GABOB / Gamalate

[Jamshyd]

Update: I am sad to report that 1g taken rectally (250mg then 750mg 45mins later) is pretty much without effect for me. Then again I do have monstrous tolerance to all receptors that this drug supposedly affects...

It seems like its main effect is a sudden increase in appetite (could be coincidence) and perhaps some mild anxiolytic effect.

Will still nonetheless be taking it regularly over the next couple of week to help completely stop benzos now that I'm done tapering. Will report on effects (if any...).

 

[Limpet_Chicken]

Bear in mind that GHBr agonists are neurotoxic, they induce glutamate release and thus cause excitotoxicity.

Are there any known positive allosteric modulators for GHBr-s, and are these neurotoxic, if any are known?

 

[Jamshyd]

^ Do you have any more detailed info on this? If this is true, it could shed some light on why so much has gone wrong in my life post-GBL, and how Ketamine seems to fix it all... (I'm half joking, but still very interested).

As for GABOB, so far my body has been hinting at "no thanks". Will try it for a bit more. Found it very hard to fall asleep and stay asleep last night...

And as for your question re: allosteric modulators, for some reason I was very sure that the sulpride drugs fit the bill, but apparently wikipedia thinks they are simpy agonists and that they somehow up-regulate the GHBr's at the same time.

 

[Phener]

Bear in mind that GHBr agonists are neurotoxic, they induce glutamate release and thus cause excitotoxicity.

I too would be interested in a reference for that

 

[Limpet_Chicken]

http://www.ncbi.nlm.nih.gov/pubmed/19288974 Suggests severe neurotoxic damage in hippocampus CA1 region and prefrontal cortex.

GABAb activation is antagonistic to glutamatergic activity, and increases synthesis of GABAa agonistic neurosteroids, BUT, the EC:50 for GABAb is higher by far than for its activity at GHBrs, thus producing a biphasic effect, at recreational doses, one where the effect is predominantly mediated by GABAb agonism, and as it tails off, then GHB receptor mediated excitatory (read potentially neurotoxic) activity.



Low doses of GHB which do not reach a sufficient level to provide enough GABAb agonistic effect to block the large scale glutamate release induced by GHBr activation cause severe excitotoxic damage to the hippocampus and prefrontal cortex, excitotoxic damage can be permanent, look at victims of domoic acid ingestion (amnesiac shellfish poisoning) for instance.

What I would like to know, is weather, as the GABAb receptor is metabotropic, is weather the hyperpolarization of hippocampal neurones will last long enough to give a preconditioning kind of effect against excitotoxic cellular damage as the level of GHB in the system declines, or will large nontoxic doses just decline to small, toxic ones.

The GHB receptor activation is pertussis toxin sensitive, so it too is metabotropic. Pharmacokinetics are going to be important here.

 

[Limpet_Chicken]

Would the body intentionally generate something neurotoxic?

Interesting question. I believe a definitive answer is dependent upon context.

Look at glutamate for instance, it is the endogenous agonist (or one of) at glutamate receptors, and it is highly neurotoxic if present in excess, and and glutamate agonists are as neurotoxic as they are efficacious at the ionotropic receptor in question.

By low doses I do not mean endogenous levels, I mean artificially administered GHB at levels insufficient to provide sufficient protection via GABAb mediated antiglutamatergic action.

The doses in the study I linked that proved neurotoxic, were 10mg/kg and (*100mg/kg???*)
10mg/kg is definately far lower than those used by people wanting to get trashed or for narcolepsy.

Offhand, do you know if GABAb antagonists/inverse agonists/negative allosteric modulators display any neurotoxicity? they should increase glutamate release, no? but if I recall, phaclofen or saclofen (phenyl/thio analogs of baclofen) were anticonvulsant in the abscence of any GHBergic activity.

I know from experience of acute GBL withdrawal, aside from its acute, hideously unpleasant effects, when withdrawal is JUST beginning to present itself after the last dose taken, a prodromal phase is exhibited, that in my personal experience characterized itself by very efficient ability to instantly plan and systematize and organize, almost to the extent of showing similarities to OCD.

