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Psychedelic drug Wikipedia

Tryptamine Psychedelics all inhibited dorsal raphe cell firing (Aghajanian et al., 1970; Aghajanian and Hailgler, 1975; deMontigny and Aghajanian, 1977), leading Aghajanian and Hailgler to hypothesize that this suppressant effect on raphe cell firing might be the underlying basis for the action of psychedelics. The reticular nucleus is known to regulate the flow of information between the thalamus and the cortex and sends inhibitory projections into the thalamus, apparently serving a negative-feedback regulatory role in thalamic function. It has been proposed to serve as a sort of “searchlight” of attention (Crick, 1984; Sherman and Guillery, 1996) and to control elements of signal to noise or the quality of information being sent to the cortex . It is clear that specific ligands interact with the 5-HT2A receptor to activate the PLC and PLA2 pathways to different extents. At the rat 5-HT2A receptor expressed in NIH3T3 cells, for example, LSD, DOB, psilocin, and 5-MeO-DMT have different EC50 values and intrinsic activities in activating the AA and PI turnover pathways (Kurrasch-Orbaugh et al., 2003b).

The authors found a high and significant correlation between the density of frontal cortical 5-HT2A receptors and the elicitation of head bobs for animals given chronic MDL11939 or BOL. Dave et al. reported that systemic administration of DOI to New Zealand white rabbits dose-dependently elicited head movements (vertical down-up head bobs) and body shakes . They reported that head bobs were mediated by 5-HT2A receptor activation, whereas body shakes were mediated by activity at the 5-HT2C receptor.

They propose that “the claustrum serves the function of segregating attention between modalities, enabling us to isolate objects of current priority for attention” (Goll et al., 2015). They draw certain parallels between the claustrum and the thalamus, proposing that both the thalamus and the claustrum have the capacity to focus attention, but at different stages of sensory processing. Milardi et al. used constrained spherical deconvolution tractography to elucidate the complex relationships between the fiber systems in the claustrum. They detected four groups of white matter fibers connecting the claustrum to the cortex and provided a detailed representation of brain areas connected to the claustrum. Although very rare, there have been reports of rhabdomyolysis after ingestion of LSD (Berrens et al., 2010). A newer tryptamine, 5-methoxy-N,N-diisopropyltryptamine (“foxy”) also produced rhabdomyolysis and transient acute renal failure in an otherwise healthy 23-year-old man (Alatrash et al., 2006).

In addition, transgenic mice have been developed with targeted mutations of specific genes, which serve as powerful tools to study mechanisms of drug action. Historically, Hirschhorn and Winter published the first report of a psychedelic producing a discriminative stimulus in rats. Using a 1-minute VI schedule of reinforcement with diluted sweetened condensed milk as the reinforcer, intraperitoneal injections of both LSD and mescaline were shown to produce discriminative stimuli in female rats.

In the rat deep nuclei, 5-HT2A immunoreactivity is seen in both GABAergic interneurons and projection neurons. 5-HT2A receptor immunoreactivity is also observed in every superficial nucleus of the rat amygdala. Although the in vivo functional interaction between 5-HT2A receptors and mGlu2 receptors is now widely accepted, González-Maeso et al. proposed that the 5-HT2A receptor formed a heterodimer with the mGlu2 receptor and identified this complex as a possible site of action for hallucinogenic drugs. They reported that the 5-HT2A and mGlu2 receptors directly interact in recombinant cell lines and are present in the same neuronal cells in culture.