Cannabidiol or CBD Oil: Help,Hope,and Hype for Psychiatric and Neurologic Conditions

Abstract

OBJECTIVE: This article presents proven, promising, and potential therapeutic uses for cannabidiol (CBD) in the treatment of psychiatric and neurologic conditions and diseases. It presents popular, but scientifically unproven health and therapeutic claims of CBD supporting the beneficial homeostatic effects of the intrinsic or endogenous cannabinoid system. It includes a review of cannabinoid pharmacology; it compares properties and the legal status of CBD and THC (delta 9-tetrahydrocannabinol) as well as the hemp and marijuana varieties of Cannabis, and it reviews the historic 2018 U.S. Food and Drug Administration approval of Epidiolex, an oral solution of cannabidiol for two rare treatment-resistant childhood epilepsies, as the first Cannabis-derived drug. METHOD: We reviewed literature on cannabidiol, CBD, the endocannabinoid neuropharmacology system, and hemp and marijuana varieties of Cannabis sativa. RESULTS: The proven and promising medical uses and deficiencies of unproven health claims for CBD, legal implications for Cannabis-derived drugs, and comparisons of CBD and THC and hemp and marijuana are summarized objectively with pertinent references. CONCLUSION: CBD and CBD and THC combinations have potential to provide safe, effective therapy for several psychiatric and neurologic conditions and diseases. However, such achievement will require a uniform standard of CBD purity and strength, and corroboration from adequately large and rigorously controlled clinical research studies.

Keywords

cannabidiol cannabis CBD endocannabinoids hemp

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References

American Psychological Association. (2017). Prolonged exposure (PE). https://www.apa.org/ptsd-guideline/treatments/prolonged-exposure

Americans for Safe Access. (2019). Patient’s guide to CBD. https://www.safeaccessnow.org/patientscbd

Atakan

(2012). Cannabis, a complex plant: Different compounds and different effects on individuals. Therapeutic Advances in Psychopharmacology, 2(6), 241–254. 10.1177/2045125312457586

Bergamaschi

M.M.

Queiroz

R.H.

Chagas

M.H.

de Oliveira

D.C.

De Martinis

B.S.

Kapczinski

Quevedo

Roesler

Schröder

Nardi

A. E.

Martín-Santos

Hallak

J. E.

Zuardi

A. W.

Crippa

J. A.

(2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology, 36(6), 1219-1226.

Black

Stockings

Campbell

Tran

L.T.

Zagic

Hall

W.D.

Farrell

Degenhardt

(2019). Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis. Lancet Psychiatry, 6(12), 995-1010. https://doi.org/10.1016/S2215-0366(19)30401-8

Boggs

D. L.

Surti

Gupta

Niciu

Pittman

Schnakenberg Martin

A. M.

Thurnauer

Davies

D’Souza

D. C.

Ranganathan

(2018). The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology, 235(7), 1923-1932. https://doi.org/10.1007/s00213-018-4885-9

Bonn-Miller

Loflin

M.J.E.

Thomas

B.F.

Marcu

J.P.

Hyke

Vandrey

(2017). Labeling accuracy of cannabidiol extracts sold online. Journal of the American Medical Association, 318(17), 708-1709. https://doi.org/10.1001/jama.2017.11909

Bridgeman

M.B.

Abazia

D.T.

(2017). Medicinal cannabis: history, pharmacology, and implications for the acute care setting. Pharmacology and Therapeutics, 42(3), 180-188.

Cadena

(2019a). Is CBD Legal? The legal status of CBD in 2019. https://cbdorigin.com/is-cbd-legal/

10.

Cadena

(2019b). Hemp vs Marijuana: The difference explained. https://cbdorigin.com/hemp-vs-marijuana/

11.

CDC Health Alert Network. (2019). Severe pulmonary disease associated with using e-cigarette products. https://emergency.cdc.gov/han/han00421.asp

12.

Congressional Research Service. (2019). Defining hemp: A fact sheet. https://fas.org/sgp/crs/misc/R44742.pdf

13.

Corroon

J. M.

Mischley

L. K.

Sexton

(2017). Cannabis as a substitute for prescription drugs—A cross-sectional study. Journal of Pain Research, 10, 989-998. https://doi.org/10.2147/JPR.S134330

14.

Crippa

J. A. S.

Derenusson

G. N.

Ferrari

T. B.

Wichert-Ana

Duran

F. L. S.

Martin-Santos

Simões

M. V.

Bhattacharyya

Fusar-Poli

Atakan

Santos Filho

Freitas-Ferrari

M. C.

McGuire

P. K.

Zuardi

A. W.

Busatto

G. F.

Hallack

J. E. C.

(2011). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. Journal of Psychopharmacology, 25(1), 121-130. https://doi.org/10.1177/0269881110379283

15.

