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Ghb
- Topic starter Akira
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During the 80's, Gamma-hydroxybutyrate (GHB), which was readily available over-the-counter in nutrition stores, enjoyed widespread popularity among bodybuilders for its ability to stimulate growth hormone release (as well as its euphoric properties). It was subsequently pulled from the marke due to a few isolated instances of abuse (all of which also involved other drugs) and, it is thought by some, to protect prescription pharmaceutical sleep-aids from safer, more effective (and less expensive) competition and to pave the way for the wave of SSRI's that started with Prozac.
Not coincidentally, since it sale became illegal in 1990, its popularity has spread considerably.
Introduction
GHB is a four carbon, fatty acid derivative originally synthesized in the early 1960's by Dr. Henry Laborit , who was looking for an analogue of GABA (the brain's primary inhibitory neurotransmitter) that would readily cross the blood brain barrier -- a property GABA lacked (1). Indeed, GHB did prove to easily cross the blood brain barrier -- However, it was found to exert of number of effects not shared by GABA (2). It is now known that it does not bind to either GABA receptor under readily achievable concentrations (3). And though it is formed from GABA in brain tissues, that is not its only or perhaps even primary source (3).
A decade after its synthesis, GHB was shown to occur naturally in the human brain (4). Twenty-five years later, specific receptors for GHB were discovered (5), and it is now thought by many to be a neurotransmitter, or at least a neuromodulator (6, 7).
GHB is also found in various peripheral tissues such as kidney, heart, skeletal muscles, and brown fat (8) -- at higher concentrations that in the brain -- but as of yet, no peripheral receptors have been discovered, thus is function in these tissues not known at this time (9, 10).
Biochemistry
As mentioned, GHB is a naturally occurring component of mammalian brain metabolism. Highest brain levels occur in the substantia nigra, thalamus, and hypothalamus, lowest levels are found in the cerebellum and frontal cortex (11). It can be formed from GABA in the brain as well as being metabolized from it -- both via the intermediate succinic semialdehyde (12), which can also enter the Krebs cycle as succinate. The recently banned supplement ingredients, gammabutyrolactone and 1,4 butanediol, are also naturally occurring precursors (13).
Pharmocokinetics
GHB is readily bioavailable with oral administration, however, oral clearance rate and % absorption decrease and half-life increases with escalating doses, indicating that these processes are capacity limited (14, 15). This does not appear to be true for GBL (15), which explains the differing subjective effects between the two.
Pharmacology
Following oral, intravenous, or intraperitoneal administration, GHB produces CNS depressant effects similar to alcohol -- and, in fact, it has been shown to substitute for alcohol in physically dependent rats (16). At doses as low as .1 mg/kg in humans, it produces a state of sedation indistinguishable from human sleep (17). The mechanism behind its subjective effects are not completely understood, and involve multiple neurotransmitter systems:
Dopamine
The central neurotransmitter dopamine has been consistently shown to be altered by GHB, and is considered as the primary mediator of its subjective effects. At low doses, it causes a reduction in dopaminergic activity, due to inhibition of dopamine releasing neurons -- which possess GHB receptors (11). This combined with GHB stimulation of tyrosine hydroxylase (18) -- the enzyme which converts the amino acid tyrosine to dopamine -- causes a buildup of dopamine, which, when finally released when the drug has worn off, is quite likely responsible for the refreshed, hyper-alert state one experiences upon waking from a GHB induced sleep.
There is animal data showing an INCREASED release of dopamine at high doses (19, 20). These are intravenous doses in the 400-700mg/kg range, which would around 50 grams for a 200 lb man. Rats metabolize GHB much faster than humans (21), but a conservative estimate would still put an equivalent dose at 15g or so (though I don't know if equivalent blood levels are even possible orally due to the afore mentioned transport saturation).
In the real world, reports of the subjective experience of doses this high are that it causes rapid onset of sleep -- which does not agree with the effects typically seen from increased dopamine release. As GHB has been found to effect several other systems, perhaps one of them is overriding the stimulant effect that would be expected to occur.
GHB has also been shown to increase mRNA for dopamine receptors D1 and D2 (22).
Serotonin
It is not known whether GHB influence serotonergic systems directly, or indirectly via dopamine or GABA, but it is known that pharmacological doses cause an increase in serotonin turnover, due to increased uptake of tryptophan (23). This action on serotonin probably at least partially accounts for its ability to stimulate growth hormone release, as co-administration with the serotonin receptor antagonist, metergoline, significantly reduced this increase (23). Metergoline has also been shown to lower GH levels in acromegaly patients (24). It seems quite possible that this system is involved in the sedating and antidepressant effects observed with GHB treatment.
Opiod
GHB has been found to increase brain levels of the endogenous opiods, dynorphin and beta-endorphin (25). The opiod receptor antagonist, nalaxone, significantly reduces the metabolic and pharmacological effects of GHB (including dopaminergic) -- leading some to suggest that the opiod system modulates its activity on dopamine (26). In addition, GHB induced EEG changes are mimicked by administration of morphine and beta-endorphin (26). As with serotonin, GHB induced sedating and antidepressant/euphoric effects could be be mediated by the opiod system.
GABA
Since its creation as a hopeful GABA analogue, it has been a common misconception that GHB exerts much of its action through binding with GABA receptors -- however its affinity is 1/1000th that of GABA, thus binding does not occur under physiological conditions (27). Nonetheless, GHB's effects are thought to be mediated, to some extent, by the GABAergic system. First, GHB is both a precursor to, and metabolite of, GABA. In addition, GHB receptors are found on GABAergic neurons, suggesting that it modulates it release (28). As GABA is the brain's primary inhibitory neurotransmitter, it is quite likely that the sedating properties of GHB are mediated by this system.
Benzodiazepine
Benzodiazepine action is mediated through the GABA(A) receptor (29), and since GHB metabolizes to GABA and also stimulates its release, it would be expected to activate this system. And, indeed, the anxiolytic effects of low dose GHB is antagonized by the benzodiazepine receptor antagonist flumazenil (29). Flumazenil also blunts the growth hormone response of GHB (30). Again, this system could be involved in the sedative/anxiolytic/antidepressant effects of GHB.
Acetylcholine
GHB has no effect on acetylcholine, though its precursor, gammabutyrolactone, has been shown to increase brain levels at high doses, suggesting that some amounts may escape hydrolysis and enter the CNS (31).
Norepinephrine
The majority of the literature suggests GHB has no effect on central norepinephrine levels, however Persson found increases in synthesis and utilization (32).
GHB and Bodybuilding: Direct Effects
Does GHB truly have a place in a bodybuilder's arsenal, or is the whole GH thing just an excuse to get twisted?? I believe it does have a place -- though, as I will show, many of its positive effects on body composition are more indirect than direct.
The first thing we should look at is its most commonly touted effect -- its stimulation of Growth Hormone release. It has, in fact, been found to raise growth hormone levels sharply in numerous studies (23, 30, 33). Some have claimed that these increases are only with intravenous administration or are the indirect result of GHB inducing sleep, as the onset of slow wave sleep is associated with increased GH levels. However, studies using oral delivery, have indeed shown increases in conscious subjects (23,30). With administration of 1.5 g of GHB, GH levels begin to rise almost immediately, reaching a peak of 3 times normal levels within 45 minutes, then rapidly falling back to within 25% of baseline by the 90 minute mark. Clearly, it does increase growth hormone.
Nonetheless, reports in both the literature and the real world on body composition, even with growth hormone injections, have been something less than spectacular. In the literature, GH has been shown to increase protein synthesis, however, it is not contractile protein (muscle) but rather visceral (organs) (34). Data on fat loss and muscle sparing with GH is a bit better. It has been shown to inhibit protein breakdown during dieting and fasting, leading to increased retention of muscle mass (35) . It is also known to be lipolytic (36). Real world reports of GH run along the same lines -- it not effective on its own for increasing muscle, but an increase it fat loss is definitely noticeable. But, again, this is with injections. once a day use of GHB is not likely to mirror these effects. However, if someone would like to take 1.5 grams every 90 minutes for an extended period, please report back with your results.
At doses of 2.5 - 3.5 grams, GHB causes increased release of prolactin, doubling levels by the 45 minute mark, followed by a gradual return to baseline (33). Increases in prolactin have been shown to proportionally raise leptin levels, so this represents a possible positive effect on fat loss and muscle retention (37). Unfortunately, similar doses also raise cortisol levels, which has exactly the opposite effect of leptin on body composition (33). This antagonism might account for the lack of effects observed with GHB, and could perhaps be remedied with a drugs or supplement such as Cytadren or phosphatidylserine.
