Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice

Volatile organic compounds, colloquially referred to as “terpenes”, have been proposed to impact the therapeutic qualities that are traditionally ascribed to cannabis. However, the contribution of these terpenes in anxiety, at relevant levels and exposure methods common with cannabis use, is lacking...

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Main Authors: Jasmin K. Wagner, Ella Gambell, Tucker Gibbons, Thomas J. Martin, Joshua S. Kaplan
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:NeuroSci
Subjects:
Online Access:https://www.mdpi.com/2673-4087/5/4/45
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author Jasmin K. Wagner
Ella Gambell
Tucker Gibbons
Thomas J. Martin
Joshua S. Kaplan
author_facet Jasmin K. Wagner
Ella Gambell
Tucker Gibbons
Thomas J. Martin
Joshua S. Kaplan
author_sort Jasmin K. Wagner
collection DOAJ
description Volatile organic compounds, colloquially referred to as “terpenes”, have been proposed to impact the therapeutic qualities that are traditionally ascribed to cannabis. However, the contribution of these terpenes in anxiety, at relevant levels and exposure methods common with cannabis use, is lacking empirical assessment. We tested the anxiolytic properties of two prominent cannabis terpenes, linalool and β-myrcene, in male and female mice using short duration vapor pulls to model human inhalation when combusting flower or vaping cannabis oil. We observed sex differences in the locomotor effects in the open field and anxiolytic properties in the elevated plus maze of these terpenes that depended on their exposure characteristics. Both linalool and β-myrcene had anxiolytic effects in female mice when delivered in discrete vapor pulls over the course of 30 min. In male mice, only a single vapor hit containing linalool or β-myrcene had anxiolytic effects. The combination of sub-effective levels of linalool and the phytocannabinoid, cannabidiol (CBD), had synergistic anxiolytic effects in females, but these entourage effects between CBD and terpenes were absent with β-myrcene for females and for either terpene in males. Together, our findings reveal sex differences in the anxiolytic properties of common cannabis terpenes and highlight the potential benefits of unique combinations of CBD and terpenes in expanding the therapeutic dose window.
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spelling doaj-art-5f47931657ae4dc7bb743fdd83e1e0ec2025-08-20T02:51:07ZengMDPI AGNeuroSci2673-40872024-12-015463564910.3390/neurosci5040045Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in MiceJasmin K. Wagner0Ella Gambell1Tucker Gibbons2Thomas J. Martin3Joshua S. Kaplan4Behavioral Neuroscience Program, Psychology Department, Western Washington University, 516 High Street, Bellingham, WA 98229, USABehavioral Neuroscience Program, Psychology Department, Western Washington University, 516 High Street, Bellingham, WA 98229, USABehavioral Neuroscience Program, Psychology Department, Western Washington University, 516 High Street, Bellingham, WA 98229, USADepartment of Research and Development, Abstrax Tech, 2661 Dow Avenue, Tustin, CA 92780, USABehavioral Neuroscience Program, Psychology Department, Western Washington University, 516 High Street, Bellingham, WA 98229, USAVolatile organic compounds, colloquially referred to as “terpenes”, have been proposed to impact the therapeutic qualities that are traditionally ascribed to cannabis. However, the contribution of these terpenes in anxiety, at relevant levels and exposure methods common with cannabis use, is lacking empirical assessment. We tested the anxiolytic properties of two prominent cannabis terpenes, linalool and β-myrcene, in male and female mice using short duration vapor pulls to model human inhalation when combusting flower or vaping cannabis oil. We observed sex differences in the locomotor effects in the open field and anxiolytic properties in the elevated plus maze of these terpenes that depended on their exposure characteristics. Both linalool and β-myrcene had anxiolytic effects in female mice when delivered in discrete vapor pulls over the course of 30 min. In male mice, only a single vapor hit containing linalool or β-myrcene had anxiolytic effects. The combination of sub-effective levels of linalool and the phytocannabinoid, cannabidiol (CBD), had synergistic anxiolytic effects in females, but these entourage effects between CBD and terpenes were absent with β-myrcene for females and for either terpene in males. Together, our findings reveal sex differences in the anxiolytic properties of common cannabis terpenes and highlight the potential benefits of unique combinations of CBD and terpenes in expanding the therapeutic dose window.https://www.mdpi.com/2673-4087/5/4/45terpenescannabidiolcannabismonoterpenesanxietylinalool
spellingShingle Jasmin K. Wagner
Ella Gambell
Tucker Gibbons
Thomas J. Martin
Joshua S. Kaplan
Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice
NeuroSci
terpenes
cannabidiol
cannabis
monoterpenes
anxiety
linalool
title Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice
title_full Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice
title_fullStr Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice
title_full_unstemmed Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice
title_short Sex Differences in the Anxiolytic Properties of Common Cannabis Terpenes, Linalool and β-Myrcene, in Mice
title_sort sex differences in the anxiolytic properties of common cannabis terpenes linalool and β myrcene in mice
topic terpenes
cannabidiol
cannabis
monoterpenes
anxiety
linalool
url https://www.mdpi.com/2673-4087/5/4/45
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