Daley

(2019). CBD: Rising star or popular fad? The Conversation. https://theconversation.com/cbd-rising-star-or-popular-fad-110146

16.

Donvito

Nass

S. R.

Wilkerson

J. L.

Curry

Z. A.

Shurman

L. D.

Kinsey

S. G.

Lichtman

A. H.

(2018). The endogenous cannabinoid system: A budding source of targets for treating inflammatory and neuropathic Pain. Neuropsychopharmacology, 43(1), 52-79. https://doi.org/10.1038/npp.2017.204

17.

Dorbian

(2019). CBD market could pull in $16 billion by 2025, says study. https://www.forbes.com/sites/irisdorbian/2019/03/12/cbd-market-could-pull-in-16-bln-by-2025-says-study/#2275f0613efd

18.

Drugs.com. (2018) Epidiolex. https://www.drugs.com/epidiolex.html

19.

Elms

Shannon

Hughes

Lewis

(2019). Cannabidiol in the treatment of post-traumatic stress disorder: A case series. Journal of Alternative and Complementary Medicine, 25(4), 392-397. https://doi.org/10.1089/acm.2018.0437

20.

Fiorillo

(2019). Is CBD oil legal in 2019? State-by-state and future legality. https://www.thestreet.com/lifestyle/health/is-cbd-oil-legal-14802001

21.

Fraser

G. A.

(2009). The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS Neuroscience and Therapeutics, 15(1), 84-88. https://doi.org/10.1111/j.1755-5949.2008.00071.x

22.

Giuffrida

Leweke

F.M.

Gerth

C.W.

Schreiber

Koethe

Faulhaber

Klosterkötter

Piomelli

(2004). Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology, 29(11), 2108-2114. https://doi.org/10.1038/sj.npp.1300558

23.

Grinspoon

(2018). Cannabidiol (CBD)—What we know and what we don’t. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476

24.

Gupta

(2013). Weed: A CNN special report. https://www.cnn.com/2013/08/08/health/gupta-changed-mind-marijuana/index.html

25.

Gupta

(2019). Weed 5: the CBD craze. Dr. Sanjay Gupta on medical marijuana: We are in an age of wisdom, but also an age of foolishness. https://www.cnn.com/2019/09/27/health/weed-5-cbd-craze-gupta/index.html

26.

GW Pharma, Ltd. (2015). Sativex product monograph. https://www.bayer.ca/omr/online/sativex-pm-en.pdf

27.

GW Pharmaceuticals, PLC. (2018). EPIDIOLEX® (cannabidiol) Oral Solution—The first FDA-approved Plant-derived Cannabinoid Medicine—Now Available by Prescription in the U.S. http://ir.gwpharm.com/news-releases/news-release-details/epidiolexr-cannabidiol-oral-solution-first-fda-approved-plant

28.

GW Pharmaceuticals, PLC. (2019). Sativex. https://www.gwpharm.com/healthcare-professionals/sativex

29.

Harrar

(2019). Medical marijuana. AARP Bulletin, 60(7, September), 10-12, 14, 16, 18, 20.

30.

Hollander

(2019). Cannabidivarin (CBDV) vs. placebo in children with autism spectrum disorder (ASD). ClinicalTrials.gov Identifier: NCT03202303. https://clinicaltrials.gov/ct2/show/NCT03202303

31.

Howlett

A. C.

Abood

M. E.

(2017). CB₁ & CB₂ receptor pharmacology. Advances in Pharmacology, 80, 169-206. https://doi.org/10.1016/bs.apha.2017.03.007

32.

Hudak

(2018). The Farm Bill, hemp legalization and the status of CBD: an explainer. https://www.brookings.edu/blog/fixgov/2018/12/14/the-farm-bill-hemp-and-cbd-explainer/

33.

Jaeger

(2019). This is why federal agencies are warning employees about CBD. https://www.marijuanamoment.net/this-is-why-federal-agencies-are-warning-employees-about-cbd/

34.

Jones

(2019). GW Pharma’s cannabis-based medicine to be tested in dementia. https://www.pmlive.com/pharma_news/gw_pharmas_cannabis-based_medicine_to_be_tested_in_dementia_1278436?SQ_DESIGN_NAME=2

35.

Kaplan

(2019). Cannabis companies push FDA to ease rules on CBD products. https://www.nytimes.com/2019/05/31/health/cannabis-fda-regulate.html

36.

Kubala

(2018). 7 benefits and uses of CBD oil (plus side effects). https://www.healthline.com/nutrition/cbd-oil-benefits

37.