In addition to these, there are several other lesser known effects of GHB which have implications for bodybuilders. It increases gastric emptying (38), which is likely what causes the temporary increase in appetite observed with GHB use . Obviously, this is not particularly beneficial on a diet, though it might be on a mass phase. It also would likely make a good addition to a post-workout drink, as it would make glucose and amino acids available more quickly. Increased protein synthesis in brain and gastric tissues has been reported, whether this is accompanied by increased skeletal muscle synthesis is not known (39). Obese rats were found to have lower brain levels of GHB than their lean counterparts, despite identical diet, which suggests GHB as a potential signaler in the regulation of bodyweight (40) -- GHB metabolite GABA increases with fat feeding, which lends further support to this hypothesis. It has been shown to function as a powerful an antioxidant, blocking free-radical formation and lipid peroxidation (10). This could aid in recovery, as well as in overall health.
One of the more fascinating possibilities, comes from a study in rats (21) which showed a remarkable increase in body temperature after administration of very low doses. Following intraperitoneal injection of 5mg/kg, body temperature rose rapidly to 1.8 degrees Fahrenheit above normal at 15 minutes, and reached a peak of almost 2.2 degrees at the hour mark. It was still elevated by 2 degrees at the 75 minute mark, and dropping only quite gradually -- in humans, this would be a profound thermogenic effect (Clenbuterol might raise body temperature by 1 degree).
Considering GHB has a half-life of 5 minutes after injection (41), it would seem that GHB was not directly mediating these effects, but rather caused the release of something with a longer half-life. I am going to go out on a limb a bit and propose that the mediator might be norepinephrine -- which has a peripheral half-life of several hours -- as long as 12 in some tissues (42 ).
As mentioned above, GHB does not seem to effect central norepinephrine levels, however it HAS been shown to effect peripheral levels -- with high doses causing profound depletion of heart and brown fat norepinephrine levels (10). And, perhaps not coincidentally, in contrast to the increase in body temperature with the low dose, these high doses consistently cause a DECREASE in body temperature (21, 43). As we have seen, GHB has been conclusively shown to exert a biphasic effect on dopamine, so the possibility certainly exists with this compound.
I want to make clear that the above is very speculative, both as to why it occurred and to its having any relevancy toward humans. First, it is only one study. Second, it used intraperitoneal injections rather than oral administration. Third, the mechanisms were not looked at. And fourth, rats have much higher levels of brown fat, thus the thermogenic effects of an increase in norepinephrine would be exaggerated compared to humans.
Nonetheless, it is certainly enticing enough to give a try, with a couple of adjustments that take into account the use of human subjects (I would not expect the pharmacokinetics of oral and i.p. administration to be significantly different with this low of doses). GHB is metabolized by rats much faster than humans, thus a lower dose would be recommended. I would estimate 1-2mg/kg at most -- meaning around 100-200 mg for a 200 lb person -- this is a tiny dose -- one which would produce no subjective psychological effects and, in fact, probably no increase in brain GHB levels (21).
Indirect Effects
Perhaps the most important applications of GHB for bodybuilders do not involve direct effects on hormones or hormone systems, anabolic or otherwise. The first is that GHB is a MAGNIFICENT sleep aid. As mentioned previously, at sufficient doses, it rapidly and predictably causes the onset of a sedation which has been characterized as identical to human sleep (17), but with a greater portion of the time spent in stage IV and R.E.M. sleep (44), which are the most beneficial for recovery. I trust I do not need to mention the importance of sleep for a bodybuilder. I trust I also do not need to mention the detrimental effect on sleep of certain common components of the bodybuilding arsenal such as EC and androgens. I will mention that GHB makes waking up in the middle of the night for a protein shake much more feasible. And, again, I trust that I do not have to mention the effects of a 6-10 hour fast on the anabolic/catabolic state of the body.
The other application for GHB is as an alcohol substitute. In addition to containing 105 calories per drink -- more if you are having beer, alcohol lowers testosterone (45) and has a tendency to cause less than optimal workouts the following day. As dedicated as we might be to improving our bodies, most of us do not want to be a slave to this pursuit when it comes to socializing/partying.
GHB is a life saver here. Its biochemical, electrophysiological, and and pharmacological effects are quite similar to alcohol (46, 47). And, in fact, it has been successfully used clinically in the treatment of alcohol dependency, where it is thought to work through a substitution mechanism -- meaning it mimics alcohol's actions on the central nervous system (46). Both activate the dopamine system -- a characteristic commonly shared by drugs of abuse, they exhibit cross-tolerance -- meaning frequent consumption of one causes tolerance to the other, and both are preferentially (vs. water) self-administered by rats (16).
Subjectively, the effects are not identical. Some prefer a GHB intoxication to alcohol, some the vice versa. I find GHB to be more sedating and slightly less uninhibiting than alcohol, but I know others for whom the opposite is true. Without question, one feels considerably better the next day with GHB vs. alcohol.
A combination of the two can allow a a shitfaced intoxication subjectively quite similar to that produced by alcohol, but with the consumption of only a few drinks, thus only a few hundred calories. It is typically strongly suggested that the two not be combined, with the argument that they have synergistic effects. However, based both on experience and the available scientific data, I tend to think the effects are mostly additive. Thus, I do not necessarily consider this activity contraindicated. The problem is that downing a "cap full" of GHB is like bonging a 6 pack, so for someone who is already quite intoxicated, this can put them over the edge.
Also, keep in mind that the metabolism of the two drugs are different -- GHB's in not saturable at typically utilized doses, thus it has a half-life (of probably 1 hr when taken orally), while alcohol's is quite saturable, thus only one drink is metabolized per hour -- meaning if one has 6g of GHB and 6 drinks at hour one (do not do this), at hour three, you would have only 1.5g of GHB in your system, but 4 drinks. As you can see, if one kept drinking, as the night went on, it would get a bit complicated, so if you do experiment with this combination, start with small amounts until you get a feel for it.
Saftey
The overall safety of GHB is well-established in experimental and clinical use. Doses as high as 30 grams a day have been used in humans (48). And acute doses of as much as 1g/kg have been used in monkeys (10). Both without ill effects. It has no toxic effects on the liver, kidneys or other organs (48, 49). In narcolepsy studies, nightly use of 2.5 to 15 grams for several years resulted in no long-term adverse effects, nor did it result in addiction/dependence.
Side effects can include dizziness, nausea, and sometimes vomiting -- particularly on an empty stomach. It almost invariably causes drowsiness, so don't take it and then hop in the bathtub. Ataxia (loss of coordination) is more severe than with alcohol, so driving could be considered contraindicated.
Maximizing Recreational Value
With our new understanding of GHB pharmacology, coupled with a basic understanding of the mechanisms of other drugs, it is apparent that we could readily manipulate our subjective experience to suit our tastes. However, an in-depth analysis is beyond the scope of this article -- though, it will likely be the subject of a future one.
Availability
Scandalously, sale or possession of GHB is now illegal in all 50 states. It is currently a "Schedule I" drug -- meaning it has no legitimate medical uses, despite over thirty years of use in Europe in everything from drug addiction treatment to childbirth.
Both gammabutyrolactone (GBL) and 1,4 butanediol (BDO) are converted into GHB upon ingestion (both are naturally occurring precursors in the human brain), and were being sold as nutritional supplements for a while (RenewTrient, SomatoPro, Blue Nitro, etc.). However, their sale for human use has now been banned as well.
GHB can be readily synthesized from GBL, however, it has been designated as a "List 1" chemical, meaning a distributor must obtain a DEA # and report all sales, along with appropriate paperwork. Thus, it is, for all intents and purposes, unavailable as well.
If none of these can be readily obtained, what is the point of all this...
The Good News
I have recently discovered a substance which, upon ingestion, is converted via lactonase catalysed hydrolysis (same mechanism as GBL) to a GHB analogue that was found to bind to the receptor with 15% GREATER affinity GHB itself. And, not only is it perfectly legal in all 50 states for sale, possession, and ingestion, but it also is Generally Regarded as Safe (G.R.A.S) by the FDA.
This product, Tranquili-G, is now available through Avant Labs. I am taking steps, as we speak, to obtain a use patent on it as a sleep aid, growth hormone releaser, anxiolytic, and good-time party drink. Until that time, I will be unable to reveal the actual name of the chemical, for obvious reasons.
