iconoclast56
Bluelighter
- Joined
- Feb 4, 2012
- Messages
- 94
Firstly, the lab study I know of which documents the potential neurotoxicity of GHB is this one:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=6137924
in which rats were repeatedly administered doses of between 10mg/kg and 100mg/kg over a 2 week period. According to that study, the concurrent administration of a selective GHB antagonist counteracted the neurotoxicity which would indicate that the GHB receptor is responsibly for the neurotoxicity, not the GABA_B receptor. According to that study, the neurotoxicity was greatest for rats who were administered the lowest doses of 10mg/kg. For a human who weights 90kg, that corresponds to a dose of 0.9g. According to this GHB pharmacology page:
https://www.erowid.org/chemicals/ghb/ghb_pharmacology1.shtml
GHB, at low doses, acts primarily on the GHB receptor and that GHB receptor activation stimulates the release of glutamate. This may explain why increased neurotoxicity was observed with lower, rather than higher doses. As far as I know, GHB has never been proven to produce neurotoxicity in humans. That doesn't mean one should assume that it doesn't produce them though. This thread is dedicated to devising ways to circumvent and prevent any potential neurotoxicity based on what is known about the pharmacology of GHB and those results from the rat study. I'll start the thread off by contributing my knowledge (which is limited) and I'll edit the thread to add in all valid info that anyone else provides.
Pharmacology:
GHB has a far greater affinity for GHB receptors, than it does GABA_B receptors. At low doses, GHB bonds primarily to the GHB receptor, whereas at higher doses it starts binding to the GABA_B receptor. When someone uses GHB to sleep, the reason they wake up after 4 hours is because by then, a large amount of the GHB has been metabolised and consequently, there is no longer much GHB binded to the GABA_B receptor, while the remaining GHB is binded primarily to the GHB receptor. There are 2 reasons why this causes a flood of glutamate activity. Firstly, GHB activation itself causes glutamate to be released. Secondly, GABA_B activity inhibits glutamate release and when GABA activity stops, there will be a rebound of glutamate release. A few selective GHB agonists have been researched and they have been observed to cause seizures, therefore the seizures caused by GBL are caused by GHB receptor activation. It seems most probable that glutamate is fully responsible for GHBs neurotoxicity. It is therefore imperative to know ways of preventing excessive glutamate buildup and the damage caused by it.
Excitotoxicity:
Excitotoxicity is where overstimulation of glutamate receptors, notably the NMDA receptor, caused neurons to die. In the brain, glutamate and GABA are like the yin and the yang. Glutamate is an excitatory neurotransmitter which is balanced by GABA, an inhibitory neurotransmitter. The two main types of GABA receptors are the GABA_A receptors (which are activated by drugs like alcohol and benzodiazepines) and GABA_B receptors (which are activated by drugs like GHB and baclofen). An excess of GABA (or GABAergic drugs) in the brain, causes the sedative effects associated with GHB and benzos. Excess glutamate causes anxiety, nervousness but far worse, neuron death. It is therefore imperative to know how to prevent glutamate excitotoxicity. The dopamine rebound that comes on after the effects of GHB wears off, is likely caused, at least partially, by a flood of glutamate which was produced and released by the brain in response to the excessive GABA_B activity that occurs while on GHB. It is worth noting that the neurotoxicity allegedly caused by various other drugs such as methamphetamine and MDMA is also supposedly caused in part by excitotoxicity.
Firstly, everyone should know that magnesium is a partial NMDA antagonist which means that it blocks NMDA receptors and protects the brain against glutamate excitotoxicity. GHB is most commonly sold as the sodium salt but GBL can be converted into other salts such as potassium, calcium and magnesium. Magnesium GHB would serve a dual purpose of inducing the effects of GHB as well as reducing potential neurotoxicity. A regular user who was ingesting only MgGHB would rapidly exceed the RDA of magnesium so it would be wiser to obtain a mixture of salts. Magnesium supplements often come as mixtures of magnesium and calcium. This is because calcium allows magnesium to be absorbed effectively by the body. Therefore, a mixture of CaGHB and MgGHB would be far healthier. A heavy user would still rapidly exceed the RDA of magnesium though so the best approach would be to throw potassium GHB into the mix. Most people ingest too much sodium and not enough potassium each day so its difficult to ingest too much potassium like this.
