The sad irony of this situation is that fluvoxamine is superior, in all respects, to Prozac! For instance, Prozac has some unwanted side-effects which fluvoxamine does not have. Moreover, fluvoxamine can suppress the side-effects of Prozac! So why use Prozac at all? This is due to the fact that Lilly was very successful in launching a blitzkrieg propaganda campaign,superbly ignoring our European product and its anteriority. Moreover, the idea of developping a specific serotonin reuptake blocker was a European idea and not an American idea as Americans did not believe in the antidepressant effects of serotonin but favoured noradrenaline... Prozac frequently inducesinsomnia and headaches while it is also slighly sub-hallucinogenic. Fluvoxamine, on the other hand,promotes sleep and alleviates headaches. Also no subhallucinogenic phenomena can be detected. One reason why Prozac has these side-effects is because Prozac,probably, preferentially, and indirectly activate serotonin 5-HT2A receptors. Activation of these receptors is a common effect of the hallucinogens. All the unwanted side-effects of, say, a dose of 40mg of Prozac are abolished by an equipotent dose of 100mg of fluvoxamine. Fluvoxamine also suppresses rapidly moral suffering (the hard-core of depression) and suicidal ideation while Prozac is slower on onset. So the big commercial problem for American companies was that fluvoxamine was marketed not in America but in Europe and a few years before they couldsell their own similar products... Moral perversion, as I said, and totally unacceptable. No comment!
What is interesting is that in Switzerland Prozac's name has been changed into Fluctine, probably for commercial reasons. In addition to fluvoxamine, citalopram, paroxetine and sertraline are available here. So Swiss people seem to have beenless stupid in front of the fluoxetine blitzkrieg! Another very good European antidepressant for which Americans have no equivalent is amineptine (Survector) and, naturally, Amineptine is not marketed in the USA even though it is a dopaminergic antidepressant and dopaminergic antidepressants are known to be more effective in treatment-resistant patients. Why Americans have not yet marketed dopaminergic antidepressants remains an enigma. As the Japanese say: "kaouaï so" for American patients, meaning American patients are most unfortunate (because money always comes before morality in the US). In fact, the activation of dopamine seemsmore crucial in obtaining a fast antidepressant effect than in modulation of other neurotransmitters as the function of dopamine in the CNS is to metabolically activate neuronal systems. Dopamine is an ubiquitous metabolic activator while serotonin has, most frequently, the opposite action (this is called the Dopamine/Serotonin balance hypothesis; there is also a Serotonin/Serotonin balance hypothesis. This hypothesis states that theglobal metabolic action of serotonin is the ratio of activation of serotonin receptors diminishing dopaminergic activity to those serotoninergic receptors which increase dopamine activity, such as the 5-HT2A receptors). Regarding novel antidepressants, the French have inventedthe very first Selective Serotonin Reuptake Accelerator (SSRA) : Tianeptine. Tianeptine acts in an opposite way as SSRIs but still, instead of inducing depressions, cures depressions! In the naive understanding of serotonin in depression such a fact cannot be understood... We will explain later on why tianeptine is, in fact, an antidepressant and even the first authentic serotoninergic antidepressant!
So we are left with the morally unacceptable fact that America has banned superior European antidepressants because the same equivalent products did not yet exist in America. This behaviour of the american pharmaceutical companies has been systematic. For instance, a good antidepressant invented in Italy called Trazodone was recently imitated in America with the creation of Nefazodone (Serzone) in order to get more money! And another novel antidepressant invented in Europe, Viloxazine (the first selective noradrenaline reuptake inhibitor or SNRI), apparently never reached the US market, etc, etc.