References:
1. Tunnicliff GJ Toxicol Clin Toxicol Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential.1997;35(6):581-90
2. Laborit H Sodium 4-hydroxybutyrate Int J neuropharmacol 1964 (3) 433-452.
3. Feigenbaum JJ, Howard SG Prog Neurobiol Gamma hydroxybutyrate is not a GABA agonist. 1996 Sep;50(1):1-7
4. Roth RH, Giarman NJ Biochem Pharmacol Conversion in vivo of gamma-aminobutyric to gamma-hydroxybutyric acid in the rat.1969 Jan;18(1):247-50
5. Ratomponirina C, Hode Y, Hechler V, Maitre M Gamma-Hydroxybutyrate receptor binding in rat brain is inhibited by guanyl nucleotides and pertussis toxin.Neurosci Lett 1995 Apr 7;189(1):51-3
6. Maitre M, Rumigny JF, Cash C, Mandel P Biochem Biophys Res Commun Subcellular distribution of gamma-hydroxybutyrate binding sites in rat brain principal localization in the synaptosomal fraction. 1983 Jan 14;110(1):262-5
7. Vayer P, Mandel P, Maitre M Life Sci Gamma-hydroxybutyrate, a possible neurotransmitter.1987 Sep 28;41(13):1547-57
8. Nelson T, Kaufman E, Kline J, Sokoloff LJ The extraneural distribution of gamma-hydroxybutyrate.Neurochem 1981 Nov;37(5):1345-8
9. Snead OC, Liu CC Biochem Pharmacol Gamma-hydroxybutyric acid binding sites in rat and human brain synaptosomal membranes.1984 Aug 15;33(16):2587-90
10. Mamelak MNeurosci Biobehav Rev Gammahydroxybutyrate: an endogenous regulator of energy metabolism.1989 Winter;13(4):187-98
11. Maitre M Prog Neurobiol The gamma-hydroxybutyrate signalling system in brain: organization and functional implications.1997 Feb;51(3):337-61
12. Doherty JD, Roth RH J Neurochem Metabolism of gamma-hydroxy-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids. 1978 Jun;30(6):1305-9
13. Doherty JD, Snead OC, Roth RH Anal Biochem A sensitive method for quantitation of gamma-hydroxybutyric acid and gamma-butyrolactone in brain by electron capture gas chromatography.1975 Nov;69(1):268-77
14. Palatini P, Tedeschi L, Frison G, Padrini R, Zordan R, Orlando R, Gallimberti L, Gessa GL, Ferrara SD Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 1993;45(4):353-6
15. Arena C, Fung HL Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption. J Pharm Sci 1980 Mar;69(3):356-8
16. Gessa GL, Agabio R, Carai MA, Lobina C, Pani M, Reali R, Colombo G Mechanism of the antialcohol effect of gamma-hydroxybutyric acid. Alcohol 2000 Apr;20(3):271-6
17. Mamelak M, Escriu JM, Stokan O The effects of gamma-hydroxybutyrate on sleep. Biol Psychiatry 1977 Apr;12(2):273-88
18. Spano PF, Tagliamonte A, Tagliamonte P, Gessa GL J Neurochem 1971 Stimulation of brain dopamine synthesis by gamma-hydroxybutyrate. Oct;18(10):1831-6
19. Godbout R, Jelenic P, Labrie C, Schmitt M, Bourguignon JJ Effect of gamma-hydroxybutyrate and its antagonist NCS-382 on spontaneous cell firing in the prefrontal cortex of the rat. Brain Res 1995 Feb 27;673(1):157-60
20. Hechler V, Gobaille S, Bourguignon JJ, Maitre M J Extracellular events induced by gamma-hydroxybutyrate in striatum: a microdialysis study.Neurochem 1991 Mar;56(3):938-44
21. Kaufman EE, Porrino LJ, Nelson T Biochem Pharmacol Pyretic action of low doses of gamma-hydroxybutyrate in rats.1990 Dec 15;40(12):2637-40
22. Schmidt-Mutter C, Muller C, Zwiller J, Gobaille S, Maitre M Gamma-hydroxybutyrate and cocaine administration increases mRNA expression of dopamine D1 and D2 receptors in rat brain. Neuropsychopharmacology 1999 Nov;21(5):662-9
23. Gerra G, Caccavari R, Fontanesi B, Fertonani Affini G, Maestri D, Avanzini P, Zaimovic A, Franchini D, Delsignore R Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid.Int Clin Psychopharmacol 1995 Nov;10(4):245-50
24. Delitala G, Masala A, Alagna S, Devilla L, Lotti G Growth hormone and prolactin release in acromegalic patients following metergoline administration. J Clin Endocrinol Metab 1976 Dec;43(6):1382-6
25. Lason W, Przewlocka B, Przewlocki R Life Sci The effect of gamma-hydroxybutyrate and anticonvulsants on opioid peptide content in the rat brain. 1983;33 Suppl 1:599-602
26. Snead OC, Bearden LJ Neurology Naloxone overcomes the dopaminergic, EEG, and behavioral effects of gamma-hydroxybutyrate. 1980 Aug;30(8):832-8
27. Mathivet P, Bernasconi R, De Barry J, Marescaux C, Bittiger Hur Binding characteristics of gamma-hydroxybutyric acid as a weak but selective GABAB receptor agonist. E J Pharmacol 1997 Feb 19;321(1):67-75
28. Hechler V, Gobaille S, Maitre M Localization studies of gamma-hydroxybutyrate receptors in rat striatum and hippocampus.Brain Res Bull 1989 Jul-Aug;23(1-2):129-35
29. Schmidt-Mutter C, Pain L, Sandner G, Gobaille S, Maitre M Eur J Pharmacol The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is reversed by the benzodiazepine receptor antagonist, flumazenil. 1998 Jan 19;342(1):21-7
30. Gerra G, Caccavari R, Fontanesi B, Marcato A, Fertonani Affini G, Maestri D, Avanzini P, Lecchini R, Delsignore R, Mutti A Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid. Int Clin Psychopharmacol 1994 Sep;9(3):211-5
31. Ladinsky H, Consolo S, Zatta A, Vezzani Mode of action of gamma-butyrolactone on the central cholinergic system.Naunyn Schmiedebergs Arch Pharmacol 1983 Feb;322(1):42-8
32. Persson B, Henning M Central cardiovascular effects of gamma-hydroxybutyric acid: interactions with noradrenaline, serotonin, dopamine and acetylcholine transmission. Acta Pharmacol Toxicol (Copenh) 1980 Nov;47(5):335-46
33. Takahara J, Yunoki S, Yakushiji W, Yamauchi J, Yamane Y Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab 1977 May;44(5):1014-7
34. Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO, Bier DM Effect of growth hormone and resistance exercise on muscle growth in young men. Am J Physiol 1992 Mar;262(3 Pt 1):E261-7
35. Norrelund H, Nair KS, Jorgensen JO, Christiansen JS, Moller N The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown.Diabetes 2001 Jan;50(1):96-104
36. de Boer H, Blok GJ, Voerman B, Derriks P, van der Veen E Changes in subcutaneous and visceral fat mass during growth hormone replacement therapy in adult men. Int J Obes Relat Metab Disord 1996 Jun;20(6):580-7
37. Mastronardi CA, Walczewska A, Yu WH, Karanth S, Parlow AF, McCann SM The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. Proc Soc Exp Biol Med 2000 Jul;224(3):152-8
38. Poggioli R, Vitale G, Colombo G, Ottani A, Bertolini A Gamma-hydroxybutyrate increases gastric emptying in rats.Life Sci 1999;64(23):2149-54
39. Mirzoian SA, Tatevosian AT, Gevorkian GA Effect of gamma-aminobutyric acid and gamma-hydroxybutyric acid on the rate of 14C-leucine incorporation into proteins of the gastric mucosa and hypothalamus.Biull Eksp Biol Med 1980 Sep;90(9):299-300
40. Fisler JS, Shimizu H, Bray GA Brain 3-hydroxybutyrate, glutamate, and GABA in a rat model of dietary obesity. Physiol Behav 1989 Mar;45(3):571-7
41. Doherty JD, Stout RW, Roth RH Metabolism of (1-14C)gamma-hydroxybutyric acid by rat brain after intraventricular injection. Biochem Pharmacol 1975 Feb 15;24(4):469-74
42. Bralet J, Rochette L Eur J Pharmacol Effect of clonidine on the turnover rate of noradrenaline in peripheral tissues of the rat. 1973 Sep;23(3):239-44
43. Snead OCNeurology Gamma hydroxybutyrate in the monkey. I. Electroencephalographic, behavioral, and pharmacokinetic studies. 1978 Jul;28(7):636-42
44. Lapierre O, Montplaisir J, Lamarre M, Bedard MA Sleep The effect of gamma-hydroxybutyrate on nocturnal and diurnal sleep of normal subjects: further considerations on REM sleep-triggering mechanisms. 1990 Feb;13(1):24-30
45. Ellingboe J Acute effects of ethanol on coïtus hormones in non-alcoholic men and women. Alcohol Alcohol 1987;Suppl 1:109-16
46. Fadda F, Colombo G, Mosca E, Gessa GL Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats. Alcohol Alcohol 1989;24(5):447-51
47. Diana M, Mereu G, Mura A, Fadda F, Passino N, Gessa G Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats. Brain Res 1991 Dec 6;566(1-2):208-11
48. Vickers MD Int Anesthesiol Clin Gammahydroxybutyric acid.1969 Spring;7(1):75-89
49. Chin MY, Kreutzer RA, Dyer JE Acute poisoning from gamma-hydroxybutyrate in California West J Med 1992 Apr;156(4):380-4
Not coincidentally, since it sale became illegal in 1990, its popularity has spread considerably.
