Preprint / Version 1

Trigeminal Neuralgia and Cannabidiol Approach

Mini Review


  • Nelson Duran Institute of Biology, University of Campinas
  • Marcos S Melo Universidade Estadual de Campinas
  • Wagner J Fávaro Universidade Estadual de Campinas
  • Cristina A A Caruy Universidade Estadual de Campinas



Chronic pain has been managed for decades, mainly by therapies based on a wide spectrum of analgesic drugs, surgical protocols and complex interventions aimed at interfering with pain outcomes or to, at least, modulate it. Unfortunately, all these techniques lead to several pharmacological hazards, besides their lack of efficacy and safety to treat chronic pain. This scenario justified the need of research focused on finding alternative treatments. Cannabinoids are naturally occurring substances deriving from Cannabis sativa L. The use of cannabinoids and their metabolites, mainly cannabidiol (CBD), emerged as option to manage different chronic pain conditions. The present review focuses on the CBD mechanism acting in chronic pain conditions, mostly on its specific use to treat trigeminal neuralgia. This review also discusses CBD’s safety and interaction with drugs prescribed for neuropathic orofacial pain, mainly Gabapentin/CBD interactions.


Cannabidiol, Trigeminal neuralgia, Gabapentin


Download data is not yet available.


Abd-Elsayed, A. (Editor) Trigeminal Nerve Pain: A Guide to Clinical Management. Springer Nature, Switzerland, pp. 246; 2020. ISBN 978-03-030-60686-2.

Almuntashiri, N., Alzahrani, H., Kofiya, R., Alzuhiri, M.E., Hamdi, A.Y., Badahdah, N.A., Almaghrabi, A., Zamil, H., Alsahafi, O., Gamaruddin, M., Mahdi, A. Synergistic Effects of Cannabis with Gabapentin and its Analog Pregabalin (Lyrica®). Biomed J Sci & Tech Res 2022; 47: 38743-38747.

Baron, E.P. Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: An update on current evidence and cannabis science. Headache 2018; 58, 1139–1186.

Barrie N, Manolios N. The endocannabinoid system in pain and inflammation: its relevance to rheumatic disease. Eur J Rheumatol 2017;4:210-218.

Bendtsen, L., Zakrzewska, J.M., Heinskou, T.B., Hodaie, M., Leal, P.R.L., Nurmikko, T, Obermann, M., Cruccu, G., Maarbjerg, S. Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet Neurol. 2020; 19: 784-96.

Bornheim, L.M., Everhart, E.T., Li, J., Correia,M.A. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochemical Pharmacol.1993; 45: 1323-1331.

Burgos, E., Pascual, D., Martín, M.I., Goicoechea, C. Antinociceptive effect of the cannabinoid agonist, WIN 55,212-2, in the orofacial and temporomandibular formalin tests. Eur. J. Pain 2010; 14: 40–48.

Canada, H. Canadian Cannabis Survey 2020: Summary. 2021 May 2, 2021]; Available from: research-data/canadian-cannabis-survey-2020-summary.html.

Chagas, M.H., Eckeli, A.L., Zuardi, A.W., Pena-Pereira, M.A., Sobreira-Neto, M.A., Sobreira, E.T., Camilo, M.R., Bergamaschi, M.M., Schenck, C.H., Hallak, J.E., Tumas, V., Crippa, J.A. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J Clin Pharm Ther 2014; 39:564–566.

Clarke, H., Kotteeswaran, Y. The future of cannabis/cannabinoid medicine and orofacial pain health care 2021. (

Consroe, P., Musty, R., Rein, J., Tillery, W. Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol 1997; 38:44–48.

Crepault, J.F. Cannabis legalization in Canada: Reflections on public health and the governance of legal psychoactive substances. Front Public Health, 2018; 6: 220.

Crescente, G., Minervini, G., Spagnuolo, C., Moccia, S. Cannabis bioactive compound-based formulations: New perspectives for the management of orofacial pain. Molecules 2023: 28 106.

