Diethyltryptamine
Diethyltryptamine
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Diethyltryptamine

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Diethyltryptamine

Diethyltryptamine (DET), also known as N,N-diethyltryptamine or T-9, is a psychedelic drug of the tryptamine family closely related to dimethyltryptamine (DMT). It is taken orally, but can also be used by parenteral routes.

The drug acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A receptor among others. It has not been found to occur endogenously. DMT is a close structural homologue of DMT and dipropyltryptamine (DPT). Other analogues of DET include 4-HO-DET (ethocin), ethocybin (4-PO-DET), and 5-MeO-DET.

DET was first synthesized in 1956 by Stephen Szára and subsequently described in material published in 1957. More systematic studies were reported later by Szára and colleagues and independently by Böszörményi and colleagues.

According to Alexander Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved), DET's dose range is 50 to 100 mg orally and its duration is 2 to 4 hours. It was also assessed at oral doses of 44 to 400 mg, though 150 mg was described as "a little too much" and the 400 mg dose was simply described as "too high". Its onset is 40 minutes to more than 1 hour and peak effects occurred at just over 1 hour. In addition to oral administration, DET was assessed by smoking at doses of 40 to 90 mg, by subcutaneous injection at a dose of 40 mg, by intramuscular injection at a dose of 60 mg, and by intravenous injection at a dose of 60 mg. By these routes, it has a faster onset than when taken orally. The drug is said to taste terrible when smoked, like "burning plastic". DET was initially assumed to be inactive orally similarly to dimethyltryptamine (DMT), but this proved to be incorrect.

The effects of DET have been reported to include similar "illusions" and hallucinations" as DMT, a wave-like time course of effects, closed-eye visuals, open-eye visuals, auditory and olfactory hallucinations, synesthesia, feeling like in another world, cosmic thinking, mystical and philosophical feelings, dream-like mysteriousness of objects, greater emotional significance of objects, peoples' faces seeming "mask-like", enhanced appreciation of art, architecture, and music, feeling like a small child perceiving the world and discovering it anew, time dilation, enjoyment and euphoria, increased empathy, and emotional insights. Additional effects included feeling stoned, alcohol-like intoxication, drifting of thoughts, and difficulty concentrating and cognitive impairment. The effects of the drug were described as highly dependent on set and setting, with prominent negative reactions in unfavorable environments or with too high of doses, including unpleasantness, anxiety, paranoia, social withdrawal, and unwillingness to take the drug again, among others. Physical effects of DET included DMT-like vegetative or autonomic symptoms, pupil dilation, sweating, slight burning and numbness of hands and feet, dizziness, vertigo, feeling sick, paleness, shakiness, muscle tremors, athetoid movements, vomiting, feeling of hollowness in the chest, pronounced tachycardia, pressor effects, and other somatic symptoms. Subsequent-day effects included an afterglow, hangover, lassitude, and cognitive fuzziness.

Similarly to other classic psychedelics, DET acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. The drug has been shown to activate Gq-mediated signaling at the serotonin 5-HT2A receptor with Emax higher than 70% and to produce the head-twitch response in rodents which is a behavioral proxy of psychedelic-like effects.

DET is a very weak reversible monoamine oxidase inhibitor (MAOI), with IC50Tooltip half-maximal inhibitory concentration values of 59 μM for serotonin and 5,000 μM for tryptamine as substrates. Injections of 30 mg/kg to rats resulted in 67% reduction of brain MAO-A activity 15 minutes after administration. The substance may also act as a serotonin reuptake inhibitor, with low affinity but moderate potency. It shows no activity as a norepinephrine or dopamine reuptake inhibitor.

DET demonstrates significant resistance to metabolism by monoamine oxidase A (MAO-A) compared to DMT. This may be due to the increased steric bulk of the N-ethyl substituents relative to the respective methyl groups of DMT which results in metabolic stability sufficient for oral activity. This is also true for many other tryptamines with larger nitrogen substituents.

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