Introduction
GHB is a four carbon, fatty acid derivative originally synthesized in the early 1960's by Dr. Henry Laborit , who was looking for an analogue of GABA (the brain's primary inhibitory neurotransmitter) that would readily cross the blood brain barrier -- a property GABA lacked (1). Indeed, GHB did prove to easily cross the blood brain barrier -- However, it was found to exert of number of effects not shared by GABA (2). It is now known that it does not bind to either GABA receptor under readily achievable concentrations (3). And though it is formed from GABA in brain tissues, that is not its only or perhaps even primary source (3).
A decade after its synthesis, GHB was shown to occur naturally in the human brain (4). Twenty-five years later, specific receptors for GHB were discovered (5), and it is now thought by many to be a neurotransmitter, or at least a neuromodulator (6, 7).
GHB is also found in various peripheral tissues such as kidney, heart, skeletal muscles, and brown fat (8) -- at higher concentrations that in the brain -- but as of yet, no peripheral receptors have been discovered, thus is function in these tissues not known at this time (9, 10).
Biochemistry
As mentioned, GHB is a naturally occurring component of mammalian brain metabolism. Highest brain levels occur in the substantia nigra, thalamus, and hypothalamus, lowest levels are found in the cerebellum and frontal cortex (11). It can be formed from GABA in the brain as well as being metabolized from it -- both via the intermediate succinic semialdehyde (12), which can also enter the Krebs cycle as succinate. The recently banned supplement ingredients, gammabutyrolactone and 1,4 butanediol, are also naturally occurring precursors (13).
Pharmocokinetics
GHB is readily bioavailable with oral administration, however, oral clearance rate and % absorption decrease and half-life increases with escalating doses, indicating that these processes are capacity limited (14, 15). This does not appear to be true for GBL (15), which explains the differing subjective effects between the two.
Pharmacology
Following oral, intravenous, or intraperitoneal administration, GHB produces CNS depressant effects similar to alcohol -- and, in fact, it has been shown to substitute for alcohol in physically dependent rats (16). At doses as low as .1 mg/kg in humans, it produces a state of sedation indistinguishable from human sleep (17). The mechanism behind its subjective effects are not completely understood, and involve multiple neurotransmitter systems:
Dopamine
The central neurotransmitter dopamine has been consistently shown to be altered by GHB, and is considered as the primary mediator of its subjective effects. At low doses, it causes a reduction in dopaminergic activity, due to inhibition of dopamine releasing neurons -- which possess GHB receptors (11). This combined with GHB stimulation of tyrosine hydroxylase (18) -- the enzyme which converts the amino acid tyrosine to dopamine -- causes a buildup of dopamine, which, when finally released when the drug has worn off, is quite likely responsible for the refreshed, hyper-alert state one experiences upon waking from a GHB induced sleep.
There is animal data showing an INCREASED release of dopamine at high doses (19, 20). These are intravenous doses in the 400-700mg/kg range, which would around 50 grams for a 200 lb man. Rats metabolize GHB much faster than humans (21), but a conservative estimate would still put an equivalent dose at 15g or so (though I don't know if equivalent blood levels are even possible orally due to the afore mentioned transport saturation).
In the real world, reports of the subjective experience of doses this high are that it causes rapid onset of sleep -- which does not agree with the effects typically seen from increased dopamine release. As GHB has been found to effect several other systems, perhaps one of them is overriding the stimulant effect that would be expected to occur.
GHB has also been shown to increase mRNA for dopamine receptors D1 and D2 (22).
Serotonin
It is not known whether GHB influence serotonergic systems directly, or indirectly via dopamine or GABA, but it is known that pharmacological doses cause an increase in serotonin turnover, due to increased uptake of tryptophan (23). This action on serotonin probably at least partially accounts for its ability to stimulate growth hormone release, as co-administration with the serotonin receptor antagonist, metergoline, significantly reduced this increase (23). Metergoline has also been shown to lower GH levels in acromegaly patients (24). It seems quite possible that this system is involved in the sedating and antidepressant effects observed with GHB treatment.
Opiod
GHB has been found to increase brain levels of the endogenous opiods, dynorphin and beta-endorphin (25). The opiod receptor antagonist, nalaxone, significantly reduces the metabolic and pharmacological effects of GHB (including dopaminergic) -- leading some to suggest that the opiod system modulates its activity on dopamine (26). In addition, GHB induced EEG changes are mimicked by administration of morphine and beta-endorphin (26). As with serotonin, GHB induced sedating and antidepressant/euphoric effects could be be mediated by the opiod system.
GABA
Since its creation as a hopeful GABA analogue, it has been a common misconception that GHB exerts much of its action through binding with GABA receptors -- however its affinity is 1/1000th that of GABA, thus binding does not occur under physiological conditions (27). Nonetheless, GHB's effects are thought to be mediated, to some extent, by the GABAergic system. First, GHB is both a precursor to, and metabolite of, GABA. In addition, GHB receptors are found on GABAergic neurons, suggesting that it modulates it release (28). As GABA is the brain's primary inhibitory neurotransmitter, it is quite likely that the sedating properties of GHB are mediated by this system.
Benzodiazepine
Benzodiazepine action is mediated through the GABA(A) receptor (29), and since GHB metabolizes to GABA and also stimulates its release, it would be expected to activate this system. And, indeed, the anxiolytic effects of low dose GHB is antagonized by the benzodiazepine receptor antagonist flumazenil (29). Flumazenil also blunts the growth hormone response of GHB (30). Again, this system could be involved in the sedative/anxiolytic/antidepressant effects of GHB.
Acetylcholine
GHB has no effect on acetylcholine, though its precursor, gammabutyrolactone, has been shown to increase brain levels at high doses, suggesting that some amounts may escape hydrolysis and enter the CNS (31).
Norepinephrine
The majority of the literature suggests GHB has no effect on central norepinephrine levels, however Persson found increases in synthesis and utilization (32).
GHB and Bodybuilding: Direct Effects
Does GHB truly have a place in a bodybuilder's arsenal, or is the whole GH thing just an excuse to get twisted?? I believe it does have a place -- though, as I will show, many of its positive effects on body composition are more indirect than direct.
The first thing we should look at is its most commonly touted effect -- its stimulation of Growth Hormone release. It has, in fact, been found to raise growth hormone levels sharply in numerous studies (23, 30, 33). Some have claimed that these increases are only with intravenous administration or are the indirect result of GHB inducing sleep, as the onset of slow wave sleep is associated with increased GH levels. However, studies using oral delivery, have indeed shown increases in conscious subjects (23,30). With administration of 1.5 g of GHB, GH levels begin to rise almost immediately, reaching a peak of 3 times normal levels within 45 minutes, then rapidly falling back to within 25% of baseline by the 90 minute mark. Clearly, it does increase growth hormone.
Nonetheless, reports in both the literature and the real world on body composition, even with growth hormone injections, have been something less than spectacular. In the literature, GH has been shown to increase protein synthesis, however, it is not contractile protein (muscle) but rather visceral (organs) (34). Data on fat loss and muscle sparing with GH is a bit better. It has been shown to inhibit protein breakdown during dieting and fasting, leading to increased retention of muscle mass (35) . It is also known to be lipolytic (36). Real world reports of GH run along the same lines -- it not effective on its own for increasing muscle, but an increase it fat loss is definitely noticeable. But, again, this is with injections. once a day use of GHB is not likely to mirror these effects. However, if someone would like to take 1.5 grams every 90 minutes for an extended period, please report back with your results.
At doses of 2.5 - 3.5 grams, GHB causes increased release of prolactin, doubling levels by the 45 minute mark, followed by a gradual return to baseline (33). Increases in prolactin have been shown to proportionally raise leptin levels, so this represents a possible positive effect on fat loss and muscle retention (37). Unfortunately, similar doses also raise cortisol levels, which has exactly the opposite effect of leptin on body composition (33). This antagonism might account for the lack of effects observed with GHB, and could perhaps be remedied with a drugs or supplement such as Cytadren or phosphatidylserine.
