon consumption. I am also more "up and down", when taking caffeine. I used to drink Red Bull to fall asleep at night. Now I am on Xyrem and do not need any added stimulation from caffeinated beverages. You look into Cataplexy, I used to be perplexed myself about my body "ignoring caffeine".

 

First of all, welcome to Longecity. I'm sorry to "call you out" , but your theory is incorrect. If it caused an overstimulation, you would be awake for a period of time.

 

As I pointed out earlier, the reason caffeine does not affect people with narcolepsy is due to the fact that people with narcolepsy are theorized to have much less Orexin (Hypocretin) neurons. Caffeine acts as an adenosine receptor antagonist. Caffeine, binds to the adenosine receptor, which prevents the usual action of adenosine inhibiting Orexin production, which in turn promotes sleep. People with narcolepsy are theorized to have a low number of Orexin neurons to begin, so the effects of caffeine, especially in terms of warding off sleep, are greatly diminished.

 

Another reason you possibly benefited from taking caffeine before you sleep is that some with Narcolepsy have an excess of REM sleep. Caffeine lessens REM sleep, which is another reason you thought it may have been beneficial.

 

 

That's interesting about adenosine inhibiting orexin production. I took 1 mg Rasagiline and 100 mg Modafinil everyday for just a little over a month before the combo stopped working, but during this time I was sensitive to caffeine. Even one cup of earl grey tea would make me overstimulated. This was unusual because not even a large cup of coffee (140 mg) would have a stimulant effect on me prior to the combo.

 

One of Modafinil's mechanism of action is through the orexin receptor so it would make sense for it to potentiate caffeine. But, before I started the R+M combo I occasionally took modafinil with caffeine and it didn't have much of an effect on caffeine. Could it be that chronic modafinil usage affects caffeine or was it the rasagiline that caused it? Rasagiline inhibits CYP1A2 which is the main enzyme caffeine is metabolized by, but I remember reading an article that showed rasagiline had no effect on caffeine metabolism.

Edited by NeuroNootropic, 17 May 2014 - 06:38 PM.

[xks201]

Has the xyrem fixed your narcolepsy?

[specs143]

Has the xyrem fixed your narcolepsy?

Yes, it has!  I have more energy now than most "normal" people, and I don't have vivid dreams all night long anymore :-)

[Raptor87]

 

Has the xyrem fixed your narcolepsy?

Yes, it has!  I have more energy now than most "normal" people, and I don't have vivid dreams all night long anymore :-)

 

 

I can't believe it. This was probably one of the cheapest streetdrugs out there 15years ago, and it was even legal in my country. Today it's almost impossible to get and it's seriously expensive with prescription. This is one of the few drugs that could actually help me. I remember how the media used to over exaggerate the sideeffect of this drug just because kids were drinking it mixing it together with alcohol and other drugs.   

 

Positive effects of GHB:

 

http://www.life-enha...ature-committee

 

There are 15 INDs filed with the FDA for GHB for:

• Improving sleep patterns and maintaining daytime alertness in narcolepsy
• Reducing schizophrenic symptoms
• Stabilizing Parkinson's disease
• Reducing nocturnal myoclonus (painful leg cramps at night)
• Improving memory problems
• Stimulating natural growth hormone release
• Decreasing pain and improving sleep in fibromyalgia patients
• Relieving symptoms associated with Huntington's chorea
• Regulating muscle tone in dystonia musculorum deformans
• Controlling tardive dyskinesia symptoms
• Decreasing drug withdrawal symptoms (alcohol and opiates)
• Decreasing hyperactivity and learning disabilities in children
• Inducing sedation and tranquilization
• Relieving anxiety
• Lowering cholesterol

 

•  

Edited by Brainfogged, 18 May 2014 - 07:26 AM.

[FW900]

 

 

Has the xyrem fixed your narcolepsy?

Yes, it has!  I have more energy now than most "normal" people, and I don't have vivid dreams all night long anymore :-)

 

 

I can't believe it. This was probably one of the cheapest streetdrugs out there 15years ago, and it was even legal in my country. Today it's almost impossible to get and it's seriously expensive with prescription. This is one of the few drugs that could actually help me. I remember how the media used to over exaggerate the sideeffect of this drug just because kids were drinking it mixing it together with alcohol and other drugs.   

