Current state of knowledge on the use of cannabidiol (CBD) in various medical conditions
DOI:
https://doi.org/10.12775/JEHS.2023.38.01.004Keywords
cannabidiol (CBD), Anxiety, Epilepsy, Pain, cannabisAbstract
INTRODUCTION AND PURPOSE
Cannabis sativa contains hundreds of compounds, referred to as cannabinoids. Two most prevalent are delta-9-tetrahydrocannabinol and cannabidiol (CBD). CBD is non-psychoactive substance that has recently gained attention in lay press and in medical research. Aim of this study is to review evidence-based data on safety, effectiveness and applicability of CBD in various medical conditions in order to provide healthcare professionals with information that may be useful in their practice.
MATERIALS AND METHODS
In April 2023, PubMed and Google Scholar databases were searched for studies that included phrases “CBD” or “cannabidiol”, and related phrases. In the review, only studies that used well-established research methods were included.
RESULTS
CBD is an effective novel treatment option in Lennox–Gastaut syndrome, tuberous sclerosis complex and Dravet syndrome. Data supporting CBD’s applicability in anxiety, Parkinson’s Disease, schizophrenia, insomnia, pain, autoimmune diseases, osteoporosis and as an anti-aging agent is promising, but more research on bigger groups of patients is needed to establish its role in modern medicine.
CONCLUSIONS
The use of CBD is associated with risks of variable dosage, contamination and adulteration. At present, there is a need of more research to establish effective and safe doses of CBD. Clinicians need to monitor new data from ongoing CBD trials, but at present there is no hard evidence supporting effectiveness of CBD in various medical conditions, apart from epilepsy.
References
Scheier LM, Griffin KW. Youth marijuana use: a review of causes and consequences. Curr Opin Psychol. 2021 Apr;38:11-18. doi: 10.1016/j.copsyc.2020.06.007.
Sánchez-Sánchez L, García J, Fernández R, Noskova E, Egiguren-Ortiz J, Gulak M, Ochoa E, Laso A, Oiarbide M, Santos JI, Fe Andrés M, González-Coloma A, Adell A, Astigarraga E, Barreda-Gómez G. Characterization of the Antitumor Potential of Extracts of Cannabis sativa Strains with High CBD Content in Human Neuroblastoma. Int J Mol Sci. 2023 Feb 14;24(4):3837. doi: 10.3390/ijms24043837
Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy. 2013 Feb;33(2):195-209. doi: 10.1002/phar.1187.
Zuardi AW. History of cannabis as a medicine: a review. Braz J Psychiatry. 2006 Jun;28(2):153-7. doi: 10.1590/s1516-44462006000200015. Epub 2006 Jun 26. PMID: 16810401.
White, CM (2019), A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential. The Journal of Clinical Pharmacology, 59: 923-934. https://doi.org/10.1002/jcph.1387
Maciejewska B; Informacja: na temat wybranych zagadnień związanych z marihuaną wykorzystywaną do celów medycznych, marihuaną posiadaną na użytek własny oraz dopuszczalnym limitem THC w konopiach przemysłowych w państwach europejskich, Biuro analiz sejmowych kancelarii sejmu, BAS-ZSP-2428/20, Warszawa, dnia 5 lutego 2021 r, [access online: 2.04.2023] https://orka.sejm.gov.pl/opinie9.nsf/nazwa/opinia_BAS_666/$file/opinia_BAS_666.pdf
Ustawa z dnia 7 lipca 2017 roku o zmianie ustawy o przeciwdziałaniu narkomanii oraz ustawy o refundacji leków, środków spożywczych specjalnego przeznaczenia żywieniowego oraz wyrobów medycznych (Dz. U. z 2017 r. poz. 1458) [access online: 2.04.2023].
Pisanti S, Malfitano AM, Ciaglia E, Lamberti A, Ranieri R, Cuomo G, Abate M, Faggiana G, Proto MC, Fiore D, Laezza C, Bifulco M. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017 Jul;175:133-150. doi: 10.1016/j.pharmthera.2017.02.041. Epub 2017 Feb 22. PMID: 28232276.
Perucca E, Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last? J Epilepsy Res. 2017 Dec 31;7(2):61-76. doi: 10.14581/jer.17012. PMID: 29344464; PMCID: PMC5767492.