I do not know, never having taken a selective GHB agonist (never going to take one either, no thanks), and never having assayed either a selective GABAb antagonist, or allosteric modulator, weather the organising/systematizing tendency is due to the obvious GABAb downregulation, which could be mimicked by application of an antagonist, or perhaps negative modulator although I am aware of only positive allosteric ligands so far for GABAb, or is it due perhaps, to some GHBr-ergic activity?

Does the GHBr downregulate/internalise or upregulate in response to chronic activation by an agonist? (using GHB as the ligand)

I wonder, because I believe that CAREFUL use of a GABAb antagonist could potentially be a useful nootropic. I at one time considered trying microdose GHB for that purpose, but I am, after reading that research paper, weather it is truly applicable to human use, or not, glad I didn't.

Edit:

That study is all the evidence I need to decide that I won't take GHB/GBL (never did take 1,4-BDO) again, granted I have had problems in the past with it, I wonder now if it contributed to my memory issues....they do show signs that would correlate with both hippocampal and prefrontal cortical damage.

 

[MeDieViL]

You know, this is really bugging me.

I went through and did a literature search this evening, and the evidence for agonism at the GHB receptor being neurotoxic is REALLY weak. At best pure GHBr agonists induce seizures/convulsions, but no evidence of neurological damage.

There is only a single study showing direct neurotoxicity in male rats getting frequent and high doses of GHB, and it is poorly done, for example, they don't control for hypoxia-induced neurotoxicity due to respiratory depression from the sick high doses they gave the animals.

Xyrem (GHB) is being used daily by many for narcolepsy and catalepsy, and it will likely also be approved soon for daily use in treatment of fibromyalgia. There is no FDA black box warning about "possible neurological damage" on the drug monograph.

I just discovered pubmed has a search box.

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).

And this study shows toxiticy at really low dosages:

Neurotoxic effects induced by gammahydroxybutyric acid (GHB) in male rats.
Pedraza C, García FB, Navarro JF.

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

Remember folks, rats arent tiny humans (i do know humans that are rats but they have nothing to do with the scientific study's).

Here is how you do it: HED(mg/kg) = Animal dose (mg/kg) multiplied by (Animal Km / Human Km)
Where Animal Km is for instance 6 for rats and 37 for an adult human of 60 kg (Table 1 in the pdf).

However, G has been used for a pretty long time in humans without major issue's, so the toxiticy wont be too bad in humans, i use G daily myself

 

[MeDieViL]

Does the GHBr downregulate/internalise or upregulate in response to chronic activation by an agonist? (using GHB as the ligand)

Yup!

Eur J Pharmacol. 1998 Apr 10;346(2-3):331-7.
Sulpiride, but not haloperidol, up-regulates gamma-hydroxybutyrate receptors in vivo and in cultured cells.
Ratomponirina C, Gobaille S, Hodé Y, Kemmel V, Maitre M.

Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, UPR 416 CNRS, Strasbourg, France.
Abstract
Five days of gamma-hydroxybutyrate (GHB) administration (3 x 500 mg kg(-1) day(-1) i.p.) to rats resulted in a significant decrease in the density of GHB receptors measured in the whole rat brain without modification of their corresponding affinity. Similar administration of (-)-sulpiride (2 X 100 mg kg(-1) day(-1) i.p. for 5 days) induces an up-regulation of GHB receptors without change in their dissociation constants (Kd). Haloperidol (2 X 2 mg day(-1) i.p. for 5 days) showed no effect. Administered chronically via osmotic minipumps directly into the lateral ventricles, (-)-sulpiride (60 microg day(-1) for 7 days) and GHB (600 microg day(-1) for 7 days) up-regulated and down-regulated rat brain GHB receptors, respectively. Finally, in a mouse hybridoma cell line (NCB-20 cells) expressing GHB receptors, the treatment of these cells with 1 mM GHB, 100 microM (-)-sulpiride or 1 mM GABA decreases, increases and induces no change, respectively, in the density of GHB receptors after 3 days of treatments. These results indicate that chronic GHB treatment modifies the expression of its receptor and that sulpiride also induces plastic changes in GHB receptors perhaps via antagonistic properties.

