Was het trouwens ook niet zo dat de neurotoxiciteit van mdma afkomstig is van het feit dat mdma zowel effect uitoefent op de serotonine- als de dopaminereceptoren? Verhoog je de activiteit van een van deze neurotransmitters, naast de mdma zelf, dan verhoog je daarmee ook de neurotoxiciteit.
Daarnaast komt die hersentemperatuur volgens mij voornamelijk door die afgifte van voornamelijk serotonine en dopamine . Kan zo snel niks anders bedenken waarom die temperatuur ineens zou stijgen.
What causes MDMA neurotoxicity?
Scientists aren’t sure yet. What we do know is that some chemical gets into the serotonin axons through the SERotonin Transporters (SERTs), tiny molecular pumps that neurons use to collect serotonin. (Visit the Ecstasy Slide Show for more information.) Once inside, this chemical is broken down by an enzyme. This breakdown process creates oxidizing chemicals (like hydrogen peroxide) that can damage the neuron. We aren’t sure what that first mystery chemical is. For a long time, we thought it was probably dopamine, which we knew played a role in neurotoxicity (dopamine is another neurotransmitter, like serotonin, that is released by MDMA.) However, more recent research has discovered that dopamine’s main role in promoting MDMA neurotoxicity is by increasing body temperature: significant overheating is a very important factor in whether or not MDMA neurotoxicity will occur.
As far as what the actual toxic chemical might be, there are several theories. The most popular theory is that a hepatic metabolite of MDMA (a broken down form of MDMA created in the liver) is to blame. Another theory suggests that MDMA itself may be the ‘toxic chemical’, since there is evidence that MDMA itself may be broken down in the brain.
How large of a dose would be neurotoxic in humans?
Unfortunately, we don’t really know. George Ricaurte, the main US-government funded researcher studying MDMA neurotoxicity, has claimed that even a small recreational dose (1.28 mg/kg) of MDMA could be neurotoxic. Other researchers have given human volunteers moderate doses (1.5 mg/kg, equivalent to about one good pill for a 150 pound person) of MDMA with before-and-after brain scans, and could find no signs of damage.
Don’t mix MDMA with other stimulants, such as amphetamines (speed/meth.) Combining other stimulant drugs with MDMA is a bad idea; the combination increases the risk of becoming seriously overheated, which we know is a major risk factor for neurotoxicity (and death and liver damage and many other bad things.)
http://www.dancesafe.org/drug-informati ... eurotoxic/
How it causes this strangely precise damage has been the subject of a lot of speculation and debate. Given the selectivity of the damage, it seemed likely that something that was damaging to the axons was being concentrated within them. As more research was done, it became clear that the toxic chemical (whatever it was) was being actively pumped in by the serotonin transporters (SERTs.) Many researchers believed (with a good deal of evidence to support the idea) that dopamine was the toxic chemical, which they thought might be getting in through the SERTs after the local serotonin supply was depleted by MDMA.
In 2002, an important new piece of research was done: Animals who had been given drugs that removed virtually all of the serotonin and dopamine in their brains were given what should have been a neurotoxic dose of MDMA. And nothing happened. There was no damage. At first, it seemed as though the 'dopamine' camp had been right. However, the scientists noticed that something else was different in these dopamine depleted animals: When they gave them the overdose of MDMA, they didn't overheat as expected.
That was significant, because research has shown that body temperature is a critically important factor in MDMA neurotoxicity. It wasn't enough to give an animal a massive dose of MDMA; if overheating didn't occur, the animal could usually cope and did not suffer damage. Knowing this, the researchers took another group of dopamine depleted animals, gave them another overdose of MDMA, and warmed them with heating pads so that their temperature reached the same levels as normal (control) animals did when given the same amount of MDMA. The results were striking: The animals with essentially no dopamine in their brains suffered the same level of neurotoxic damage as the control animals did when their body temperatures were kept as high. Something else was at work; dopamine was not the toxic chemical in question. (Ironically, dopamine and norepinephrine release appears to still be important in MDMA neurotoxicity because it promotes activity/heat production, increasing the risk of overheating (which in turn greatly increases the risk of neurotoxicity.))
• The MAO enzymes break down many chemicals similar to MDMA (including dopamine, which is one of the reasons dopamine had been a suspect.)
• When MAO breaks down one of these drugs, it produces reactive oxygen species...chemicals like hydrogen peroxide and superoxide (a more reactive form of oxygen.)
• Your brain has other enzymes that protect it from superoxide and hydrogen peroxide by breaking them down into less reactive chemicals (including water.) As temperatures rise, these enzymes become less effective, and eventually stop working altogether, leaving the reactive oxygen species to run wild and attack the axon.
Stressful and other high-activity situations such as interaction with a conspecific female are also known to induce a significant hyperthermic response in the rat. A combination of social interaction and METH administration was tested for additive effects.
Although the combined effect of the hyperthermic events was not additive, METH administration during social interaction produced stronger and longer-lasting increases in brain and body temperature than that induced by drug alone, heating the brain in some animals near its biological limit (>41°C).
Hyperthermia potentiates dopamine and tyrosine-hydroxylase depletion and astrocytosis and also exacerbates oxidative stress (Omar et al., 1987; Lin et al., 1991)
Brain Hyperthermia Is Induced by Methamphetamine and Exacerbated by Social Interaction, The Journal of Neuroscience, May 1, 2003 23(9):3924–3929
Despite the fact that there is more compelling evidence for amphetamines-induced neurotoxicity in rodents than in humans, it is unlikely that the human brain is less vulnerable than the rodent brain to neurotoxic insult. It remains a challenge to directly compare amphetamines neurotoxicity in rodents and humans, given that (a) the pattern of animal drug exposure and human drug abuse are different, and (b) the methods for assessment of neurotoxicity in rodents and humans are not always alike. Nevertheless, it is now clear that METH and MDMA cause serious cognitive impairments in humans and neurotoxicity to dopaminergic and serotonergic neurons in rodents. It
appears that different mechanisms underlie the development of dopaminergic and serotonergic neurotoxicity, and further studies in mice should advance our knowledge of these mechanisms. Likewise, investigation of the behavioral out-come of the neurotoxic insults caused by amphetamines in mice is essential for better understanding the consequences of human abuse of amphetamines
Methamphetamine and MDMA (Ecstasy) Neurotoxicity: 'of Mice and Men' (2004). IUBMB Life, 56: 249–255.
Tevens ook een aanrader voor de echte "nerds": The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”), Pharmacological Reviews September 2003 vol. 55 no. 3 463-508