Page 120 - Pagetit

4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

MDMA is widely distributed, easily crossing membranes and the blood-
brain barrier. Its clearance depends partially on metabolism by the liver,
between 3–7% is converted to the active substance methylenedioxyam-
phetamine (MDA), 28% is biotransformed to other metabolites, and around
65% is eliminated, unchanged, via the kidneys (Verebey, Alrazi & Jafre, 1988;
Cami et al., 1997).
The half-life of ecstasy in plasma is 7.6 hours. This information is relevant
when treating intoxication: 6–8 half-lives are necessary for complete
elimination of ecstasy, giving a total time of around 48 hours for the drug to be
completely eliminated. It can also be seen that at a plasma level of 8 mg/l –
considered to be the level of severe intoxication – more than 24 hours would
be necessary to decrease this to a plasma level lower than 1 mg/l, which
produces less clinical effects. Therefore, 24 hours would be the estimated time
of intensive care needed by intoxicated patients who had taken a few ecstasy
capsules.

Behavioural effects
MDMA may produce subjective effects in humans that are similar to, but
distinguishable from, those of the psychostimulants ∆-amphetamine and
cocaine. Increased self-confidence, understanding and empathy together
with enhanced sensation of proximity and intimacy with other people, and
improvement of communication and relationship skills are described in
uncontrolled studies. Euphoria and increased emotional and physical energy
are presumed to occur with this psychostimulant (Downing, 1986; Nichols,
1986; WHO, 2001). Negative psychological effects of anxiety, paranoia, and
depression can also occur (WHO, 2001).
Intravenous self-administration behaviour in primates (Beardsley, Balster
& Harris, 1986) and in rats (Acquas et al., 2001) is maintained across a range
of doses of ecstasy.

Mechanism of action
Similar to other amphetamines (McKenna & Peroutka, 1990), the effects of
ecstasy may be related to several neurotransmitters including serotonin,
dopamine, and norepinephrine (Downing, 1986; Nichols, 1986; Kalant, 2001;
Montoya et al., 2002). However, serotonin plays the main role in mediating
the effects of ecstasy (Shulgin, 1986; Mascaro et al, 1991; Marona-Lewicka
et al., 1996; Kalant, 2001; Montoya et al., 2002). There is increased net
serotonin release because MDMA binds to and blocks the serotonin
transporter, thus blocking serotonin reuptake (Kalant, 2001). Eventually this
leads to long-term depletion of serotonin and metabolite concentrations
in the brain (WHO, 2001). MDMA also increases the release of dopamine
(WHO, 2001).

99

Chapter_4 99 19.1.2004, 11:43