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The UC Berkeley Center for the Science of Psychedelics BCSP

Reduced extrastriate visual cortex activation during the time range of the N170 also identifies it as a potential key component of 5-HT2A agonist–induced visual hallucinations. The most salient behaviors induced in rodents by psychedelics generally have been shown due to activation of the 5-HT2A receptor. Nevertheless, higher doses of particular psychedelics may lead to activation of the 5-HT2C receptor, which often functionally opposes the effects of 5-HT2A receptor activation. For example, low doses of DOI increase locomotor activity in mice, whereas higher doses attenuate it, leading to an inverted U type of dose-response curve.

For example, Shu et al. demonstrated that operation of local cortical circuits could generate activity that exhibited a proportional increase in feedback excitation and inhibition, keeping the network in relative balance. It would be most interesting to carry out a similar experiment, but with the addition Psychedelic of DOI or LSD to observe the effect on cortical circuit activity. 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.

A significant 30% increase in 5-HT2A receptor density was seen in cortex 24 hours after the first MDL11939 injection, increasing to 81% above controls after the eighth injection. These increases roughly parallel the increases seen in DOI-induced head bobs after MDL11939 treatments. By contrast, chronic BOL significantly reduced the number of DOI-induced head bobs to 19%, 12%, and 11% of controls, respectively.

Activation of 5-HT2A receptors also leads to stimulation of phospholipase A2 , which preferentially hydrolyzes arachidonic acid –containing phospholipids at the sn-2 position to produce free AA and lysophospholipid. This PLA2 pathway is independent of PLC-mediated signaling (Berg et al., 1998; Kurrasch-Orbaugh et al., 2003b) and has been demonstrated in hippocampal slices (Felder et al., 1990) and cellular systems (Berg et al., 1994; Tournois et al., 1998). The PLA2 signaling pathway is more complex than the PI turnover cascade, apparently involving multiple G proteins and the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases , at least in NIH3T3 cells (Kurrasch-Orbaugh et al., 2003a). Quednow et al. , using altanserin PET, found that the intensity of psilocybin-induced subjective effects measured using the 5D-ASC was directly correlated with the level of 5-HT2A receptor occupation by psilocin in the ACC and medial prefrontal cortex . A statewide survey of the adult population in Colorado sought to determine whether psychedelic use was correlated with the lifetime risk of panic attacks (Bonn-Miller et al., 2007).

Building on the positive results from the Spring Grove group, Grob et al. recently used a crossover design and administered 0.2 mg/kg psilocybin versus niacin placebo to 12 patients with advanced-stage cancer with a diagnosis of anxiety related to their cancer. Grob et al. reported nonsignificant trends for benefits of psilocybin compared with placebo on measures of depression and anxiety. Compared with pretreatment baseline, however, the patients’ Spielberger State-Trait Anxiety Inventory trait anxiety subscale scores revealed a significant reduction in anxiety at 1 and 3 months after treatment.