8 Incredible Creation Transformations

Psychedelics

Due to the small number of patients involved, conclusions about overall efficacy cannot be drawn, however Phase II trials provide guidance on how to optimally design larger Phase III trials to test the drug’s safety and efficacy. A self-reported measure, in the form of a survey, used by researchers to understand whether a participant had a mystical experience (e.g., after ingesting psychedelics in a study). The conventional version, which has 43 items, was developed by Walter Pahnke and William Richards in the 1960s. A revised version, including 30 items, was validated in 2015 (Barrett et al., 2015) and is often used in contemporary research. Monoamine oxidase inhibitors change the levels of the brain chemicals norepinephrine, serotonin and dopamine called neurotransmitters which act to stabilize mood.

This dose of 5-HTP produced the HTR only in WT mice, and the dose of 5-MeO-DMT induced the greatest HTR in both genotypes. Treating WT mice with 5-HTP led to phosphorylation of Akt at threonine 308, but no Akt phosphorylation was observed in KO mice. 5-MeO-DMT did not lead to Akt phosphorylation in either genotype, but there was no difference in Akt phosphorylation after vehicle treatment in either genotype. These findings suggest that serotonin and 5-MeO-DMT have different abilities to activate Akt, and that serotonin requires β-arrestin-2, whereas 5-MeO-DMT does not.

Serotonin reduced the amplitude of synchronous evoked EPSCs, with an increase in frequency of spontaneous excitatory postsynaptic currents both before and after electrical stimulation. Although late evoked EPSCs were not evident, when 5-HT was washed out and synchronous evoked EPSCs and sEPSCs were returning to normal, late evoked EPSCs began to appear that resembled the asynchronous evoked EPSCs observed after Sr2+ substitution. It was speculated that 5-HT produced a hyperpolarizing effect, mediated through 5-HT1A receptors, which might be masking the 5-HT2A–mediated excitatory late component. As the 5-HT was washed out of the preparation, the 5-HT2A receptor–mediated late component would be unmasked.

Most of these drugs are believed to primarily affect the neurotransmitter serotonin, although many have multiple effects. Ololiuqui's effects are similar to those of LSD, but the drug has many unpleasant side effects including nausea, vomiting, headache, high blood pressure, and drowsiness. Magic mushroomscontain a naturally occurring type of hallucinogen, called psilocybin, which is found in certain fungi. There is a wide variety of hallucinogenic mushrooms, and their legal status is somewhat ambiguous, as they can be found growing wild in many parts of the world. Ololiuqui is a naturally occurring psychedelic that is found in the seeds of the morning glory flower, which grows in Central and South America. Like mescaline, ololiuqui has a long history of use in spiritual rituals among indigenous groups where the plant grows but unlike mescaline, it is not a controlled substance in the U.S. leading some to consider it a free "herbal high."

Although treatment with antidepressants and risperidone did not ameliorate her symptoms, treatment with the antiseizure drug lamotrigine almost completely abolished her visual disturbances (Hermle et al., 2012). Andreasen et al. reported a fatality involving the potent synthetic psychedelic phenethylamine compound 1-(8-bromobenzo[1,2-b; 4,5-b′]difuran-4-yl)-2-aminopropane, known commonly as Bromo-Dragonfly. An 18-year-old woman was found dead after ingesting 1 ml of a “hallucinogenic liquid.” She and her boyfriend had ingested it between 10 and 11 PM on the previous evening and then they both fell asleep. On awakening at 5 AM the next morning, the woman’s boyfriend discovered that she was dead. Autopsy findings 3 days after her death included edema of the lungs, slight edema of the brain, spleen enlargement, irritation of the mucous membrane in the stomach, and ischemic changes in the kidneys.

A herb mixture known as changa employs the ayahuasca vine with DMT-containing herbs to create a smokable form of this powerful hallucinogenic substance. Ayahuasca is a traditional South American entheogen used for the purposes of spiritual healing and connection. Just one cup of ayahuasca has profound psychedelic effects — often leading to ego death, encounters with “other beings,” and profound introspection. The same dose can cause profound hallucinations one day and little to no effects the next. The active ingredients in this mushroom are muscimol and ibotenic acids — which are highly psychoactive.

Based on the work from Aghajanian’s laboratory (Aghajanian and Marek, 1997; Marek and Aghajanian, 1998a), the authors speculated that this activation could result from glutamatergic thalamocortical inputs. Delving more deeply into these mechanistic findings, Marek et al. studied the effect of the selective mGlu2/3 agonist LY and the selective mGlu2/3 antagonist LY on the 5-HT–induced EPSPs and electrically evoked EPSPs in pyramidal cells from layer V in the rat mPFC. They also examined the effect of these two ligands on the effects of DOI, reporting that the mGlu2/3 antagonist LY enhanced the frequency and amplitude of Psychedelic 5-HT–induced EPSCs by 30%–65% and 12%–21%, respectively. The mGlu2/3 agonist LY was equipotent in suppressing both 5-HT–induced EPSCs and DOI-enhanced electrically evoked late EPSPs. Their findings were consistent with the hypothesis that mGlu2/3 receptors function as inhibitory autoreceptors in cortical glutamatergic terminals that are positively regulated by activation of 5-HT2A receptors. Using autoradiography, these authors further demonstrated that the highest density of mGlu2/3 receptor binding in the mPFC is expressed in cortical layers I and Va, in a laminar distribution similar to 5-HT2A receptor expression.

Natural psychedelic compounds have been integrated with human culture for thousands of years for spiritual healing, divination, and sacrament. A dissociative is a substance that disconnects you from your reality — often creating a completely different reality. Most of the substances on this list can be classified as psychedelic, and even some of the other categories start out as psychedelic at lower doses. Other well-known hallucinogens include psilocybin, which occurs naturally in certain wild mushrooms, commonly known as magic mushrooms, or shrooms, and mescaline, which is found in the peyote cactus in Mexico and the Southwest United States. The flashbacks appear to come out of nowhere, and individuals are totally surprised by them.

Psychedelic soul was pioneered by Sly and the Family Stone with songs like ""I Want to Take You Higher" , and The Temptations with "Cloud Nine", "Runaway Child, Running Wild" and "Psychedelic Shack" . The term "chillwave" was coined in July 2009 on the Hipster Runoff blog by Carles (the pseudonym used by the blog's author) on his accompanying "blog radio" show of the same name. In August 2009, "hypnagogic pop" was coined by journalist David Keenan to refer to a developing trend of 2000s lo-fi and post-noise music in which artists from varied backgrounds began to engage with elements of cultural nostalgia, childhood memory, and outdated recording technology. The introduction of the Controlled Substances Act in 1970 saw psychedelics research slow to a trickle as government-sanctioned research ceased, and the compounds became tarred by the War on Drugs.

The guidelines they outline have certain parallels with ritual uses of hallucinogens by older indigenous cultures. In particular, Johnson et al. cite the need for structured use and restrictions on use, including the need for guidance and appreciation of the powerful psychologic effects of hallucinogens . Psychedelic administration in humans results in a unique profile of effects and potential adverse reactions that need to be appropriately addressed to maximize safety. The primary safety concerns with psychedelics are largely psychologic rather than physiologic in nature.