Whether or not MDMA is neurotoxic in humans has not been established,
though it is known to cause damage to brain serotonin neurons in
experimental animals.
30 MDMA users and 28 controls matched for weight, height, education and
other drug use were admitted to a controlled inpatient setting after at
least 2 weeks abstinence. On average, they had taken 170mg doses of MDMA
weekly on 95 occasions over 5 years. As there is no method for detecting
serotonergic neurotoxicity in the living human brain, an indirect method
was used consisting of measuring the concentration of 5-HIAA in spinal
fluid. Previous studies in monkeys had established a relationship between
serotonergic neurotoxicity and concentration of 5-HIAA in spinal fluid.
Assessments were also made of pain endurance since serotonin has been
associated with pain. In addition, personality assessments were made and
compared with the control group.
Results showed that MDMA users had lower levels of 5-HIAA, implying their
serotonin levels were lower. However, there was no significant correlation
between 5-HIAA levels and number of uses of MDMA; nor duration or frequency
of use, nor time since last MDMA exposure. It is suggested that trials are
made among users of fenfluramine, which is "taken by more people and more
frequently than MDMA, and is highly toxic to 5-HT neurons in non-human
primates" produces similar results.
There was no difference in pain endurance between MDMA users and controls.
Personality measurements showed statistically significant differences
between MDMA users and controls: MDMA users were assessed as "less
impulsive, more harm-avoidant, and have decreased indirect hostility". This
was unexpected, since it had been previously assumed that lower serotonin
levels corresponded to increased impulsive aggressive behaviour.
Alternative explanations for these findings were discussed and dismissed as
unlikely.
Conclusions:
1. The finding that spinal 5-HIAA levels were lower in MDMA users, and
therefore by implication also brain serotonin "may reflect MDMA
neurotoxicity" in users. The supposed toxicity was greater in women, which
may have been due to them having higher concentrations through being
smaller or using the drug more frequently.
2. The findings that MDMA users were less impulsive, more harm-avoidant,
and have decreased indirect hostility supports the notion that these
personality characteristics are modulated by serotonin.