In addition to these, there are several other lesser known effects of GHB which have implications for bodybuilders. It increases gastric emptying (38), which is likely what causes the temporary increase in appetite observed with GHB use . Obviously, this is not particularly beneficial on a diet, though it might be on a mass phase. It also would likely make a good addition to a post-workout drink, as it would make glucose and amino acids available more quickly. Increased protein synthesis in brain and gastric tissues has been reported, whether this is accompanied by increased skeletal muscle synthesis is not known (39). Obese rats were found to have lower brain levels of GHB than their lean counterparts, despite identical diet, which suggests GHB as a potential signaler in the regulation of bodyweight (40) -- GHB metabolite GABA increases with fat feeding, which lends further support to this hypothesis. It has been shown to function as a powerful an antioxidant, blocking free-radical formation and lipid peroxidation (10). This could aid in recovery, as well as in overall health.
One of the more fascinating possibilities, comes from a study in rats (21) which showed a remarkable increase in body temperature after administration of very low doses. Following intraperitoneal injection of 5mg/kg, body temperature rose rapidly to 1.8 degrees Fahrenheit above normal at 15 minutes, and reached a peak of almost 2.2 degrees at the hour mark. It was still elevated by 2 degrees at the 75 minute mark, and dropping only quite gradually -- in humans, this would be a profound thermogenic effect (Clenbuterol might raise body temperature by 1 degree).
Considering GHB has a half-life of 5 minutes after injection (41), it would seem that GHB was not directly mediating these effects, but rather caused the release of something with a longer half-life. I am going to go out on a limb a bit and propose that the mediator might be norepinephrine -- which has a peripheral half-life of several hours -- as long as 12 in some tissues (42 ).
As mentioned above, GHB does not seem to effect central norepinephrine levels, however it HAS been shown to effect peripheral levels -- with high doses causing profound depletion of heart and brown fat norepinephrine levels (10). And, perhaps not coincidentally, in contrast to the increase in body temperature with the low dose, these high doses consistently cause a DECREASE in body temperature (21, 43). As we have seen, GHB has been conclusively shown to exert a biphasic effect on dopamine, so the possibility certainly exists with this compound.
I want to make clear that the above is very speculative, both as to why it occurred and to its having any relevancy toward humans. First, it is only one study. Second, it used intraperitoneal injections rather than oral administration. Third, the mechanisms were not looked at. And fourth, rats have much higher levels of brown fat, thus the thermogenic effects of an increase in norepinephrine would be exaggerated compared to humans.
Nonetheless, it is certainly enticing enough to give a try, with a couple of adjustments that take into account the use of human subjects (I would not expect the pharmacokinetics of oral and i.p. administration to be significantly different with this low of doses). GHB is metabolized by rats much faster than humans, thus a lower dose would be recommended. I would estimate 1-2mg/kg at most -- meaning around 100-200 mg for a 200 lb person -- this is a tiny dose -- one which would produce no subjective psychological effects and, in fact, probably no increase in brain GHB levels (21).
Indirect Effects
Perhaps the most important applications of GHB for bodybuilders do not involve direct effects on hormones or hormone systems, anabolic or otherwise. The first is that GHB is a MAGNIFICENT sleep aid. As mentioned previously, at sufficient doses, it rapidly and predictably causes the onset of a sedation which has been characterized as identical to human sleep (17), but with a greater portion of the time spent in stage IV and R.E.M. sleep (44), which are the most beneficial for recovery. I trust I do not need to mention the importance of sleep for a bodybuilder. I trust I also do not need to mention the detrimental effect on sleep of certain common components of the bodybuilding arsenal such as EC and androgens. I will mention that GHB makes waking up in the middle of the night for a protein shake much more feasible. And, again, I trust that I do not have to mention the effects of a 6-10 hour fast on the anabolic/catabolic state of the body.
The other application for GHB is as an alcohol substitute. In addition to containing 105 calories per drink -- more if you are having beer, alcohol lowers testosterone (45) and has a tendency to cause less than optimal workouts the following day. As dedicated as we might be to improving our bodies, most of us do not want to be a slave to this pursuit when it comes to socializing/partying.
GHB is a life saver here. Its biochemical, electrophysiological, and and pharmacological effects are quite similar to alcohol (46, 47). And, in fact, it has been successfully used clinically in the treatment of alcohol dependency, where it is thought to work through a substitution mechanism -- meaning it mimics alcohol's actions on the central nervous system (46). Both activate the dopamine system -- a characteristic commonly shared by drugs of abuse, they exhibit cross-tolerance -- meaning frequent consumption of one causes tolerance to the other, and both are preferentially (vs. water) self-administered by rats (16).
Subjectively, the effects are not identical. Some prefer a GHB intoxication to alcohol, some the vice versa. I find GHB to be more sedating and slightly less uninhibiting than alcohol, but I know others for whom the opposite is true. Without question, one feels considerably better the next day with GHB vs. alcohol.
A combination of the two can allow a a shitfaced intoxication subjectively quite similar to that produced by alcohol, but with the consumption of only a few drinks, thus only a few hundred calories. It is typically strongly suggested that the two not be combined, with the argument that they have synergistic effects. However, based both on experience and the available scientific data, I tend to think the effects are mostly additive. Thus, I do not necessarily consider this activity contraindicated. The problem is that downing a "cap full" of GHB is like bonging a 6 pack, so for someone who is already quite intoxicated, this can put them over the edge.
Also, keep in mind that the metabolism of the two drugs are different -- GHB's in not saturable at typically utilized doses, thus it has a half-life (of probably 1 hr when taken orally), while alcohol's is quite saturable, thus only one drink is metabolized per hour -- meaning if one has 6g of GHB and 6 drinks at hour one (do not do this), at hour three, you would have only 1.5g of GHB in your system, but 4 drinks. As you can see, if one kept drinking, as the night went on, it would get a bit complicated, so if you do experiment with this combination, start with small amounts until you get a feel for it.
Saftey
The overall safety of GHB is well-established in experimental and clinical use. Doses as high as 30 grams a day have been used in humans (48). And acute doses of as much as 1g/kg have been used in monkeys (10). Both without ill effects. It has no toxic effects on the liver, kidneys or other organs (48, 49). In narcolepsy studies, nightly use of 2.5 to 15 grams for several years resulted in no long-term adverse effects, nor did it result in addiction/dependence.
Side effects can include dizziness, nausea, and sometimes vomiting -- particularly on an empty stomach. It almost invariably causes drowsiness, so don't take it and then hop in the bathtub. Ataxia (loss of coordination) is more severe than with alcohol, so driving could be considered contraindicated.
Maximizing Recreational Value
With our new understanding of GHB pharmacology, coupled with a basic understanding of the mechanisms of other drugs, it is apparent that we could readily manipulate our subjective experience to suit our tastes. However, an in-depth analysis is beyond the scope of this article -- though, it will likely be the subject of a future one.
Availability
Scandalously, sale or possession of GHB is now illegal in all 50 states. It is currently a "Schedule I" drug -- meaning it has no legitimate medical uses, despite over thirty years of use in Europe in everything from drug addiction treatment to childbirth.
Both gammabutyrolactone (GBL) and 1,4 butanediol (BDO) are converted into GHB upon ingestion (both are naturally occurring precursors in the human brain), and were being sold as nutritional supplements for a while (RenewTrient, SomatoPro, Blue Nitro, etc.). However, their sale for human use has now been banned as well.
GHB can be readily synthesized from GBL, however, it has been designated as a "List 1" chemical, meaning a distributor must obtain a DEA # and report all sales, along with appropriate paperwork. Thus, it is, for all intents and purposes, unavailable as well.
If none of these can be readily obtained, what is the point of all this...
The Good News
I have recently discovered a substance which, upon ingestion, is converted via lactonase catalysed hydrolysis (same mechanism as GBL) to a GHB analogue that was found to bind to the receptor with 15% GREATER affinity GHB itself. And, not only is it perfectly legal in all 50 states for sale, possession, and ingestion, but it also is Generally Regarded as Safe (G.R.A.S) by the FDA.
This product, Tranquili-G, is now available through Avant Labs. I am taking steps, as we speak, to obtain a use patent on it as a sleep aid, growth hormone releaser, anxiolytic, and good-time party drink. Until that time, I will be unable to reveal the actual name of the chemical, for obvious reasons.
