Partial (70%) hepatectomy was performed in mice, in which platelet function was inhibited pharmacologically or platelets were depleted. When mice were treated with a 5-HT2A antagonist, hepatocyte proliferation was reduced compared with vehicle-treated controls. The authors suggest that 5-HT2A and 5-HT2B receptor subtypes mediate serotonin-dependent liver regeneration. These studies demonstrate that selective 5-HT2A agonists may have application when topically applied to reduce IOP in glaucoma. The caveat here, which drove much of the more recent drug development efforts, was to identify potent agonists that would not penetrate the CNS and thus would lack psychedelic activity.
Church historian Richard Hughes reflects on a lifetime of ‘Troublesome Questions’
Studerus et al. pooled raw data from eight double-blind placebo-controlled experimental psilocybin studies conducted between 1999 and 2008. The data were analyzed for acute, short- and long-term subjective effects of psilocybin in 110 healthy human subjects who had received between one and four doses of 45–315 μg/kg psilocybin. Studerus et al. reported that nearly 40% of the participants in their laboratory studies of psilocybin claimed positive long-term changes in aesthetic experience and in their relationship with the environment (i.e., nature) after their psilocybin sessions. At 8–16 months after psilocybin sessions, more than 60% of subjects rated the experience as “very enriching,” and more than 90% described it as enriching to at least a medium degree. These effects occurred despite the fact that no attempt was made in their experiments to optimize conditions for a spiritual or mystical experience, which contrasts with the setting and preparations used in the two Griffiths studies cited above.
Mental health company Compass was the first to be granted a patent for synthetic psilocybin in early 2020. It was subsequently granted another two in March for an oral psilocybin depression treatment, but faces criticism for an alleged intellectual property land grab that may hinder scientific research by limiting competition. Another 37 patents are being considered by US authorities, with 66 already granted, according to a patent tracker. One company even patented LSD for eating disorders before they had begun investigating whether it was effective.
One use of psilocybin, which should not be confused with standard treatment described above, is microdosing. By taking small doses — perhaps 10 percent of a standard dose — every few days, some people might experience mental health benefits without the high. But microdosing psilocybin can be harmful, and there is some evidence that it can damage the heart over time. Recent research also suggests that the positive impacts of microdosing in humans may be largely caused by the placebo effect.
We downloaded RLOVE, a dating app for psychonauts and “light warriors.” Here’s what happened
When your eyes are open, the eyes never tire of seeing, and awareness never tires of being aware. And so when you open yourself up to these experiences, that 1% shift, even if it’s just like I’m going to do this more and I want to explore this more, that’s a decision that sticks with you for life. It’s always been the case, at least in my experience, that people who are into psychedelic therapies and psychedelics, they bring the right openness and welcomeness, I think as a therapist in general, you probably bring that vibe. But people in the psychedelic space also bring a lot of warmth, acceptance, loving, welcoming wherever you are on your journey. In Toronto, a psilocybin mushroom dispensary just open just around the corner from our office, openly selling mushrooms to people who walk in off the street.
Both kinds of receptors are found in the brain’s prefrontal cortex, which might explain why ketamine and the other psychedelics seem to have similar impacts on mental health. The mechanisms of long-term effects of one or several psychedelic experiences are even less well understood. The initial agonist action on serotonin receptors does not explain the long-term effects seen 14 months after these experiences with “positive changes in attitudes, mood, life satisfaction, behavior, and altruism/social effects” (Griffiths et al., 2011).
Tim Ferriss Blog » Psychedelic Drugs
The activity maximum in layer V was always larger and persisted longer than in any other layers and seemed to be initiated in layer V as an excitatory interaction between pyramidal neurons that propagated through the neocortex. These workers suggest that the basic operation of cortical networks is the generation of self-maintained depolarized states that are tightly regulated through interaction with local GABA/GABAergic neurons and intrinsic membrane conductances. They suggest that the ability of cortical networks to generate persistent and recurring activities even in the absence of ongoing subcortical inputs may be a process that underlies perceptual influences on sensory information processing. Using a variety of different techniques, Béïque et al. challenged the hypothesis that activation of 5-HT2A receptors led to the production of a retrograde transmitter, which resulted in release of glutamate from thalamocortical afferents. In one experiment, they transfected cortical pyramidal cells with a construct coding for the C-terminal portion of PLCβ1, which acts as a dominant negative to suppress Gαq/11 signaling. The 5-HT2A agonist AMS induced a small inward current in nontransfected cells, but not in neighboring neurons transfected with PLCβ-ct.
