Slide #21-b (Advanced)
MDMA Makes the Serotonin Transporters Work In Reverse!

A new theory is gaining wider acceptance among researchers about exactly how MDMA causes serotonin to be released into the synapse after it enters the axon. It is no longer assumed that the MDMA somehow interacts with the vesicle, ausing it to pour its serotonin into the synapse. Rather, the MDMA is thought to make the transporters work backwards, transporting serotonin from inside the axon to the synapse!

Here's the theory:

Once the MDMA enters the transporter, it falls off inside the axon terminal, and leaves the transporter in such a state that a serotonin molecule now binds to the place where the MDMA fell off. The transporter then spins around and deposits the serotonin molecule into the synapse, where another MDMA molecule binds to where this serotonin molecule used to be.

This all happens through a four-step process:

  1. MDMA is released from the transporter into the axon when the transporter undergoes a change in "configuration." (The transporter is basically a group of proteins that can change configuration, or "shape." Depending on its configuration, certain molecules are more likely to bind to it. This is called "affintity." When a molecule with a high affinity binds to a transporter, it changes the transporter's configuration, which eventually causes the molecule to unbind or "fall off," possibly on the other side. This is what makes the transporter capable of "transporting" molecules between the synapse and the axon.)
  2. The transporter now has the correct configuration to attract and bind cytoplasmic serotonin inside the axon.
  3. The bound serotonin is then transported out of the presynaptic cell, and when the transporter changes configuration again, the serotonin falls off into the synapse.
  4. The transporter is now in the correct configuration to attract more MDMA in the synapse, and the whole process is repeated.

Remember, serotonin is produced inside the axon (through the conversion of 5-htp), and under normal circumstances it enters the vesicles, which release it, over time, into the synapse. The reuptake transporters then bring some of the serotonin back into the axon, where it enters the vesicles again and is recycled. On MDMA, however, most of the serotonin enters the synapse directly through the reuptake transporters (in the opposite direction from what is normal).

So now let's go back to a previous slide and look at your brain on ecstasy again.

Ecstasy Health and Safety