4-Fluoro-DMT

4-Fluoro-DMT (or 4-F-DMT), also known as 4-fluoro-N,N-dimethyltryptamine, is a serotonin receptor agonist of the tryptamine family and a close analogue of psilocin (4-HO-DMT) and dimethyltryptamine (DMT). It is a modestly selective serotonin 5-HT_2C receptor full agonist and doesn't appear to produce psychedelic-like effects in animals but instead produces antiobsessional-like effects. It has been encountered online as a novel designer drug, with claimed mild entactogen-like effects.

According to an unverified online anecdotal report, 4-fluoro-DMT is said to produce mild entactogen-like effects, such as enhanced sociability, empathy, and communication and a feeling of peace, with few or no psychedelic effects. It was described as being like a lighter version of MDMA and being like an LSD or psilocybin afterglow. However, there was also said to be a slight feeling of "psychedelic dissociation". The drug is said to be active at doses of 10 to 30 mg sublingually and 15 mg by inhalation. Its onset is said to be 40 minutes and its duration is said to be 2 to 3 hours.

4-Fluoro-DMT's affinity (K_i) for the serotonin 5-HT_1A receptor was 135 nM. This can be compared to psilocin's affinity of 378 nM and serotonin's affinity of 1.7 nM. In another study, 4-F-DMT showed affinities (K_i) of 335 nM for the serotonin 5-HT_2A receptor, 8.39 nM for the serotonin 5-HT_2B receptor, and 82–84 nM for the serotonin 5-HT_2C receptor. Its activational potencies (EC₅₀Tooltip half-maximal effective concentration) and efficacies (E_maxTooltip maximal efficacy) were 949 nM (49%) at the serotonin 5-HT_2A receptor, 1,180 nM (38%) at the serotonin 5-HT_2B receptor, and 99 nM (93%) at the serotonin 5-HT_2C receptor. 4-F-DMT showed dramatically less potent EC₅₀ values at the serotonin 5-HT_2A and 5-HT_2B receptors compared to psilocin (40- and 20-fold less potent), whereas its potency was less markedly reduced at the serotonin 5-HT_2C receptor (about 3-fold less potent). Hence, whereas psilocin is a balanced agonist of the serotonin 5-HT₂ receptors, 4-F-DMT is a selective serotonin 5-HT_2C receptor agonist with about 10-fold preference for activation of this receptor over the serotonin 5-HT_2A and 5-HT_2B receptors. Moreover, whereas psilocin was a partial agonist of the serotonin 5-HT_2C receptor (E_max = 51%), 4-F-DMT had higher efficacy and was a full agonist (E_max = 93%).

4-F-DMT produced partial generalization (0–56%) to LSD in animal drug discrimination tests, but this was not statistically significant and an ED₅₀Tooltip median effective dose was not calculated. It also failed to substitute for DOI in drug discrimination tests (10–33%). Conversely, psilocin produced full generalization at much lower doses. Hence, 4-F-DMT may not be hallucinogenic in humans. On the other hand, the drug was dose-dependently and strongly active in producing antiobsessional-like effects in an animal model of obsessive–compulsive disorder (OCD) (specifically inhibition of serotonin-induced scratching behavior), an effect that it is thought may be mediated by serotonin 5-HT_2C receptor agonism.

4-F-DMT is more lipophilic than psilocin (4-HO-DMT) due to lacking its hydrophilic hydroxyl group, and hence 4-F-DMT might cross the blood–brain barrier more readily than psilocin.

The chemical synthesis of 4-fluoro-DMT has been described.

Analogues of 4-F-DMT include dimethyltryptamine (DMT), psilocin (4-HO-DMT), 4-methyl-DMT, and 4-MeO-DMT, among others. Derivatives of 4-F-DMT such as 4-fluoro-5-methoxy-DMT (4-F-5-MeO-DMT) have also been synthesized and studied.

4-F-DMT was first synthesized and described in the scientific literature by 1964. It was encountered online as a novel designer drug in 2025.