 

Positive effects of GHB:

 

http://www.life-enha...ature-committee

 

There are 15 INDs filed with the FDA for GHB for:

• Improving sleep patterns and maintaining daytime alertness in narcolepsy
• Reducing schizophrenic symptoms
• Stabilizing Parkinson's disease
• Reducing nocturnal myoclonus (painful leg cramps at night)
• Improving memory problems
• Stimulating natural growth hormone release
• Decreasing pain and improving sleep in fibromyalgia patients
• Relieving symptoms associated with Huntington's chorea
• Regulating muscle tone in dystonia musculorum deformans
• Controlling tardive dyskinesia symptoms
• Decreasing drug withdrawal symptoms (alcohol and opiates)
• Decreasing hyperactivity and learning disabilities in children
• Inducing sedation and tranquilization
• Relieving anxiety
• Lowering cholesterol

 

•  

 

 

GHB is very neurotoxic, even in small amounts. Chronic administration, results in impaired memory and worsened mental performance. It might "help you" but at what cost?

 

There are dozens of studies on PubMed pertaining to GHB's neurotoxicity. http://www.ncbi.nlm....rotoxicity GHB

 

The wikipedia page sums it up well.

 

 

In multiple studies, GHB has been found to impair spatial memory, working memory, learning and memory in rats with chronic administration.^{[43][44][45][46]} These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.^[43]

Pedraza et al. (2009) found that repeated administration of nGHB to rats for 15 days drastically reduced the number of neurons and non-euronal 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.

Hippocampal and PFC neurotoxicity is a big reason to avoid GHB/Xyrem. Specs143, likely has no alternatives, and otherwise would be sleeping all day, so it his/her case, it might be worth it. Unless you are under similar extreme circumstances, I suggest you avoid it. I have excessive daytime sleepiness and I would never ingest GHB due to neurotoxicity concerns.

[Raptor87]

 

 

 

Has the xyrem fixed your narcolepsy?

Yes, it has!  I have more energy now than most "normal" people, and I don't have vivid dreams all night long anymore :-)

 

 

I can't believe it. This was probably one of the cheapest streetdrugs out there 15years ago, and it was even legal in my country. Today it's almost impossible to get and it's seriously expensive with prescription. This is one of the few drugs that could actually help me. I remember how the media used to over exaggerate the sideeffect of this drug just because kids were drinking it mixing it together with alcohol and other drugs.   

 

Positive effects of GHB:

 

http://www.life-enha...ature-committee

 

There are 15 INDs filed with the FDA for GHB for:

• Improving sleep patterns and maintaining daytime alertness in narcolepsy
• Reducing schizophrenic symptoms
• Stabilizing Parkinson's disease
• Reducing nocturnal myoclonus (painful leg cramps at night)
• Improving memory problems
• Stimulating natural growth hormone release
• Decreasing pain and improving sleep in fibromyalgia patients
• Relieving symptoms associated with Huntington's chorea
• Regulating muscle tone in dystonia musculorum deformans
• Controlling tardive dyskinesia symptoms
• Decreasing drug withdrawal symptoms (alcohol and opiates)
• Decreasing hyperactivity and learning disabilities in children
• Inducing sedation and tranquilization
• Relieving anxiety
• Lowering cholesterol

 

•  

 

 

GHB is very neurotoxic, even in small amounts. Chronic administration, results in impaired memory and worsened mental performance. It might "help you" but at what cost?

 

There are dozens of studies on PubMed pertaining to GHB's neurotoxicity. http://www.ncbi.nlm....rotoxicity GHB

 

The wikipedia page sums it up well.

 

 

In multiple studies, GHB has been found to impair spatial memory, working memory, learning and memory in rats with chronic administration.^{[43][44][45][46]} These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.^[43]

Pedraza et al. (2009) found that repeated administration of nGHB to rats for 15 days drastically reduced the number of neurons and non-euronal 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.

Hippocampal and PFC neurotoxicity is a big reason to avoid GHB/Xyrem. Specs143, likely has no alternatives, and otherwise would be sleeping all day, so it his/her case, it might be worth it. Unless you are under similar extreme circumstances, I suggest you avoid it. I have excessive daytime sleepiness and I would never ingest GHB due to neurotoxicity concerns.

