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Psychedelic Definition & Meaning

Sorted populations were processed for RNA extraction and subjected to quantitative RT-PCR for gene expression analysis. Only about 3% of total mPFC cells were activated in response to DOI; after identification, it was found that these activated cells displayed a 10-fold higher expression of 5-HT2A receptors than the nonactivated population. The highest 5-HT2A receptor expression and cellular activation was seen in these cells, which were identified as claustral cells, in which nearly Psychedelic one-half of the neurons were directly activated by DOI. Pazos et al. examined 5-HT2 receptor distribution in the human brain using light microscopic autoradiography with the 5-HT2A antagonist ligand ketanserin. A heterogeneous distribution of 5-HT2 receptor densities was observed, with high expression localized over layers III and V of several cortical areas, including the frontal, parietal, temporal, and occipital lobes, the anterogenual cortex, and the entorhinal area.

Overall, the presence of α1 adrenergic receptors in such a large proportion of pyramidal and GABAergic neurons suggested to the authors that NE can modulate the activity of most PFC output neurons via direct or indirect actions. Thus, activation of 5-HT2A receptors by psychedelics would be expected to modulate dopaminergic activity of VTA cells either directly or indirectly through nondopaminergic neurons, and effect excitatory dopamine release from projections in cortical and limbic structures. In GABAergic interneurons, 5-HT2A mRNA was expressed in 45%–69% of parvalbumin and 61%–87% of calbindin-positive cells. Parvalbumin cells are fast-spiking interneurons with the morphology of chandelier and large basket cells, whereas calbindin cells are nonfast-spiking interneurons with a double-bouquet cell morphology (see Mengod et al., 2015, and references therein).

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One might speculate that the initial phase of pharmacology for LSD involves activation of serotonin 5-HT2A receptors, and that this action leads to a sensitization of dopaminergic systems in the CNS. Then, the intrinsic dopaminergic effects of LSD would become potentiated, leading to a delayed dopamine-mediated action in the effect of LSD. It also seems possible that one of the metabolites of LSD (e.g., 13-hydroxyLSD; see Parli et al., 1978) might be a highly potent dopaminergic agonist; thus far, no one has studied the pharmacology of hydroxylated metabolites of LSD. However, in current-clamp recordings in acute rat PFC slices, Béïque et al. noticed a subpopulation of large neurons in deep layers that was highly sensitive to 5-HT and that responded with strong membrane depolarizations capable of initiating spiking activity. Thus, their results indicated that within the cortex, there is a subpopulation of 5-HT2A–expressing cells that when excited by a 5-HT2A agonist leads to increases in the frequency of sEPSCs in layer V pyramidal neurons. Finally, they note earlier work by Marek and Aghajanian , who showed that μ-opioid agonists abolished the ability of 5-HT to increase sEPSC activity and who also suggested that there was possibly a subcortical source for afferents on which 5-HT2 receptors could induce glutamate release.

Following the late 1960s work of Jimi Hendrix, psychedelia began to have a widespread impact on African American musicians. Black funk artists such as Sly and the Family Stone borrowed techniques from psychedelic rock music, including wah pedals, fuzz boxes, echo chambers, and vocal distorters, as well as elements of blues rock and jazz. In the following years, groups such as Parliament-Funkadelic continued this sensibility, employing synthesizers and rock-oriented guitar work into open-ended funk jams. Producer Norman Whitfield would draw on this sound on popular Motown recordings such as the Temptations' "Cloud Nine" and Marvin Gaye's "I Heard It Through the Grapevine" . Another development of the post-psychedelic era was more freedom with marketing of the artist and their records, such as with album artwork. According to him, post-psychedelic musicians like Brian Eno and Robert Fripp "explicitly advocated" this disconnection between the artist and their work or stardom.

To determine whether these metabolites might be formed and relevant, mice were pretreated with the MAO-A–elective inhibitor clorgyline. After clorgyline administration, the HTR dose-response curve was left-shifted and occurred in β-arrestin-2 KO mice at 5-HTP doses that were ineffective if given alone. When methimazole, an N-methyltransferase inhibitor was preadministered, the number of HTR responses after 5-HTP treatment was decreased in both WT and β-arrestin-2 KO mice, although the inhibitory effect was more marked in the β-arrestin-2 KO mice. The effects of clorgyline and methimazole pretreatment suggest that the HTR after 5-HTP treatment may be due to N-methyltryptamines instead of serotonin itself.

Their results strongly suggest that DOI has a greater effect on temporal discrimination than on light-intensity discrimination. Carter et al. studied perceptual rivalry with low-dose (115 μg/kg) and high-dose (250 μg/kg) psilocybin in 12 healthy human volunteers. Stationary green vertical and horizontal gratings were presented to the subject’s left eye and right eye, respectively. Vertical and horizontal gratings were presented alternately, in rapid succession at 120 Hz. Subjects reported a dominance of vertical gratings by pressing one computer key, and by pressing another when they experienced a dominance of horizontal gratings. Psilocybin dose-dependently increased binocular rivalry phase duration in a manner reflecting subjective changes in state of consciousness, as assessed with the 5D-ASC rating scale developed by Dittrich .

Their findings parallel an earlier study by Gewirtz and Marek , who also had shown that a 30-minute pretreatment with the mGlu2/3 agonist LY suppressed 5.0 mg/kg DOI–induced HTR in the mouse. In addition, these researchers also demonstrated that the mGlu2/3 antagonist LY enhanced the frequency of the DOI-induced HTR. These studies all show that a functional mGlu2/3 receptor system is required for expression of the mouse HTR. An earlier section discussed in more detail what is currently known about the role of glutamate in the actions of psychedelics.