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\begin{document}

\title{Molecular and structural insights into the serotonin 5-HT2C receptor as
a therapeutic target for substance use disorders}



\author[1]{Maleesha Ubhayarathna}%
\author[1]{Chris Langmead}%
\author[2]{Natalie Diepenhorst}%
\author[1]{Gregory Stewart}%
\affil[1]{Monash Institute of Pharmaceutical Sciences Drug Discovery Biology}%
\affil[2]{Monash Institute of Pharmaceutical Sciences}%


\vspace{-1em}



  
  \date{May 22, 2024}


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\begin{abstract}
Substance use disorder (SUD) is a chronic condition with maintained
abuse of a substance leading to physiological and psychological
alterations and often changes in cognitive and social behaviours.
Current therapies mainly consist of psychotherapy coupled with
medication; however, alarmingly high relapse rates reveal the
shortcomings of the current standard of care. The signalling and
expression profile, and neurological function of the serotonin 2C
receptor (5-HT2C receptor) make it an ideal candidate of interest for
the treatment of SUD. This is further corroborated by pre-clinical and
clinical evidence of therapeutically relevant compounds acting at the
5-HT2C receptor. Notwithstanding, drug binding at closely related
serotonin receptor subtypes has impeded drug development. More recently,
psychedelics, which broadly act at 5-HT2 receptors, have indicated
promising potential for the treatment of SUD, implicating in part, the
5-HT2C receptor. The modern psychedelic movement has rekindled
therapeutic interest in the 5-HT2C receptor, resulting in an influx of
new studies, especially structural analyses. This review delves into the
structural, molecular and cellular mechanisms governing the 5-HT2C
receptor function, in the context of SUD. This provides the basis of the
preclinical and clinical evidence for their role in SUD and highlights
the potential for future exploration.%
\end{abstract}%



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