GHB: The First Authentic Antidepressant

Claude Rifat

GHB was discovered by a friend of mine (the late Dr Henri Laborit) in 1961 in France.

GHB 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 GHB "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. GHB 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).  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.

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 sociability and 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.  GHB is the first molecule ever discovered which does just this: it stimulates sociability. This is why GHB is called a sociabiliser. GHB 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. GHB 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. GHB is the fastest antidepressant known and can, often, suppress severe depressive ideation within just hours while conventional thymoanaesthetics take weeks or months to alleviate suffering.  GHB therapy is also very short: less than a month of treatment is effective, as opposed to months or years of treatment with other treatments.

How to use GHB

GHB should be used as follows: Three doses of 2g per day on an empty stomach. For instance, 2g in the morning, then 2g before eating your first meal, at noon, then the last dose at around 6 in the evening.  If you suffer from intractable moral pain you will be surprised to feel that your blocked gratifying emotions come back very, very fast! GHB is a self-limiting medicine, which means that you discover by yourself when it is time to stop medication.  Why? Because GHB induces emotional satiety and when you are emotionally satiated you do not feel like asking for more joy as you feel already fed up with happiness!!!  Yes, you can be fed up with happiness!  This is why people using GHB do not become addicted. In fact, GHB is even used to treat alcohol and opiate addicts.

GHB 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 GHB 3 times a week, which kept him in amazing shape!  However, GHB 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 GHB a non-addictive medicine as people will, spontaneously, stop medication when they feel these phenomena!

GHB 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 GHB has a small regulatory dopaminergic activity: it regularises dopaminergic activity.  GHB 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 GHB or GHTC bind to these GABA-C receptors.  There are specific receptors to 4-OHB (another name of GHB!) and GHTC in the brain.  These receptors are called GHB 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.  GHB 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 and this is the reason why GHB should always be better absorbed with clonazepam or other benzodiazepines.  Benzodiazepines seem to have a good protective effects against the eventual minor side-effects of GHB.  For instance, short term use of GHB 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 GHB 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 GHB start to wane. GHB invariably induces vomiting in people chronically intoxicated with alcohol or people having liver problems.  In fact, GHB can be used as a test of liver functioning!  However, as GHB 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 6 hours.

Italians have used GHB 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 GHB 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.  

Many years ago I discovered a second 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 GHB is more potent and perfectly safe while MDMA is neurotoxic and cardiotoxic. MDAI is a non-neurotoxic analogue of MDMA.  New analogues of both GHB and MDMA have been invented but not yet tested.  The sociabilising 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 GHB 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.  GHB is a pure 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 GHB ia equivalent to 200mg of MDMA.  GHB might, theoretically, be also effective against the negative symptoms of schizophrenia but this remains to be tested.

If GHB is demonstrated to be the superior antidepressant which I claim, then it would throw away most of the antique antidepressants!  GHB is sometimes very effective against migraines but only for an hour and a half! The activity of GHB against migraines is not predictable, like many other medicines used for that.

GHB 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 GHB.   Amineptine does not seem to modify the psychotropic effects of GHB while L-dopa intensifies the hypnotic effects of this molecule. The recommended dose of GHB should not be exceeded.  If you overdose, you fall into a hypnotic sleep from which you cannot awaken for hours. Moreover, it could promote "petit mal" epilepsy in such overdoses, plus nausea and vomiting. Vomiting is a clear sign of relative over-dosage of GHB and is related, apparently, both to the dopaminergic activity of this molecule and to liver function.  Anyhow, there is no need for overdosing.  If used as prescribed here it is a very safe antidepressant and anti-panic medication.  I advise those people who see everything in term of white or black to look into the considerable benefits for sufferers that GHB could bring if it is demonstrated to be the superior antidepressant I claim here.  Afterwards, more research will certainly lead to refined versions of GHB with minimal side-effects.

The demonisation of GHB in North America: A New Form of Inquisition

We have been living, since the 1960s, in a world of Inquisition against all psychotropic molecules which generate some forms of pleasure.  This modern Inquisition started in America as a puritanical expression of American society to ban pleasure from life. This Inquisition should be fought against as it has halted the development of scientific research on the mind. 30 years of research have been lost because Americans imposed an intellectual embargo on many forms of research involving the mind.  For instance, all research on the hallucinogens was stopped, thanks to this perverse Inquisition.  This intellectual embargo should be lifted and scientists and laymen should fight for that.

No Inquisition can be accepted in the scientific field. American society has systematically demonised all psychotropic molecules which can give pleasure.  (Even alcohol was demonised but this demonisation was not successful.)  This is sheer madness and should strongly be opposed.  One of the reasons which motivated me to write what you are reading is that GHB 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.  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.  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.

