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Each α1 adrenergic receptor type was extensively coexpressed with 5-HT2A receptors, indicating a convergence of excitatory noradrenergic and serotonergic signals in the same PFC neurons. The different α1 adrenergic receptors also were expressed in a high proportion of GABAergic interneurons, similar to that seen in pyramidal neurons (69%–74% in superficial layers; 52%–73% in deep layers). 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. The reticular nucleus is of particular interest here because it is thought to serve as a sort of gate for processing signals to the cortex.

Sunness described a 15-year-old female patient with a 2-year history of afterimages and photophobia after a history of drug use that included LSD, marijuana, and other illicit drugs. Although the author connected her visual problems with her prior LSD use, it is not at all clear from the report that her LSD use was the cause of her visual problem. Balíková reports a fatal and nonfatal overdose after ingestion of the psychedelic phenethylamine 2,5-dimethoxy-4-bromoamphetamine by two male individuals. Gas chromatography–mass spectrometry was used to detect the presence of DOB in both gastric and urine samples of the two men. Although one subject survived, the other suffered convulsions and metabolic acidosis and died 6 days after admission. Important examples of these substances include a substance used in ancient India known as Soma, which was highly revered and is frequently mentioned in the Rigveda, with numerous Vedic hymns written in praise of Soma .

On the basis of favorable early results, ongoing research is examining proposed psychedelic therapies for conditions including major depressive disorder, and anxiety and depression linked to terminal illness. The United States Food and Drug Administration has granted "breakthrough therapy" status, which expedites the assessment of promising drug therapies for potential approval, to psilocybin therapy for treatment-resistant depression and major depressive disorder. In research published last year, Kwan used two-photon microscopy to show that a single dose of psilocybin increased Psychedelics the number of neuronal connections in a mouse brain by about 10%. That finding generated a number of follow-up questions – why are new neuronal connections being created, which pathways are strengthened and do these changes underlie psilocybin’s therapeutic effects? – that Kwan is now able to explore after receiving a 2022 One Mind Rising Star Award for Mental Health Research in August. The three-year, $300,000 grant supports early-career scientists in neuroscience, psychiatry and related disciplines who are pursuing high-risk, high-reward research that address mental health.

As the 5-HT was washed out of the preparation, the 5-HT2A receptor–mediated late component would be unmasked. After application of DOI, a mixed 5-HT2A/2C agonist that lacks 5-HT1A effects, the late component was evoked by every stimulus in all tested cells. The authors note that their data with Ca2+ and Sr2+ point to a presynaptic 5-HT2A action, although 5-HT2A receptors are known to be expressed primarily postsynaptically on pyramidal cell apical dendrites. To examine in vivo signaling, Schmid et al. treated mice with either 5-HTP or DOI, and the frontal cortices were dissected 15 minutes after drug treatment, when behavioral responses were maximal.

Although further research is needed, existing results suggest that psychedelics could be effective treatments for certain forms of psychopathology. Proponents believe that the increase in consumption of psychedelics in defiance of the law is likely to result in more widespread legalization and decriminalization of the substances . Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips"). Sometimes, they are called classic hallucinogens, serotonergic hallucinogens, or serotonergic psychedelics, and the term psychedelics is used more broadly to include all hallucinogens; this article uses the narrower definition of psychedelics.

A recent study by Turton et al. reported on the subjective experience of intravenous psilocybin administered during a functional magnetic resonance imaging examination. Fifteen volunteers were administered an intravenous infusion of either placebo or 2 mg psilocybin and were blinded as to whether they would receive placebo or drug for a particular experiment. Subjects completed a visual analog scale rating the intensity of the drug experience at the start of the scan and prior to drug infusion, 5 minutes postinfusion, and 12 minutes postinfusion. All subjects subsequently were interviewed about the drug effects, and interviews were analyzed using interpretative phenomenological analysis, a qualitative method.

This advancement allows the HTR to be used as a fairly rapid high-throughput assay that has eliminated the need for tedious visual scoring by an observer, and it gives reliable, unbiased, and reproducible results. Use of the mouse HTR to study psychedelics has recently been reviewed (Fantegrossi et al., 2008a; Canal and Morgan, 2012; Halberstadt and Geyer, 2013a; Hanks and González-Maeso, 2013). Serotonin regulates amygdalar activity through activation of the 5-HT2 receptor family, which includes the 5-HT2A, 5-HT2B, and 5-HT2C receptors. In the deep nuclei of the amygdala, the 5-HT2A receptor is expressed on both excitatory pyramidal and inhibitory nonpyramidal neurons, potentially playing a crucial role in the formation of emotional memories. In the rat, 100% of pyramidal cells in the deep nuclei express the 5-HT2A receptor, where it is strongly expressed in the apical dendrites, similarly to cortical pyramidal cells, and may induce excitatory synaptic currents.

Rats were randomly injected with either vehicle or the mGlu2/3 agonist LY (0.5 mg/kg, i.p.) 20 minutes prior to DOI (3 mg/kg, s.c.) or vehicle. Pretreatment of Wistar rats with LY (1 mg/kg) attenuated the DOI-induced PPI disruption and reduction of ASR magnitude. Their data are consistent with the notion of functionally antagonistic interactions between 5-HT2A and mGlu2/3 receptors that might regulate sensorimotor gating mechanisms. That is, when LSD was given 30 minutes prior to training the stimulus was, as expected, mediated by activation of the 5-HT2A receptor. However, when LSD was administered 90 minutes prior to training, the cue was found to be mediated by activation of the dopamine D4 receptor (Marona-Lewicka et al., 2005, 2009, 2011; Marona-Lewicka and Nichols, 2007, 2011).