References:
1. Tunnicliff GJ Toxicol Clin Toxicol Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential.1997;35(6):581-90
2. Laborit H Sodium 4-hydroxybutyrate Int J neuropharmacol 1964 (3) 433-452.
3. Feigenbaum JJ, Howard SG Prog Neurobiol Gamma hydroxybutyrate is not a GABA agonist. 1996 Sep;50(1):1-7
4. Roth RH, Giarman NJ Biochem Pharmacol Conversion in vivo of gamma-aminobutyric to gamma-hydroxybutyric acid in the rat.1969 Jan;18(1):247-50
5. Ratomponirina C, Hode Y, Hechler V, Maitre M Gamma-Hydroxybutyrate receptor binding in rat brain is inhibited by guanyl nucleotides and pertussis toxin.Neurosci Lett 1995 Apr 7;189(1):51-3
6. Maitre M, Rumigny JF, Cash C, Mandel P Biochem Biophys Res Commun Subcellular distribution of gamma-hydroxybutyrate binding sites in rat brain principal localization in the synaptosomal fraction. 1983 Jan 14;110(1):262-5
7. Vayer P, Mandel P, Maitre M Life Sci Gamma-hydroxybutyrate, a possible neurotransmitter.1987 Sep 28;41(13):1547-57
8. Nelson T, Kaufman E, Kline J, Sokoloff LJ The extraneural distribution of gamma-hydroxybutyrate.Neurochem 1981 Nov;37(5):1345-8
9. Snead OC, Liu CC Biochem Pharmacol Gamma-hydroxybutyric acid binding sites in rat and human brain synaptosomal membranes.1984 Aug 15;33(16):2587-90
10. Mamelak MNeurosci Biobehav Rev Gammahydroxybutyrate: an endogenous regulator of energy metabolism.1989 Winter;13(4):187-98
11. Maitre M Prog Neurobiol The gamma-hydroxybutyrate signalling system in brain: organization and functional implications.1997 Feb;51(3):337-61
12. Doherty JD, Roth RH J Neurochem Metabolism of gamma-hydroxy-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids. 1978 Jun;30(6):1305-9
13. Doherty JD, Snead OC, Roth RH Anal Biochem A sensitive method for quantitation of gamma-hydroxybutyric acid and gamma-butyrolactone in brain by electron capture gas chromatography.1975 Nov;69(1):268-77
14. Palatini P, Tedeschi L, Frison G, Padrini R, Zordan R, Orlando R, Gallimberti L, Gessa GL, Ferrara SD Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 1993;45(4):353-6
15. Arena C, Fung HL Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption. J Pharm Sci 1980 Mar;69(3):356-8
16. Gessa GL, Agabio R, Carai MA, Lobina C, Pani M, Reali R, Colombo G Mechanism of the antialcohol effect of gamma-hydroxybutyric acid. Alcohol 2000 Apr;20(3):271-6
17. Mamelak M, Escriu JM, Stokan O The effects of gamma-hydroxybutyrate on sleep. Biol Psychiatry 1977 Apr;12(2):273-88
18. Spano PF, Tagliamonte A, Tagliamonte P, Gessa GL J Neurochem 1971 Stimulation of brain dopamine synthesis by gamma-hydroxybutyrate. Oct;18(10):1831-6
19. Godbout R, Jelenic P, Labrie C, Schmitt M, Bourguignon JJ Effect of gamma-hydroxybutyrate and its antagonist NCS-382 on spontaneous cell firing in the prefrontal cortex of the rat. Brain Res 1995 Feb 27;673(1):157-60
20. Hechler V, Gobaille S, Bourguignon JJ, Maitre M J Extracellular events induced by gamma-hydroxybutyrate in striatum: a microdialysis study.Neurochem 1991 Mar;56(3):938-44
21. Kaufman EE, Porrino LJ, Nelson T Biochem Pharmacol Pyretic action of low doses of gamma-hydroxybutyrate in rats.1990 Dec 15;40(12):2637-40
22. Schmidt-Mutter C, Muller C, Zwiller J, Gobaille S, Maitre M Gamma-hydroxybutyrate and cocaine administration increases mRNA expression of dopamine D1 and D2 receptors in rat brain. Neuropsychopharmacology 1999 Nov;21(5):662-9
23. Gerra G, Caccavari R, Fontanesi B, Fertonani Affini G, Maestri D, Avanzini P, Zaimovic A, Franchini D, Delsignore R Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid.Int Clin Psychopharmacol 1995 Nov;10(4):245-50
24. Delitala G, Masala A, Alagna S, Devilla L, Lotti G Growth hormone and prolactin release in acromegalic patients following metergoline administration. J Clin Endocrinol Metab 1976 Dec;43(6):1382-6
25. Lason W, Przewlocka B, Przewlocki R Life Sci The effect of gamma-hydroxybutyrate and anticonvulsants on opioid peptide content in the rat brain. 1983;33 Suppl 1:599-602
26. Snead OC, Bearden LJ Neurology Naloxone overcomes the dopaminergic, EEG, and behavioral effects of gamma-hydroxybutyrate. 1980 Aug;30(8):832-8
27. Mathivet P, Bernasconi R, De Barry J, Marescaux C, Bittiger Hur Binding characteristics of gamma-hydroxybutyric acid as a weak but selective GABAB receptor agonist. E J Pharmacol 1997 Feb 19;321(1):67-75
28. Hechler V, Gobaille S, Maitre M Localization studies of gamma-hydroxybutyrate receptors in rat striatum and hippocampus.Brain Res Bull 1989 Jul-Aug;23(1-2):129-35
29. Schmidt-Mutter C, Pain L, Sandner G, Gobaille S, Maitre M Eur J Pharmacol The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is reversed by the benzodiazepine receptor antagonist, flumazenil. 1998 Jan 19;342(1):21-7
30. Gerra G, Caccavari R, Fontanesi B, Marcato A, Fertonani Affini G, Maestri D, Avanzini P, Lecchini R, Delsignore R, Mutti A Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid. Int Clin Psychopharmacol 1994 Sep;9(3):211-5
31. Ladinsky H, Consolo S, Zatta A, Vezzani Mode of action of gamma-butyrolactone on the central cholinergic system.Naunyn Schmiedebergs Arch Pharmacol 1983 Feb;322(1):42-8
32. Persson B, Henning M Central cardiovascular effects of gamma-hydroxybutyric acid: interactions with noradrenaline, serotonin, dopamine and acetylcholine transmission. Acta Pharmacol Toxicol (Copenh) 1980 Nov;47(5):335-46
33. Takahara J, Yunoki S, Yakushiji W, Yamauchi J, Yamane Y Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab 1977 May;44(5):1014-7
34. Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO, Bier DM Effect of growth hormone and resistance exercise on muscle growth in young men. Am J Physiol 1992 Mar;262(3 Pt 1):E261-7
35. Norrelund H, Nair KS, Jorgensen JO, Christiansen JS, Moller N The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown.Diabetes 2001 Jan;50(1):96-104
36. de Boer H, Blok GJ, Voerman B, Derriks P, van der Veen E Changes in subcutaneous and visceral fat mass during growth hormone replacement therapy in adult men. Int J Obes Relat Metab Disord 1996 Jun;20(6):580-7
37. Mastronardi CA, Walczewska A, Yu WH, Karanth S, Parlow AF, McCann SM The possible role of prolactin in the circadian rhythm of leptin secretion in male rats. Proc Soc Exp Biol Med 2000 Jul;224(3):152-8
38. Poggioli R, Vitale G, Colombo G, Ottani A, Bertolini A Gamma-hydroxybutyrate increases gastric emptying in rats.Life Sci 1999;64(23):2149-54
39. Mirzoian SA, Tatevosian AT, Gevorkian GA Effect of gamma-aminobutyric acid and gamma-hydroxybutyric acid on the rate of 14C-leucine incorporation into proteins of the gastric mucosa and hypothalamus.Biull Eksp Biol Med 1980 Sep;90(9):299-300
40. Fisler JS, Shimizu H, Bray GA Brain 3-hydroxybutyrate, glutamate, and GABA in a rat model of dietary obesity. Physiol Behav 1989 Mar;45(3):571-7
41. Doherty JD, Stout RW, Roth RH Metabolism of (1-14C)gamma-hydroxybutyric acid by rat brain after intraventricular injection. Biochem Pharmacol 1975 Feb 15;24(4):469-74
42. Bralet J, Rochette L Eur J Pharmacol Effect of clonidine on the turnover rate of noradrenaline in peripheral tissues of the rat. 1973 Sep;23(3):239-44
43. Snead OCNeurology Gamma hydroxybutyrate in the monkey. I. Electroencephalographic, behavioral, and pharmacokinetic studies. 1978 Jul;28(7):636-42
44. Lapierre O, Montplaisir J, Lamarre M, Bedard MA Sleep The effect of gamma-hydroxybutyrate on nocturnal and diurnal sleep of normal subjects: further considerations on REM sleep-triggering mechanisms. 1990 Feb;13(1):24-30
45. Ellingboe J Acute effects of ethanol on coïtus hormones in non-alcoholic men and women. Alcohol Alcohol 1987;Suppl 1:109-16
46. Fadda F, Colombo G, Mosca E, Gessa GL Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats. Alcohol Alcohol 1989;24(5):447-51
47. Diana M, Mereu G, Mura A, Fadda F, Passino N, Gessa G Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats. Brain Res 1991 Dec 6;566(1-2):208-11
48. Vickers MD Int Anesthesiol Clin Gammahydroxybutyric acid.1969 Spring;7(1):75-89
49. Chin MY, Kreutzer RA, Dyer JE Acute poisoning from gamma-hydroxybutyrate in California West J Med 1992 Apr;156(4):380-4
Marky
Monstrous Giant
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Heb dit de afgelopen 2 maanden dagelijks genomen, erg lekker en lichtelijk anabool.