Overactivation of the NMDA receptor caused an excessive influx of calcium ions into the cell which causes a chain reaction of events which contribute towards the destruction of the cell. One of the main causes of the cell destruction of free radical damage. Therefore, on top of helping prevent the excessive excitation with magnesium, one can also prevent the damage caused by overexcitation by ingesting antioxidants. I like to drink berry tea because I like the taste and all types of berries are excellent sources of antioxidants. I use ginkgo biloba for its vasodilating properties, to counteract the vasoconstriction caused by amphetamines but there are plenty of additional good reasons to use this substance. Firslty, it is a potent antioxidant, secondly, there is evidence to suggest that it protects the brain against glutamate excitotoxicity:
http://www.ncbi.nlm.nih.gov/pubmed/13130395
http://www.res-medical.com/chinese-medicine/20692
http://www.hopkinsguides.com/hopkin...ced_by_NMDA_receptors_and_mechanism_thereof]_
I recently came across this article:
http://www.wellnessresources.com/he..._protects_brain_cells_from_excitotoxic_death/
which claims that carnosine is a potent antioxidant that protects against excitotoxicity. I'm not sure if this is due, solely to its antioxidant properties though. Heres an interesting article:
http://www.nature.com/nm/journal/v17/n6/full/nm.2387.html
about a substance called iduna. Heres a good article that lists various substances to protect the brain against excitotoxicity:
http://www.naturalnews.com/026216.html
A possible way to prevent the excessive buildup of glutamate in the first place is the use of adaptogens such as Siberian ginseng. Adaptogens help maintain homeostasis meaning they counteract neurochemical imbalances and help bring ones neurochemistry back to a more balanced state. I'd advise against rhodiola rosea since it also has mild MAOI properties, there are plenty of other potent adaptogenic herbs one can use.
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=6137924
in which rats were repeatedly administered doses of between 10mg/kg and 100mg/kg over a 2 week period. According to that study, the concurrent administration of a selective GHB antagonist counteracted the neurotoxicity which would indicate that the GHB receptor is responsibly for the neurotoxicity, not the GABA_B receptor. According to that study, the neurotoxicity was greatest for rats who were administered the lowest doses of 10mg/kg. For a human who weights 90kg, that corresponds to a dose of 0.9g. According to this GHB pharmacology page:
https://www.erowid.org/chemicals/ghb/ghb_pharmacology1.shtml
GHB, at low doses, acts primarily on the GHB receptor and that GHB receptor activation stimulates the release of glutamate. This may explain why increased neurotoxicity was observed with lower, rather than higher doses. As far as I know, GHB has never been proven to produce neurotoxicity in humans. That doesn't mean one should assume that it doesn't produce them though. This thread is dedicated to devising ways to circumvent and prevent any potential neurotoxicity based on what is known about the pharmacology of GHB and those results from the rat study. I'll start the thread off by contributing my knowledge (which is limited) and I'll edit the thread to add in all valid info that anyone else provides.
Pharmacology:
GHB has a far greater affinity for GHB receptors, than it does GABA_B receptors. At low doses, GHB bonds primarily to the GHB receptor, whereas at higher doses it starts binding to the GABA_B receptor. When someone uses GHB to sleep, the reason they wake up after 4 hours is because by then, a large amount of the GHB has been metabolised and consequently, there is no longer much GHB binded to the GABA_B receptor, while the remaining GHB is binded primarily to the GHB receptor. There are 2 reasons why this causes a flood of glutamate activity. Firstly, GHB activation itself causes glutamate to be released. Secondly, GABA_B activity inhibits glutamate release and when GABA activity stops, there will be a rebound of glutamate release. A few selective GHB agonists have been researched and they have been observed to cause seizures, therefore the seizures caused by GBL are caused by GHB receptor activation. It seems most probable that glutamate is fully responsible for GHBs neurotoxicity. It is therefore imperative to know ways of preventing excessive glutamate buildup and the damage caused by it.