Lafaye

Karila

Blecha

Benyamina

(2017). Cannabis, cannabinoids, and health. Dialogues in Clinical Neuroscience, 19(3), 309-316.

38.

Laprarie

R. B.

Bagher

A. M.

Kelly

M. E.

Denovan-Wright

E. M.

(2015). Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. British Journal of Pharmacology, 172(20), 4790-4805. https://doi.org/10.1111/bph.13250

39.

Leweke

F. M.

(2012). Anandamide dysfunction in prodromal and established psychosis. Current Pharmaceutical Design, 18(32), 5188-5193. https://doi.org/10.2174/138161212802884843

40.

Leweke

F. M.

Piomelli

Pahlisch

Muhl

Gerth

C. W.

Hoyer

Klosterkötter

Hellmich

Koethe

(2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational psychiatry, 2(3), e94. https://doi.org/10.1038/tp.2012.15

41.

H-C.

Mackie

(2016). An introduction to the endogenous cannabinoid system. Biological Psychiatry, 79(7), 516-525. https://doi.org/10.1016/j.biopsych.2015.07.028

42.

McGuire

Robson

Cubala

W. J.

Vasile

Morrison

P. D.

Barron

Taylor

Wright

(2018). Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. American Journal of Psychiatry, 175(3), 225-231. https://doi.org/10.1176/appi.ajp.2017.17030325

43.

Minichino

Senior

Brondino

Zhang

S. H.

Godlewska

Burnet

P. W. J.

. . . Lennox

(2019). Measuring disturbance of the endocannabinoid system in psychosis: a systematic review and meta-analysis. JAMA Psychiatry, 76(9), 914-923. https://doi.org/10.1001/jamapsychiatry.2019.0970

44.

National Cancer Institute. (2019). Cannabis and cannabinoids (PDQ®)—Health professional version. https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq

45.

National Institute on Drug Abuse. (2019). Opioid overdose crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis

46.

Natural Force. (2019). Hemp oil vs CBD oil: Everything you need to know. https://naturalforce.com/blogs/nutrition/hemp-oil-vs-cbd-oil

47.

Neumeister

Normandin

M.D.

Peitrzak

R.H.

Piomelli

Zheng

M.Q.

Gujarro-Anton Potenza

M. N.

Bailey

C. R.

Lin

S. F.

Najafzadeh

Ropchan

Henry

Corsi-Travali

Carson

R. E.

Huang

(2013). Elevated brain cannabinoid CB₁ receptor availability in post-traumatic stress disorder: a positron emission tomography study. Molecular Psychiatry, 18(9), 1034-1040. https://doi.org/10.1038/mp.2013.61

48.

Nichols

(2019). “The FDA is struggling”: Former US Surgeon General Carmona on government’s approach to CBD. https://hempindustrydaily.com/former-us-surgeon-general-richard-carmona-talks-about-cbd-trend/

49.

Pacher

Batkai

Kunos

(2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacological Reviews, 58(3), 389-462. https://doi.org/10.1124/pr.58.3.2

50.

Paton

(2019). THC overdose: Has first death from marijuana exposure been recorded in the United States? https://www.newsweek.com/thc-overdose-death-marijuana-exposure-united-states-1442742

51.

Pertwee

R. G.

(2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. British Journal of Pharmacology, 156(3), 397-411. https://doi.org/10.1111/j.1476-5381.2008.00048.x

52.

Perucca

(2017). Cannabinoids in the treatment of epilepsy: hard evidence at last? Journal of Epilepsy Research, 7(2), 61-76. https://doi.org/10.14581/jer.17012

53.

Petkovic

(2019). Hemp oil vs CBD oil: How different are they exactly? https://loudcloudhealth.com/hemp-oil-vs-cbd-oil/

54.

Pierre

J. M.

(2019). Cannabidiol (CBD) for schizophrenia: Promise or pipe dream? Current Psychiatry, 18(5), 12-16, 19-20.

55.

Project CBD. (2019). What is CBD? https://www.projectcbd.org/cbd-101/what-is-cbd

56.

Rawls

(2019). The CBD oil: Everything you need to know. https://rawlsmd.com/health-articlesciencebehind/science-behind-cbd-everything-want-know

57.

Royal Society of Chemistry. (2019a). CBD. http://www.chemspider.com/Chemical-Structure.24547.html

58.

Royal Society of Chemistry. (2019b). (−)-δ-9-trans-Tetrahydrocannabinol. http://www.chemspider.com/Chemical-Structure.15266.html

59.

Rudd

(2018). CBD vs THC—What are the main differences? https://www.analyticalcannabis.com/articles/cbd-vs-thc-what-are-the-main-differences-297486

60.