Ik heb zin om dichter tot anderen te komen, emotioneel, intelectueel en seksueel. Het voelt uiterst bevredigend om teder lichamelijk contact te hebben, een gevoel van geilheid, maar geen mannelijk opdringerigheid als je een volle zak hebt maar meer gericht op verleiding/aanraking sensualiteit. Dit in tegenstelling tot alcohol waarin je je zin sneller wil doordrukken. Met G zal je meer scoringstactieken toepassen.
Alles ziet er levendig en fris uit, en ik voel milde euforie en kan intenser in dingen opgaan. Ik zie afstanden duidelijker dan wanneer ik nuchter, iets meer 3D, en ben en door de ontspannende werking relax in m'n omgang met anderen. Het is echt lekker om te knuffelen en daarna coïtus te hebben.
Het dempt cortisol en verbrand lichtelijk wat vet terwijl je spieren extra rusten en je zowel lichamelijk als geestelijk in een zeer ontspannen staat komt. Lopen voelt minder belastend.
De dosis komt nauw te liggen, hoewel wanneer je bij iets teveel outgaat, wordt je naderhand gewoon weer wakker als het iets teveel was. Maar dan ben je wel verward en voelt het alsof je zwaar dronken bent.
Het is een geweldig substituut voor alcohol en alcoholverslaving. Lichamelijk is het niet schadelijk bij een proper dosering. Zijn alleen een aantal idioten geweest die het anderen ongewenst hebben toegediend of zelf niet hebben negedacht. Voor mij persoonlijk snap ik niet waarom ik alcohol zou drinken zolang er GHB bestaat. Spotgoedkoop en gezonder.
Mijn ervaring is, is dat wanneer je met verstand doseerd het gewoon niet mis kan gaan.
Ik heb zin om dichter tot anderen te komen, emotioneel, intelectueel en seksueel. Het voelt uiterst bevredigend om teder lichamelijk contact te hebben, een gevoel van geilheid, maar geen mannelijk opdringerigheid als je een volle zak hebt maar meer gericht op verleiding/aanraking sensualiteit. Dit in tegenstelling tot alcohol waarin je je zin sneller wil doordrukken. Met G zal je meer scoringstactieken toepassen.
Alles ziet er levendig en fris uit, en ik voel milde euforie en kan intenser in dingen opgaan. Ik zie afstanden duidelijker dan wanneer ik nuchter, iets meer 3D, en ben en door de ontspannende werking relax in m'n omgang met anderen. Het is echt lekker om te knuffelen en daarna coïtus te hebben.
Het dempt cortisol en verbrand lichtelijk wat vet terwijl je spieren extra rusten en je zowel lichamelijk als geestelijk in een zeer ontspannen staat komt. Lopen voelt minder belastend.
De dosis komt nauw te liggen, hoewel wanneer je bij iets teveel outgaat, wordt je naderhand gewoon weer wakker als het iets teveel was. Maar dan ben je wel verward en voelt het alsof je zwaar dronken bent.
Het is een geweldig substituut voor alcohol en alcoholverslaving. Lichamelijk is het niet schadelijk bij een proper dosering. Zijn alleen een aantal idioten geweest die het anderen ongewenst hebben toegediend of zelf niet hebben negedacht. Voor mij persoonlijk snap ik niet waarom ik alcohol zou drinken zolang er GHB bestaat. Spotgoedkoop en gezonder.
Mijn ervaring is, is dat wanneer je met verstand doseerd het gewoon niet mis kan gaan.
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Echt goed verwoord bro.
Met ghb is het idd ****ing lekker om iemand aan te raken / te strelen, en niet direct met de intensie om haar een uur later flink neuquen.
Vooral het "liefdevol" strelen is echt apart als je kort bent van de G.
Daarom is G ook goed om te versieren, het is net alsof je heel liefdevol overkomt, alsof je echt verliefd en teder bent.
Maar als puntje bij paaltje komt en je bent eenmaal bezig
porno gek!
pipo
Advanced Bodybuilder
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Ghb: een goedje Gammabutyrolactone welke je samen met wat andere vieze goedjes mengt vormt het produkt GHB. Inname van die produkt is zeer bitter, en na vaak gebruiken, zal je het kokhalzend tot je nemen. Na een minuut of 45 vormt er een raar gevoel door je lichaam wat resulteert in een xtc achtige trip na ongeveer 75 minuten.
Je wordt een bloedgeil van, maar een tikje te veel GHB wil dus ook zeggen dat je op een gegeven ogenblik niet eens meer klaarkomt. Je wordt er ook heel slaperig van. Iemand die ik ken is tijdens het bffen in slaap gevallen bovenop het k*tje.
Alles wordt intensiever, zoals muziek of een neukpartij. Tis zeer af te raden te veel alcohol te drinken, daar GHB met alcohol kan lijden tot een coma of bewusteloosheid wat zelfs de dood als vervolg kan hebben. Men kan ook stikken in hun bewusteloosheid in hun eigen kots of het inslikken van de tong.
Na een uur of 3 begint de werking zichtbaar af te nemen, maar dan werkt het nog steeds uitstekend als een slaapmiddel. Nadeel is dat je er dieper en zwaarder van kan gaan ademen, wat dus een flinke snurkpartij teweeg kan brengen. De dag erna heb je nergens last van. Geen kater, geen hoofdpijn etc.
Aanbevolen hoeveelheid voor mannen zal om en nabij de 5ml zijn, voor vrouwen zou ik zeker beginnen met de helft of iets minder. Vrouwen worden achterlijk nat van dit goedje, dus weet waar je aan begint
Kerel,
iemand in slaap gevallen op een k*tje? zou mij nooiit overkomen
loekie
Advanced Bodybuilder
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dat gevoel had ik dus ook, net of ik raar draaiierig zat was en na een tijdje was ik gewoon moe en slaperig.
Wil het binnenkort toch nog wel eens een keer proberen. Tot nu toe waren de ervaringen niet wat ik er van verwacht had.
Maten van mij zijn er lyrisch over en gaan helemaal uit hun dak.... en ik... wordt er alleen beetje draaiierig en moe van.
stillbuilding
Dutch Bodybuilder
- Lid sinds
- 1 nov 2005
- Berichten
- 420
- Waardering
- 1
Als je het goed weet te doseren is het GODLIKE spul!
Daarintegen is het een HELL als je het overdoseerd!
Heb zelf gelukkig nooit het pech gehad dat ik het heb overdoseerd maar een maat van me wel (en niet zo'n klein beetje ook niet.) Hij ging knock, kotste z'n eigen helemaal onder en werd na een goeie 3 uur pas enigzinds aanspreekbaar.
Over het algemeen is het wel een lekker goedje niet schadelijk en na een dag niet aantoonbaar.
Daarintegen is het een HELL als je het overdoseerd!
Heb zelf gelukkig nooit het pech gehad dat ik het heb overdoseerd maar een maat van me wel (en niet zo'n klein beetje ook niet.) Hij ging knock, kotste z'n eigen helemaal onder en werd na een goeie 3 uur pas enigzinds aanspreekbaar.
Over het algemeen is het wel een lekker goedje niet schadelijk en na een dag niet aantoonbaar.
loekie
Advanced Bodybuilder
- Lid sinds
- 4 apr 2006
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- 1.287
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de eerste keer dat ik het nam was na het uitgaan bij vrienden thuis, natuurlijk van te voren gezopen en xtc op.
Na een paar minuten na de ghb lag ik tegen de kast aan in slaap te vallen. het is dat mijn maten me steeds wakker schopte anders was ik echt gan pitten. het was toen naturlijk al rond een uur of 7 smorgens dus was zowiezo wel bek-af.
daarna voelde ik me misselijk en wilde in de tuin gaan kotsen maar het lukte niet echt. wel neigingen maar geen kots. later toch nog ff gekotst en in mijn nest gedoken.
