Selective Serotonin Receptor Modulators for Use in the Treatment of Psychological Disorders

Abstract

Early-phase clinical trials assessing psilocybin-assisted therapy have been reported in unipolar mood disorders, anxiety, substance use disorders, and most recently major depressive and treatment-resistant disorders. The duration of action of classical psychedelics varies considerably. For oral ingestion, the subjective effect of lysergic acid diethylamide (LSD) lasts approximately 12 h, while psilocybin lasts approximately 6 h. The quest for short-acting psychedelics, if efficacious, may have therapeutic benefits of being short acting and possibly lower treatment costs. The present Patent Highlight showcases aerosols of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT, WO 2021170614 A1) and its derivatives as pharmaceutically acceptable salts which are useful for administration to a patient through an appropriate route whereby the medication is delivered to the patient systemically. 5-MeO-DMT is a short-acting serotonergic tryptamine which acts as a 5-HT 1A and 5-HT 2A receptor agonist that was first synthesized in 1936 and later isolated from Dictyoloma incanescens in 1959. Subsequently, it has been found in a large number of plants and fungi as well as the gland secretions of the Sonoran Desert toad. The therapeutic potentials of 5-MeO-DMT have garnered renewed interest based on its pharmacological activities, which require controlled administration, exact quantity, and high purity for uses in human clinical trials. It may induce intense altered states of consciousness, including transcendence of time and space, euphoria, trance, spiritual experiences, dissolution of self-boundaries, or even near-death experiences. Due to the rapid onset of the psychedelic effects of 5-MeO-DMT, it is imperative to administer the complete or almost complete target dosage to a patient, whereas vaporization possibly lacks specificity and accuracy and in some instances may not be ideal for medical application. During vaporization, exposure of 5-MeO-DMT to undefined high temperatures over a long period of time would lead to the formation of unknown pharmacological degradants, which are also inhaled. Consequently , there is need to provide a well-controlled, standardized, and reproducible conditions for 5-MeO-DMT administration. Previously disclosed thermally generated condensation aerosols of drug molecules have shown high variability for the amount of degradation products and yields of active drug molecules. A reproducible method is showcased for administration of 5-MeO-DMT or a pharmaceutically acceptable salt through an inhalation route with a suitable aerosol particle mass density that delivers the therapeutically effective dose of the aerosol to a patient via a single inhalation. The 5-MeO-DMT aerosol was