 

[Jamshyd]

However, G has been used for a pretty long time in humans without major issue's, so the toxiticy wont be too bad in humans, i use G daily myself

I dunno, all it took me is less than 2 months of 24/7 use to figure out that GHB is the most destructive thing to happen to me, ever. I cannot imagine something so safe as GHB is claimed to be is at once so painful.

I actually think that GHB's use in narcolepsy is achieved through a constant state of mild-withdrawal from the chronic low-dose use.

 

[MeDieViL]

I dunno, all it took me is less than 2 months of 24/7 use to figure out that GHB is the most destructive thing to happen to me, ever. I cannot imagine something so safe as GHB is claimed to be is at once so painful.

I actually think that GHB's use in narcolepsy is achieved through a constant state of mild-withdrawal from the chronic low-dose use.

I only use it at the evenings, (first took it in 2008 with some periods of no use) never had any issue, no withdrawal, tolerance nothing.

Once you start using 24/7 and the body gets addicted some brain chemistry changes occur and everytime it wears off you could be getting a spike of glutamate (if withdrawal is simular to benzo's, and those glutamate spikes are neurotoxic), rapid increase in heartrate eg a state that is highly unhealthy, and because of its half life your body can get a lot of those shocks wich isnt particurally healthy.

Some ppl land into severe addiction, however others use it regurally without ending physically addicted and they are usually fine, togheter with the fact that narcolepsy patients appear to be fine id say that with proper use G isnt too bad.

 

[Jamshyd]

Yes, what you describe is very much what I experienced. That was some 3 years ago and I still don't feel as though I ever recovered fully. I can use almost any drug in moderation, but GHB proved to be utterly uncontrollable and ever since then my self-control over drug use has also been less reliable.

I suppose some may know how to use it responsibly, but I cannot imagine how

 

[MeDieViL]

Yes, what you describe is very much what I experienced. That was some 3 years ago and I still don't feel as though I ever recovered fully. I can use almost any drug in moderation, but GHB proved to be utterly uncontrollable and ever since then my self-control over drug use has also been less reliable.

I suppose some may know how to use it responsibly, but I cannot imagine how

Well i find the G the most addictive thing ive ever taken, it stays with me forever, even if i didnt take it for a year i will still miss it, however i'm capable of waiting till its evening to grab my G, i'm utterly convinced that taking more then that will end in a terrible disaster, but i still use it daily, waiting a few hours to take (while looking forward to it) is something i'm capable of doing.

 

[ebola?]

Think about it... why would the body intentionally generate something neurotoxic?

I'll assume that you mean neurotoxic at levels commonly found in vivo (likely an overly stringent stipulation). To the extent that this neurotoxicity directly effects or is bound with things that increase rates of survival and procreation, above and beyond the ways in which neurotoxicity decreases rates of survival to the end of child-rearing, this neurotoxicity could be selected for evolutionarily.

ebola

 

[raybeez]

I'll assume that you mean neurotoxic at levels commonly found in vivo (likely an overly stringent stipulation). To the extent that this neurotoxicity directly effects or is bound with things that increase rates of survival and procreation, above and beyond the ways in which neurotoxicity decreases rates of survival to the end of child-rearing, this neurotoxicity could be selected for evolutionarily.

ebola

Are you trying to say that people with less neurological potential (read:stupid) procreate more? :D

 

[Phener]

An entire class of anti-psychotic (dopamine-antagonist) drugs used as therapeutic agents in schizophrenia in multiple western countries bind the GHB receptor at their therapeutic doses. We even have these guys calling for the use of GHB analogues with higher GHBr binding as anti-psychotics.

That is interesting, one thing I noted when using GBL was it's amazing ability to nullify any psycadelic. (I possibly didn't try the high doses but still)


I DEFINATELY second people opinions above on GHB/GBL, well in my case GBL - up to that point had handled all drugs completely sensibly but GBL destroyed me, the addiction wasn't even a craving - it snuck up on me until it was too late and my life for a good while was ruined.

Whilst as a result you may think I am in agreement to all the neurotoxicity studies - Some of the above do seem to be reminisent of many "Ecstasy/MDMA = danger" trials, i.e slightly biast. I do think GBL/GHB is potentially dangerous and hideous but kind of hope neurotoxicity is not so much the key problem. I always figured the rebound glutaminergic transmission might be neurotoxic\harmful but to what extent, am hoping not so severe!

