A comprehensive review cataloging the therapeutic potential of endocannabinoid-targeting drugs across dozens of conditions, while acknowledging setbacks including rimonabant's psychiatric side effects and a FAAH inhibitor trial disaster.
Read this if you want a broad overview of how the endocannabinoid system is being targeted for treating a wide range of medical conditions.
Therapeutic potential identified across dozens of conditions, from cancer to neurodegeneration
What the researchers found
This review provides a panoramic view of the endocannabinoid system as a therapeutic target, covering its role across a remarkable range of conditions: nausea, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disease, cancer, obesity, metabolic syndrome, Parkinson's, Huntington's, Alzheimer's, and Tourette's syndrome.
Approved drugs at the time included nabilone and dronabinol (for chemotherapy-induced nausea) and Sativex (for MS spasticity). Epidiolex was under investigation for childhood seizures.
The review also addressed major setbacks: rimonabant's psychiatric side effects leading to its withdrawal, and the serious adverse events in a clinical trial of a FAAH inhibitor that raised safety concerns for the entire class.
The authors identified key challenges: developing tissue-selective cannabinoid drugs, creating peripherally restricted compounds that avoid brain effects, and designing appropriate dosage forms.
Why it matters
This review provides a snapshot of the cannabinoid therapeutics landscape at a pivotal moment, when both promise and peril were evident. Understanding both the successes and failures helps contextualize the ongoing effort to develop safe, effective cannabinoid medicines.
The numbers in context
Approved drugs: nabilone, dronabinol (nausea), Sativex (MS spasticity). Under investigation: Epidiolex (seizures). Failed: rimonabant (obesity, psychiatric side effects), FAAH inhibitor (serious adverse events in trial). Dozens of potential therapeutic applications identified.
How the study worked
Comprehensive narrative review of the endocannabinoid system's therapeutic applications, covering approved drugs, drugs in development, and failed candidates across multiple disease areas.
What this study cannot tell us
Narrative review without systematic methodology. The breadth of coverage necessarily limits depth in any one area. Rapidly evolving field means some information was already outdated at publication.
How to read the evidence
Broad narrative review providing comprehensive overview but without systematic search methodology.
When this study was published
Published in 2016. Epidiolex has since been FDA-approved, and several other cannabinoid drugs have advanced or failed in development.
The bigger picture
The breadth of conditions potentially treatable through the endocannabinoid system is remarkable, but so are the challenges. The field needs to move beyond the all-or-nothing approaches of direct receptor agonists and antagonists toward more nuanced strategies like allosteric modulators, enzyme inhibitors, and peripherally restricted agents.
Questions still open
- Which of the many potential therapeutic applications will prove viable in clinical trials? Can tissue-selective cannabinoid drugs be developed to avoid systemic side effects? Will the setbacks with rimonabant and FAAH inhibitors ultimately be overcome?
Common questions
What diseases could be treated through the endocannabinoid system?
Why have some cannabinoid drugs failed?
Read the original research
Endocannabinoid System: A Multi-Facet Therapeutic Target.
Current clinical pharmacology, 11(2), 110-7
Citation
Kaur, Rimplejeet; Ambwani, Sneha R; Singh, Surjit. (2016). Endocannabinoid System: A Multi-Facet Therapeutic Target.. Current clinical pharmacology, 11(2), 110-7.
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