 

 

I don´t have time to read this now. But was the drug tested during wake hours on the rats? Any drug that causes intoxication is bound to impair cognition and memory. This doesn't necessarily mean the same for when the drug is administered for sleep hours because the brain get's its daily exercise. Yes, I have a medical condition. 

[xks201]

Hey FW90p I think GHB studies are a little more complicated than just rat analysis. People with narcolepsy have brain functiom abnormalities. Clearly it is inducing slow wave sleep and or correcting those abnormalities. Clearly it is working for many. test need to be done on humans with those disordered. If I was sleepy all day and something helped many people I wouldn't be so quick to damn it and thank my government for making it illegal.
Sorry typed this on my phone. GHB naturally occurs in the human body.

[FW900]

 

 

GHB is very neurotoxic, even in small amounts. Chronic administration, results in impaired memory and worsened mental performance. It might "help you" but at what cost?

 

There are dozens of studies on PubMed pertaining to GHB's neurotoxicity. http://www.ncbi.nlm....rotoxicity GHB

 

The wikipedia page sums it up well.

 

 

In multiple studies, GHB has been found to impair spatial memory, working memory, learning and memory in rats with chronic administration.^{[43][44][45][46]} These effects are associated with decreased NMDA receptor expression in the cerebral cortex and possibly other areas as well.^[43]

Pedraza et al. (2009) found that repeated administration of nGHB to rats for 15 days drastically reduced the number of neurons and non-euronal 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.

Hippocampal and PFC neurotoxicity is a big reason to avoid GHB/Xyrem. Specs143, likely has no alternatives, and otherwise would be sleeping all day, so it his/her case, it might be worth it. Unless you are under similar extreme circumstances, I suggest you avoid it. I have excessive daytime sleepiness and I would never ingest GHB due to neurotoxicity concerns.

 

 

I don´t have time to read this now. But was the drug tested during wake hours on the rats? Any drug that causes intoxication is bound to impair cognition and memory. This doesn't necessarily mean the same for when the drug is administered for sleep hours because the brain get's its daily exercise. Yes, I have a medical condition. 

 

 

You raise a good point, I believe at least a few of them were, and many of them did not state whether the drug was tested during wake hours in the summary. Other studies, (especially the studies related to neurotoxicity, measured)  measured performance after the biological half-life of GHB expired (such as the first below). Nonetheless, the rats demostrated a noticlble loss of neurons due to even low dose GHB administration, which clearly points to neurotoxicicty.

 

 

http://www.ncbi.nlm....pubmed/19288974

 

Gammahydroxybutyric acid (GHB) is an endogenous constituent of the central nervous system that has acquired great social relevance for its use as a recreational 'club drug'. GHB, popularly known as 'liquid ecstasy', is addictive when used continuously. Although the symptoms associated with acute intoxication are well known, the effects of prolonged use remain uncertain. We examined in male rats the effect of repeated administration of GHB (10 and 100 mg/kg) on various parameters: neurological damage, working memory and spatial memory, using neurological tests, the Morris water maze and the hole-board test. The results showed that repeated administration of GHB, especially at doses of 10 mg/kg, causes neurological damage, affecting the 'grasping' reflex, as well as alteration in spatial and working memories. Stereological quantification showed that this drug produces a drastic neuronal loss in the CA1 hippocampal region and in the prefrontal cortex, two areas clearly involved in cognitive and neurological functions. No effects were noted after quantification in the periaqueductal grey matter (PAG), a region lacking GHB receptors. Moreover, NCS-382, a putative antagonist of GHB receptor, prevented both neurological damage and working- memory impairment induced by GHB. This suggests that the effects of administration of this compound may be mediated, at least partly, by specific receptors in the nervous system. The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects. This is very relevant because its abuse, especially by young persons, could produce considerable neurological alterations after prolonged abuse.