Now I will come to a remarkable antidepressant called Gamma-OH (brand name since 1961), and which could save lots of depressed people when it is marketed to that effect. Gamma-OH has never been studied as an antidepressant because of what is called the imipraminomimetic dogma. This dogma states that antidepressants can only be found by those pharmacological methods which have been applied to discover imipramine, the first alleged antidepressant! Clearly, this dogma isnonsense and it has hampered research on antidepressants for more than 30 years, forbidding the discovery oftrue fast-acting antidepressants. This dogma also states that it is not possible to achieve an antidepressant effect immediately but that one has to suffer for weeks before starting to feel better with medication... What is funny about this grotesque dogma is that imipramine was discovered by chance! At that time nobody believed in imipramine except one lone researcher whose obstinate perserverance was rewarded... Gamma-OH (or gamma-hydroxybutyrate, a quite simple molecule with a vast array of psychotropic properties) has proved that this statement wassheer nonsense. Gamma-OH was discovered by a friend of mine (the late Dr Henri Laborit who introduced the use of chlorpromazine(Largactil) in psychiatry around 1952) in 1961 in France and since that time scientists had been unable to discover somerather extraordinary properties of this molecule on depression, anxiety and sociability! Why? Because nobodyseriously studied the psychotropic effects of this molecule until I started to do the job. This stems from the fact that most "scientists" are not real scientists or savants but only civil servants: they work to earn their food, not to really discover nature's mysteries. These civil servants (called "fonctionnaires" in French, a simpler word) work like soldiers in an army, not like true researchers, because they are not authentic researchers! They have ideas and interests of "fonctionnaires" not of savants... For some years Gamma-OH was used as an hypnotic in France but people complained that they did not sleep long enough on it and would awake too early in the morning! Then, according to Henri Laborit, came May 1968 and Gamma-OH was considered subversive: it thus became a medicine only available on prescription. And of course a medicine which can enhance sociability is indeed subversive because sociability does not go well along with business and merchants! To be a good merchant you need to block your sociable feelings psychologically: you should cease to consider other human beings as human beings butjust as things which can bring you money and power. You have to learn to be selfish, that is non-sociable!
Gamma-OH is a remarkable molecule because it can suppress depressive ideation and anxiety, sometimes within less than 30 minutes. It also seems to be immediately active on the most severe and treatment-resistant forms of depression. Because of such remarkable properties I jokingly used to call Gamma-OH "Or Potable", which means "drinkable gold" in French! Indeed a molecule which can block your depression and suicidal ideas, anxiety, etc, in such an efficient way is as precious as gold because it can save your life. Gamma-OH saved my own life many times when all other antidepressants failed. For years I suffered of depressive episodes which did not react to conventional "antidepressants". Why? Because, in fact, most antidepressants (an antidepressant is also called a thymoanaleptic, which is a molecule that stimulates mood) are not really "antidepressants" per se but thymoanaesthetics. A thymoanaesthetic is a molecule which anaesthetises emotions and which thus blunts feelings. For instance, if you give "antidepressants" to, say, two lovers together, you will notice that their love feelings towards one another become anesthesised, blunted... Clearly, a molecule which blunts rewarding emotions is definitely not an authentic antidepressant but rather a "mind Xylocaine" (xylocaine is an anesthesiser used for haemorrhoids and all kinds of similar pains!). A thymoanaesthetic takes away a part of your personality and makes you a bit similar to people suffering from negative schizophrenia. On the contrary if you administer gamma-hydroxybutyrate to a pair of lovers you will notice that it will enhance their love feelings because it stimulates sociability.
