Ariadne (drug)

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin reported human tests of Ariadne at doses of up to 32 mg orally, finding that it produced "the alert of a psychedelic, with none of the rest of the package".^[1] Very little published data exists about the human pharmacology of Ariadne apart from Shulgin's limited testing; unpublished human trials reportedly observed some psychoactive effects, but no hallucinogenic effects.^[9][5] Ariadne is one of Shulgin's "ten classic ladies", a series of methylated DOM derivatives.^[1][10]

In his book The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds, Shulgin described (R)-Ariadne as increasing mental alertness and producing feelings of well-being at doses of 25 to 50 mg orally.^[2] It was claimed to improve symptoms of manic depression in psychotic individuals at doses of 50 to 100 mg orally and to improve symptoms of Parkinson's disease at a dosage of 100 mg/day orally.^[2][5] Doses of up to 300 mg resulted in an altered state of consciousness but still no psychedelic effects.^[5][2] For comparison, DOM shows psychoactive sub-hallucinogenic effects at doses of 1 to 3 mg orally and psychedelic effects at doses of more than 3 mg orally.^[5]

The effects of Ariadne have been said to have a duration of 2 to 5 hours.^[4]

Another related drug with similar psychoactive effects as Ariadne is thiobuscaline.^[1]

Ariadne, as the (R)- enantiomer, is active at doses as low as 25 mg and was tested in clinical trials at doses of 50 to 100 mg.^[5] Doses as high as 300 mg have been assessed, more than 10 times higher than the minimum reported active dose.^[5] No psychedelic effects occurred at this or lower doses, but therapeutic effects were observed.^[5]

Hamilton Morris has described the combination of (R)-Ariadne and fluoxetine as unexpectedly strongly potentiating the effects and duration of (R)-Ariadne such that (R)-Ariadne became potently psychedelic in its effects and lasted over 24 hours.^[11] Morris assumed that this was due to some kind of enzyme inhibition caused by fluoxetine, for instance cytochrome P450 inhibition.^[11]

Ariadne, also known as 4-methyl-2,5-dimethoxy-α-ethylphenethylamine, is a substituted phenethylamine and amphetamine derivative.^[1][2] It is the analogue of 2,5-dimethoxy-4-methylamphetamine (DOM) in which the α-methyl group has been replaced with an α-ethyl group and is the analogue of 2,5-dimethoxy-4-methylphenethylamine (2C-D) with an ethyl group substituted at the α carbon.^[5][1][2]

Ariadne was first synthesized by Alexander Shulgin in 1968 and he discovered its psychoactive effects in 1969.^[8][5][1] He introduced it to Bristol Laboratories and they began clinical trials of the drug for various medical uses in 1974.^{[8][5][1][19]} Shulgin disclosed an anecdote in which he had convinced the board of directors of the company to try it themselves before initiating clinical trials.^[6] The drug was evaluated as an antidepressant, for increasing mental alertness in geriatric individuals, treating Parkinson's disease, and treating psychosis and manic depression.^[2][5] The tentative commercial name of Ariadne was Dimoxamine.^[2] (R)-Ariadne was said to have completed phase 2 clinical trials and to have reached phase 3 trials, but the actual clinical data were never disclosed and further development was halted due to strategic economic reasons.^[8][5] However, according to journalist Hamilton Morris, the United States Central Intelligence Agency (CIA) may have had involvement in the discontinuation of Ariadne's development.^[20]

• 4C (psychedelics)
• Non-hallucinogenic 5-HT_2A receptor agonist
• Stimulant § Serotonin 5-HT_2A receptor agonists
• Motivation-enhancing drug § Serotonin 5-HT_2A receptor agonists
• 5C-D (5C-DOM; α-propyl-2C-D)
• ASR-2001 (2CB-5PrO)
• DOET
• N-Methyl-DOET
• Thiobuscaline