Sadock

B. J.

Sadock

V. A.

Ruiz

(2017). Kaplan & Sadock’s comprehensive textbook of psychiatry (10th ed.; Vol. 1; pp. 1303-1312). Walters Kluwer.

61.

Samuelsson

(2000). The discovery of the leukotrienes. American Journal of Respiratory and Critical Care Medicine, 61(Suppl. 1), S2-S6. https://doi.org/10.1164/ajrccm.161.supplement_1.ltta-1

62.

Sanders

(2019). The CBD boom is way ahead of the science. https://www.sciencenews.org/article/cbd-product-boom-science-research-hemp-marijuana

63.

Sides

Johnson

(2015). High science. National Geographic, 227(6), 30-57.

64.

Tesséra Naturals. (2019). Hemp oil vs CBD oil. https://tesseranaturals.com/hemp-oil-vs-cbd-oil/

65.

United Nations Office on Drugs and Crime. (2017). World drug report. https://www.unodc.org/wdr2017/field/WDR_2017_presentation_lauch_version.pdf

66.

United States Pharmacopeial Convention, Inc. (2019) United States Pharmacopeia 42–National Formulary 37. Digoxin.

67.

Urits

Borchart

Hasegawa

Kochanski

Orhurhu

Viswamath

(2019). An update of current Cannabis-based pharmaceuticals in pain medicine. Pain and Therapy, 8(1), 41-51. https://doi.org/10.1007/s40122-019-0114-4

68.

U.S. Code Title 21-Food and Drugs, Chapter 9-Federal Food, Drug and Cosmetic Act . (2018). https://uscode.house.gov/view.xhtml?path=/prelim@title21/chapter9&edition=prelim

69.

U.S. Drug Enforcement Administration. (2018). Schedules of controlled substances: Placement in Schedule V of Certain FDA-approved drugs containing cannabidiol; corresponding change to permit requirements. https://www.federalregister.gov/documents/2018/09/28/2018-21121/schedules-of-controlled-substances-placement-in-schedule-v-of-certain-fda-approved-drugs-containing

70.

U.S. Food and Drug Administration. (2006). Cesamet (nabilone) oral capsules full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf

71.

U.S. Food and Drug Administration. (2018). Epidiolex (cannabidiol) oral solution full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

72.

U.S. Food and Drug Administration. (2019). Remarks by Dr. Sharpless at the FDA public hearing on scientific data and information about products containing cannabis or cannabis-derived compounds. https://www.fda.gov/news-events/speeches-fda-officials/remarks-dr-sharpless-fda-public-hearing-scientific-data-and-information-about-products-containing

73.

U.S. Senate. (2018). Agriculture Improvement Act of 2018. https://www.agriculture.senate.gov/imo/media/doc/Agriculture%20Improvement%20Act%20of%202018.pdf

74.

VA Office of Research and Development. (2019). Cannabidiol as an Adjunctive to prolonged exposure for the treatment of PTSD. ClinicalTrials.gov Identifier: NCT03518801. https://clinicaltrials.gov/ct2/show/NCT03518801?term=cbd&cond=ptsd&draw=2&rank=1

75.

Wan

(2019). Many unanswered questions, concerns about CBD products, says FDA acting chief at first public hearing. https://www.washingtonpost.com/business/2019/05/31/amid-flood-cbd-products-fda-holds-first-public-hearing-cannabis-extract/?utm_term=.af68c83a1a7a

76.

World Health Organization. (2016). The health and social effects of nonmedical cannabis use. https://www.who.int/substance_abuse/publications/msbcannabis.pdf

77.

World Health Organization. (2017). CANNABIDIOL (CBD) Pre-Review Report, Agenda Item 5.2. Thirty-ninth meeting. Geneva, November 6-10. https://www.who.int/medicines/access/controlled-substances/5.2_CBD.pdf

78.

Wong

(2019). CBD Oil: Benefits, uses, side effects, and safety. https://www.verywellhealth.com/cbd-oil-benefits-uses-side-effects-4174562

79.

Yakish

T. L.

Wallace

M. S.

(2011). Opioids, Analgesia and Pain Management. In Brunton

L. L.

Chabner

B. A.

Knollman

B. C.

(Eds.), Goodman & Gilman’s the pharmacological basis of therapeutics (12th ed.; pp. 482-484). McGraw-Hill.

80.

Zou

Kumar

(2018). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International Journal of Molecular Sciences, 19(3), E833. https://doi.org/10.3390/ijms19030833

81.

Zuardi

A. W.

Rodrigues

N. P.

Silva

A. L.

Bernardo

S. A.

Hallak

J. E. C.

Guimarães

F. S.

Crippa

J. A. S.

(2017). Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Frontiers in Pharmacology, 8, 259. https://doi.org/10.3389/fphar.2017.00259