Dopamine (D4) receptor activation comparison of LSD and DOI - Brain's Trigger for LSD

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Article Published: 2008

Nice, purely pharmacological, study confronting the differences between phenethylamines and LSD. They suggest that the introspective cue that triggers the LSD psychedelic experience is mediated and modulated by activation of the dopamine D4 receptor. Interestingly, however, the DOI psychedelic experience was not found to be triggered by the same receptor. They suggest that a different cue is likely responsible for enhancement of the 5-HT2a current (something like the magnitude of the psychedelic experience).
D4 receptors are known to be negatively coupled with cAMP. Atypical antipsychotics like clozapine have high affinities for this receptor as well as the 5-HT2a and D1 receptors. Such drugs only partially inhibited the onset of the DOI experience, while they dose-dependently terminated the onset of the LSD.

This study presents another mechanism by which LSD can be differentiated from most of the phenethylamine family.