 

[MeDieViL]

Only a few antipsychotics bind to the GHB receptor and that also hasnt anything to do with normal antipsychotics aborting trips (wich they do with blocking 5HT2A).

 

[Phener]

Only a few antipsychotics bind to the GHB receptor and that also hasnt anything to do with normal antipsychotics aborting trips (wich they do with blocking 5HT2A).

I wasn't suggesting that modern antipsychotics work to abort trips by binding to GHB! Equally modern antipsychotics do not rely soly on 5ht2a antagonism, it's been tested and alone does not work. D2 antagonism is still fundamentally requiredn but various adjunt receptor antagonism/agonism is theorised to be useful.

I was suggesting that from experience GHB nullilfied some psychadelics when taken in combination (I am using psychadelic as a model of schizophrenia which I agree is flawed and as seen confuses my point). I hessitate to speculate (it may be via a different mechanism) but the dopamine rebound is a common theory in GHB withdrawal - might the opposite somehow reduce or be a useful theorised (not necessarily practical) adjunt to antipsychotics? Hence the publication.

http://www.ncbi.nlm.nih.gov/pubmed/8095552

 

[AlphaOdure]

Well I am rebounding this thread for the 2nd time..although, i wanted to discuss GABOB more so; but I can't help but comment on the following.....

I hessitate to speculate (it may be via a different mechanism) but the dopamine rebound is a common theory in GHB withdrawal - might the opposite somehow reduce or be a useful theorised (not necessarily practical) adjunt to antipsychotics? Hence the publication.

http://www.ncbi.nlm.nih.gov/pubmed/8095552

This dopaminergic effect from GHB was a result of binding at GHB receptors (at least according to the NCBI study you referenced); and most of GHB's withdrawal symptoms are a result of acute reduction of exogenous GABA-b agonism (which i'd assume would be more responsible for dopamine release--and not at the good sort of dopamine release; the sort of dopamine release that makes you go half head-fucked... albeit this action would be from a secondary effect). & there is little information on up/downregulation of GHB receptors and/or its interaction w/ other receptor complexes.

Also, "the opposite being true" (meaning, use of GHB) wouldn't induce "practical" & efficient antipsychotic effects, since antipsychotics are selective to dopaminergic subunits (the subunits most effective for inhibiting psychosis). Not to mention the article references general dopaminergic action, not good for antipsychotic effects. Additionally, antagonism of specific 5-HT receptor subunits is important in the treatment of some types of psychosis (and related psychiatric dysfunctions). Coincidentally, this impact on serotonin receptors is also a pharmacodynamical effect of some antipsychotic medications (especially the atypicals). So therefore, use of GHBergics is not nearly as effective as currently available antipsychotics in my view...

So, unless i'm missing something here, I wager you should've "hesitated to speculate" a a bit longer

 

[MeDieViL]

GHB may release dopamine but that doesnt make it bad as a potential antipsychotic as things are pretty complicated, ap's work for positives indeed because of the D2 antagonism but that is because they cause downstream changes witch are beneficial, shizophrenia is also marked by deficient phasic da levels wich is why amphetamine is a succesfull adjunct to ap's for the treatment of negatives.

 

[MeDieViL]

That said:

Psychiatry Res. 1983 May;9(1):1-8.
Gamma-hydroxybutyrate in the treatment of schizophrenia.
Levy MI, Davis BM, Mohs RC, Trigos GC, Mathé AA, Davis KL.
Abstract
Gamma-Hydroxybutyrate (GHB) inhibits firing of dopaminergic neurons and is thus potentially useful in the treatment of schizophrenia. GHB was administered to 10 schizophrenics concurrently with low-dose fluphenazine in a 6-week double-blind crossover study. No antipsychotic efficacy of GHB was noted. GHB had little if any effect on plasma prolactin levels after a single administration and caused few side effects. Trials with higher doses of GHB may be warranted.

I wonder wheter they only looked at effects for positive symptions as id definatly expect it to work for negatives (mainly anhedonia, depression, anxiety etc), amisulpiride is effective for those because of the GHB agonism.