Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice.
The Journal of pharmacology and experimental therapeutics December 1, 2014 Douglas A Smith, Jessica M Bailey, Diarria Williams et al. 31 citations
Tolerance developed to the head twitch response (HTR) elicited by daily administration of the phenethylamine-derived hallucinogens DOI and 2C-T-7 in mice, but not to the tryptamine-derived drugs DPT and DIPT. Tolerance to DOI was insurmountable by increasing dose, and cross-tolerance to 2C-T-7 and DPT was also insurmountable in DOI-tolerant mice. These results suggest that phenethylamine-derived 5-HT2A agonists may be limited for chronic therapeutic use by rapid tolerance development that persists even when switching to a different structural class. Tryptamine-derived hallucinogens may have a reduced tolerance potential and could be more suitable for long-term administration.