Journal of Neuroscience
November 30, 2020
Danilo de Gregorio, Argel Aguilar‐valles, Katrin H. Preller et al.
258 citations
A renewed interest in hallucinogens for treating psychiatric disorders has emerged. Preclinical and clinical studies have confirmed ketamine's efficacy for depression. Emerging evidence points to psilocybin and LSD's therapeutic properties and their ability to modulate functional brain connectivity. MDMA, an entactogen, has shown usefulness for post-traumatic stress disorder. This review summarizes the pharmacology of hallucinogenic compounds, highlighting differences between psychedelic and nonpsychedelic hallucinogens and entactogens, and describes their behavioral effects in animals and humans. Together, these data substantiate the potential of these compounds for treating mental diseases.
Proceedings of the National Academy of Sciences
January 25, 2021
Danilo de Gregorio, Jelena Popić, Justine P. Enns et al.
137 citations
Repeated doses of LSD (30 μg/kg daily for 7 days) increase social behavior in male mice without producing antidepressant or anxiety-reducing effects. The prosocial effect requires the integrity of mTORC1 in excitatory glutamatergic neurons of the medial prefrontal cortex (mPFC), as shown by optogenetic inhibition and conditional knockout experiments. LSD potentiates AMPA and 5-HT2A synaptic responses in the mPFC and increases phosphorylation of Akt and mTOR, but does not affect NMDA or 5-HT1A responses. In mice lacking Raptor in GABAergic neurons, LSD still promotes social behavior. The findings suggest that 5-HT2A/AMPA/mTORC1 signaling in mPFC excitatory neurons mediates LSD's prosocial effects, offering a potential target for treating social deficits in autism and social anxiety.
Carleton undergraduate journal of science.
September 2, 2025
Kaylee Reid, Dhiral Kot, Argel Aguilar‐valles
Major depressive disorder affects about 280 million people globally, and many do not respond to first-line antidepressants, leading to treatment-resistant depression. Psychedelics like psilocybin show rapid antidepressant effects by enhancing neuroplasticity through 5-HT2A receptor activation, but their hallucinogenic properties limit clinical use. A non-hallucinogenic analog, 2-bromo-lysergic acid diethylamide (2-Br-LSD), may promote neuroplasticity without hallucinations, though it is unclear if hallucinatory activity is necessary for therapeutic benefit. This thesis examines both compounds in rodent models of chronic stress, hypothesizing that both will reduce depression-like behaviors by modulating mood-regulating neural circuits, aiming to assess 2-Br-LSD as a more accessible treatment for treatment-resistant depression.