TiHKAL #17 4-HO-DIPT

SYNTHESIS : A solution of 0.50 g 4-acetoxyindole (see under 4-HO-DET for its preparation) in 5 mL Et2O was stirred and cooled to 0 °C with protection from atmospheric moisture. There was then added 0.5 mL oxalyl chloride. The reaction mixture was stirred for an additional 30 min, and the intermediate indoleglyoxyl chloride separated as a yellow crystalline solid but was not isolated. This was treated with a 40% solution of diisopropyl amine in anhydrous Et2O, dropwise, until the pH was 8-9. The reaction was diluted with 100 mL CHCl3 and shaken with 30 mL of a 5% aqueous NaHSO4 followed by 30 mL of a saturated aqueous NaHCO3 solution. After drying over anhydrous MgSO4, the organic solvents were removed under vacuum. The residue was recrystallized from EtOAc / hexane to give 0.33 g (35%) of 4-acetoxyindol-3-yl-N,N-diisopropylglyoxylamide with a mp 204-206 °C. Anal: C,H,N.

To a stirred suspension of 0.25 g LAH in 10 mL anhydrous THF, stirred, under nitrogen and at room temperature, there was added a solution of 0.33 g 4-acetoxyindol-3-yl-N,N-diisopropylglyoxylamide in 10 mL anhydrous THF. This was added dropwise at a rate that maintained the reaction at reflux. When the addition was complete, the reflux was maintained for an additional 15 min and then the reaction was cooled to 40 °C. The excess hydride and the product complex were destroyed by the addition of 0.5 mL EtOAC followed by 1.5 mL H2O. The solids were removed by filtration, the filter cake washed with THF, the filtrate and washings pooled, and the solvents removed under vacuum. The residue was distilled at the KugelRohr and the distillate dissolved in 1 mL MeOH. One equivalent of dilute HCl was added, and the volatiles were removed under vacuum. The solid residue was recrystallized from MeOH/Et2O to give 0.13 g (47%) of 4-hydroxy-N,N-diisopropyltryptamine hydrochloride (4-HO-DIPT) with a mp 263 °C with decomposition. Anal: C,H,N.

QUALITATIVE COMMENTS : (with 10 mg, orally) "I feel it in my legs! Within the hour I have leg tremors, a mild physical awareness for another hour. Mentally, probably nothing."

(with 15 mg, orally) "There was an alerting, noisy and nice, in 30 minutes. I swear I am already there. Nice friendly place. Perhaps some light tension, like a chill, maybe my body temperature response is confused. At the two hour point I am substantially out of the experience. Short, intense experience, basically enjoyable. Another hour and I am back to where I started in every way."

(with 20 mg, orally) "It has a bitter taste. Early signs noted at 15-20 minutes which include mild sensation of central stimulation, 'loosening' of muscles in arms, legs, and neck. Mild distortion of objects and slight color effects, typically 'rainbow halos' around objects. Plateau reached in 20 minutes. Mild elation with relatively simple intellectual musings about the nature of the compound and how one could describe the nature of the state of mind and body caused by this material. 2.0 hours, mild effects. 2.5 hours, nearly normal. Mild but entirely pleasant experience with rather abrupt termination of effects. Could be a good candidate for psychotherapy sessions, certainly good for 'novice' introduction to hallucinogens."

(with 20 mg, orally) "Fifteen minutes, it starts and develops fast -- very nice -- some leg tremor. Thirty minutes, I am already well over a plus 2. Speed of onset is incredible -- I could not drive -- I feel robbed of voluntary action. Forty minutes, this could not get any deeper. Fifty minutes, incredible orgasm. Fifty five minutes, I struggle to put a name to it, just +++ smashed -- with eyes closed very little -- I am somewhat chilled -- no visual, no sensory, this seems like an extreme Aleph-7 beth state as it was described in PIHKAL. One hour ten minutes, Rubenesque fancy -- no sex but back-to-mother cuddly imagery -- removed from physical angles. One hour thirty minutes, go for two very significant pieces of wood for the fireplace -- if all my actions are preprogrammed and I am following commands, then I have no free will -- if the command is 'to have free will', then I obey. Whom? Who? Why obey an undefined, unheard commander? Still +++. Nothing is inventive, all is preprogrammed. One hour forty minutes, back to ++, still very much in the grips of 'lack of self determination.' I could function rationally in the lab, but following 'whose' directions? Is this finally God? Is this a religious experience? One hour fifty minutes, down to +, This has to have been a religious awakening. Two hours, still a little zombie-like, but largely down. Two hours twenty minutes, I am still shaken to my roots by these realizations. Three hours, completely together."

EXTENSIONS AND COMMENTARY : I truly doubt that there is another psychedelic drug, anywhere, that can match this one for speed, for intensity, for brevity, and sensitive to dose, at least one that is active orally. These reports have been taken from different experimenters, but they share some rather consistent features:

Speed: The effects are noted with a quarter hour following ingestion. LSD is one of the few psychedelic drugs that can show its early effects in the first few minutes. This suggests fundal absorption.

Intensity: The second 20 milligram report sounds as if there was some flirting with the magical plus-four transcendental peak experience. I happened to be the subject, and I was impressed.

Brevity: To be on a trip and then to be back pretty much in two hours and really baseline in another hour? Most unusual. If there will ever be an acceptance of drugs such as these, in a psychotherapeutic context, a short duration is of extreme value to both the patient and the therapist.

Sensitivity to dose: There have been a number of trials at and below the 10 milligram bottom, and most have been substantially without activity. And yet, there have been no trials at higher than 20 milligrams, as far as I know. That is a lot of steepness in the dose-response curve.

And similar comments can be made regarding the consistency of physical side-effects. There seemed to be a muscular tremor, and a vague body malaise, that is part of the trip. At least when the psyche got going, the body going got less noticeable.

An interesting sideline. This is the same nitrogen substitution pattern, N,N-diisopropyl, that is present in the rather dramatic sex-enhancer 5-MeO-DIPT. I wonder what might come out of an exploration of this substitution pattern in the world of the phenethylamines? As a rule, most phenethylamines lose their appeal with substitution on the nitrogen atom. But has anyone tried to make an N,N-diisopropyl homologue of MDMA, for example? Or of mescaline? Or of DOM? It would be interesting to explore these areas.

#17. 4-HO-DIPT