E for Ecstasy by Nicholas Saunders
Appendix 1: Reference Section

71 Assessing Neurotoxicity of Drugs of Abuse, by Dr. James O'Callaghan, NIDA monograph 1993

Dr. O'Callaghan was contracted to do some research to establish a method of assessing neurotoxicity - this was a $750,000 project over 3 years. He says that the term neurotoxicity has no precise meaning, but he is taking it to imply that physical damage has been done to the brain which affects its function.

He found that, with rats, "even when we increased the methamphetamine dosage to as much as 150mg/kg, twice daily for two days, we failed to see marked increases in Glial Fibrillary Acidic Protein (GFAP) at time points ranging from 2 to 9 days post dosing". Though "as little as a single administration of 20mg/kg to the rat results in long-lasting decreases in 5HT levels" he found that 30mg/kg MDMA twice daily for 7 days did not cause an increase in GFAP in the cortex, striatum and hippocampus although there was a decrease in 5HT. ". . . MDMA dosage regimen sufficient to produce a large and long-lasting decrease in 5HT was not sufficient to induce an astrocyte reaction characteristic of neural injury". When he increased the dose to 75-150 mg twice daily for two days, MDMA "produced a dose-dependent increase in the levels of GFAP in cortex and striatum at 2 days post dosing".

"Evidence for MDMA-induced neural damage . . . was not necessarily linked to . . . decreases in levels of 5HT".

O'Callaghan established Reactive Gliosis, a more direct and reliable method of testing for neurotoxicity. He also found that a method called silver staining produced reliable results.

[The relevant conclusion is that previous work on MDMA gave false results by assuming that damage was caused by a decrease in 5HT or serotonin. Extremely large doses, equivalent to someone taking 50 Es twice daily, did cause damage.]