Pharmacology of cannabinoids in the treatment of epilepsy

@article{Gaston2017PharmacologyOC,
  title={Pharmacology of cannabinoids in the treatment of epilepsy},
  author={Tyler E. Gaston and Daniel Friedman},
  journal={Epilepsy \& Behavior},
  year={2017},
  volume={70},
  pages={313-318}
}
Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy
TLDR
Preliminary results from a recently completed controlled trial indicate that efficacy of CBD extends to the treatment of seizures associated with the tuberous sclerosis complex and to precipitation of some adverse effects, particularly somnolence.
Cannabis for the Treatment of Epilepsy: an Update
TLDR
Understanding of CBD’s efficacy and safety in the treatment of TRE has expanded significantly in the last few years, and data from both open-label expanded access programs (EAPs) and randomized placebo-controlled trials (RCTs) of a highly purified oral preparation of CBD are presented.
Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
  • E. Perucca
  • Medicine, Psychology
    Journal of epilepsy research
  • 2017
TLDR
There is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes, for the first time, according to currently available information.
Cannabinoid therapy in epilepsy
TLDR
Based on clinical trial data, Epidiolex is the first CBD medication approved by a national regulatory agency (US Food and Drug Administration for Dravet and Lennox Gastaut syndrome) and the complete spectrum of use of cannabis-derived products, and the use of CBD for other epilepsy syndromes remains to be determined.
Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease
TLDR
Cannabidiol, through multi-target mechanisms, represents a valid therapeutic tool for the management of epilepsy, Alzheimer's disease, multiple sclerosis and Parkinson’s disease.
Therapeutic Potential of Cannabis, Cannabidiol, and Cannabinoid-Based Pharmaceuticals
TLDR
Data support a role for cannabis/cannabinoids in pain, seizure disorders, appetite stimulation, muscle spasticity, and treatment of nausea/vomiting, but much more careful research is required.
The pharmacokinetics and the pharmacodynamics of cannabinoids.
TLDR
The limited availability of applicable pharmacokinetic and pharmacodynamic information highlights the need to initiate prescribing cannabis medicines using a 'start low and go slow' approach, carefully observing the patient for desired and adverse effects.
Cannabidiol Therapy for Refractory Epilepsy and Seizure Disorders.
TLDR
Overall, adjunct CBD has been found to be generally safe and effective for treatment-resistant seizures in children with severe early-onset epilepsy, and whether an add-on CBD is efficacious for the long-term treatment of various epilepsy and seizure types in adults being tested in various clinical trials.
Investigational cannabinoids in seizure disorders, what have we learned thus far?
TLDR
Preclinical studies confirmed anticonvulsant activity of Cannabidiol and cannabidivarin in a variety of epilepsy models, and the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.
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References

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Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders
TLDR
CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic‐ischemic encephalopathy, however, data from well‐powered double‐blind randomized, controlled studies on the efficacy of pure CBD for any disorder is lacking.
Human Cannabinoid Pharmacokinetics
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TLDR
The cardiovascular and subjective effects of cannabis are blocked by rimonabant, the first CB-1 cannabinoid-receptor antagonist, documenting thatCB-1 receptors mediate these effects of smoked cannabis in humans.
Molecular Targets of Cannabidiol in Neurological Disorders
TLDR
CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent with modulation of such targets that would derive a therapeutically beneficial outcome.
Cannabinoids and Epilepsy
TLDR
These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures.
Pharmacokinetics and Pharmacodynamics of Cannabinoids
TLDR
Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.
The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy
TLDR
A role for the endogenous cannabinoid system in modulating neuroexcitation is defined and plasticity of the CB1 receptor occurs with epilepsy, and data indicate not only anticonvulsant activity of exogenously applied cannabinoids but also suggest that endogenous cannabinoid tone modulates seizure termination and duration.
Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review
TLDR
In vitro data were identified that characterize cytochrome P-450 (CYP-450) enzymes as potential significant contributors to the primary metabolism of several exogenous cannabinoids, and clinical pharmacogenetic data further support CYP2C9 as a significant contributor to THC metabolism, and a pharmacokinetic interaction study using ketoconazole with oromucosal cannabis extract further supports CYP3A4 as asignificant metabolic pathway for THC and CBD.
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