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Psychedelic Drugs: Types, Uses, and Effects

The ability of the compounds to induce release of stored monoamines from rat brain synaptosomes also was studied. The six phenethylamines were virtually inactive, as was DPT, having no effect at 10−4 M of the drug. These results seem to suggest that, in general, effects of psychedelics on monoamine reuptake and release may not be relevant and that direct receptor actions remain most important. Schmid and Bohn followed up on this in vivo finding by studying Akt phosphorylation in primary neuronal cultures from the frontal cortex of WT and β-arrestin-2 KO neonates. Serotonin (1 μM) gave a robust phosphorylation of Akt in WT cortical neurons, but neither N-methylserotonin nor 5-MeO-DMT activated Akt. Pretreatment with M blocked Akt phosphorylation in WT neurons after serotonin treatment, showing that the effects of serotonin were mediated through the 5-HT2A receptor.

Szabo concluded that dimethyltryptamines may serve as important regulators of both innate and adaptive immunity. The most significant limiting factor for survival after liver surgery and transplantation of a partial graft is the ability of the remnant liver to regenerate (Furrer et al., 2011, and references therein). Serotonin, derived from platelets, is thought to be involved in liver regeneration after major tissue loss.

Buchborn et al. concluded that the differential receptor adaptations observed for DOB and LSD, respectively, indicate that tolerance to serotonergic hallucinogens can arise at two levels. That is, if a psychedelic (e.g., LSD) for some reason fails to downregulate 5-HT2A receptors, glutamate receptors might adapt instead and thus prevent cortical overstimulation. These substances do not lead to addiction or dependence and are not considered to be reinforcing (O'Brien, 2001). This is understandable when one realizes that the serotonergic hallucinogens do not have direct effects on brain dopaminergic systems, a pharmacology that appears essential for nearly all drugs that can engender dependence.

The way in which these genes contribute to downstream transcriptional, structural, and functional sequelae of neuronal activation, however, remains poorly understood. Moya et al. compared two homologous series of substituted psychedelic phenethylamines and phenylisopropylamines for signaling at the 5-HT2A receptor through PLC and PLA2 responses. They employed Chinese hamster ovary -FA4 cells stably expressing the human 5-HT2A receptor that had similar maximal responses for inositol phosphate accumulation and AA release in response to serotonin. Relative efficacies for AA release and IP accumulation varied within the series, and the substituted amphetamines had higher efficacy in both pathways.

Antiwar attitudes and rejection of conventional social norms by adolescents and college students were often perceived by the mainstream culture to be a consequence of drug use; hence, these substances were often believed to be “perverting” the minds of our youth. Furthermore, the outspoken Harvard University professor and firebrand Timothy Leary encouraged young people to “turn on, tune in, and drop out,” essentially coaching them to take drugs, discover their true selves, and abandon convention. Such messages did not play well with the mainstream culture, all while the mass media fanned the flames of public hysteria with greatly exaggerated reports of drug-induced insanity, chromosomal damage, attempts to fly, and so forth. Risks do exist during an unsupervised Psychedelic experience, however; Ira Byock wrote in 2018 in the Journal of Palliative Medicine that psilocybin is safe when administered to a properly screened patient and supervised by a qualified professional with appropriate set and setting.

Although lacking detailed specifics as well as a follow-up, this early report does suggest that psychedelics might acutely improve creativity. More recently, Hasselbalch et al. used altanserin PET to assess cerebral 5-HT2A receptor density in 16 patients with mild cognitive impairment of the amnestic type, compared with 17 age and sex-matched controls. Patients with mild cognitive impairment are considered at increased risk of developing AD, and their inclusion criteria were deliberately aimed at including patients with symptoms of very early AD. Indeed, at 1-year follow-up, six of their patients had progressed clinically and fulfilled AD criteria.

Medical Reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. May et al. discovered indazole-based 5-HT2A agonists with poor CNS activity and solution stability superior to conventional tryptamine-based 5-HT2 agonists such as serotonin and AMS. They identified one compound, 1-(-2-aminopropyl)-1H-indazol-6-ol), with an EC50 of 43 nM and Emax of 89% that lowered intraocular pressure by 33% in conscious ocular hypertensive monkeys. In addition to these reports of LSD treatment, anecdotal accounts of OCD symptom reduction by consumption of Psilocybe mushrooms have also been published (Leonard and Rapoport, 1987; Moreno and Delgado, 1997). Hanes reported on a 27-year-old male patient with body dysmorphic disorder who spent up to 4 hours every day checking his appearance in the mirror. The intensity of his somatic distress markedly improved on occasions when he had ingested psilocybin mushrooms, noting that at those times, when he looked in the mirror, he no longer appeared deformed.