Excitotoxicity:
Excitotoxicity is where overstimulation of glutamate receptors, notably the NMDA receptor, caused neurons to die. In the brain, glutamate and GABA are like the yin and the yang. Glutamate is an excitatory neurotransmitter which is balanced by GABA, an inhibitory neurotransmitter. The two main types of GABA receptors are the GABA_A receptors (which are activated by drugs like alcohol and benzodiazepines) and GABA_B receptors (which are activated by drugs like GHB and baclofen). An excess of GABA (or GABAergic drugs) in the brain, causes the sedative effects associated with GHB and benzos. Excess glutamate causes anxiety, nervousness but far worse, neuron death. It is therefore imperative to know how to prevent glutamate excitotoxicity. The dopamine rebound that comes on after the effects of GHB wears off, is likely caused, at least partially, by a flood of glutamate which was produced and released by the brain in response to the excessive GABA_B activity that occurs while on GHB. It is worth noting that the neurotoxicity allegedly caused by various other drugs such as methamphetamine and MDMA is also supposedly caused in part by excitotoxicity.
Firstly, everyone should know that magnesium is a partial NMDA antagonist which means that it blocks NMDA receptors and protects the brain against glutamate excitotoxicity. GHB is most commonly sold as the sodium salt but GBL can be converted into other salts such as potassium, calcium and magnesium. Magnesium GHB would serve a dual purpose of inducing the effects of GHB as well as reducing potential neurotoxicity. A regular user who was ingesting only MgGHB would rapidly exceed the RDA of magnesium so it would be wiser to obtain a mixture of salts. Magnesium supplements often come as mixtures of magnesium and calcium. This is because calcium allows magnesium to be absorbed effectively by the body. Therefore, a mixture of CaGHB and MgGHB would be far healthier. A heavy user would still rapidly exceed the RDA of magnesium though so the best approach would be to throw potassium GHB into the mix. Most people ingest too much sodium and not enough potassium each day so its difficult to ingest too much potassium like this.
Overactivation of the NMDA receptor caused an excessive influx of calcium ions into the cell which causes a chain reaction of events which contribute towards the destruction of the cell. One of the main causes of the cell destruction of free radical damage. Therefore, on top of helping prevent the excessive excitation with magnesium, one can also prevent the damage caused by overexcitation by ingesting antioxidants. I like to drink berry tea because I like the taste and all types of berries are excellent sources of antioxidants. I use ginkgo biloba for its vasodilating properties, to counteract the vasoconstriction caused by amphetamines but there are plenty of additional good reasons to use this substance. Firslty, it is a potent antioxidant, secondly, there is evidence to suggest that it protects the brain against glutamate excitotoxicity:
http://www.ncbi.nlm.nih.gov/pubmed/13130395
http://www.res-medical.com/chinese-medicine/20692
http://www.hopkinsguides.com/hopkin...ced_by_NMDA_receptors_and_mechanism_thereof]_
I recently came across this article:
http://www.wellnessresources.com/he..._protects_brain_cells_from_excitotoxic_death/
which claims that carnosine is a potent antioxidant that protects against excitotoxicity. I'm not sure if this is due, solely to its antioxidant properties though. Heres an interesting article:
http://www.nature.com/nm/journal/v17/n6/full/nm.2387.html
about a substance called iduna. Heres a good article that lists various substances to protect the brain against excitotoxicity:
http://www.naturalnews.com/026216.html
A possible way to prevent the excessive buildup of glutamate in the first place is the use of adaptogens such as Siberian ginseng. Adaptogens help maintain homeostasis meaning they counteract neurochemical imbalances and help bring ones neurochemistry back to a more balanced state. I'd advise against rhodiola rosea since it also has mild MAOI properties, there are plenty of other potent adaptogenic herbs one can use.
