The drug has been found to substitute for DOM and hence to produce hallucinogen-like effects in animal drug discrimination tests.[1][5] However, it has greatly reduced hallucinogenic potential in terms of the head-twitch response, a behavioral proxy of psychedelic effects, compared to 5-MeO-DMT.[2][3][4] It has even been described as "non-hallucinogenic" in at least one publication.[6] Conversely, 6-MeO-isoDMT has comparable psychoplastogenic potency and effects compared to 5-MeO-DMT.[2][3] These effects are blocked by the serotonin 5-HT2A receptor antagonistketanserin.[3][4] Certain analogues of 6-MeO-isoDMT, like isoDMT, 5-MeO-isoDMT, and AAZ-A-154 (DLX-001; (R)-5-MeO-α-methyl-isoDMT), produce no head-twitch response at all and hence appear to be fully non-hallucinogenic, similarly to 6-MeO-DMT.[1][3][4][5] However, like 6-MeO-isoDMT, they retain potent psychoplastogenic effects.[1][3][4]
6-MeO-isoDMT was first described in the scientific literature by 1984.[5] It was subsequently further characterized in 2020.[3][4] Confusingly, the drug has been referred to as "5-MeO-isoDMT" (or rather "5-OMe-isoDMT") in some publications.[7]
^ abcdDuan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chem Rev. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID38033123.
^ abcdOlson DE (April 2021). "The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects". ACS Pharmacol Transl Sci. 4 (2): 563–567. doi:10.1021/acsptsci.0c00192. PMC8033607. PMID33861218. [6-MeO-isoDMT] exhibits significantly reduced hallucinogenic potential, as measured by the mouse head-twitch response (HTR) assay, while retaining psychoplastogenic potency comparable to its hallucinogenic congener (Figure 1).31 Because 6-MeO-isoDMT is at least equipotent to 5-MeO-DMT with respect to its ability to promote neural plasticity, it cannot simply be viewed as a less potent hallucinogen. In fact, many of the nonhallucinogenic analogues of psychedelics that our group has developed will not produce hallucinogenic behavioral responses in rodents even at extremely high doses. [...] Figure 1. Hallucinogenic and psychoplastogenic effects can be decoupled through careful chemical design. [...]
^ abcdGlennon RA, Jacyno JM, Young R, McKenney JD, Nelson D (January 1984). "Synthesis and evaluation of a novel series of N,N-dimethylisotryptamines". J Med Chem. 27 (1): 41–45. doi:10.1021/jm00367a008. PMID6581313.
^Langlitz, Nicolas (2024). "Psychedelic innovations and the crisis of psychopharmacology". BioSocieties. 19 (1): 37–58. doi:10.1057/s41292-022-00294-4. ISSN1745-8552. [...] David Olson's laboratory [...] developed the psychedelic 5-Meo-DMT into the supposedly nonpsychedelic 6-Meo-isoDMT, which enhanced neuroplasticity without inducing a head-twitch response in mice. [...] But, since no self-experimental reports on how drugs like 6-Meo-isoDMT [...] affect the human mind have been published and preclinical human trials are still far of, it is not certain whether these drugs are actually free of psychedelic effects, and if they would be clinically efficacious.
^Glennon RA, Young R (5 August 2011). "Role of stereochemistry in drug discrimination studies". In Glennon RA, Young R (eds.). Drug Discrimination: Applications to Medicinal Chemistry and Drug Studies. Wiley. pp. 129–161. doi:10.1002/9781118023150. ISBN978-0-470-43352-2.
