8 replies to this topic

[Chessfan]

Hello everyone at Longecity. Have been a longtime forum lurker. This is my first posting. I have noticed that many among us have created and are consuming suppliment stacks which ideally elevate levels of cAMP. While doing seemingly dissimilar research on GHB, I found an interesting quote on wikipedia suggesting GHB is endogeneously produced within the body by reducing Succinic semialdehyde, (a GABA analogue) via the enzyme succinic semialdehyde dehydrogenase, and this enzyme is induced by cAMP. So, those consuming the forskolin and PDEI stacks may be unwittingly elevating GHB in their bloodstream . Given the pharmacological aspects of GHB, (similar to alcohol) this would not seem to produce nootropic effects. For those that argue that the increase in GHB is not significant for any negative effects, observe this quote from a study done on rats:
"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"

It is interesting to note that GHB is found in many fermented beverages such as wine or beer, so the effects may not be deleterious. But, perhaps their is a certain threshold which proves unhealthy.

So what is the jury on GHB? Could those on the cAMP stacks unknowingly expose themselves to harmful levels of GHB?

[Chessfan]

Hmm.. Does anyone have any input? I figured this would prove more interesting than critiquing supp stacks.

[renfr]

GHB is not found in wine or beer, rather GBL is, this is not the same molecule at all.
Raising GHB levels may NOT be a bad idea at first sight, GHB becomes deleterious to the brain when it's taken in therapeutic (via Xyrem) or recreational dosages.
Endogenous production of GHB doesn't activates GABAB receptors but only the GHB receptor. Though it has been scientifically proven that activation of the GHB receptor makes you dumb, this was only confirmed for 10mg/kg dosages.
100mg/kg dosages and endogenous production do not cause brain "damage".
However there's a study out there on pubmed saying that high endogenous GHB (which you want to reach) among young people makes them dumber on long term.
Therefore I would not advise elevating endogenous GHB levels, if you want to enjoy GHB effects just take GHB itself recreationally reasonably, it will cause largely less brain damage than long-term elevated GHB in your bloodstream.
Besides endogenous GHB doesn't cause alcohol-like effects because GABAB is not activated at such doses, only the GHB receptor is, that latter causes euphoria effects but long-term high GHB levels cause its downregulation therefore this is pointless.

Edited by renfr, 13 October 2012 - 06:52 PM.

[Chessfan]

Thank you for the input, renfr. I appologize about the GHB GBL mix-up in alcoholic beverages. But, GBL is nothing more than a prodrug of GBH, and is likely more potent. "GBL is rapidly converted into GHB by lactonase enzymes found in the blood. GBL is more lipophilic (fat soluble) than GHB, and so is absorbed faster and has higher bioavailability; the paradox is that this can mean that GBL has a faster onset of effects than GHB itself, even though it is a prodrug"-Wiki. Other than the potency and onset of action, the two are interchangeable with regard to the activation of the GHB receptor. When I said alcohol- like effects, I was referring to the physical experience, and am full aware that they activate different neuro-chemical pathways; I was only trying to draw a parallel to those unfamilliar to the effects: effects that are not conducive to learning. More importantly, I want some input on those who are considering, or are currently taking, cAMP stacks, because this could prove a situation in which long-term elevated levels of GHB may arise.
Also, I never suggested that GHB activates the GABA receptors, only that the GBH molecule is produced endogeneously by a GABA analogue (which is true). Secondly, you first said that GBH becomes deleterious when taken in theraputic or recreational doses, but then suggested taking it recreationally because it would cause less damage than long term exposure. Frankly, I (and I assume others on this forum) are looking for NO brain damage.

[renfr]

GBL is indeed more potent and onsets more rapidly however it's much more dangerous as it causes your blood to become very acidic and it can also harm your kidneys. That's why GHB should always be used if possible.
When I was saying it was deleterious I was talking of chronic use, addiction or use in narcolepsy (narcoleptic people using Xyrem do have a better memory because their lack of sleep caused them poor memory but a normal person would get a worse memory).
Even a single dose can cause short-term memory loss (hopefully temporary) due to serotonin depletion however it doesn't impair medium and long-term memories. This effect can be easily and fastly canceled out with bacopa supplementation (or any other substance upregulating 5HT receptors) AFTER using GHB.
As we can see in the study you quoted, long term use destroy neurons, that is a very deleterious effect and can impair your memory.
I'm not sure if this is the same kind of cognitive function loss induced by alcohol but the effects are pretty much the same.