Prozac and Fluvoxamine and all SSRIs are in fact thymoanaesthetics, not authentic thymoanaleptics. They block depression by suppressing or reducing feelings, euphoric or dysphoric, and you become a kind of satisfied zombie! Another thymoanaesthetic, which is not an SSRI, and which quite spectacularly blocks love feelings is maprotiline, a slightly modified tricyclic. In my opinion, maprotiline is psychotoxic because it can induce indifference in otherwise normal subjects. No more suffering but no more real happiness. On the contrary,Amineptine does not suppress emotions but it does not intensify them either. So amineptine is an antidepressant but still not the ideal thymoanaleptic. Now we can come back to tianeptine. Why istianeptine an antidepressant? We have seen that serotoninergics alleviate depression by reducing emotions. Enhancing serotonin neurotransmission, in fact, anaesthetises emotions. Thus it is logical that reducing serotonin neurotransmission (in some unknown brain areas) shouldstimulate the expression of emotions. This is demonstrated bytianeptine and by some tryptophan hydroxylase inhibitors such as MDA or MDMA. What is more interesting is that even though MDMA selectively destroys the axons of the raphe nucleus the behavioural consequences of this areapparently non-existent. Further reducing serotonin neurotransmission with tianeptine in MDMA subjects having a depressive episode can suppress depression in these people! One person who had taken MDMA at high doses for 5 years and who became depressed reported that, under tianeptine, he would feel as if under MDMA!!! Of course no normal patient has ever reported an MDMA-like effect with tianeptine... As tianeptine activates emotions instead of reducing them tianeptine can thus be considered as the first authentic serotoninergic anti-depressant. But who knows tianeptine in North America? Nearly nobody because the French are very, very bad businessmen, unlike Lilly! French can invent good novel products but are not good at propaganda ! Lilly invented a mediocre product but persuaded everybody that their product was the best ever... If the French had been as clever as Lilly, Amineptine, for instance, would have invaded the whole world years and years ago, not to speak about tianeptine! The French have invented many novel antidepressant but did practically nothing to spread them. Some of these are: médifoxamine (Clédial), minaprine (Cantor), Viloxazine (Vivalan), not to mention amineptine and tianeptine! What's more, they invented (by chance!) Gamma-OH and never discovered that this was avery novel antidepressant! Knowledgeable people just used Gamma-OH likeChampagne or Beaujolais but did nothing more... Gamma-OH stayed for the élite and the élite were not interested in studying the peculiar psychotropic effects of this molecule!
After years of reflexions on depression I realised one day that a real antidepressant should stimulate sociability. Why? Because depression is basically a defect of sociability. Depression is a state of lowered sociabilityand when natural sociability is lowered in a human brain (for instance through competition, etc) then this brain starts to suffer morally. Experience has shown that when sociability is enhanced, depression vanishes.Gamma-OH is the first molecule ever discovered which does just this: it stimulates sociability. This is why Gamma-OH is called a sociabiliser. Gamma-OH is hypothesised to cure depression by stimulation of brain oxytocin neurotransmission. Oxytocin is a very important molecule responsible of sociable states, of the maternal instinct and of all activities related to the maintainance of life. For instance, oxytocin is involved in sex and orgasm and orgasm intensity seems directly linked to enhanced oxytocin neurotransmission. Gamma-OH suppresses depressed ideation with amazing rapidity. You may feel uncurable dysphoria with suicidal ideation, anxiety, etc, and think that no medicine or no one could help you until you try gamma-hydroxybutyrate!Afterwards you might just think how crazy you were and feel how life is beautiful and deserves to be lived and enjoyed! Gamma-hydroxybutyrate strongly stimulates the desire to be and to remain alive despite unfavourable circumstances. No conventional so-called antidepressant does that.Gamma-OH is the fastest antidepressant known and can, often, suppress severe depressive ideationwithin just hours while conventional thymoanaesthetics take weeks or months to alleviate suffering... Gamma-OH therapy is also very short: less than a month of treatment is effective,as opposed to months or years of treatment with other treatments.
Gamma-OH gives you a strong desire to live whatever the circumstances. This is why it is the only authentic antidepressant available. Gamma-hydroxybutyrate was the first sociabiliser which I discovered through Henri Laborit. Laborit is well-known in France for his many books on society. He used to drink Gamma-OH 3 times a week, which kept him in amazing shape! However, Gamma-OH cannot normally be taken for a long period of time continuously as it tends to induce fatigue and sometimes anxiety. So emotional satiety or fatigue, etc, make Gamma-OH a non-addictive medicine as people will, spontaneously, stop medication when they feel these phenomena.
