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Updated: Aug 31, 2025

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Cannabinoid CB1 receptors regulate salivation.

Kelsey Andreis1, Jenna Billingsley1, Kian Naimi Shirazi1

  • 1Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Program in Neuroscience, Indiana University, Bloomington, IN, 47405, USA.

Scientific Reports
|August 19, 2022
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Summary
This summary is machine-generated.

Cannabis compound THC reduces saliva production by activating CB1 receptors on nerves in salivary glands. This explains the dry mouth experienced by cannabis users and highlights a new way the body regulates salivation.

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Area of Science:

  • Physiology
  • Neuroendocrinology
  • Pharmacology

Background:

  • Saliva is crucial for oral health, digestion, and pathogen defense.
  • Dry mouth is a common side effect of medications and a symptom of Sjögren's syndrome.
  • Cannabis use frequently leads to dry mouth, but the underlying mechanism is unclear.

Purpose of the Study:

  • To investigate the role of the endogenous cannabinoid signaling system in regulating salivation.
  • To determine if cannabinoid receptors are present in salivary glands and mediate salivation changes.
  • To elucidate the mechanism behind cannabis-induced dry mouth.

Main Methods:

  • Immunohistochemistry to detect cannabinoid CB1 receptors in mouse submandibular salivary glands.
  • Administration of THC, CP55940, CBD, SR141716, and JWH133 to assess effects on salivation.
  • Analysis of salivation in fatty acid amide hydrolase (FAAH) knockout and treated mice, and CB1 knockout mice.
  • Lipidomics to analyze endocannabinoid levels in FAAH knockout mice.

Main Results:

  • CB1 receptors are expressed on cholinergic nerve axons innervating the submandibular gland, not on epithelial cells.
  • THC and CP55940 significantly reduced salivation in mice; CBD reversed THC's effect.
  • FAAH knockout mice and mice treated with a FAAH blocker (URB597) exhibited reduced salivation.
  • URB597's effect on salivation was abolished in CB1 knockout mice, indicating CB1 receptor involvement.

Conclusions:

  • Endocannabinoids activate CB1 receptors on cholinergic axons in the salivary gland to regulate salivation.
  • THC reduces salivation by activating this pathway, explaining cannabis-induced dry mouth.
  • The endocannabinoid system represents a novel mechanism for controlling salivation.