Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.
Open accessAbstract
To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Δ(9) -Tetrahydrocannabinol (Δ(9) -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and Δ(9) -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ(9) -THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Δ(9) -THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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CBD does not produce psychotropic effects, probably because of its low affinity for CB1 receptors.
“Unlike THC, CBD does not produce psychotropic effects and this is probably because of its low affinity for CB1 receptors 55– 57.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [56]
The ‘Cannabinoid pharmacology and mechanisms of action’ section says CBD lacks psychotropic activity and that its failure to activate CB1 and CB2 receptors likely accounts for this. It does not identify low affinity for CB1 receptors as the reason; affinity and activation are distinct claims. No page number is available in our copy. (LLM, conf=0.83)
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A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy
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- Authors
- Devinsky, O., Cilio, M. R., Cross, H., Fernandez‐Ruiz, J., French, J., Hill, C., Katz, R., Di Marzo, V., Jutras‐Aswad, D., Notcutt, W. G., Martinez‐Orgado, J., Robson, P. J., Rohrback, B. G., Thiele, E., Whalley, B., & Friedman, D.
- Affiliations
- NYU Langone Health (US)
- University of California, San Francisco (US)
- Great Ormond Street Hospital for Children NHS Foundation Trust London United Kingdom
- Department of Biochemistry and Molecular Biology Faculty of Medicine Complutense University of Madrid Center for Networked Biomedical Research on Neurodegenerative Diseases; and Ramon and Cajal Institute for Health Research Madrid Spain
- University of Reading (GB)
- Endocannabinoid Research Group (ERG) Institute of Biomolecular Chemistry National Research Council of Italy Pozzuoli Naples Italy
- Université de Montréal (CA)
- University of East Anglia (GB)
- Neonatology, Pediatric Department University Hospital Puerta de Hierro Madrid Spain
- GW Research Ltd Salisbury United Kingdom
- Infometrix, Inc. Bothell Washington U.S.A
- Massachusetts General Hospital (US)
- Corresponding author
- Devinsky, Orrin
- ORCID
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2014-05-22
- Volume
- 55
- Issue
- 6
- Pages
- 791-802
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- PMC
- PMC4707667
- OpenAlex
- W2129406235
- Cited by
- 1,000
- References
- 80
- Citations by year
- 2026: 30 · 2025: 50 · 2024: 65 · 2023: 80 · 2022: 98 · 2021: 123 · 2020: 158 · 2019: 83 · 2018: 84 · 2017: 68 · 2016: 76 · 2015: 68 · 2014: 15
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR000053, UL1TR000038)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabidiol, epilepsy, neuropsychiatric disorders, anticonvulsant mechanism, equilibrative nucleoside transporter, GPR55, TRPV1, 5-HT1A receptor, glycine receptor, neuroprotection, anti-inflammatory activity, medical cannabis, THC:CBD ratio, drug-resistant epilepsy, Dravet syndrome, Lennox-Gastaut syndrome, anxiety, schizophrenia, addiction, neonatal hypoxic-ischemic encephalopathy
- MeSH terms
- Animals, Anticonvulsants, Mental Disorders, Brain, Cannabidiol, Cannabinoids, Epilepsy, Epilepsies, Myoclonic, Humans, Phytotherapy, Intellectual Disability, Plant Extracts, Seizures, Spasms, Infantile, Lennox Gastaut Syndrome
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