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Psychedelic Definition & Meaning

Between 1959 and 1974, a number of studies were reported on the use of LSD to treat children with autism. Typically, after the drug was administered, the children were simply observed and their reactions were recorded in a narrative format. Thus, the resulting data were for the most part qualitative and were presented in a form that was highly subjective, potentially biased by observer expectations, and of unknown reliability and validity. Furthermore, when enthusiastic investigators obtained neutral or negative findings, they often were cast in a more positive light than was warranted. Despite a good number of independent studies, it remains impossible to determine whether LSD had any therapeutic value for children with autism. When judged by today’s standards of randomized controlled trials, or a properly controlled and systematically replicated single-case study, most of the early autism/LSD studies were so flawed as to be little better than anecdotal.

Individuals using psychedelics, pretending to be able to provide benefits to the community would have found it very difficult to fake these qualities convincingly, making deception by shamans much less likely. To gain prestige and maintain authority shamans needed to show charisma and ostensibly display their capacity to enter into contact with supernatural realms and powers, but they also were required to demonstrate to others their specialized knowledge by effectively healing and resolving social conflicts. Hominins developed an egalitarian political system in which interdependence and the availability of lethal weapons (e.g., wooden spears and lithic points) made possible group control of leaders; consequently, group success came to depend greatly on the ability of leaders to persuade (Gintis et al., 2015). Undermining the ability of dominants to exploit others helped our ancestors replace hierarchical social dominance with a more equitable sociopolitical structure based on knowledge, conflict resolution, generosity, and status leveling mechanisms .

Companies are also looking to improve the timing, intensity, and duration of the psychedelic experience. Psychedelics can take an hour or two to begin working, and once they do the experience lingers; about 10 hours for LSD trips and six for psilocybin. And because the psychedelic experience can be intense, those with a history of psychosis or schizophrenia are generally excluded from clinical trials on psychedelic drugs. In response to a request for information on research efforts into the use of psychoactive drugs in treating mental illness, NIH and FDA acknowledged some potential therapeutic uses of these substances, as well as the need for additional research.

The head twitch in mice is operationally defined as a rapid rhythmic paroxysmal side-to-side rotational head movement that occurs after administration of serotonergic hallucinogens . Although it has most often been visually scored in real time, or scored from videos taken during the drug effect, Halberstadt and Geyer recently developed an automated and relatively rapid method for assessing the mouse HTR. They first analyzed the kinematics of head twitches using high-speed video recordings, reporting that the HTR was highly rhythmic, occurring within a specific frequency range (mean head movement frequency of 90.3 Hz). On the basis of this analysis, they developed a system using a head-mounted magnet and a magnetometer coil, followed by extensive validation using video analysis and an observer blind to the treatment.

As a “novelty detector,” the LC has been viewed as enhancing the signal to noise ratio in modulating postsynaptic activity throughout the brain; suppression of basal activity concomitantly with enhanced responding to external sensory stimuli would amplify this effect . Thus, after application of a psychedelic, one might speculate that sensory events that would be perceived as ordinary might instead be perceived as having increased novelty. Indeed, it is a well known anecdote that under the influence of psychedelics, one may perceive very ordinary objects as new or novel. Nordstrom et al. used N-methylspiperone PET analysis in four human subjects with the 5-HT2A receptor inverse agonist ACP-103 [N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide]. Displacement of NMS was about half-maximal after a 5-mg dose and near maximal displacement after 10- to 20-mg doses. Nevertheless, Miner et al. did identify a significant 24% fraction of 5-HT2A receptor immunoreactive profiles that were presynaptic.

For example, PKC phosphorylation of serine residue S291 in the 5-HT2A receptor is also thought to play a role in modulation of receptor signaling. Using five different ligands that activate the 5-HT2A receptor, Raote et al. showed that different biochemical pathways are involved in receptor trafficking. These investigators used the fluorescence of rat 5-HT2A enhanced green fluorescent protein to follow receptor internalization. This transcript was stably transfected into HEK-293 cells to generate what the authors designated as an SB1 cell population.

For DOB-tolerant animals, both 5-HT2A and glutamate binding were highly correlated with the number of shaking behaviors observed on the last day of repeated DOB treatment, whereas only glutamate binding correlated with shaking behavior for LSD-tolerant animals. Repeated treatment of rats with DOM also led to rapid desensitization and downregulation of central 5-HT2 receptors (Leysen et al., 1989), with a significant reduction in the total number of cortical 5-HT2 sites after only two drug treatments (2.5 mg/kg s.c. every 8 hours). Smith et al. similarly found that tolerance to the discriminative stimulus effect of DOI in rats correlated with downregulation of 5-HT2A receptors, but they observed no change in density of 5-HT2C receptors.