Cooray R, Gupta V, Suphioglu C, Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson’s and Alzheimer’s Diseases: a Review. Mol Neurobiol 57, 4878–4890 (2020). https://doi.org/10.1007/s12035-020-02054-6
Pavlovic R, Panseri S, Giupponi L, Leoni V, Citti C, Cattaneo C, Cavaletto M, Giorgi A. Phytochemical and Ecological Analysis of Two Varieties of Hemp (Cannabis sativa L.) Grown in a Mountain Environment of Italian Alps. Front Plant Sci. 2019 Oct 15;10:1265. doi: 10.3389/fpls.2019.01265. PMID: 31708938; PMCID: PMC6822994.
Klinowski M, Medyczne konopie i problematyka regulacji produktów, PRZEGLĄD PRAWA MEDYCZNEGO TOM 4 NR 2 (2022): 4-62, published: 5.12.2022
Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 2017 Nov 7;318(17):1708-1709. doi: 10.1001/jama.2017.11909. PMID: 29114823; PMCID: PMC5818782.
Horth RZ, Crouch B, Horowitz BZ, et al. Notes from the Field: Acute Poisonings from a Synthetic Cannabinoid Sold as Cannabidiol — Utah, 2017–2018. MMWR Morb Mortal Wkly Rep 2018;67:587–588. DOI: http://dx.doi.org/10.15585/mmwr.mm6720a5external icon
Hazekamp A. The Trouble with CBD Oil. Med Cannabis Cannabinoids. 2018 Jun 12;1(1):65-72. doi: 10.1159/000489287. PMID: 34676324; PMCID: PMC8489347.
Graeme J. Sills, Michael A. Rogawski, Mechanisms of action of currently used antiseizure drugs,
Neuropharmacology, Volume 168, 2020, 107966, ISSN 0028-3908, https://doi.org/10.1016/j.neuropharm.2020.107966.
Doodipala Samba Reddy, Therapeutic and clinical foundations of cannabidiol therapy for difficult-to-treat seizures in children and adults with refractory epilepsies, Experimental Neurology, Volume 359, 2023, 114237, ISSN 0014-4886, https://doi.org/10.1016/j.expneurol.2022.114237.
Santiago-Castañeda C, Huerta de la Cruz S, Martínez-Aguirre C, Orozco-Suárez SA, Rocha L. Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery. Pharmaceutics. 2022 Aug 2;14(8):1609. doi: 10.3390/pharmaceutics14081609. PMID: 36015236; PMCID: PMC9414526.
Hosseinzadeh M, Nikseresht S, Khodagholi F, Naderi N, Maghsoudi N. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure. J Mol Neurosci. 2016 Apr;58(4):432-40. doi: 10.1007/s12031-015-0703-6. Epub 2016 Jan 6. PMID: 26738731.
Crippa JA, Guimarães FS, Campos AC, Zuardi AW. Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age. Front Immunol. 2018 Sep 21;9:2009. doi: 10.3389/fimmu.2018.02009. PMID: 30298064; PMCID: PMC6161644.
Blessing EM, Steenkamp MM, Manzanares J. et al. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics 12, 825–836 (2015). https://doi.org/10.1007/s13311-015-0387-1
Zuardi AW, Rodrigues NP, Silva AL, et al. Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life [published online ahead of print May 11, 2017]. Front Pharmacol. https://doi.org/10.3389/fphar.2017.00259.
Crippa JAS, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of Psychopharmacology. 2011;25(1):121-130. doi:10.1177/0269881110379283
Skelley JW, Deas CM, Curren Z, Ennis J. Use of cannabidiol in anxiety and anxiety-related disorders. J Am Pharm Assoc (2003). 2020 Jan-Feb;60(1):253-261. doi: 10.1016/j.japh.2019.11.008. Epub 2019 Dec 19. PMID: 31866386.
Spinella, TC, Stewart, SH, Naugler J. et al. Evaluating cannabidiol (CBD) expectancy effects on acute stress and anxiety in healthy adults: a randomized crossover study. Psychopharmacology 238, 1965–1977 (2021). https://doi.org/10.1007/s00213-021-05823-w
Narayan AJ, Downey LA, Manning B, Hayley AC. Cannabinoid treatments for anxiety: A systematic review and consideration of the impact of sleep disturbance. Neurosci Biobehav Rev. 2022 Dec;143:104941. doi: 10.1016/j.neubiorev.2022.104941. Epub 2022 Nov 9. PMID: 36370842.
McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018 Mar 1;175(3):225-231. doi: 10.1176/appi.ajp.2017.17030325. Epub 2017 Dec 15. PMID: 29241357.
Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, Schnakenberg Martin AM, Thurnauer H, Davies A, D'Souza DC, Ranganathan M. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology (Berl). 2018 Jul;235(7):1923-1932. doi: 10.1007/s00213-018-4885-9. Epub 2018 Apr 5. PMID: 29619533.
Leweke FM, Rohleder C, Gerth CW, Hellmich M, Pukrop R, Koethe D. Cannabidiol and amisulpride improve cognition in acute schizophrenia in an explorative, double-blind, active-controlled, randomized clinical trial. Front Pharmacol. 2021;12:614811.
Chagas MH, Zuardi AW, Tumas V, Pena-Pereira MA, Sobreira ET, Bergamaschi MM, dos Santos AC, Teixeira AL, Hallak JE, Crippa JA. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J Psychopharmacol. 2014 Nov;28(11):1088-98. doi: 10.1177/0269881114550355. Epub 2014 Sep 18. PMID: 25237116.
Fox SH, Kellett M, Moore AP, Crossman AR, Brotchie JM. Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord. 2002 Jan;17(1):145-9. doi: 10.1002/mds.1280. PMID: 11835452.
Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, Parkin SG, Fox P, Wright D, Hobart J, Zajicek JP. Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology. 2004 Oct 12;63(7):1245-50. doi: 10.1212/01.wnl.0000140288.48796.8e. PMID: 15477546.
Mesnage V, Houeto JL, Bonnet AM, Clavier I, Arnulf I, Cattelin F, Le Fur G, Damier P, Welter ML, Agid Y. Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. Clin Neuropharmacol. 2004 May-Jun;27(3):108-10. doi: 10.1097/00002826-200405000-00003. PMID: 15190231.
Sieradzan KA, Fox SH, Hill M, Dick JP, Crossman AR, Brotchie JM. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study. Neurology. 2001 Dec 11;57(11):2108-11. doi: 10.1212/wnl.57.11.2108. PMID: 11739835.
Gorelick DA, Goodwin RS, Schwilke E, et al. Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers. Am J Addict. 2013;22(5):510–514. doi: 10.1111/j.1521-0391.2013.12003.x
Haney M, Gunderson EW, Rabkin J, et al. Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep. J Acquir Immune Defic Syndr. 2007;45(5):545–554. doi: 10.1097/QAI.0b013e31811ed205
Maddison KJ, Kosky C, Walsh JH. Is There a Place for Medicinal Cannabis in Treating Patients with Sleep Disorders? What We Know so Far. Nat Sci Sleep. 2022 May 18;14:957-968. doi: 10.2147/NSS.S340949. PMID: 35611178; PMCID: PMC9124464.
Ranum RM, Whipple MO, Croghan I, Bauer B, Toussaint LL, Vincent A. Use of Cannabidiol in the Management of Insomnia: A Systematic Review. Cannabis Cannabinoid Res. 2023 Apr;8(2):213-229. doi: 10.1089/can.2022.0122. Epub 2022 Sep 23. PMID: 36149724.
Soliman N, Haroutounian S, Hohmann AG, Krane E, Liao J, Macleod M, Segelcke D, Sena C, Thomas J, Vollert J, Wever K, Alaverdyan H, Barakat A, Barthlow T, Bozer ALH, Davidson A, Diaz-delCastillo M, Dolgorukova A, Ferdousi MI, Healy C, Hong S, Hopkins M, James A, Leake HB, Malewicz NM, Mansfield M, Mardon AK, Mattimoe D, McLoone DP, Noes-Holt G, Pogatzki-Zahn EM, Power E, Pradier B, Romanos-Sirakis E, Segelcke A, Vinagre R, Yanes JA, Zhang J, Zhang XY, Finn DP, Rice ASC. Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain. Pain. 2021 Jul 1;162(Suppl 1):S26-S44. doi: 10.1097/j.pain.0000000000002269. PMID: 33729209; PMCID: PMC8216112.
Palmieri B, Laurino C, Vadalà M. Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination. Isr Med Assoc J. 2017 Feb;19(2):79-84. PMID: 28457055.
Nichols JM, Kaplan BLF. Immune Responses Regulated by Cannabidiol. Cannabis Cannabinoid Res. 2020 Feb 27;5(1):12-31. doi: 10.1089/can.2018.0073. PMID: 32322673; PMCID: PMC7173676.
Lowin T, Tingting R, Zurmahr J, Classen T, Schneider M, Pongratz G. Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis. 2020 Sep 1;11(8):714. doi: 10.1038/s41419-020-02892-1. PMID: 32873774; PMCID: PMC7463000.
Katz-Talmor D, Katz I, Porat-Katz BS, Shoenfeld Y. Cannabinoids for the treatment of rheumatic diseases - where do we stand? Nat Rev Rheumatol. 2018 Aug;14(8):488-498. doi: 10.1038/s41584-018-0025-5. PMID: 29884803.
Carvalho ACA, Souza GA, Marqui SV, Guiguer ÉL, Araújo AC, Rubira CJ, Goulart RA, Flato UAP, Bueno PCDS, Buchaim RL, Barbalho SM. Cannabis and Canabidinoids on the Inflammatory Bowel Diseases: Going Beyond Misuse. Int J Mol Sci. 2020 Apr 22;21(8):2940. doi: 10.3390/ijms21082940. PMID: 32331305; PMCID: PMC7215817.
Abdel-ilah Aziz, Long Chi Nguyen, Loubna Oumeslakht, Armand Bensussan, and Sanae Ben Mkaddem.
Cannabinoids as Immune System Modulators: Cannabidiol Potential Therapeutic Approaches and Limitations.
Cannabis and Cannabinoid Research.Apr 2023.254-269.http://doi.org/10.1089/can.2022.0133
Nichols JM, Kummari E, Sherman J, Yang EJ, Dhital S, Gilfeather C, Yray G, Morgan T, Kaplan BLF. CBD Suppression of EAE Is Correlated with Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation. J Neuroimmune Pharmacol. 2021 Jun;16(2):346-362. doi: 10.1007/s11481-020-09917-8. Epub 2020 May 21. PMID: 32440886; PMCID: PMC7679272.
Furgiuele A, Cosentino M, Ferrari M, Marino F. Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. J Neuroimmune Pharmacol. 2021 Jun;16(2):251-269. doi: 10.1007/s11481-021-09982-7. Epub 2021 Jan 25. PMID: 33492630; PMCID: PMC7829325.
Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. 2007 Jan;23(1):17-24. doi: 10.1185/030079906x158066. PMID: 17257464.
Raphael-Mizrahi B, Gabet Y, The Cannabinoids Effect on Bone Formation and Bone Healing. Curr Osteoporos Rep 18, 433–438 (2020). https://doi.org/10.1007/s11914-020-00607-1
Clouse G, Penman S, Hadjiargyrou M et al. Examining the role of cannabinoids on osteoporosis: a review. Arch Osteoporos 17, 146 (2022). https://doi.org/10.1007/s11657-022-01190-x
Ferreira BP, Costa G, Mascarenhas-Melo F et al. Skin applications of cannabidiol: sources, effects, delivery systems, marketed formulations and safety. Phytochem Rev (2023). https://doi.org/10.1007/s11101-023-09860-5
Koshy ST, Zhang DKY, Grolman JM, Stafford AG, Mooney DJ (2018) Injectable nanocomposite cryogels for versatile protein drug delivery. Acta Biomater 65:36–43. https://doi. org/10.1016/j.actbio.2017.11.024
Buchtova T, Lukac D, Skrott Z, Chroma K, Bartek J, Mistrik M. Drug–Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics. International Journal of Molecular Sciences. 2023; 24(3):2885. https://doi.org/10.3390/ijms24032885
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Zuzanna Lubczyńska, Jakub Przeradzki, Aleksandra Borycka, Maria Kotulska, Martyna Lichman, Barbara Jędrzejewska, Paulina Laskus, Zofia Potocka, Nikola Siekierko, Maja Żołnierek
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 586
Number of citations: 0