Corder, G., Castro, D.C., Brucha, M.R., Scherrer, G. Endogenous and exogenous opioids in pain. Annu. Rev. Neurosci. 2018; 41: 453–473.

Doss, A.X. Trigeminal neuralgia treatment: A case report on short-term follow up after ultrasound guided autologous platelet rich plasma injections. Neurology. 2012; 3:1-5.

DrugBank 2023.Gabapentin. 2023;

Durán, N., Fávaro, W.J., Durán,G., Bíscaro, G.G., Leme, K.C., Luzo, A.C.M. Is an alternative of platelet-rich plasma on trigeminal neuralgia? A mine-Review. SSRN Preprint. Available at SSRN: or (2023),

Fiani, B., Sarhadi, K.J., Soula, M., Zafar, A., Quadri, S.A. Current application of cannabidiol (CBD) in the management and treatment of neurological disorders. Neurol Sci. 2020;41:3085-3098.

Gajofatto A. Refractory trigeminal neuralgia responsive to nabiximols in a patient with multiple sclerosis. Mult Scler Relat Disord. 2016; 8:64-5.

Gambeta, E., Chichorro, J.G., Zamponi, G.W. Trigeminal neuralgia: An overview from Fpathophysiology to pharmacological treatments. Mol Pain 2020; 16: 1–18.

Genovese,A,. Calabrò, A., Capon, D. Cannabinoids in trigeminal neuralgia. Pathos 2021; 28: 2. Online 2021, Sep 5

Grossman, S., Tan, H., Gadiwalla, Y. Cannabis and orofacial pain: A systematic review. Br. J. Oral Maxillofac. Surg. 2022; 60: e677–e690.

Henshaw, F.R., Dewsbury, L.S., Lim, C.K., Steiner, G.Z. The effects of cannabinoids on pro- and anti-inflammatory cytokines: A systematic review of in vivo studies. Cannabis Cannabinoid Res. 2021; 6: 177–195.

Kaufmann, A.M., Patel, M. Trigeminal Neuralgia. 2001. (accessed on November 08, 2021).

Kim, A.L., Yun, Y.J., Choi, H.W., Hong, C.-H., Shim, H.J., Lee, J.H., Kim, Y.-C. Profiling cannabinoid contents and expression levels of corresponding biosynthetic genes in commercial cannabis (cannabis sativa l.) cultivars. Plants 2022, 11, 3088.

Klumpers, L.E., Thacker, D.L. A brief background on cannabis: from plant to medical indications. J AOAC Inter. 2019; 102: 412-420.

Kopustinskiene, D.M., Masteikova, R., Lazauskas, R., Bernatoniene, J. Cannabis sativa L. Bioactive compounds and their protective role in oxidative stress and inflammation. Antioxidants 2022; 11: 660.

Kuffler, D.P., Foy, C. Restoration of neurological function following peripheral nerve trauma. Int. J. Mol. Sci. 2020; 21: 1808.

Landucci, E., Pellegrini-Giampietro, D., Gianoncelli, A., Ribaudo, G. Cannabidiol preferentially binds TRPV2: A novel mechanism of action. Neural Regen. Res. 2022, 17, 2693–2694.

Liang, Y-C., Huang, C-C., Hsu, K-S. Therapeutic potential of cannabinoids in trigeminal neuralgia. Curr Drug Targets CNS Neurol Disord 2004; 3: 507-14

Lile, J.A., Wesley, M.J., Kelly, T.H., Hays, L.R. Separate and combined effects of gabapentin and ?9-THC in humans discriminating ?9-THC. Behavioural Pharmacol. 2016; 27(2-3 Spec Iss): 215-224.

Lim, X.Y., Tan, T.Y.C., Rosli, S.H.M., Sa’At, M.N.F., Ali, S.S., Mohamed, A.F.S. Cannabis sativa subsp. sativa’s pharmacological properties and health effects: A scoping review of current evidence. PLoS ONE 2021; 16: e0245471.

