GHB neurotoxiticy

[clay404]

10mg/kg is the very toxic dose and 100mg/kg is the dose that is less toxic. But i dont know how many ml GHB is how many grams, and i dont know wheter you could just translate the doses to humans like that, i hope anyone else can answer your question.

well lets say I weigh 160 lbs. That is 72 kg. so 10 x 72 = 720. and so is that .72 grams or 720 mg? I am confused.

 

[seep]

well lets say I weigh 160 lbs. That is 72 kg. so 10 x 72 = 720. and so is that .72 grams or 720 mg? I am confused.

Same thing.

Assuming you drank wine that had 21.4 mg GHB per liter, and setting a bottle at 750 mL, that's 16.05 mg GHB per bottle.

Lets say for argument's sake that GHB is chronically neurotoxic at 10 mg per kg of body weight per day. 160 lbs = 72.6 kg. You'd need to consume 726 mg GHB per day. If your source of GHB is the red wine in question, you'd need to drink roughly 45 wine bottles per day for as long as it takes to develop the chronic GHB toxicity we've assumed.

Which isn't gonna happen.

 

[clay404]

Same thing.

Assuming you drank wine that had 21.4 mg GHB per liter, and setting a bottle at 750 mL, that's 16.05 mg GHB per bottle.

Lets say for argument's sake that GHB is chronically neurotoxic at 10 mg per kg of body weight per day. 160 lbs = 72.6 kg. You'd need to consume 726 mg GHB per day. If your source of GHB is the red wine in question, you'd need to drink roughly 45 wine bottles per day for as long as it takes to develop the chronic GHB toxicity we've assumed.

Which isn't gonna happen.

who takes a low dose like 726 mg or something similar?

 

[seep]

who takes a low dose like 726 mg or something similar?

Sorry. I misunderstood your other post. I thought we were still on the wine thing.

The point here is that even at low doses it may do nerve damage if you use it every day for some time (which I've been tempted to do before, and which I currently do with the far-weaker phenibut).

 

[MeDieViL]

A few more studies regarding GHB's neurotoxiticy.

Adolescent gamma-hydroxybutyric acid exposure decreases cortical N-methyl-D-aspartate receptor and impairs spatial learning.
Sircar R, Basak A.

Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA. [email protected]
gamma-hydroxybutyric acid (GHB), which belongs to the class of substances referred to as "club drugs", is abused for its euphoric, sedative and anabolic effects. GHB use and abuse is most prevalent among adolescents and young adults. In almost all cases of GHB abuse, subjects report of amnesia. Behavioral effects of GHB in animals, particularly on learning and memory are not known. In this study, effects of GHB exposure on spatial learning and memory in adolescent rats were tested using the Morris water maze (MWM). Adolescent male rats were treated with a single daily injection of one of three doses of GHB for 5 days; control rats received equivalent volumes of saline. GHB-treated rats took longer and swam greater distances to find the hidden platform than control rats. Swim speed in GHB-treated rats was no different from that in vehicle-treated rats. In the probe trial, adolescent rats exposed to GHB spent less time in the target quadrant than control rats. In the visual task, drug-treated rats did not perform any differently than control rats. Brain regions from GHB-exposed and saline-treated rats were examined for N-methyl-D-aspartate (NMDA) receptor changes using [3H]MK-801 binding as a biochemical marker for NMDA channel function. [3H]MK-801 binding in the frontal cortex was significantly reduced compared to saline-treated controls. Together, these data indicate that GHB exposure in adolescent rats negatively impacts spatial learning and this is associated with altered regulation of cortical NMDA receptor.

[Effects of subchronic administration of gammahydroxybutyrate (GHB) on spatial working memory in rats]
[Article in Spanish]

García FB, Pedraza C, Arias JL, Navarro JF.

Universidad de Málaga, Spain.
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.

Gamma-hydroxybutyric acid induces oxidative stress in cerebral cortex of young rats.
Sgaravatti AM, Sgarbi MB, Testa CG, Durigon K, Pederzolli CD, Prestes CC, Wyse AT, Wannmacher CM, Wajner M, Dutra-Filho CS.

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
GHB is a naturally occurring compound in the central nervous system (CNS) whose tissue concentration are highly increased during drug abuse and in the inherited deficiency of succinic semialdehyde dehydrogenase (SSADH) activity. SSADH deficiency is a neurometabolic-inherited disorder of the degradation pathway of gamma-aminobutyric acid (GABA). It is biochemically characterized by increased concentrations of gamma-hydroxybutyric acid (GHB) in tissues, cerebrospinal fluid (CSF), blood and urine of affected patients. Clinical manifestations are variable, ranging from mild retardation of mental, motor, and language development to more severe neurological symptoms, such as hypotonia, ataxia and seizures, whose underlying mechanisms are practically unknown. In the present study, the in vitro and in vivo effects of GHB was investigated on some parameters of oxidative stress, such as chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), as well as the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in homogenates from cerebral cortex of 15-day-old Wistar rats. In vitro, GHB significantly increased chemiluminescence and TBA-RS levels, while TRAP and TAR measurements were markedly diminished. In contrast, the activities of the antioxidant enzymes SOD, CAT and GPX were not altered by GHB in vitro. Acute administration of GHB provoked a significant enhance of TBA-RS levels and a decrease of TRAP and TAR measurements. These results indicate that GHB induces oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats. If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals who consume GHB or its prodrug gamma-butyrolactone.

