Slow oscillatory activity reflects alternating periods of activity and silence (“up” and “down” states) of cortico–thalamo–cortical networks that result from synchronized changes in membrane potential and synaptic activity of neuronal ensembles. It has been known for some time that several serotonin receptor types are expressed in ocular tissues of the human eye (Martin et al., 1992), and May et al. (2003) demonstrated that 5-HT2 receptors were involved in local control of intraocular pressure (IOP) in cynomolgus monkeys. The nonselective 5-HT2A/2C agonist R-DOI also was shown to have are psychedelics addictive a dose-dependent reducing effect on IOP in the cynomolgus monkey (May et al., 2003). Sharif and Senchyna (2006) used RT-PCR to demonstrate that human ocular tissues expressed mRNA for the 5-HT2A and 5-HT2B receptors, with greatest abundance in the retina, ciliary body, ciliary epithelium, choroid, conjunctiva, and iris. Sharif et al. (2006) also reported that human trabecular meshwork cells expressed robust mRNA signals for 5-HT2A and 5-HT2B receptors. A number of 5-HT2 agonists were demonstrated to stimulate PI turnover and Ca2+ mobilization in human trabecular meshwork cells.

• Twenty-four hours after the last treatment, rats were decapitated and the frontal cortices were dissected and homogenized.
• It has been known for some time that several serotonin receptor types are expressed in ocular tissues of the human eye (Martin et al., 1992), and May et al. (2003) demonstrated that 5-HT2 receptors were involved in local control of intraocular pressure (IOP) in cynomolgus monkeys.
• González-Maeso et al. (2003) then compared effects on in vivo gene expression of three agonists evaluated in the HTR.
• When serotonin receptor–selective antagonists became available, it was Glennon et al. (1983, 1984) who demonstrated in a rat drug discrimination model that the 5-HT2 antagonists ketanserin and pirenperone blocked the discriminative cue of a psychedelic.

Dangerous Behavior

For example, Espiard et al. (2005) reported HPPD in an 18-year-old man after mixed intoxication with psilocybin and cannabis. Ikeda et al. (2005) reported flashbacks after use of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) by a 35-year-old man without a previous psychiatric history. He had used the substance six or seven times over 5 months but discontinued it after he had a bad trip, with anxiety, palpitations, auditory oversensitiveness, and visual distortions.

C. Functional Selectivity at the Serotonin 5-Hydroxytryptamine 2A Receptor

Interestingly, in a later study, Li et al. (2003) reported that 5-HT2A receptor density was reduced only in the claustrum and ventral striatum of SERT KO mice, whereas Rioux et al. (1999) reported decreased expression of 5-HT2A receptors also in the cortex. More important, however, has been the use of animal models to dissect the underlying neuropharmacology and physiology of psychedelics. During the past 5 decades, when human research was essentially nonexistent, numerous laboratories continued to study the effects of psychedelics in animal models.

XI. Use as Tools to Study Brain Function and Connectivity

Information provided by NIDA is not a substitute for professional medical care or legal consultation. Among people aged 12 or older in 2021, 2.6% (or about 7.4 million people) reported using hallucinogens in the past 12 months. “In light of the federal illegality of psilocybin and ibogaine, there are many unresolved legal questions, some challenging legal questions and questions of potential liability, as well for licensed healthcare professionals who choose to get involved in these programs,” Marks said.

F. Possible Role of Other Receptors

III. Mechanism of Action

Tolerance and Addiction

• Psilocybin may also be helpful in the treatment of depression and anxiety when these mental health conditions are specifically linked to life threatening diseases, according to a 2020 systematic review and meta-analyses of clinical trials in Biomedicines.
• Massé et al. (2007) investigated the role of the GABA system in the anxiolytic activity of DOI.
• There are no documented cases of physical dependence, or withdrawal symptoms, regarding psilocybin-containing mushrooms.
• Ololiuqui is a naturally occurring psychedelic that is found in the seeds of the morning glory flower, which grows in Central and South America.
• Interestingly, Ca2+ mobilization is classically considered to be a downstream consequence of Gq/11 activation and subsequent PLC stimulation.

C. Obsessive-Compulsive Disorder