Martínez, V., Iriondo De-Hond, A.; Borrelli, F., Capasso, R., Del Castillo, M.D., Abalo, R. cannabidiol and other non-psychoactive cannabinoids for prevention and treatment of gastrointestinal disorders: useful nutraceuticals? Int. J. Mol. Sci. 2020; 21: 3067.

Mastinu, A., Ribaudo, G., Ongaro, A., Bonini, S.A., Memo, M., Gianoncelli, A. Critical Review on the Chemical Aspects of Cannabidiol (CBD) and Harmonization of Computational Bioactivity Data. Curr. Med. Chem. 2021, 28, 213–237.

McDonough, P., McKenna, J.P., McCreary, C., Downer, E.J. Neuropathic orofacial pain: cannabinoids as a therapeutic avenue. Int J Biochem Cell Biol 2014; 55:72–78.

Mechtler, L., Hart, P., Bargenes, V., Saikali,N. Medica treatments in patients with trigeminal neuralgia. Neurology 92.15 Supplement (2019): P5.10-020. Web. 13 Aug. 2023.

Mechtler, L., Hart, P., Bargnes, V., Saikali, N. Medical cannabis treatment in patients with trigeminal neuralgia. Neurol. J. 2019 (15 suppl) P5. 10-020.

Minervini, G., Fiorillo, L., Russo, D., Lanza, A., D’Amico, C., Cervino, G. Meto, A., Di Francesco, F. Prosthodontic treatment in patients with temporomandibular disorders and orofacial pain and/or bruxism: A Review of the literature. Prosthesis 2022a; 4: 253–262.

Minervini, G., Russo, D., Herford, A.S., Gorassini, F., Meto, A., D’Amico, C., Cervino, G., Cicciù, M., Fiorillo, L. Teledentistry in the management of patients with dental and temporomandibular disorders. BioMed. Res. Int. 2022b; 2022: 7091153.

Minervini, G., Romano, A., Petruzzi, M., Maio, C., Serpico, R., Lucchese, A., Candotto, V., Di Stasio, D. Telescopic overdenture on natural teeth: Prosthetic rehabilitation on (OFD) syndromic patient and a review on available literature. J. Biol. Regul. Homeost. Agents 2018; 32: 131–134,

Mlost, J., Bryk, M., Starowicz, K. Cannabidiol for pain treatment: focus on pharmacology and mechanism of action. Intern. J. Mol. Sci. 2020; 21: 8870.

NAS-2017. National Academies of Sciences, E., and Medicine, The health effects of cannabis and cannabinoids: Current state of evidence and recommendations for research 2017, The National Academies Press: Washington, DC.

NCoS, L. State Medical Marijuana Laws. National Conference of State Legislatures 2021 [cited Updated April 5, 2021]. Accessed April 30, 2021. Available from:

Nebert, D.W., Wikvall, K., Miller, W.L. Human cytochromes P450 in health and disease. Philos Trans R Soc Lond B Biol Sci 2013; 368:20120431.

NMAR-2013-Canada, H. Marihuana medical access program (MMAR) statistics 2013. 2014; Available from:

Patil, S., Testarelli, L. Assessment of growth factors, cytokines, and cellular markers in saliva of patients with trigeminal neuralgia. Molecules 2021; 26: 2964,

Pellati, F., Borgonetti, V., Brighenti, V., Biagi, M., Benvenuti, S., Corsi L. Cannabis sativa l. and nonpsychoactive cannabinoids: Their chemistry and role against oxidative stress, inflammation, and cancer. BioMed. Res. Int. 2018; 2018: 1691428.

Pellati, F., Brighenti, V., Sperlea, J., Marchetti, L., Bertelli, D., Benvenuti, S. New methods for the comprehensive analysis of bioactive compounds in cannabis sativa l. (hemp). Molecules 2018, 23, 2639.

Radwan, M., Chandra, S., Gul, S., ElSohly, M. Cannabinoids, Phenolics, Terpenes and Alkaloids of Cannabis. Molecules 2021; 26: 2774.

