(S1.3) The development of novel non-hallucinogenic drugs based on known psychedelics

Psychedelic compounds hold enormous promise for the treatment of an array of neuropsychiatric disorders. However, an important challenge facing psychedelic-based treatments is the limited patient population that can access them. For various medical, personal, or financial reasons, not everyone will be able or willing to take psychedelic-based treatments. For example, psychedelics may be contraindicated for patients with schizophrenia or dementia. A new type of medication is emerging that may be able to address these concerns: “non-hallucinogenic” psychedelics, also called neuroplastogens. Emerging preclinical data indicate that the therapeutic efficacy and the hallucinations are likely produced in different pathways in the brain and these effects can be differentiated. By modifying the chemical structure of psychedelic compounds, scientists have created compounds that, at least in animals, have maintained the therapeutic efficacy of historic compounds, but are predicted to not produce hallucinations. The hypothesis that the related non-hallucinogenic compounds can have the same therapeutic effect as the classic hallucinogenic drugs is an empirical question and will be answered as these compounds progress through imminent clinic studies. Ultimately, both types of compounds may show efficacy, but their efficacy may vary by the patient population treated. However, when it comes to the treatment of disorders like schizophrenia and Alzheimer’s Disease, it seems almost certain that a non-hallucinatory neuroplastogen will be needed.