Linalool

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Introduction

Linalool is the terpene that gives flowers and rosewood their characteristic taste/smell but it can also be found in many cannabis strains. Preclinical research indicates that linalool can be therapeutic in many diseases. However, it must be noted that linalool is only present in trace amounts (0.01-1%) in cannabis flowers which may not be enough to exert therapeutic effects on its own. Still linalool may prove to be of therapeutic value at higher concentrations (extracts) or in combination with other cannabinoids and terpenes found in cannabis.

Chemical Name

3,7-Dimethylocta-1,6-dien-3-ol

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Literature Discussion

Preclinical research has shown linalool to be effective in the following diseases:

  • Modulation of GABAAr currents (Milanos et al., 2017)
  • pain (Rombolà et al., 2016)(Hosseinzadeh et al., 2012)(Batista et al., 2008)(Peana et al., 2006)(Peana et al., 2004)(Peana et al., 2003)
  • Anti-bacterial (Kalily et al., 2016)
  • Anti-depressant (Guzmán-Gutiérrez et al., 2015)
  • Anti-nociceptive (Katsuyama et al., 2013)
  • Reduces plasma triglycerides (Jun et al., 2014)
  • Paclitaxel-induced pain (Katsuyama et al., 2012)
  • Opioid dependence/Addiction (Hosseinzadeh et al., 2012)

 

 

 

Receptors:

  • TRPA1 (Fothergill et al., 2016)(Riera et al., 2009)
  • 5-HT3 (Jarvis et al., 2016)
  • 5-HT1a (Guzmán-Gutiérrez et al., 2015)
  • μ-opioid (Katsuyama et al., 2013)
  • δ-opioid (Katsuyama et al., 2013)
  • PPARγ (Jun et al., 2014)
  • NMDA (Batista et al., 2008)(Brum et al., 2001)
  • A2A (Peana et al., 2006)
  • TRPM8 (Behrendt et al., 2004)
  • nAChR (Re et al., 2000)

 

References:

Batista, P.A., Werner, M.F. de P., Oliveira, E.C., Burgos, L., Pereira, P., Brum, L.F. da S., and Santos, A.R.S.D. (2008). Evidence for the involvement of ionotropic glutamatergic receptors on the antinociceptive effect of (-)-linalool in mice. Neurosci. Lett. 440, 299–303.

Behrendt, H.-J., Germann, T., Gillen, C., Hatt, H., and Jostock, R. (2004). Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br. J. Pharmacol. 141, 737–745.

Brum, L.F., Elisabetsky, E., and Souza, D. (2001). Effects of linalool on [(3)H]MK801 and [(3)H] muscimol binding in mouse cortical membranes. Phytother. Res. PTR 15, 422–425.

Fothergill, L.J., Callaghan, B., Rivera, L.R., Lieu, T., Poole, D.P., Cho, H.-J., Bravo, D.M., and Furness, J.B. (2016). Effects of Food Components That Activate TRPA1 Receptors on Mucosal Ion Transport in the Mouse Intestine. Nutrients 8.

Guzmán-Gutiérrez, S.L., Bonilla-Jaime, H., Gómez-Cansino, R., and Reyes-Chilpa, R. (2015). Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sci. 128, 24–29.

Hosseinzadeh, H., Imenshahidi, M., Hosseini, M., and Razavi, B.M. (2012). Effect of linalool on morphine tolerance and dependence in mice. Phytother. Res. PTR 26, 1399–1404.

Jarvis, G.E., Barbosa, R., and Thompson, A.J. (2016). Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling. J. Pharmacol. Exp. Ther. 356, 549–562.

Jun, H.-J., Lee, J.H., Kim, J., Jia, Y., Kim, K.H., Hwang, K.Y., Yun, E.J., Do, K.-R., and Lee, S.-J. (2014). Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J. Lipid Res. 55, 1098–1110.

Kalily, E., Hollander, A., Korin, B., Cymerman, I., and Yaron, S. (2016). Mechanisms of resistance to linalool in Salmonella Senftenberg and their role in survival on basil. Environ. Microbiol. 18, 3673–3688.

Katsuyama, S., Kuwahata, H., Yagi, T., Kishikawa, Y., Komatsu, T., Sakurada, T., and Nakamura, H. (2012). Intraplantar injection of linalool reduces paclitaxel-induced acute pain in mice. Biomed. Res. Tokyo Jpn. 33, 175–181.

Katsuyama, S., Mizoguchi, H., Kuwahata, H., Komatsu, T., Nagaoka, K., Nakamura, H., Bagetta, G., Sakurada, T., and Sakurada, S. (2013). Involvement of peripheral Cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. Eur. J. pain Lond. Engl. 17, 664–675.

Milanos, S., Elsharif, S.A., Janzen, D., Buettner, A., and Villmann, C. (2017). Metabolic Products of Linalool and Modulation of GABAA Receptors. Front. Chem. 5, 46.

Peana, A.T., D’Aquila, P.S., Chessa, M.L., Moretti, M.D.L., Serra, G., and Pippia, P. (2003). (-)-Linalool produces antinociception in two experimental models of pain. Eur. J. Pharmacol. 460, 37–41.

Peana, A.T., De Montis, M.G., Nieddu, E., Spano, M.T., D’Aquila, P.S., and Pippia, P. (2004). Profile of spinal and supra-spinal antinociception of (-)-linalool. Eur. J. Pharmacol. 485, 165–174.

Peana, A.T., Rubattu, P., Piga, G.G., Fumagalli, S., Boatto, G., Pippia, P., and De Montis, M.G. (2006). Involvement of adenosine A1 and A2A receptors in (-)-linalool-induced antinociception. Life Sci. 78, 2471–2474.

Re, L., Barocci, S., Sonnino, S., Mencarelli, A., Vivani, C., Paolucci, G., Scarpantonio, A., Rinaldi, L., and Mosca, E. (2000). Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse neuromuscular junction. Pharmacol. Res. 42, 177–182.

Riera, C.E., Menozzi-Smarrito, C., Affolter, M., Michlig, S., Munari, C., Robert, F., Vogel, H., Simon, S.A., and le Coutre, J. (2009). Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels. Br. J. Pharmacol. 157, 1398–1409.

Rombolà, L., Amantea, D., Russo, R., Adornetto, A., Berliocchi, L., Tridico, L., Corasaniti, M.T., Sakurada, S., Sakurada, T., Bagetta, G., et al. (2016). Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic pain. Mini Rev. Med. Chem.