(from ) A solution of 0.75 g crystalline free-base MDOH in a few mL MeOH was treated with a solution of 0.4 g sodium cyanoborohydride in 10 mL MeOH, and there was then added 2 mL of 35% formaldehyde. The stirred reaction mixture was kept at a neutral pH with the occasional addition of HCl. After several days (when additional acid was no longer required) the excess solvent was removed under vacuum, and the residue poured into dilute H₂SO₄. This was washed with 2×75 mL CH₂Cl₂ and then, following the addition of base, this was extracted with 3×75 mL CH₂Cl₂. Removal of the solvent from the pooled extracts gave a viscous oil residue of 0.53 g. The free-base product from these preparations was distilled at 110–120 °C at 0.2 mm/Hg to give the N-hydroxy-N-methyl product as a white oil. An alternate methylation procedure used a solution of MDOH in a 4:1 MeOH/acetic acid solution containing formaldehyde which was reduced with sodium borohydride at dry ice temperatures. Its work-up is identical to that involving sodium cyanoborohydride.

The distilled product was dissolved in an equal volume of MeOH, and treated with a half-equivalent of oxalic acid dihydrate, dissolved in 10 volumes of MeOH. This combination gave the slow deposition of crystals of the full oxalate salt (one acid, two bases) as a white crystalline product. The mp of the crude salt was in the 130–150 °C range, and after recrystallization from CH₃CN, N-hydroxy-N-methyl-3,4-methylenedioxyamphetamine oxalate (FLEA) had a mp of 146–147 °C.

(with 110 mg) “We found this very similar to , but perhaps slightly slower. I plateau’d at 2:30 hours and had a very gradual descent. My friend had a marvelous and private ‘cone of silence’ that was to him unique to MDMA or to . Teeth problems were minor, and the descent from the top of the experience showed less interactive, and more contemplative action, than with MDMA. Very similar to MDMA, but with its own character.”

(with 110 mg) “The onset was at about a half-hour. The come-on was more gradual and much easier than with , and it seemed to be more head than body oriented. I had about two hours of very complex and personal self-evaluation, and I am not at peace in putting all of it down here in writing. Overall I like it, and I would be interested to see if there’s a difference in conjunction with MDMA. Thanks very much.”

(with 110 mg + 35 mg) “I saw my onset at 20 minutes, and it was subtle, and very pleasant, and had a mild amphetamine-like elevation for me (body lightness, cognitive functions seemed clear and clean, heightened visual awareness and with some enhancement of color). It seemed as if I were on the fringe of -like visual changes, but that never materialized. The affect was very good, communicative, friendly, accepting, but without the profound emotional bonding of . The following day felt very much like a post-LSD day; we felt great. The body was light, energy good, emotions high, several insights throughout the day, interactions clear and open—a magnificent gift of a day. I started a menstrual period the day of the experience and it lasted 6 to 7 days; all of this was a couple of weeks early. I have a very favorable impression of FLEA although the body penalty seems high.”

And from the scientific point of view, it lends more weight to a hypothesis that just might be a tremendous research tool in pharmacology. I first observed the intimate connection between an amine and a hydroxylamine with the discovery that N-hydroxy-MDA () was equipotent and of virtually identical activity to the non-hydroxylated counterpart (). And I have speculated in the recipe for MDOH about the possible biological interconversions of these kinds of compounds. And here, the simple addition of a hydroxyl group to the amine nitrogen atom of produces a new drug that is in most of its properties identical to MDMA. The concept has been extended to , , and , where each of these three active compounds was structurally modified in exactly this way, by the addition of a hydroxyl group to the amine nitrogen atom. The results, , and were themselves all active, and compared very closely with their non-hydroxylated prototypes.

Just how general might this concept be, that an N-hydroxyl analog of an active amine shall be of similar action and duration as the parent drug? What if it really were a generality! What havoc it would wreak in the pharmaceutical industry! If I could patent the concept, then I would be able to make parallel best sellers to all of the primary and secondary amines out there in the industry. Perhaps 90% of all the commercially available drugs that are concerned with the human mental state are amines. And a goodly number of these are primary or secondary amines. And each and every one of these could be converted to its N-hydroxyl analogue, effectively by-passing the patent protection that the originating corporation so carefully crafted. An example, just for fun. A run-away best seller right now is an antidepressant called fluoxetine, with the trade name Prozac. I will make a small wager that if I were to synthesize and taste N-hydroxy-N-methyl-3-phenyl-3-((α,α,α-trifluoro-p-tolyl)oxy)propylamine, I would find it to be an active antidepressant. Remember, Mr. Eli Lilly and Company; you read about it first, right here!

Of course, I was asked, why call it FLEA? The origin was in a classic bit of poetry. A commonly used code name for was ADAM, and I had tried making several modest modifications of the MDMA structure in the search for another compound that would maintain its particular music without the annoying tooth-grinding and occasional nystagmus, or eye-wiggle, that some users have mentioned. One of these was the 6-methyl homologue which was, with some perverse logic, called MADAM. And, following this pattern, the 6-fluoroanalogue was to be FLADAM. So, with the N-hydroxy analogue, what about HADAM? Which brought to mind the classic description of Adam’s earliest complaint, an infestation of fleas. The poem was short and direct. “Adam had ‘em.” So, in place of HAD ’EM, the term FLEA jumped into being.