 

http://www.ncbi.nlm....pubmed/17296081

 

GHB, a popularly known drug as "liquid ecstasy", is a substance with abuse potential. Among the possible described side-effects after the continued consumption of GHB are amnesia and deterioration of memory. Likewise, recent studies indicate the existence of neurotoxicity in certain brain regions after its prolonged treatment. The aim of this study was to examine the effect of the subchronic administration of GHB (10 and 100 mg/kg) on spatial memory and sensoriomotor reflexes in male rats, using the Morris water maze and a battery of sensoriomotor tests, respectively. The results indicated that animals treated with GHB (10 mg/kg) showed a greater latency of escape during the phase of acquisition in the days first and third of tests, as compared with the control group (p<0.05), as well as a deterioration of grasping reflex with the two doses of GHB (p<0.01). Numerous studies indicated that the medial prefrontal cortex is a crucial neuronal substrate in the working memory and grasping reflex modulation. These results suggest that prolonged administration of GHB could alter structure and/or function of the medial prefrontal cortex, as well as its interconnections with other brain regions involved in the evaluated cognitive and neurological processes.

[FW900]

Hey FW90p I think GHB studies are a little more complicated than just rat analysis. People with narcolepsy have brain functiom abnormalities. Clearly it is inducing slow wave sleep and or correcting those abnormalities. Clearly it is working for many. test need to be done on humans with those disordered. If I was sleepy all day and something helped many people I wouldn't be so quick to damn it and thank my government for making it illegal.
Sorry typed this on my phone. GHB naturally occurs in the human body.

 

I'm not thanking its illegality and I didn't say that I agree with it being illegal. I do have a sleep disorder and realize how debilitating it can be; I am merely illustrating that it is neurotoxic, knowing which can be of critical importance for brain health.

Edited by FW900, 19 May 2014 - 01:32 PM.

[machete234]

Hippocampal and PFC neurotoxicity is a big reason to avoid GHB/Xyrem. Specs143, likely has no alternatives, and otherwise would be sleeping all day, so it his/her case, it might be worth it. Unless you are under similar extreme circumstances, I suggest you avoid it. I have excessive daytime sleepiness and I would never ingest GHB due to neurotoxicity concerns.

 

 

But couldnt it be the absence of GHB that starts neurotoxicity?

I mean obviously its not a good idea to propose constant levels of GHB but doesnt the neurotoxicity happen the next morning when the rebound effect happens?

A lower dose would cause less of a rebound effect.

 

I took it recreationally and knocked myself out on purpose one or two times with a few grams each time (2x a night) for 2x 4h of deep sleep.

In the morning you can feel that something is off but its still not as bad as an alcohol hangover.

 

 

A completely different question: should we stop drinking caffeine?

For me it does not do that much other than giving me a little clarity and caffeine itself is probably is the reason I need it.

Maybe I would just get up in the morning and be reasonably alert once I am not dependent on it anymore.

 

I mean similarly the smoker thinks cigarettes calm him down but in fact his stress levels are constantly elevated because theres never enough nicotine.

Maybe you feel tired in the morning because thats when your body gets the caffeine.

 

Edited by machete234, 19 May 2014 - 05:49 PM.

[FW900]

 

 

But couldnt it be the absence of GHB that starts neurotoxicity?

I mean obviously its not a good idea to propose constant levels of GHB but doesnt the neurotoxicity happen the next morning when the rebound effect happens?

A lower dose would cause less of a rebound effect.

 

I took it recreationally and knocked myself out on purpose one or two times with a few grams each time (2x a night) for 2x 4h of deep sleep.

In the morning you can feel that something is off but its still not as bad as an alcohol hangover.

 

Absence as in taking the drug and ceasing it or an absence of GHB to begin with in the brain? The first scenario is plausible. I'm not certain if "rebound" is a fair comparison to to neurotoxicity and if the rebound of any particular drug is viable as a measure of neurotoxicity.  A lower dosage may cause less "rebound" but will it be less neurotoxic? At least one of the studies previously quoted specially outlines that a low dose of GHB is neurotoxic. "The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects."

 

I say, we return this thread to it's original topic, "people who are unaffected by caffeine". Enough with GHB/Xyrem. If anyone wishes to continue the neurotoxicity debate, we should start a new thread rather than continue it here..

[Raptor87]

 

 

 

But couldnt it be the absence of GHB that starts neurotoxicity?

I mean obviously its not a good idea to propose constant levels of GHB but doesnt the neurotoxicity happen the next morning when the rebound effect happens?

A lower dose would cause less of a rebound effect.

