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http://www.erowid.org/archive/rhodium/pharmacology/sociabi...
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http://www.erowid.org/archive/rhodium/pharmacology/sociabi...
knew that this discovery was potential gold for the study of human behaviour and intraspecic aggression. Three classes of sociabilisers have been now dened: 1. Tyrosine Hydroxylase activators based on the prototypal Gamma-OH. 2. Tryptophan Hydroxylase inhibitors based on the prototypal MDMA. 3. Mixed Tyrosine Hydroxylase activators/Tryptophan Hydroxylase inhibitors. This last class may represent powerful novel sociabilisers, but this is not yet known. Since the discovery of Gamma-OH, in France, the French were unable to classify this molecule under anything known and so the classication of Gamma-OH has been rather erratic! It was, rst, a hypnotic. Then it became a pre-anaesthetic and now, it became an anti-addictive medicine for alcoholism! It may or may not become also an anti-addictive medication against opiate intoxication, as shown in Italy. After about 15 years of studying this molecule I nally arrived at the conclusion that Gamma-OH was the rst molecule in a serie of novel molecules to be correctly called the sociabilisers (Sociabilisants, en francais) because they act by enhancing sociability. Experimenting with both Gamma-OH and MDMA, on myself and volunteers, I soon discovered that these two molecules had subjectively indistinguishable actions on sociability though the sociabilising action of MDMA is rst masked because of its serotonin releasing property which is subjectively quite similar to the effects of uvoxamine (the rst specic serotoninergic reuptake blocker which was successfully put on the market) on consciousness and behaviour.
Gamma-OH and non-neurotoxic MDMA derivatives: A Revolution for Mankind - On the Road to Sociability
Gamma-OH is a pure sociabiliser as its sociabilising effects are not hindered by other antagonistic actions such as enhancement of serotoninergic neurotransmission. Gamma-OH and MDMA have been both classied under the novel concept of Sociabilisers, together with the yet to be synthesised molecules sharing the properties of both Gamma-OH and MDMA which I already nickname "sociabilines". When human beings interact on increasingly friendly terms, natural base-line paranoia progressively disappears to be replaced by a feeling of intense pleasure, which is the result of social interaction.This is believed to involve oxytocine pathways in the brain and MDMA and Gamma-OH are both hypothesised to act, directly or indirectly, on oxytocin. In fact the effects of both MDMA and Gamma-OH mirror the behavioural effects of oxytocin and oxytocin has been demonstrated to have anti-depressant properties in Italy. The lower natural paranoia becomes, the more sociability intensies. Theory demonstrates that such consciousness states as "love" or "mystical" states are only states of exceedingly low paranoia and of progressively intensied sociability. In fact,there seems to be a "circuit of paranoia"in the CNS which would generate both paranoia and sociability, depending on how it is activated. Hyperactivation of this system would generate paranoid states while hypoactivation would generate sociable states, from love to mystical states. It is thus hypothesised that depressing paranoia (naturally or pharmacologically) leads automatically to increased sociability (probably through oxytocinergic neuromediation, etc) while increasing paranoia (like with pentazocine, phenylisopropylamines, cannabinoids) leads to associability and some psychopathologies
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such as paranoid schizophrenia, etc. Modulating the sociability states of human beings can represent a powerful therapeuthics in depression and in the suppression of anxiety or suppression of the negative symptoms of schizophrenia and paranoid symptoms. For instance,depression arises when sociability is decreased: intensifying sociability will thus have a thymoanaleptic (anti-depressant) effect. This is demonstrated by the powerful thymoanaleptic properties of Gamma-OH. Unfortunately for depressed patients, and because of the imipraminomimetic dogma, the thymoanaleptic properties of Gamma-OH remained essentially crypto-thymoanaleptic properties until the author discovered the remarkable effects of gamma-hydroxybutyrate on depression!
http://www.erowid.org/archive/rhodium/pharmacology/sociabi...
alkaloid and, according to international law of nomenclature, the "e" should be added!). This combination of GHB effects, SSRIs-mimetic effects and low hallucinosis is the very essence of the MDMA experience. I have, recently, reclassied all the molecules formerly called "hallucinogenic" as "cogitatiogens" or "pensogens", from the Latin and the French, meaning: molecules which generate and increase, specically, thought. Thus the cogitatiogenic effect of MDMA is quite an important psychotropic effect of this molecule, as a medicine.It is the specic mixture of increased thought, increased sociability with decreased anxiety and stress which is the basis of the therapeutical effect of MDMA. Coming back to Tianeptine, novel non-neurotoxic derivatives of MDMA will be found to have not only anti-depressant but also anxiolytic and anti-stress effects and we can safely assume that they will start, in concomittance with the development of Gamma-OH mimetics, a new psychopharmacological revolution. The fact that depression in priorly exposed MDMA individuals can be reversed with tianeptine is a very important fact which will, obviously, be noticed by all our readers. As increasing, globally, serotoninergic neurotransmission gives a net effect of blunting of affect it is logical (and demonstrated with Stablon) to expect that reducing serotonin action in some specic crucial loci will stimulate affect. Regarding this, an interesting observation has been made with the drug NAN-190 which increases tyrosine hydroxylase activity, nearly to GHB levels, by an action at 5-HT1a post-synaptic heteroreceptors. The net effect of this might mean that a reduction of serotoninergic neurotransmission could lead to an increase in dopaminergic neurotransmission. In fact the antagonistic links between dopamine and serotonin in the central nervous system has led me to the concept of the serotonin/balance hypothesis. This hypothesis predicts that MDMA sociabilising effects should be linked to both dopamine and serotonin. My present working hypothesis, as stated before, is that the sociabilisers exert a chain of neurochemical events leading to an increased oxytocinergic function. Sociabilisers will probably throw most SSRIs to the wastebasket once they are fully developed! How many lives could had been saved had the research on anti-depressants not stayed conned on the invention of imipraminomimetics only. The present working hypothesis on the mechanism of action of sociabilisers is that they depress paranoia, as we noticed, thus leading, as natural sociability, to a vast array of potentially useful therapeutic effects. From the effects of natural (non-pharmacological) sociability it can be predicted that full sociabilisers should have the following properties: 1. 2. 3. 4. 5. Very fast thymoanaleptics. Potent anxiolytics. Agressolytics. They should reverse the negative symptoms of schizophrenia. Paranolytics.
