Neuroprotective Antioxidants Can Reduce MDMA Tolerance in Rats

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Why is this interesting?[edit]

If tolerance is correlated to "losing the magic", then using neuroprotective measures (limiting dose amount and pre-loading with supplements) may prevent or reduce the risk of "losing the magic".

Am I at risk of "losing the magic"?[edit]

We don't have conclusive evidence. The below quote from Ann Shulgin ("American author and the widow of chemist Alexander Shulgin", Alexander Shulgin "is credited with introducing MDMA (ecstasy) to psychologists in the late 1970s") provides anecdotal information.

Ann Shulgin:

The only thing that has happened with everyone I know who has used MDMA a great deal is that if they used it more than 4 times a year, they developed a tolerance, and after a few years, it begins to not work for them.

Why is avoiding "losing the magic" important?[edit]

By 2021 MAPS hopes to have MDMA approved by the FDA for treatment of PTSD. After that, you may one day step into a couples counseling session and take MDMA with your partner to strengthen your marriage, or to repair a relationship with your child.

If you've "lost the magic" of MDMA by then you may be forever unable to use a vital treatment method.

Ascorbic acid (vitamin C) prevents MDMA tolerance in rats[edit]

Effect of ascorbic acid in combination with a neurotoxic regimen of MDMA on the subsequent MDMA-induced increase in the extracellular concentration of 5-HT in the striatum.
Impact of prior-week regimen on MDMA behavioral effects from a new MDMA dose.

Key takeaway:

"The concomitant administration of ascorbic acid with the neurotoxic regimen of MDMA prevented the diminished neurochemical and behavioral responses to a subsequent injection of MDMA."


"Rats were housed two per cage at 22–24°C and randomly assigned to one of four groups that received either vehicle, ascorbic acid (100 mg/kg, i.p. every 2 h for a total of 5 injections), MDMA (10 mg/kg, i.p. every 2 h for a total of 4 injections), or a combination of both MDMA and ascorbic acid, in which ascorbic acid was given 1 h before each MDMA injection and 1 h after the last MDMA injection. The neurochemical, behavioral, and thermal responses to a subsequent injection of MDMA were assessed in separate groups of rats 1 week after drug treatment."

Ascorbic Acid Prevents 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Hydroxyl Radical Formation and the Behavioral and Neurochemical Consequences of the Depletion of Brain 5-HT (2001)