Underlying Similarities Between Psychedelic and Schizophrenia Hallucinations

Hallucinations in schizophrenia and those induced by psychedelic drugs, though distinct, share underlying molecular and neural mechanisms. This review examines historical studies from the 1950s-1960s that administered hallucinogens to schizophrenic patients, then details overlaps at the molecular, cellular, and network levels—including neuroplasticity, cortico-striatal-thalamo-cortical (CSTC) circuitry, serotonin (5-HT) signaling, triple network disconnectivity, and synaptic disconnection in computational models. It also discusses nicotine's effects on schizophrenia patients. The paper synthesizes these parallels to advocate for targeted treatments informed by the neuropharmacological commonalities between the two phenomena.

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Abstract

Though distinctly different in their effects, hallucinations occurring from schizophrenia (SCZ) symptoms and psychedelic drug action can appear similar. To investigate how different mechanisms underlie these effects, this paper highlights similarities at the molecular and anatomical network level and identifies potential new therapeutic applications and directions for research. This paper explores the 1950s-1960s studies involving schizophrenic patients, hallucinogenic drugs, and their historical significance. Next, the paper dives into overlaps between schizophrenic and psychedelic hallucinations– from molecular to cellular levels. The paper’s overlaps section starts with Neuroplasticity overlaps between SCZ and Psychedelics; then is followed by the cortico-striatal-thalamo-cortical (CSTC) theory in psychedelics and schizophrenia’s hallucinations; serotonin (5-HT) mediated hallucinations and psychotic effects; triple network disconnectivity in psychopathology and schizophrenia pathology; and finally, synaptic disconnections role in neuropharmacology of hallucinations seen by computational modeling. The paper includes a final section of how the drug, nicotine, impacts SCZ patients. This paper aims to clarify the neuropharmacological overlap between these phenomena to call for further research in developing targeted treatments.