Its pharmacodynamic mechanisms of action are primarily attributed to the interaction with the serotonergic 5-HT2A-C receptors, and therefore clinical effects are similar to those elicited by other psychoactive substances, such as lysergic acid diethylamide (LSD) and psilocybin, which include euphoria, hallucinations, depersonalization and psychoses.
In summary, these data suggest that a shift towards increased availability (and G-protein coupling) of cortical 5-HT2A vs. mGlu2 receptors may represent a common neurobiological mechanism underlying the emergence of psychosis and cognitive deficits observed in subjects with meth use disorder and schizophrenia.
In this review we primarily focus on psychosis in PD, the current treatment possibilities and the new, emerging therapy, pimavanserin, a selective 5-HT2A inverse agonist.
While the hypo-activity of serotonin signaling is involved in the pathogenesis of depression, anxiety and obsessive compulsive disorder; LSD, an agonist of serotonin type 2 receptor (5-HTR2A) induces psychosis.
HTR2A gene has been the subject of numerous studies in psychiatric genetics because LSD, which resembles serotonin causes psychosis and atypical antipsychotic drugs target the HTR2A receptor.
The strong and robust positive association that was noted between the C allele of HTR2A and psychosis suggests that the HTR2AT102C polymorphism is a significant risk factor for psychosis of AD.
These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis.
No significant differences in the distribution of allele and genotype frequencies of the 5-HTTLPR (p>0.01) and 5-HT2AT102C (p>0.05) were found between patients and controls as well as between the patients' subgroups without and with psychosis.
There was no genetic association between HTR2AT102C with either schizophrenia or bipolar disorder under the assumption of a parent-of-origin effect, and these data together essentially exclude imprinting at this locus as a potential explanation for the complex inheritance observed in major psychoses.
Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were genotyped for the HTR2AT102C polymorphism and reassessed every 6 months until psychosis onset.
No association between the 5-HT2AC102T polymorphism and suicidal behavior in major psychoses was detected with the transmission/disequilibrium test (TDT).
Based on the literature, we hypothesized that the 5-HT2A and 5-HT2C receptor polymorphisms would be associated with agitation/aggression and psychosis and the 5-HTTPR or 5-HTTVNTR polymorphisms, with agitation/aggression or depression and anxiety.