GHB in France and North-America

GHB was invented by Dr Wermuth, in France, for Dr Henri Laborit who is the father of chlorpromazine and modern psychopharmacology.  Wermuth created gamma-hydroxybutyrate in 1961 in the search of a GABA analogue which could readily penetrate the blood-brain barrier.  Gamma-OH soon went on the market as an hypnotic which could be obtained with no medical prescription. The French, until I started to study this molecule, were unable to classify it under any existing class, because sometimes it was an hypnotic inducing a form of sleep very similar to normal sleep, then it became a pre-anaesthetic, etc.  About 15 years ago, I finally discovered that GHB was, in fact, a molecule to be classified under the novel class of the Sociabilisers, together with its butyrolactone form which is readily transformed into GHB in the blood by a non specific lactonase.   In fact, butyrolactone is a pro-drug giving rise to gamma-hydroxybutyric acid. GHB has a recognised peripheric oxytocinergic action while its central oxytocin properties are still to be demonstrated but seem very likely.

GHB is known in France through the many books of Henri Laborit and his conferences!   Laborit always praised the properties of GHB and, as France is definitely not a puritanical society banning pleasure from existence, GHB has always been available, even though its stimulates pleasure.  Laborit always advocated the general use of GHB 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. GHB 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 GHB arrived in puritanical North America it would one day be demonised. Unfortunately for North Americans, the ayatollahs of the pleasure Inquisition 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 GHB 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 GHB but he never fully realised that GHB could open a new era in the management of depression and anxiety.  He never fought to promote the study of the psychotropic effects of GHB, he never discovered that GHB was the first molecule of a novel class: the Sociabilisers.  He just enjoyed GHB, with his friends, while conducting other researches.  All the people who have surrounded Laborit have naturally more or less been exposed to GHB! I was lucky to be one of these people. GHB 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. GHB 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 GHB and novel analogs reduce wars, at last?  I leave this question opened for your reflexion.

 I will now summarise the psychotropic profile of GHB, something which I did in a lengthy paper many years ago, in French.

Description of the Psychotropic Effects of GHB (1985)

GHB has the following properties:

1)   GHB stimulates sociability, which means that you feel like communicating with other people in all ways: emotionally, intellectually, sexually. And from this communication you feel a very strong and deep happiness.

2)   GHB gives you a strong desire to touch others, physically and psychologically.

3)   Communication becomes extremely gratifying as you feel you want to become close to people, not to isolate yourself.

4)   GHB induces a strong sense of beauty. Everything looks so beautiful, so vivid, so enjoyable, so pleasurable, so important, so "deep".

5)   The perception of movement is enhanced.

6)   Three-dimensional perception is enhanced and vision seems more clear, better than usual.

7)    The contrast of colours between objects is increased. A yellow "pissenlit" (dandelion), or a rose, etc, situated in front of, say, green grass, looks brighter, more real, closer to you.

8)    If you are a man, a woman will look magnificent and very attractive. She may become just like a goddess to your eyes. Women will experience the same feelings towards men. However, these kinds of feelings depend of your cultural background. For instance, a simple Siamese woman will not feel such intense feelings but will report that she feels drunk! GHB is a very important tool in investigating the emotional background of a person. For instance loving people will become more loving while people devoid of these feelings will just feel in good mood, only. Some people may cry, which demonstrates that they have a lot of repressed material in themselves, etc. Crying under GHB is a very liberating experience because you can take out and release things which you normally keep deep inside and which thus hurt you. Crying under GHB takes away accumulated inner moral pains.

9)    Sensuality becomes very intense. You want to touch, to kiss, to caress, to hold, to love, to hug, to make love. In summary, you want to contact others through any means available because you are just highly sociable!

10)   According to Henri Laborit, GHB renders the clitoris more sensitive. Moreover, GHB increases love and sexual desires both in women and men.

11)   You can sometimes feel a deep sense of "meaningfulness". Things become meaningful to you, even you are unable to scientifically define such a mystical feeling. This meaningfulness of reality is a very interesting phenomenon from a scientific point of view as it seems to show that there exists a "circuit" of meaningfulness in our nervous system. Non-specific activation of this circuit, under GHB, would give us a "deep" sense of "meaningfulness" which is, of course, imaginary.

12)   GHB stimulates your recall abilities related to previous GHB experience. Each time you take GHB you can often clearly remember memories stored under another GHB context. Emotions are especially well-remembered and reexperienced. From these and other observations, I think GHB should be a tool of choice in psychoanalysis.

13)   Some people feel an urge to defecate after GHB, probably because of muscle relaxation!   One of the first reactions from a colleague of mine, after GHB, is to go to the toilet!!!

14)   In fact, GHB induces a very pleasant sense of muscle relaxation, especially in the legs.

15)   One of the most remarkable action of GHB is that it gives you a strong desire to live and to remain alive, despite unfavourable conditions.

When is GHB contraindicated?

Untreated epilepsy, eclampsia, hypokalemia, severe hypertension, alcoholism, association with opiates, antibiotics. For depressed patients, GHB should be taken only under medical supervision.

 Claude Rifat, biologist, Gen & Egraveve, Suisse. 

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