Investigation of 1P-LSD as a Novel Drug Therapy for Autism Spectrum Disorders

Abstract

Autism spectrum disorders (ASD), defined by repetitive behaviors or impaired social communication, is a prevalent yet relatively misunderstood set of conditions. ASD encompasses a series of neurodevelopmental disorders that have various physiological manifestations (Goines & Ashwood, 2013). Due to the heterogeneity of ASD, the true mechanisms leading to the development of ASD and its symptoms remain unclear and require more research (Rossignol & Frye, 2012; Watts, 2008). The purpose of this project is to test whether or not 1P-LSD, an analogue of LSD (lysergic acid diethylamide), has the potential to treat symptoms of ASD, specifically the hyperexcitation of N-methyl-D-aspartate (NMDA) receptors in the brain which causes the neuronal excitotoxicity highly implicated in the pathology of ASD. We will determine the two highest doses of 1P-LSD which do not result in any hallucinogenic side effects in Phase 1 of this protocol and utilize these doses towards treatment of symptoms associated with ASD in Phase 2 of this protocol. We will monitor NMDA receptor activity, which is usually impaired in ASD, following microdosing of 1P-LSD. For these experiments, we will be using an autistic mouse model (Slc6a4) compared to normal mice (C57BL/6J). The efficacy of the treatment model will be assessed by measuring the levels of a subunit of the NMDA receptor, the NR2B subunit, using western blotting and immunohistochemistry, and by measuring the levels of glutamate using gas chromatography-mass spectrometry (GC-MS).