C 5HT2A Agonism LSD and Model Psychosis

The observation of an LSD-induced psychosis in healthy subjects was the first indication of a potential relationship between serotonin function and schizophrenia. The early reports in the 1950s emphasized the clinical similarities between LSD-induced psychosis and schizophrenia.113 These were followed by numerous studies which carefully examined the differences, such as the prevalence of visual as opposed to auditory hallucinations, the absence of thought disorder, and the preservation of affect and insight.114 However, these differences were lessened when the comparison involved early as opposed to chronic schizophrenics115 and when cross-cultural differences in schizophrenic symptomatology were examined.116 One study117 attempted to compare LSD effects to the different subtypes of schizophrenia and found similarities between the drug group and the paranoid but not the undiffer-entiated patients. Interestingly enough, the authors described a higher rate of overlap of symptoms for those drug subjects with poorly integrated premorbid personality. Overall, LSD-induced psychosis seemed to be a potential model for some (i.e., hallucinations and paranoid delusions), but not all aspects of schizophrenia (such as disorganization and negative symptoms).118 Administration of mescaline (3,4,5-trimethoxy-phenethylamine), a phenethylamine hallucinogen, to healthy volunteers resulted, similarly, in symptoms of dissolution of ego boundaries, visual hallucinations, "oceanic boundlessness," and passivity experiences.119 Similar findings were described in humans with psilocybin.120 Disturbances in performance on neuropsychological tasks and alterations of cerebral blood flow measured with single photon emission tomography and 99Tm-HMPAO have also been described.119

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