Gamma-OH is a so-called GABA-B agonist and a tyrosine hydroxylase activator. At pharmacological doses, it has recently been found, in Strasbourg (France), to be a tryptophan hydroxylase activator. At the normal doses used for depression and anxiety Gamma-OH has a small regulatory dopaminergic activity: it regularises dopaminergic activity. Gamma-OH is found naturally in the brain together with another more rigid analogue called gamma-hydroxy-trans-crotonate (GHTC). GHTC is a close analogue of gamma-amino-trans-crotonate (GATC) which is one of the most potent agonist of the newly discovered GABA-C receptors. It is not known yet whether Gamma-OH or GHTC bind to these GABA-C receptors. There are specific receptors to 4-OHB (another name of Gamma-OH!) and GHTC in the brain. These receptors are calledGHB receptors. French scientists have found that some benzamide neuroleptics bind with high affinity to these receptors. Nobody knows yet what 4-OHB and GHTC do, exactly, in the brain! They may serve as neuromodulators. The only rather clear thing we know is that stimulation of these receptors could be involved in the generation of "petit mal" epilepsy. Gamma-OH can induce, very rarely (and this is not dose-dependent!), slight subjective effects reminiscent of petit mal epilepsy. These effects are adequately blocked by clonazepam. Benzodiazepines seem to have a good protective effects against the eventual minor side-effects of Gamma-OH. For instance, short term use of Gamma-OH is strongly anxiolytic and a very effective medication for panic attacks which are reversed within 15 to 20 minutes (on an empty stomach only). However, if Gamma-OH is taken for weeks it can induce what looks like a "rebound" anxiety phenomenon. This anxiety manifests itself as plain anxiety or a panic attack just when the psychotropic effects of Gamma-OH start to wane. In such cases of anxiety, clonazepam (2mg), midazolam (15mg, triazolam (0,5mg) or chlorazépate (Tranxène, 25 mg) should be used. Gamma-OH invariably induces vomiting in people chronically intoxicated with alcohol or people having liver problems. In fact, Gamma-OH can be used as a test of liver functioning! However, as Gamma-OH stimulates dopamine activity it can give rise to nausea and vomiting with very slight increases in the normal dose range which should never exceed 2.5g within 4 hours. Italians have used Gamma-OH to treat alcoholics and opiate addicts, without serious side effects. They have been using shorter time intervals than that which I recommend and big daily doses with heroin addicts with no apparent serious side-effects. This is in contradiction to what Americans have reported... So is there now an American and a European science??? Why are Gamma-OH side-effects "serious" in North-America and "negligible" in Europe (Italy)? Are these differences of opinions related to science OR culture??? My opinion is that demonisation of so-and-so is strongly entrenched in North American culture. In North America things have to be good or bad, black or white. Something cannot be good and bad at the same time, out there... This is an ayatollah way of thinking: it is cultural Inquisition. We are more realistic and pragmatic in Europe. Even water can lead to intoxication if taken in sufficient amounts... Words can also intoxicate but words are far more potent than molecules! Adolf Hitler could intoxicate and make millions of people hallucinate just with a few words... The words of Hitler were hallucinogenic and far, far more potent than lysergamide (LSD)! Hitler was a potential emotional hallucinogen, like some mushrooms are potential hallucinogens. But this is a philosophical discussion which does not have its place here! Just good to know because some North American "scientists" are also hallucinogenic and spread hallucinations... The whole North American system is strongly hallucinogenic with its insidious commercial and puritanical flavour. This is another debate... Concerning hallucinogens, a famous scientist speculated once that 5-methoxy-DMT (a hallucinogen!) might lift rapidly depressive ideation. Hallucinogens have not been experimented with as antidepressants yet but some facts suggest that some might have an action. This remains to be determined.
