Cannabis Therapeutics and the Future of Neurology

Ethan B. Russo  (October 2018)

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After elucidation of phytocannabinoid structures in the 1960s, their pharmacology was slowly revealed (reviewed by Cascio and Pertwee, 2014; Pertwee and Cascio, 2014; Russo and Marcu, 2017; Figure 1). Various components were tested for anticonvulsant activities with findings of ED50in mice of 80 mg/kg for tetrahydrocannabinol (THC), 120 mg/kg for cannabidiol (CBD) and 200 mg/kg for tetrahydrocannabinolic acid A (THCA-A), the carboxylic acid precursor to THC found in raw cannabis flowers (Karler and Turkanis, 1979). Although dose-response was tested, it is unclear that very low doses were assessed and given the biphasic tendencies of cannabinoids, it is possible that positive lower dose effects may have remained unnoticed. CBD was considered an excellent candidate for development based on its lack of untoward psychoactive sequelae.

Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study

Jerzy P. SzaflarskiElizabeth Martina BebinGary Cutter, Jennifer DeWolfeLeon S.Dure, Tyler E. GastonPongkiat Kankirawatana, Yuliang Liu, Rani SinghDavid G. Standaert, Ashley E. ThomasLawrence W. Ver Hoef  (August 2018)

The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures.

A prospective open‐label trial of a CBD/THC cannabis oil in dravet syndrome

Bláthnaid McCoy, Laura Wang, Maria Zak, Sameer Al‐Mehmadi, Nadia Kabir, Kenda Alhadid, Kyla McDonald, Grace Zhang, