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Johns Hopkins Center for Psychedelic and Consciousness Research

They propose that the marked α power decreases observed with psilocybin were likely due to interference with the intrinsic α oscillations of deep-layer pyramidal neurons via stimulation of the 5-HT2A receptor. To test the potential efficacy of R-DOI to treat a human inflammatory disease, the Nichols group (Nau et al., 2015) assessed the effects of R-DOI in a mouse model of allergic asthma. In this model, BALB/c mice were sensitized with chicken egg white protein [ovalbumin ] to generate an IgE allergic response. To induce asthma-like symptoms after sensitization, the mice were then exposed to nebulized OVA (nose-only). This treatment results in the mice developing pulmonary inflammation, airways hyperresponsiveness, eosinophilia, and mucus hyperproduction, each representative of hallmark symptoms of human allergic asthma. Remarkably, R-DOI at doses as low as 0.01 mg/kg administered nose-only prior to OVA administration prevented the symptoms of allergic asthma from developing, including inflammation and eosinophilia.

One pilot study using psilocybin in major depressive disorder has also been published in the modern literature. 25, 26In this, our own open-label pilot study, we gave two doses of psilocybin (a 10-mg “test” dose and a 25-mg therapeutic dose) 1 week apart with psychological support before and after the experience to 20 patients with treatment-resistant depression who were moderately to severely depressed. In reality the participants were mostly multiply treatment-resistant (mean number of failed medications was 4.6 ± 2.6), and the illness was very long-standing (mean duration of illness 17.7 years ± 8.4 years). As serotonergic antidepressants and 5-HT2A receptor antagonist antipsychotics block the effects of psilocybin, patients were withdrawn from these before getting the psilocybin treatment. The primary outcome measure was the mean change in the participant-rated quick inventory of depressive symptoms (QIDS-SR) rating scale with follow-up was for 6 months, Highly significant improvements in depression ratings were seen at all time points with the maximal significance of effect seen at 5 weeks. The trial established feasibility and evidence of safety, but efficacy interpretations are limited by the open-label design.

For comparison, in 1960, there were only 197 publications about norepinephrine /noradrenaline, a neurotransmitter that had been discovered and studied in the mid-1940s. Green provides an interesting overview of the 1950–1970 period of intense research activity after the discovery of serotonin in the brain. After the passage of the Controlled Substances Act of 1970, LSD and other psychedelics known at the time were placed into the most restrictive category of drugs, Schedule 1. This classification made them virtually impossible to study clinically and effectively ended any significant research into the pharmacology and medical value of psychedelics for more than 3 decades. Nevertheless, there can be no doubt that psychedelics played a substantial role in defining the youth culture of the 1960s and 1970s, with books and essays too numerous to cite being written on this topic. One suspects that had LSD never been discovered, the world might look very different today than it does now, for better or worse, depending on one’s perspective.

Krox-20 is also known as early growth response protein, or egr-2, and is the same gene identified by González-Maeso et al. whose expression is specifically increased in response to treatment with hallucinogenic 5-HT2A agonists, as contrasted with a nonhallucinogenic 5-HT2A agonist (i.e., lisuride). Krox-20 (egr-2) has been shown to be necessary for normal brain development and may be involved in the maintenance of long-term potentiation (see references in Nichols and Sanders-Bush, 2002). A second Psychedelics study using a similar protocol with 18 volunteers examined dose effects of psilocybin, using 0, 5, 10, 20, and 30 mg/70 kg (Griffiths et al., 2011). The percentage of subjects who met the criteria for having a complete mystical-type experience increased with dose. Overall, 72.2% of volunteers had complete mystical experiences at either or both doses of 20 and 30 mg/70 kg. Positive ratings about life, attitudes about self, mood, social effects, and behavior also increased as a function of dose.

“Historically, some people seek out psychedelics for healing when other conventional treatments have failed them,” Abedi said. Psychedelics can help bring “material to the surface that needs to come up for processing,” Abedi said, which helps people address the root causes of some of their health concerns. PsyBio Therapeutics’ compound, not yet named, has been found to improve PTSD in lab animals without generating a high, says Levine. He believes such a drug could be particularly beneficial for severely anxious patients because they may not feel comfortable surrendering control of their consciousness. Senators Brian Schatz (D-Hawai‘i) and Cory Booker (D-N.J.) today called on the National Institutes of Health and the Food and Drug Administration to conduct more research into the potential therapeutic uses of psychedelics.

In a subsequent study, Bernasconi et al. carried out electrical neuroimaging analyses on visual evoked potentials in response to facial expressions under placebo and psilocybin treatment. The aim of the study was to identify neurophysiological modulation induced by psilocybin to emotional face processing. The experiment consisted of an EEG passive-viewing emotional face task, in which participants were instructed to determine the emotional valence of each face; no response was required. They found a first time period of strength (i.e., Global Field Power) modulation of the 168- to 189-millisecond poststimulus interval, induced by psilocybin. They also identified a second time period of strength modulation of the 211- to 242-millisecond poststimulus interval.

Double staining for both fos immunoreactivity and the 5-HT2A receptor revealed that LSD did not induce fos in pyramidal cells expressing 5-HT2A receptors in either the PFC or parietal cortex. Increased fos expression was induced in cortical cells in layers III and IV, with only rare occurrence of a doubly labeled pyramidal cell, suggesting fos induction by some indirect mechanism. 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.

In fact, neuroscientists are observing that, when taken in a controlled setting, these substances are beneficial to the brain, especially for people who have certain psychiatric disorders. Landmark studies in 2014 and 2016 showed that LSD and psilocybin alleviated existential anxiety in patients with life-threatening illnesses for up to a year after beginning the treatment. Other studies have shown that ketamine may strengthen neurons against the damage from chronic stress by preventing synapses from being flooded with glutamate, an amino acid that, in excess, withers dendrites. And researchers continue to investigate whether psychedelics are useful as anti-inflammatory agents. With that in mind, if the positive therapeutic effects of psychedelics continue to be validated by additional well designed clinical studies, it opens up a whole new dimension of medical research.

Kometer et al. found that psilocybin increased reaction time, which was generally faster for Kanizsa than for non-Kanizsa figures. After psilocybin treatment, the P1 amplitude (90–144 milliseconds) was increased and was locally restricted to occipital electrode sites. Source estimation revealed activity within LOC and V2 in both hemispheres, with current source density stronger within the right-lateralized LOC and V2 in the Kanizsa compared with the non-Kanizsa condition.