Many years ago I discovered asecond class of Sociabilisers (though less potent
because of a mixed pro-serotoninergic action) called the tryptophan hydroxylase inhibitors, such as MDMA
(3,4 methylenedioxymethylphenylisopropylamine) or MDAI (5,6
methylenedioxyaminoindane). The sociabilising
actions per se of MDMA are similar but Gamma-OH is more potent and perfectly safe while
MDMA is neurotoxic and cardiotoxic. MDAI is a non-neurotoxic
analogue of MDMA. New analogues of both Gamma-OH
and MDMA have been invented but not yet tested. Thesociabilising action of MDMA is related to its
indirect blocking of serotonin
neurotransmission in a brain structure called the median raphe nucleus. When the median raphe nucleus is inactivated then
sociability spontaneously appears. In fact, both Gamma-OH and MDMA could act at a common site modulating oxytocinergic neurotransmission. I
have now a hypothesis which could link the effects on sociability
of these two molecules. Basically this hypothesis states that MDMA
might be an indirect tyrosine hydroxylase activator by suppressing
the action of serotonin at post-synaptic 5-HT1A
heteroreceptors, thus enhancing the activity of tyrosine
hydroxylase in some unidentified locus. There exists a molecule,
NAN-190, which could help in evaluating
this hypothesis. Another hypothesis is that MDMA decreases
serotonin neurotransmission,through action at self-inhibitory
serotoninergic receptors.In both case,however,serotonin action
should be blocked,because increasing serotonin action leads to
blunting of emotions and,logically,then,decreasing serotoninergic
action should lead to stimulation of emotions.
Gamma-OH is apure
sociabiliser while MDMA and MDMA-mimetics are partial sociabilisers. At low doses of MDMA the
sociabilising action of this substance is masked by a pro-serotoninergic action as MDMA is also a
serotonin releaser. This effect of MDMA produces a psychotropic
action similar to the serotoninergic
thymoanaesthetics such as fluvoxamine, citalopram,
sertraline, etc. At higher dosage the sociabilising action of MDMA
becomes manifest. Subjectively speaking 2.5g of Gamma-OH are equivalent to 200mg of MDMA.
Haloperidol 1mg does not block the sociabilising actions of Gamma-OH while it blocks the dopaminergic effects
of a dose of 200mg of Amineptine, a dopamine re-uptake blocker.
Haloperidol might block the sociabilising effects of MDMA. This is
not clear yet. Gamma-OH might, theoretically, be
also effective against the negative symptoms of schizophrenia but
this remains to be tested.
Gamma-OH can be obtained in France under this name. It has been produced since its discovery by theLaboratoire Egic, Amilly, France (telephone: 30-67-16-16). Now it is apparently produced by another company and this company does not know yet that they have potential gold in their hands because if Gamma-OH is demonstrated to be the superior antidepressant which I claim, then it would throw away most of the antique antidepressants! You getGamma-OH in vials of 2.5g to be dissolved in orange juice or milk (Henri Laborit's advice!), as it doesn't taste that good.Gamma-OH boxes are blue in colour and contain only 6 vials. A box costs about 10 swiss francs. Gamma-OH is sometimes very effective against migraines but only for an hour and a half! The activity of Gamma-OH against migraines is not predictable, like many other medicines used for that. MDMA is also very effective against migraines but this has not been studied...
Gamma-OH should never be mixed with alcohol,
opiates, antibiotics, or anything else except
benzodiazepines, Amineptine, or Fluvoxamine. The psychotropic
effects of 100mg of fluvoxamine will be suppressed for about an
hour and a half by a dose of 2.5g of Gamma-OH. Amineptine does not seem to modify the
psychotropic effects of Gamma-OH while
L-dopa intensifies the hypnotic effects of this molecule. The
recommended dose of Gamma-OH should not be exceeded. If you overdose, you fall into a
hypnotic sleep from which you cannot awaken for hours. Moreover, it
might promote "petit mal" epilepsy in such overdoses, plus nausea
and vomiting. Vomiting is a clear sign of relative over-dosage of
Gamma-OH and is related, apparently, both
to the dopaminergic activity of this molecule and to liver
function. Anyhow, there is no need for overdosing. If usedas prescribed here it is a very safe antidepressant and anti-panic medication. Gamma-OH is available only on prescription. I
advise those people who see everything in term of white or black to
look into the considerable benefits for sufferers that Gamma-OH could bring if it is demonstrated to be
the superior antidepressant I claim here. Afterwards, more research
will certainly lead to refined versions of Gamma-OH with minimal side-effects.
