How MDMA("extasy")may stimulate SOCIABILITY

Claude de Contrecoeur Cyrano at beehive.twics.com
Mon Jun 3 01:36:18 EST 1996




How MDMA may enhance Sociability:An Hypothesis.
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MDMA(3,4 Methylenedioxymethylphenylisopropylamine) has been defined,together with 
another molecule(Gamma-OH)as being a representative of a novel class of psychotropic 
agents:the SOCIABILISERS.
Sociabilisers act by stimulating and enhancing natural sociability.
The sociabilising actions of Gamma-OH(a Tyrosine Hydroxylase Activator)and MDMA cannot 
be subjectively distinguished.But MDMA does not indce,immediately,a full-blown effect 
due to its mixed pro-serotoninergic and anti-serotoninergic effects.Due to many 
experimental and theoretical reasons it is logical to think that it is the 
anti-serotoninergic effect of MDMA which
seems responsible of its sociabilising effects.Serotonin is,mainly,a molecule which 
attenuates behaviours and decreases emotions,probably by decreasing dopaminergic 
neurotransmission.In the rare instances where serotonin stimulates dopamine like,for 
instance,through the 5-HT2A receptors we may,theoretically,expect an enhancement of 
sociability.However,such a typical 5-HT2A agonist as psilocine does not enhance 
sociability.

The sociabilising action of MDMA is,very probably, related to its indirect blockade 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(gamma-hydroxybutyrate) and MDMA could act at a common site 
modulating oxytocinergic neurotransmission(Oxytocin is postulated to be of crucial 
importance in the expression of sociable states).The following hypothesis  could link 
the effects on sociability of these two molecules.Basically this hypothesis states 
that MDMA might be an indirect tyrosine hydroxylase activator(Gamma-OH is a direct 
tyrosine 
hydroxylase activator) by suppressing the action of serotonin at post-synaptic 5-HT-IA 
heteroreceptors,thus enhancing the activity of tyrosine hydroxylase in some 
unidentified locus normally controlled by the release of serotonin from the Median 
Raphe Nucleus.There is one molecule, called NAN-I9O ,which could help in evaluating 
this hypothesis.
GAMMA-OH 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 
thymoanesthesisers such as fluvoxamine,citalopram,sertraline,etc.At higher dosage the 
sociabilising action of MDMA becomes manifest.Subjectively speaking 2.5gr of GAMMA-OH 
are equivalent to 2OOmgr o
f MDMA.Haloperidol Imgr does not block the sociabilising actions of Gamma-OH while it 
blocks the dopaminergic effects of a dose of 2OOmgr of Amineptine,a dopamine re-uptake 
blocker.Haloperidol might block the sociabilising effects of MDMA.This is not clear 
yet and should be studied.
People who have used MDMA chronically seem to become abnormally responsive to some 
serotonin re-uptake blockers,such as fluvoxamine and clomipramine.
In particular they react with dysphoria to fluvoxamine while many effects of 
fluvoxamine(such as attenuation of thought flow and induction of sleep)are no more 
observed.
In one person who used MDMA less than IO times,normal reactivity to fluvoxamine 
disappeared for about 4 years then,all of a sudden,reappeared but,first,in a modified 
way!
In this person low doses of fluvoxamine paradoxically induced long-term enhancement of 
sociability,as if experiencing MDMA or Gamma-OH.
This lasted for about 3 weeks.
Thereafter,this person started to react normally with fluvoxamine.
Fluvoxamine induced in this person a continuous state of very pleasurable enhancement 
of sociability.
Another person who had taken MDMA for 5 years and who was treated with Tianeptine for 
depression reported feeling similar effects under tianeptine as with MDMA !
Tianeptine is an anti-depressant which reduces serotoninergic neurotransmission.




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