2,5-Dimethoxy-4-trifluoromethylamphetamine (DOTFM) is a psychedelic drug of the phenethylamine, amphetamine, and DOx (where 'x' indicates a 4-substitution on the phenyl group of 2,5-dimethoxyamphetamine) families. It was first synthesized in 1994 by a team at Purdue University led by David E. Nichols.[3] DOTFM is the α-methylated analogue of 2C-TFM. It is the most potent DOx psychedelic.[1][2]
According to Daniel Trachsel, DOTFM is active as a psychedelic in humans at doses of 0.3 to 1 mg (300–1,000 μg) and its duration is not listed.[1][2] It is the most potent psychedelic of the DOx family, followed by DOB (dose range 1–3 mg).[1][2]
DOTFM acts as an agonist at the serotonin 5-HT2A and 5-HT2C receptors.[3] In drug discrimination tests in rats, DOTFM fully substituted for LSD and was slightly more potent than DOI.[3] In addition, (R)-DOTFM robustly induces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, with equivalent potency as (R)-DOI.[4] The drug is around twice as potent as 2C-TFM in animal studies.
In contrast to (R)-DOI, which has extraordinarily potent serotonin 5-HT2A receptor-mediated anti-inflammatory effects,[5][6] DOTFM shows no anti-inflammatory effects.[7] The differences between the drugs in this regard appear to be due to differences in functional selectivity at the serotonin 5-HT2A receptor.[7][4]
The effects of (R)-DOTFM were examined in the head-twitch response (HTR) assay. (R)-DOTFM produced a strong HTR with a potent ED 50 of 0.60 μmol/kg. These values are equivalent to (R)-DOI, as previously determined.