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The Neuroprotective & Anti-seizure Properties of Phytocannabinoids

By Sherry Christiansen

Medically reviewed by Dr. George Gavrilos, Dr. Steven Salzman

Key Takeaways

  1. Cannabinoids from plants such as cannabis (phytocannabinoids) are known to have anticonvulsant and neuroprotective properties. 
  2. A Stanford University study showed endocannabinoid action in the ECS as it unfolded in real time.  
  3. Phytocannabinoids such as CBD, CBDV, CBG, and delta-9-THCV exhibit anticonvulsant properties  
  4. A 2019 review study revealed evidence supporting the use of CBD with antiepileptic drugs as a safe and effective treatment for seizures.  

The Neuroprotective & Anti-seizure Properties of Phytocannabinoids

Epilepsy is a neurological disorder with primary symptoms of recurring seizures. The disease has no cure. Cannabinoids, such as cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC), have been shown to have anti-seizure properties. Scientists are interested in learning more about cannabinoids, particularly those that are non-psychoactive, such as cannabidiol (CBD), cannabidavarin (CBDV), delta-9-THCV (delta-9-THCV) and cannabigerol (CBG) for the treatment of seizures. Some studies have discovered that when combined, cannabinoids may potentiate the anti-seizure effects of antiepileptic medications.  

What is Epilepsy? 

Epilepsy is a neurological disorder with primary symptoms of recurring seizures. The disease has no cure. Many patients are diagnosed as having treatment-resistant epilepsy (TRE). The presence of TRE is identified when two or more antiepileptic drugs (AEDs) cannot induce seizure remission.1 

The Endocannabinoid System (ECS) & Seizure Control

In the brain, endogenous cannabinoids are thought to inhibit excessive excitement. As excitatory neurons release chemical signals, they trigger the release of endocannabinoids, which bind to CB1 on excitatory neurons to calm them down. 

According to a 2021 Stanford University School of Medicine study, a substance called 2-arachidonolyglycerol (2-AG) functions in the endocannabinoid system (ECS) to reduce seizure activity. Stanford explains that 2-AG is released in response to seizures. 2 

2-AG is considered an endocannabinoid, as compared to CBD which is a plant-based or phytocannabinoid. Cannabinoids, such as delta-9-tetrahydrocannabinol (THC) mimic the action of 2-AG in the ECS; this is how they impose their anti-seizure properties in people with epilepsy. 2 

But 2-AG has a flip side; after it is released, it starts a chain reaction of biochemical responses, resulting adverse aftereffects of a seizure, including: 

  • Constriction of blood vessels in the brain 
  • Disorientation 
  • Amnesia  

According to the study authors at Stanford, “There have been lots of studies providing evidence for a connection between seizures and endocannabinoids. What sets our study apart is that we could watch endocannabinoid production and action unfold in, basically, real time.” 

Cannabinoids & Anti-Seizure Activity

Stanford study authors reported that non-psychoactive phytocannabinoids, cannabidiol (CBD), cannabidavarin (CBDV), delta-9-THCV (Δ9-THCV) and cannabigerol (CBG), have anti-seizure properties and a favorable side-effect profile (i.e., minimal side effects). They speculated that phytocannabinoids “present a [realistic] solution to the neurodegenerative deficits associated with epilepsy. A clear neuroprotective/neurogenerative characteristic has been identified and associated with these phytocannabinoid compounds.” 2

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Studies

2021 Review Study 

In many neurological disorders, phytocannabinoids have shown therapeutic benefits. According to a 2021 review, three phytocannabinoids (CBDV, THCV, CBG) that have not been extensively studies, might be effective anticonvulsants.1  The review study encourages further investigation of these compounds through the lens of epilepsy  — particularly for younger patients — based on their molecular targets and their preclinical results.1  In addition to seizure reducing properties, these phyotocannaboids (e.g., CBDV, THCV, and CBG) also have neurogerative and neuroprotective properties. 

2019 Review of Clinical Trials 

 A 2019 review study, published in the journal, “Molecules,” concluded that randomized controlled clinical research studies revealed evidence that CBD was safe and effective when administered as an adjunctive treatment to common antiepileptic drugs (AEDs). The study reiterated that the exact mechanism by which CBD is effective when given along with AEDs is not completely understood because of the many metabolic pathways and molecular targets involved, some of which are not yet known.4 

Resources

  1. Farrelly AM, Vlachou S, Grintzalis K. Efficacy of phytocannabinoids in epilepsy treatment: novel approaches and recent advances. IJERPH. 2021;18(8):3993. doi: 10.3390/ijerph18083993 
  2. Stanford University School of Medicine. Marijuana-like brain substance calms seizures but increases aftereffects, study finds. Published April, 2021.  
  3. Billakota S, Devinsky O, Marsh E. Cannabinoid therapy in epilepsy. Current Opinion in Neurology. 2019;32(2):220-226. doi:10.1097/wco.0000000000000660  
  4. Silvestro S, Mammana S, Cavalli E, Bramanti P, Mazzon E. Use of cannabidiol in the treatment of epilepsy: efficacy and security in clinical trials. Molecules. 2019;24(8):1459. doi:10.3390/molecules24081459  
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