Rodriguez, C.E.B., Ouyang, L., Kandasamy, R. Antinociceptive effects of minor cannabinoids, terpenes and flavonoids in Cannabis. Behav. Pharmacol. 2022; 33: 130–157.

Schiavone, M., Ziccardi, V.B. Trigeminal nerve injuries in oral and maxillofacial surgery: a literature review. Front Oral Maxillofac Med 2021; 3:28.

Schifano, F. Misuse and abuse of pregabalin and gabapentin: cause for concern. CNS drugs. 2014; 28: 491-496.

Shehata, I., Hashim, A., Elsaeidy, A.S., Nair, A., Urits, I., Viswanath, O., Kaye, A.D., Habib, M. General Cannabinoids and Their Role in Chronic Pain Treatment: Current Concepts and a Comprehensive Review Trigeminal neuralgia (TN). Health Psychol Res. 2022;10: 1-19. doi:10.52965/001c.3584.

Staiger, B. Neurontin (Gabapentin) With CBD Oil Interaction. 2018; ile:///E:/ NEURALGIA TRIGEMICA-20223/Neurontin (Gabapentin) With CBD Oil Interaction.html.

Carlini, E.A, Cunha, J.M. Hypnotic and Antiepileptic Effects of Cannabidiol. Jo Clin Pharmacol. 1981; 21: 417S–427S.

Statista. Monthly retail sales of legal cannabis stores in Canada from October 2018 to November 2020 (in million Canadian dollars). 2021 Last accessed May 2, 2021]; Available from:

Tamba, B.I., Stanciu, G.D., Urîtu, C.M., Rezus, E., Stefanescu, R., Mihai, C.T., Luca, A., Rusu-Zota, G., Leon-Constantin, M.-M., Cojocaru, E., et al. Challenges and opportunities in preclinical research of synthetic cannabinoids for pain therapy. Medicina 2020; 56: 24.

Takeda, M., Shimazu, Y. Modulatory mechanism underlying how dietary constituents attenuate orofacial pain. J. Oral Sci. 2020; 62: 140–143.

Tedesco, I., Spagnuolo, C., Russo, G., Russo, M., Cervellera, C., Moccia, S. the pro-oxidant activity of red wine polyphenols induces an adaptive antioxidant response in human erythrocytes. Antioxidants 2021; 10: 800.

Therapeutic Research Centre. Natural Medicines, 2019. (date last accessed, 12 February 2019).

TRC-2019 Therapeutic Research Centre. Natural Medicines, 2019.

UPMC-2021. Trigeminal Neuralgia Treatment. (accessed on November 08, 2021).

Wilson-Morkeh, H., Al-Abdulla, A., Sien, L., Mohamed, H., Youngstein, T. Important drug interactions exist between cannabidiol oil and commonly prescribed drugs in rheumatology practice. Rheumatology 2020; 59:249-251.

Yamaori, S., Ebisawa, J., Okushima, Y., Yamamoto, I., Watanabe, K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci 2011; 88:730-736.

Yamaori, S., Koeda, K., Kushihara, M. et al. Comparison in the in vitro inhibitory effects of major phytocannabinoids and polycyclic aromatic hydrocarbons contained in marijuana smoke on cytochrome P450 2C9 activity. Drug Metab Pharmacokinet 2012;27:294-300.

Yamaori, S., Kushihara, M., Yamamoto, I., Watanabem, K. Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem. Pharmacol., 2010; 79: 1691–1698.

Yamaori, S., Okamoto Y., Yamamoto, I., Watanabe, K. Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6. Drug Metabol Disposition. 2011; 39: 2049-2056,

Zarembinski, C., Omrani K. Platelet-rich plasma as a novel treatment of painful traumatic trigeminal neuropathy (PTTN)-Six Month results. IIth Congress of European Pain Federation - European Federation of IASP Chapters) (EFIC) Congress 2019, Valencia, Spain.