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Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration

The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.

Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.

Authors: Serena Silvestro, Santa Mammana, Eugenio Cavalli, Placido Bramanti, Emanuela Mazzon
Molecules, April 2019

Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, n…

Cannabis use predicts risks of heart failure and cerebrovascular accidents: results from the National Inpatient Sample.

Authors: Aditi Kalla, Parasuram Krishnamoorthy, Akshaya Gopalakrishnan, Vincent Figueredo
Journal of Cardiovascular Medicine, September 2018

BACKGROUND: Cannabis for medicinal and/or recreational purposes has been decriminalized in 28 states as of the 2016 election. In the remaining states, cannabis remains the most commonly used illicit drug. Cardiovascular effects of cannabis use are not well established due to a…

Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence.

Authors: Emily Stockings, Dino Zagic, Gabrielle Campbell, Megan Weier, Wayne D Hall, et al
Journal of Neurology, Neurosurgery & Psychiatry, July 2018

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerab…

Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

Authors: Giulia S. Porcaria, Cary Fub, Emily D. Doll, Emma G. Carter, Robert P. Carson
Epilepsy & Behavior, March 2018

Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has rece…

Cannabinoids in treatment-resistant epilepsy: A review.

Authors: Brooke K. O’Connell, David Gloss, Orrin Devinsky
Epilepsy & Behavior, May 2017

Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality. Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequ…

Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex.

Authors: Evan J. Hess, Kirsten A. Moody, Alexandra L. Geffrey, Sarah F. Pollack, et al
Epilepsia, October 2016

OBJECTIVE: Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment-resistant epilepsy. He…

Δ9-THC Intoxication by Cannabidiol-Enriched Cannabis Extract in Two Children with Refractory Epilepsy: Full Remission after Switching to Purified Cannabidiol.

Authors: José A. S. Crippa, Ana C. S. Crippa, Jaime E. C. Hallak, Rocio Martín-Santos, Antonio W. Zuardi
Frontiers in Pharmacology, 30 September 2016

Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the c…

Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.

Authors: Ethan B. Russo
Cannabis and Cannabinoid Research, 1 July 2016

Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected p…

Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial.

Authors: Orrin Devinsky, Eric Marsh, Daniel Friedman, Elizabeth Thiele, Linda Laux, et al
The Lancet Neurology, March 2016

BACKGROUND: Almost a third of patients with epilepsy have a treatment-resistant form, which is associated with severe morbidity and increased mortality. Cannabis-based treatments for epilepsy have generated much interest, but scientific data are scarce. We aimed to establish w…

Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy.

Authors: Alexandra L. Geffrey, Sarah F. Pollack, Patricia L. Bruno, Elizabeth A. Thiele
Epilepsia, August 2015

OBJECTIVE: Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are…

Use of cannabis in severe childhood epilepsy and child protection considerations.

Authors: Megan Yap, Laura Easterbrook, Jan Connors, Laura Koopmans
Journal of Paediatrics and Child Health, May 2015

The use of medical cannabis in chronic illness is increasingly investigated, yet little is known about its use in paediatric populations. As child protection clinicians are often asked to provide advice around whether parents’ actions to give medical cannabis to their chronica…