Marky
Monstrous Giant
- Lid sinds
- 27 jun 2003
- Berichten
- 12.706
- Waardering
- 333
Impulsief GHB gebruik. Wat met XTC kan, 1 pill voelt goed, 2 pillen ook maar met negatieve sides, kan met GHB zeker niet.
Dosis moet de eerste keer nooit gebaseerd worden op de hoeveelheid met de mensen met wie je het doet. Een maat van me kan 2,5 ml GBL slikken en wat biertjes drinken en blijft bij bewustzijn, terwijl een lichtgewicht vriendin maximaal 0,5 ml kan hebben.
Je moet gewoon LAAG beginnen en zodoende de dosis naar voorkeur en persoonlijke tolerantie ophogen en je daaraan houden. Er is nauwelijks tolerantie.
En mocht je iets teveel hebben genomen, ga niet zitten freaken maar ga rustig zitten. Als je je druk maakt ga je sneller out. Als je echt wegvalt ga in de zijhouding liggen pitten. Wordt je gewoon weer wakker na verloop van tijd.
Marky, neem jij gbl of ghb dan? Ik altijd gbl, maar vind het toch raar spul. Al het plastic wat ik ook maar lichtelijk aanraak smelt weg. Deze week moest mijn toetsenbord eraan geloven, hiervoor al telefoons, laptop, pennen noem maar op. Nu is mijn maag niet van plastic, maar ik vraag me af wat het daar doet.
Marky
Monstrous Giant
- Lid sinds
- 27 jun 2003
- Berichten
- 12.706
- Waardering
- 333
Ik neem 99,95% GBL. Het schijnt niet helemaal goed te zijn wat de betreft de passering langs je slokdarm, interieurweefsel en je maag. De geur kun je beter ook niet onnodig opsnuiven. GHB is daarintegen geen probleem.
Heb zelf geen last van maagklachten afgezien van lichtelijk maagzuur soms, maar ben ook een zware koffiedrinker.
Iig op een lege maag nemen en 30 min wachten met je maaltijd daarna.
Heb zelf geen last van maagklachten afgezien van lichtelijk maagzuur soms, maar ben ook een zware koffiedrinker.
Iig op een lege maag nemen en 30 min wachten met je maaltijd daarna.
Ja dat doe ik ook. Wacht geen 30 minuten, op een lege maag voel ik em al na 10minuten volgens mij.
Een maat van me (grootverbruiker GHB) is een tijd geleden opgenomen in het ziekenhuis en onderzocht.
Artsen kwamen er achter dat zijn maagwanden ENORM zijn beschadigd en voorzien van rare kleuren "plekken"
Tot opo de dag van vandaag weten ze nog steeds niet wat het is.
Maar t'is bijna weer weekend en we kunnen nog hakken!Wat dacht je van andersom? Maybee is het wel een soort "regenboog"!?
Ga me niet vertellen dat het gezond is en dat het GEEN gezondheidsrisico's met zich mee brengt. Ik ben niet bepaald de heilige maagd maria, en heb liters van die zooi gehad, en MISBRUIK ( extreem hoge doseringen) zullen op lange termijn leiden tot gezondheidsklachten zoals dat met alles is
Er zit een wereld van verschil tussen af en toe 1 pijpje knallen om brute porno te gaan maken, dan jezelf wekelijks "out" te zuipen op een zondagmorgen-afterfeestje en doseringen "uit de losse pols" zomaar even je gezonde glaasje sinaasappelsap in te keilen
Amen
- Lid sinds
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- Lid sinds
- 1 aug 2005
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Handig als je geopstipeerd bent.
- Lid sinds
- 16 okt 2002
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- 28.231
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- Lid sinds
- 28 aug 2005
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Die "gootsteenontstopper" is gewoon Noah, wel niet zuiver genoeg om voor de aanmaak van GHB te dienen.
GBL is de directe precursor van GHB, met hetzelfde effect maar 2 keer zo krachtig. GHB wordt gemaakt door GBL en food grade Naoh.
Waaruit GHB wordt verworven wilt niks zeggen of een stof goed of slecht is. Als je dat niet geloofd moet je maar eens nazien uit wat gewoon keukenzout bestaat.
GHB is zowat de enige drug die echt gezond is voor het lichaam, hoe raar het ook klinkt. Het vormt geen schadelijke afvalstoffen als het wordt afgebroken, en het is een lichaamseigen stof(ik heb gelezen dat het verwant zou zijn aan het vrouwelijk coïtushormoon, maar ben ik niet zeker van). Het is niet lichaamelijk verslavend.
Je kan pure GHB verkrijgen in poedervorm, maar in de Benelux komt dat amper voor. Meestal is het een doorzichtig plakkerig goedje(GHB+water). Hoe "dikker" de samenstelling, hoe puurder.
Het stimuleerd de aanmaak van groeihormoon(en als wisselwerking bij grotere hoeveelheden ook cortisol), het is ontspannend, het is een antidepressiva, pijnstiller, een afrodisiacum, een goed slaapmiddel en een perfect middel om speed en xtc-katers tegen te gaan.
Qua dosering zitten de meesten tussen de 4-7ml en hangt dan nog eens af van de mg/ml verhouding). Doseren is ****ing moeilijk en komt uit ervaring, zit je ook maar een ml te laag van de "goede" dosis vind je er amper een **** aan, en zit je een ml te hoog zit je dicht bij nokken. Het smaakt trouwens verschrikkelijk zout. Als je het puur drinkt zonder iets erachter, mag je er 90% zeker van zijn dat je over je nek gaat en dat de smaak nog 2 uur in je bek blijft hangen. Doe je het in je drinken smaakt je biertje of je cola echt naar zeewater, en het meeste blijft vanonder zitten. De beste manier vind ik nog steeds binnekappen en direct een frisdrank erachterna spoelen.
Het is nergens te vergelijken met de trip van xtc. Het begint zo rond een half uurtje na inname goed te werken, je voelt je "op je gemak", onspannen, je kan lekker lullen, alles is wat grappiger, en als je op de goede dosis zit en het op coïtus aankomt, ben je evengeil als een 13jarige die voor het eerst een echte tiet ziet. Als het ergens wat mee te vergelijke is is het drank.
Zit je "te ver" en ga je nokken voel je je compleet onspannen, relaxed, en moe. Je valt in een soort comateuse toestand voor een uur of 3-4, en daarna is de ghb uitgewerkt en voel je je, raar genoeg en indien je enkel ghb gebruikt, kiplekker, alsof je de beste nachtrust van je leven hebt gehad. Het is vrijwel onmogelijk om door enkel ghb te komen overlijden. Voor omstaanders is deze soort "coma" wel erg scary en bellen ze de ambulance. Compleet onnodig. Als hij enkel ghb heeft gebruikt, leg hem op zijn zij omdat hij zijn tong niet zou inslikken of in zijn eigen kots kan stikken en laat hem rustig slapen. Zijn adem zal traag gaan en af en toe een toch overslaan, dit is perfect normaal, ook al is het scary, aangezien ghb de zuurstofopname in het bloed enorm verbeterd. Check van tijd tot tijd zijn hartslag eens en laat hem niet in een te koude omgeving liggen.
GHB heeft de onterechte reputatie als rape-drug, terwijl de echte boosdoener rohypnol(sp?) is. De reputatie wordt er niet beter op als elk wijf dat nokt en het niet wil hebben dat het aan de hoeveelheid drank kan liggen loopt te verkondigen dat "ze iets in haar drinken gedaan zouden hebben". In een Britse studie werd dat eens getest en minder dan 5% had werkelijk ook iets van "drugs" gekregen.
Beste combinatie zijn met mdma en speed of only. Drank en GHB versterken elkaars werking, dus zijn erg af te raden. Dé topcombinatie is nog steeds, 22.00 ghb 01.00uur speed of mdma, half uurtje voor je gaat slapen terug GHB voor tegen de kater. Je mdma/speedkater zal 10x minder zijn en je zal ook goed slapen.
Vroeger werd GHB in de geneeskunde gebruikt als verdoving, maar aangezien het "spierverslappend" werkt en niet "spierontspannend" zoals normale verdovingsmiddelen moeten doen wordt het niet meer gebruikt.
Nog een raar weetje over GHB, het lichaam zou het in het laatste uur voor de dood na een lange slepende ziekte massaal produceren, als voorbereiding voor het "inslapen". Dat zou die "vredige glimlach" op sommige overledenen verklaren.
Ik vind het schandalig dat op een board vol bodybuilders die zelf de vooroordelen en de propaganda tegen anabolen moeten ervaren, er nog zoveel heeft tegenover sommige drugs.
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