As for cAMP enhancing stacks, their effect might not sufficient to cause a significant rise of GHB levels, at least not to an harmful level such as the one in the abstract correlating GHB with neuronal loss.
The enzyme will be in any case be constantly downregulated as unless you supplement yourself succinic semialdehyde its levels won't get higher and therefore whether the enzyme is abundant or not this won't increase GHB levels, rather just increase its metabolism which might just rise slightly your GHB levels but shortage of the GABA analogue will bring back homeostasis.
Again, meaning that it induces higher concentrations of this enzyme doesn't mean the concentration is high enough to be deleterious and doesn't mean the more enzymes you put the more GHB is produced in general (not at once).

[Chessfan]

Have you any quotes for much of these statements? Especially the statement about how bacopa can almost instantaneously reverse GHB induced memory impairment, or is this just conjecture? Also, a lack of a specific precursor would result in upregulation, as the enzyme would have to compensate for the deficit. I agree that it is unlikely that elevating cAMP would not produce dangerous effects, but that there may be a threshold where the ideal LTP initiation would be squandered by the dumbing effects of even low amounts of GHB.

[renfr]

I don't have any quote, it's my personal experience.
When I occasionally take GHB in parties afterwards I have sometimes serotonin syndrome symptoms and my short term memory is very poor (occurs all the time, you could just tell me anything and I'd forget it in the next 5 seconds), I took bacopa because I suspected this was all due to the serotonergic system and seems like it did work.
However bacopa and GHB supplementation should be carefully spaced out, Bacopa being an antagonist it can allow GHB to make a huge reserve of extracellular serotonin and then causing massive downregulation (i.e. serotonin syndrome).
Onset is quite fast, a couple hours to reverse temporary damage, if it was up to natural homeostasis, it would likely take several days.

Problem is that there is no scientific accurate data to say that LTP can be inhibited due to rise on GHB levels however we can very roughly deduce GHB concentrations with cAMP levels (are you using the CILTEP stack?).
Personally I think the CILTEP stack has a positive benefits/risks balance and therefore you'd rather take it than not take it despite rise on GHB levels. GHB receptor activation will cause its downregulation which will prevent dumbing down.

There's a study here about induced cognitive deficits : http://www.ncbi.nlm....les/PMC3137190/
You can read that cognitive deficits are mostly induced by NMDA overactivation, this is done at very high doses (100mg/kg), I frankly doubt that such low rise can induce high glutamate release and cause neuronal death.
There's a huge difference between 10 and 100mg/kg because at 10mg/kg not enough GABA is released to compensate glutamate flood, this is why it is admitted that 10mg/kg is more deleterious than 100mg/kg.
But what is 8ng/mL endogenous GHB compared to such amounts? Not enough to cause brain damage

[Chessfan]

I agree that a CILTEP stack is unlikely to precipitate any damage due to increased GHB production, but I have yet to hear anyone on this forum mention this possibility. My main point in starting this thread is essentially to make the point that we really know very little about the consummate effects that raising cAMP has on our bodies. Regarding myself, I have taken Forskolin extract, but experience diarreha every time I try it, even if I space it over a few days or months. (At the risk of this thread closing) I must ask, when you do take GHB recreationally, do you experience anything that could make it worthy for use other than a social lubricant? For instance, I find that alcohol has been conducive to solving personal, or relationship problems, provided that I dont make myself hammered. And if so, do you believe it to be worth the potential negative side effects, given that you believe it negatively affects your serotonin system? I noticed as well that you are from France; I find your English to be very impressive.

[neuropill]

Worthwhile reading.

GHB (gamma-hydroxybutyrate) by John Morgenthaler and Dan Jo: http://www.ceri.com/feature.htm


http://www.antiaging...-elixir-of-life

http://www.antiaging...ne-secretagogue

This is one of the better ones.

http://www.antiaging.../132-ghb-review