From my experience with Gamma-OH, I found that this remarkable molecule had most of the above mentioned properties (but, curiously, baclofen, which mimics Gamma-OH on many points, is not a sociabiliser, though it can elevate mood and potently stimulate sexuality in man while depressing sexuality in the mouse! Here are some properties of Gamma-OH:
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1. It is a very fast acting anti-depressant and will work in the most severe cases of depression where imipraminomimetics will have no action. Depression disappears to be replaced by an exhilarating feeling of joy and happiness of being alive, associated with a desire of communication with other human beings. Suddenly, suicidal ideation seems grotesque and you wonder how come you were suffering so much for nothing! Life is seen again as beautiful and worth living. Foregone hopes and dreams come back into your existence making yourself again full of enthusiasm and activity. Stress is completely suppressed. This is why, for instance, my late friend Dr.Henri Laborit used to take a Gamma-OH drink just before making lectures at conferences. He would then radiate to the audience with joy, enthusiasm, and happiness! Henri Laborit is, maybe, the scientist who best understood the human psyche and especially human stereotypes and intra-specic aggressivity. He worked all his life to combat those stereotypes and aggressive behaviours which sterilise the "adult" human mind. His recent death this year is a tragedy for Science. 2. It is a powerful anxiolytic and very useful against panic attacks which are replaced by a state of happy and tranquil well-being. 3. It can suppress suicidal ideation within less than an hour. 4. It brings back old repressed memories and induces a very positive state of crying. After crying under Gamma-OH you feel relieved. 5. It enhances recall of dreams which are remembered more vividly, with colours, realism, etc. 6. It acts a bit like an electronic "Diode" on consciousness as, under Gamma-OH, we are normally sensitive only to positive ideas and feelings while psychotoxic ideas or emotions are simply automatically discarded. 7. It depresses aggression. Suddenly you may wish to communicate with the persons you would normally consider as enemies. This is a very important property which should be used in politics, in the same way Kava was used in the Pacic, to induce a tranquil state of mind for discussion. The same holds true for scientists. 8. And of course, as its name implies, it promotes social interaction and the pleasure associated with social interaction. 9. It enhances love feelings in "lovers", contrary to many imipraminomimetics whick block these subjective emotions and thus induce an emotional decit. We might expect many of those effects to be found, also, in newnon-neurotoxic analogs of MDMA. MDMA and GHB are, inextricably,linked and should NOT at all be studied as a separate group but as one group only. A substantial number of the imipraminomimetics are, in fact, thymoanaesthetics and not authentic thymoanaleptics: they "suppress" depression by inducing a decit: blunting of
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affect, that is an anaesthesia of emotions. So, thymoanaesthetics cannot be classied as authentic anti-depressants but only as pseudo-antidepressants. Why is Gamma-OH so efcient in depression? Because depression can be dened as a decit of pleasure, due to inhibition of social contacts. Some cultures are more depressogenic than others in this respect. For example, protestant cultures generate more psychopathologies than other cultures because of the extreme repression of emotions. They are thus psychotoxic and psychopathogenic. By stimulating the desire to interact with others, depression is automatically switched off under Gamma-OH! The psychopharmacology of Gamma-OH is still largely unknown but we should focus our attention, I think, on the psychopharmacology of what is called the "maternal instinct" in order to unravel the remarkable properties of this old but unknown molecule, as sociability seems a manifestation of maternal behaviours but expressed differently in adulthood. The development of Sociabilisers will, in my opinion, lead to a complete revolution in the therapy of many psychopathologies, including human intra-specic aggression (competition, war, etc). But why did we wait until now to discover the remarkable properties of a molecule invented 33 years ago? One reason is because Gamma-OH is a short acting medicine: its effects subside within 1 and a half to 2 hours and repeated doses during the day should be used in order to obtain an anti-depressant response. Another reason is that the imipramnomimetic dogma sterilised research and, as all dogma, completely blocked the research of authentic thymoanaleptics. Moreover and worse: due to the chronic lack of enthusiasm of most scientists in the elds of psychiatry and psychopharmacology and also due to the absence of serious research on human beings (isolated people, like Alexander Shulgin, still do introspective research), it took a great deal of time for this researcher to discover, at last, the concept of thymoanaesthesia and to understand that research in depression, for instance, was going nowhere because of a constant confusion concerning the logical nature of what authentic anti-depressants should be like.
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