# Multiple Roles of Cannabinoids in the Olfactory System

## TL;DR

This paper reviews how cannabinoids influence the olfactory system, linking internal states like hunger and stress to smell perception and behavior.

## Contribution

The paper provides a comprehensive synthesis of the endocannabinoid system's role in olfactory processing, neurodevelopment, and disease.

## Key findings

- Endocannabinoid signaling via CB1 receptors modulates synaptic transmission and sensory gain in the olfactory bulb.
- The endocannabinoid system influences olfactory neurodevelopment and adult neurogenesis through stem cell regulation.
- Dysfunction in endocannabinoid signaling is linked to olfactory impairments and neurological disorders.

## Abstract

The endocannabinoid system is a ubiquitous neuromodulatory network that links internal physiological state to neural circuit function across the brain. While its roles in memory, reward, pain, and motor control are well established, its contribution to olfactory processing has only recently gained attention. This review synthesizes the current knowledge on the anatomical, cellular, and functional interactions between the endocannabinoid system and the olfactory pathway, from the olfactory epithelium and main olfactory bulb to higher order cortical targets. We highlight how endocannabinoid signaling, primarily via cannabinoid receptor type 1 (CB1), shapes synaptic transmission within olfactory bulb microcircuits, modulates centrifugal feedback, and adjusts sensory gain in a state-dependent manner, particularly in relation to hunger, feeding behavior, stress, and reward. In addition, we review evidence that the endocannabinoid system regulates olfactory neurodevelopment and adult neurogenesis by influencing neural stem cell proliferation, migration, and integration into existing circuits. Emerging links between endocannabinoid signaling, olfactory dysfunction, neuropsychiatric disease, metabolic disorders, and neurodegeneration underscore the translational relevance of this system. We also discuss methodological challenges inherent to studying endocannabinoid signaling and outline future directions, including circuit-specific targeting and intranasal delivery strategies. Together, these findings position the olfactory system as a powerful and accessible model for understanding how endocannabinoids couple internal state to perception and behavior, with important implications for therapeutic development.