Tryp Therapeuatics (TRYPF) Coverage Report

administration of a psychedelic drug to facilitate a therapeutic process (J Psychopharmacol. 2015;29(3):241-53). Typically, this takes place in the presence of one or two therapists, and often involves the use of music to facilitate an introspective experience (Kaelen’s thesis. Imperial College London; 2017. https://spiral.imperial.ac.uk/handle/10044 /1/55900) . Studies have found the importance of subjective experiences, including psychological flexibility (J Context Behav Sci. 2020;15:92–102.), emotional breakthroughs (J Psychopharmacol.2019;33(9):1076–87), psychological insights (Drug Test Anal. 2012;4(7–8):543–55), and the loss of self (e.g., ego dissolution; Front Pharmacol. 2018;8(974):974). With these nontraditional qualities of psychedelic-assisted psychotherapies’ benefits the subjective qualities may not be fully captured via standardized mental health scales. Psychiatry professors from medical centers in The Netherlands tried to quantify these experiences via a review of 15 papers published within the past five years, half of which included quantitative measurements (CNS Drugs (2020) 34:925–946). Despite the range of pharmacologically diverse substances, they found, “…the subjective experience induced by these compounds is relevant for their therapeutic effect”. While Reiff, his colleagues and many other researchers have defined the specific roles for each type of psychedelic, we have found there are common themes reported by psychiatrists and others with experience in using psychedelics for various mental health disorders (CNS Drugs (2020) 34:925–946), including:  Compared to traditional counseling, the integration of psychedelics includes personally gratifying feelings of improved trust, safety, interpersonal rapport, attention, and an appropriate length of treatment sessions.  Patients that have psychedelics integrated with counseling sessions also report overlapping mental health benefits, regardless of underlying condition, which include improved insights, altered self-perception, connectedness to others, and an expanded emotional spectrum. Patterns of psychedelics’ impact on neurotransmitters provides evidence of activity. Previously, we had briefly reviewed evidence on the changes being on the brain’s activity from psychedelics to the behaviors, emotions, and settings of a psychedelic counseling session. Here, we begin to gain an understanding of the mechanisms from psychedelics’ activity on both the functional activity of neuroreceptors as well as the neuroanatomical distribution of these receptors throughout the cortex. We review evidence from researchers at SUNY who gathered word usage from 6,850 testimonials from 27 psychedelics on 40 neurotransmitter receptor subtypes by mapping the 3D coordinates in the brain via their gene transcription levels from invasive tissue probes (see Exhibit 9; bioRxiv preprint doi: https://doi.org/10.1101/2021.07.13.452263) . While most psychedelics clearly have an effect on the 5HT2A receptor, psychedelics also have minimal, indirect, or no effect at all on the receptor (PLoS One. 2010; 5(2): e9019; Pharmacol Rev. 2018 Jul;70(3):621-660), which suggests there are difference between these drugs worth exploring. An improved understanding of the mechanisms of hallucinogenic drugs should appreciate both the functional activity at receptors as well as the neuroanatomical distribution of these receptors throughout the cortex. In theory, we may find functional selectivity and binding characteristics to optimize a treatment for each patient. But with the evidence from SUNY, researchers and investors can begin to appreciate the locations of activities from psychedelics in the brain. Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 16