Gamma-hydroxybutyric acid-induced cognitive deficits in the female adolescent rat.
Sircar R, Basak A, Sircar D.

Departments of Psychiatry and Behavioral Sciences, Neurology,and Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
gamma-hydroxybutyric acid (GHB), a "club drug," is abused for its euphoric, sedative, and anabolic effects. GHB use and abuse is most prevalent among adolescents and young adults. Most GHB users report amnesia. In the present study, we tested the hypothesis that GHB treatment in female adolescent rats causes deficits in spatial learning and memory. Adolescent female rats were treated daily with GHB (100 mg/kg) for 5 consecutive days. Control rats received isovolumetric saline. Experimental and control rats were tested in the hidden platform task (reference memory) of the Morris water maze. GHB-treated adolescent female rats had significantly longer latencies than saline-treated controls, and in the probe trial drug-treated rats spent less time in the quadrant where the platform was present prior to its removal than did control adolescent rats. Together, these data indicate that GHB exposure in adolescent female rats has a negative impact on spatial learning and memory.

Effects of 1,4-butanediol administration on oxidative stress in rat brain: study of the neurotoxicity of gamma-hydroxybutyric acid in vivo.
Sgaravatti AM, Magnusson AS, Oliveira AS, Mescka CP, Zanin F, Sgarbi MB, Pederzolli CD, Wyse AT, Wannmacher CM, Wajner M, Dutra-Filho CS.

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, RS, Brazil.
gamma-Hydroxybutyric acid (GHB) is a naturally occurring compound in the central nervous system (CNS) whose tissue concentration are highly increased in the neurometabolic-inherited deficiency of succinic semialdehyde dehydrogenase (SSADH) activity or due to intoxication. SSADH deficiency is biochemically characterized by increased concentrations of GHB in tissues, cerebrospinal fluid, blood and urine of affected patients. Clinical manifestations are variable and include retardation of mental, motor, and language development along with other neurological symptoms, such as hypotonia, ataxia and seizures, whose underlying mechanisms are practically unknown. The precursor of GHB, 1,4-butanediol (1,4-BD) has been used to study the mechanisms of in vivo GHB neurotoxicity. Therefore, in the present work, the effect of acute administration of 20 or 120 mg/Kg 1,4-BD was investigated on various parameters of oxidative stress, such as spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total antioxidant reactivity (TAR), sulfhydryl and protein carbonyl contents, as well as the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in homogenates from cerebral cortex of 14-day-old Wistar rats. Acute administration of 120 mg/Kg 1,4-BD significantly increased spontaneous chemiluminescence and TBA-RS levels, while TAR measurement was markedly diminished, whereas injection of a lower dose (20 mg/Kg) did not change the parameters examined. Other parameters of oxidative stress evaluated were not affected by administration of 1,4-BD. These results indicate that 1,4-BD induces in vivo oxidative stress by stimulating lipid peroxidation and decreasing the non-enzymatic antioxidant defenses in cerebral cortex of young rats. If these effects also occur in humans, it is possible that they might contribute to the brain damage found in SSADH-deficient patients and possibly in individuals intoxicated by GHB or its prodrugs (gamma-butyrolactone or 1,4-BD).

 

[RacerAtom]

Some of you guys are confusing rat doses with human doses, 10mg/kg in a rat != 10mg/kg in a human, it's a lot lower due to metabolic differences among other things. Going by the available information, an estimate of the equivalent human dosage would be around 0.8mg/kg. So drinking wine could lead to the equivalent toxic dose in humans.

http://www3.interscience.wiley.com/journal/119823649/abstract?CRETRY=1&SRETRY=0

As you can see here the doses start at 250mg/kg which would possibly kill a human.

Typically you use a body surface area (BSA) calculation to calculate human starting doses, where you take the animal LD10 of a drug, divide by 10, multiply by 6 in the case of a rat and then divide by 37 in the case of a human. I imagine then multiplying it by the animal LD10/animal desired dose would yield an equivalent human dose.

 

[clay404]

^ if the doses they are talking about are along the lines of what is in a glass of wine and they postulate that much larger doses are neuroprotective, then why do they seem to imply that this will give insight into brain damage incurred through recreational use, when recreational use is nowhere near the lower toxic dose but most likely more like the higher neuroprotective dose.