 

I took it recreationally and knocked myself out on purpose one or two times with a few grams each time (2x a night) for 2x 4h of deep sleep.

In the morning you can feel that something is off but its still not as bad as an alcohol hangover.

 

Absence as in taking the drug and ceasing it or an absence of GHB to begin with in the brain? The first scenario is plausible. I'm not certain if "rebound" is a fair comparison to to neurotoxicity and if the rebound of any particular drug is viable as a measure of neurotoxicity.  A lower dosage may cause less "rebound" but will it be less neurotoxic? At least one of the studies previously quoted specially outlines that a low dose of GHB is neurotoxic. "The results show for the first time that the repeated administration of GHB, especially at very low doses, produces neurotoxic effects."

 

I say, we return this thread to it's original topic, "people who are unaffected by caffeine". Enough with GHB/Xyrem. If anyone wishes to continue the neurotoxicity debate, we should start a new thread rather than continue it here..

 

 

It's already out there man!!! 

 

http://www.longecity...he-jury-on-ghb/

 

http://www.longecity...agentnootropic/

 

http://www.longecity...as-a-nootropic/

 

http://www.longecity...e-nerve-damage/

 

http://www.longecity...0h-and-fatigue/

 

http://www.longecity...b-and-deprenyl/

[oneshot2shots]

Try BP coffee(good quality coffee with butter and coconut oil). You should have steady, healthy energy for 4 hours after it with no hunger(healthy depending on your view of saturated fat:)

 

Some types of coffee everyone will get tired after.

[pheanix997]

Just an update regarding the potential sleep issues... I had an overnight EEG test done, and the specialist found no major issues. My sleep efficiency was 86%, with minimal amount of awakenings and bodily movement. He still acknowledged the possibility of idiopathic hypersomnia, though, which is basically another way of saying "unknown cause of excessive daytime sleepiness." He's going to bring me in for a day time alertness/ nap testing, and if I show problems he may consider prescribe me modafinil, even though here, in Ontario, it's a scheduled substance! 

[pheanix997]

Try BP coffee(good quality coffee with butter and coconut oil). You should have steady, healthy energy for 4 hours after it with no hunger(healthy depending on your view of saturated fat:)

 

Some types of coffee everyone will get tired after.

I'm going to experiment with this sometime, but apparently Joe Rogan found evidence that debunked Asprey's claim of "mytotoxins" in coffee, lol. 

[FW900]

Just an update regarding the potential sleep issues... I had an overnight EEG test done, and the specialist found no major issues. My sleep efficiency was 86%, with minimal amount of awakenings and bodily movement. He still acknowledged the possibility of idiopathic hypersomnia, though, which is basically another way of saying "unknown cause of excessive daytime sleepiness." He's going to bring me in for a day time alertness/ nap testing, and if I show problems he may consider prescribe me modafinil, even though here, in Ontario, it's a scheduled substance! 

 

It is a shame that you have to go through all these tests to "prove" you have a sleeping disorder. Isn't the excessive sleep, tiredness, and the ineffectiveness of caffeine enough for a doctor to realize that this person has excessive daytime sleepiness?

[pheanix997]

 

Just an update regarding the potential sleep issues... I had an overnight EEG test done, and the specialist found no major issues. My sleep efficiency was 86%, with minimal amount of awakenings and bodily movement. He still acknowledged the possibility of idiopathic hypersomnia, though, which is basically another way of saying "unknown cause of excessive daytime sleepiness." He's going to bring me in for a day time alertness/ nap testing, and if I show problems he may consider prescribe me modafinil, even though here, in Ontario, it's a scheduled substance! 

 

It is a shame that you have to go through all these tests to "prove" you have a sleeping disorder. Isn't the excessive sleep, tiredness, and the ineffectiveness of caffeine enough for a doctor to realize that this person has excessive daytime sleepiness?

 

Yeah it really sucks and frustrating that there are no solutions; sleep is just simply not refreshing. I'm not even sure modafinil would help me... 

[xks201]

There have to be more symptoms than just sleepiness. Hypoglycemia, minor neuropathy, muscle weakness, mood swings...etc.?

[pheanix997]

There have to be more symptoms than just sleepiness. Hypoglycemia, minor neuropathy, muscle weakness, mood swings...etc.?

I have all of these symptoms except neuropathy.