The serotonin 1B receptor as a target for the treatment of depression and anxiety

Abstract

INTRODUCTION: Depressive and anxiety disorders impose a substantial public health burden, yet current serotonergic therapies are limited by delayed onset, modest remission rates, and adverse side effects. Here we put forward the serotonin 1B receptor (5-HT1BR) as an important therapeutic target for mood related pathology. AREAS COVERED: We synthesize converging evidence from human and preclinical studies that link 5-HT1BR expression and function to affective phenotypes. Importantly, agonists and the p11 dependent surface trafficking pathway produce antidepressant like effects. Additionally, recent work demonstrates that 5-HT1BR signaling is required for the sustained pro-hedonic and anxiolytic actions of psilocybin. Mechanistically, 5-HT1BR modulates corticolimbic synaptic plasticity and regulates neurotransmitter release from both serotonergic and non-serotonergic terminals, positioning it to reshape dysfunctional neural circuitry. FDA-approved drugs that have 5-HT1BR agonist activity show favorable safety profiles, but there is limited clinical data from brain penetrant selective ligands. EXPERT OPINION: We propose prioritized research avenues: PET-based occupancy biomarkers, clinical trials with 5-HT1BR agonists, and exploration of sex and stress dependent effects. Additionally, in the recent drive to study and develop novel psychedelic-related compounds, it is important to consider 5-HT1BR activation. Collectively, preclinical evidence supports 5-HT1BR as a tractable, high-impact target poised to contribute to antidepressant strategies.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Anxiety ↑Supports

  Argues that the serotonin 1B receptor is a tractable therapeutic target for depression and anxiety, citing preclinical evidence that 5-HT1BR signaling is required for psilocybin's sustained anxiolytic actions.

  Synthesized October 19, 2026

• State of the evidence: Serotonin ↑Supports

  Argues that the serotonin 1B receptor is a tractable therapeutic target for depression and anxiety, citing preclinical evidence that 5-HT1B signaling is required for psilocybin's sustained pro-hedonic and anxiolytic effects.

  Synthesized October 19, 2026

Comparable studies

Other narrative reviews on serotonin, most cited first.