Likewise, in humans, daily administration of the hallucinogenic amphetamine 2,5-dimethoxy-4-methylamphetamine also led to significant tolerance to the drug effect by day 3 (Angrist et al., 1974). In humans, cross-tolerance occurs between mescaline and LSD and between psilocybin and LSD (Isbell et al., 1961). Tolerance and cross-tolerance to hallucinogens also develops in animal models (Freedman et al., 1958; Smythies et al., 1966; Appel and Freedman, 1968; Winter, 1971; Freedman and Boggan, 1974; Wallach et al., 1974; Trulson et al., 1977; Commissaris et al., 1980). It was only a decade after the discovery of the remarkable psychopharmacology of LSD that the presence of serotonin was demonstrated in the mammalian brain . A comparison of the chemical structures of LSD and serotonin led to early hypotheses that the action of LSD was due to an interaction with serotonin systems in the brain. Ten years after the discovery of LSD, Gaddum reported that LSD antagonized the action of serotonin in peripheral tissues.
Psilocybin does not always cause active visual or auditory hallucinations. Instead, it distorts how some people that use the drug perceive objects and people already in their environment. The hard part is realizing the same things you find fascinating and beautiful aren’t always what other people will react to and it’s frustrating and disappointing at times to think someone can’t experience what you are because describing it can only go so far. Psychedelic https://hookupinsight.com/summer-dating-review/ Press UK is an online rhizome of psychedelic drugs, writing, and culture. The Pearl Psychedelic Institute is a nonprofit that aims to bring psychedelic-assisted psychotherapy & MDMA-Assisted Psychotherapy into mainstream practice through research, treatment, PTSD therapy, and training while reducing the barriers to patient access. PSI is a Psychedelic Therapy Training Institute providing cannabis and psilocybin-assisted psychedelic training and therapy.
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Systemic injection of 5-MeO-DMT gave a greater HTR in β-arrestin-2 KO mice than in their WT littermates. These results were interpreted to suggest that N-methyltryptamines do not require β-arrestin-2 for the HTR, and that β-arrestin-2 may be a negative regulator in this cascade because KO mice consistently display greater responses to N-methyltryptamines. Thus, the behavioral response to serotonin in β-arrestin-2 KO mice may fundamentally differ from that in WT mice. LSD and DOB induce a ketanserin-sensitive increase in shaking behavior in mice and rats, which includes both head twitches and wet dog shakes. Substantial evidence suggests that shaking behavior primarily results from metabotropic glutamate mGlu2/3-sensitive glutamate release downstream of frontocortical 5-HT2A activation . Buchborn et al. investigated whether behavioral tolerance to LSD and DOB resulted from adaptations of 5-HT2A and mGlu2/3 signaling, or of 5-HT2A and/or overall-glutamate binding sites in the frontal cortex.
Using a 1-minute VI schedule of reinforcement with diluted sweetened condensed milk as the reinforcer, intraperitoneal injections of both LSD and mescaline were shown to produce discriminative stimuli in female rats. Based on testing of varying doses Hirschhorn and Winter found that 40 μmol/kg mescaline and 0.06 μmol/kg LSD were equivalent in their ability to produce discriminated responding when paired with saline. This potency ratio, approximately 670, is only 3- to 4-fold off from the ratio in humans . ED50 values in several rat drug discrimination studies have been contrasted with their dosages in humans and a general correlation is seen, as shown in Table 1. In a subsequent study, Wackermann et al. reanalyzed the data from the Wittmann et al. study and added an additional group of nine subjects that was administered a very low dose of psilocybin (12 μg/kg). Their new analysis employed a “dual klepsydra” model of duration reproduction.