No Inquisition can be accepted in the
scientific field. American society has systematically demonised all psychotropic
molecules which can givepleasure. (Even
alcohol was demonised but this demonisation was not successful and
was abandoned when it was noticed that the creation of Al Capone and other similar people was a
consequence of this demonisation!) This is sheer madness and should
strongly be opposed. The right to use our brain in the way we want
should be a fundamental right of man and put in
the Declaration of Human Rights. I hope
this goal will be achieved in the future. One of the reason which
motivated me to write what you are reading is that Gamma-OH has been in use, by knowledgeable people
in Europe, for decades. Now it has reached
the USA, unfortunately because, as usual,
some American inquisitors are
trying to demonise this very useful molecule.These pseudo-scientific ayatollahs should
be put back in their medieval churches. In Iran, ayatollahs are
condemning sex. In America, the ayatollahs want,
desperately, to control the use of our mind. This is an
untolerable situation. Progress is made through freedom and
knowledge, not under the guidance of any ayatollah. Let us make a
grassroot movement against all these ayatollahs! Ayatollahs and
similar Inquisitors should go back into their dungeons!!! The
Middle Ages are over.The quest for Freedom is a
never-ending quest. It is surprising that you do not yet
need a prescription for champagne, wines and other alcohols in
North America because if alcohol were judged by pharmaceutical
standards it would have been banned a long time ago...
Gamma-OH is known in France through the many books of Henri Laborit and his conferences! Laborit always praised the properties of Gamma-OH and, as France is definitely not a puritanical society banning pleasure from existence, Gamma-OH has always been available, even though its stimulates pleasure.Laborit always advocated the general use of Gamma-OH in society, like butter or milk! Why? Because it takes away your stress, makes you more positive towards life, suppresses selectively, like a kind of "psychological diode", your painful feelings, stimulates your sociability and makes you more tender, more loving, more concerned by others. Also you become keenly aware that you have only one life and that life should be a quest for happiness. Gamma-OH makes you realise how much you need others (not something for businessmen and militaries or gangsters!!!) and this is a highly positive thing. I always knew that when Gamma-OH arrived in puritanical North America it would one day be demonised... Unfortunately for North Americans, the ayatollahs of the pleasureInquisition have struck again and banned gamma-hydroxybutyrate! Laborit just died, recently, a few months ago at an old age. Sometimes he used to joke that Gamma-OH made him live longer as he would suppress his stress with this "drinkable gold" in cases of need!!! He always said that his two greatest discoveries were chlorpromazine and Gamma-OH but he never fully realised that Gamma-OH could open a new era in the management of depression and anxiety. He never fought to promote the study of the psychotropic effects of Gamma-OH, he never discovered that Gamma-OH was the first molecule of a novel class: the Sociabilisers. He just enjoyed Gamma-OH, with his friends, while conducting other researches. All the people who have surrounded Laborit have naturally more or less been exposed to Gamma-OH! I was lucky to be one of these people. Gamma-OH is still a crude medicine. It should be properly studied and better analogues should be invented. The use of sociabilisers may have tremendous effects on our societies, reducing intra-specific aggression and enhancing cooperation instead of competition. Gamma-OH is a convivial medicine as it shows you that you need others to be happy. Long term on-and-off use seems to make you more immune to stress and dysphoria, more loving towards people in general, more active in your life as it stimulates your enthusiasm because you are so aware that life can be a fantastic thing, every day. The general use of sociabilisers may be a temporary solution for the intra-specific aggressivity of the human kind. Can Gamma-OH and novel analogs reduce wars, at last? I leave this question opened for your reflexion.
I will now summarise the psychotropic profile of Gamma-OH, something which I did in a lengthy
paper many years ago, in French.
Gamma-OH shares some properties
with another tyrosine hydroxylase
activator which is not
classified as a sociabiliser, despite the fact that it can,
sometimes, increase sociability and decrease depressive ideation.
On the contrary, this other molecule (baclofen) has been reported to have
anti-depressive and depressogenic properties simultaneously.
Claude
Rifat, biologiste, Genève, Suisse.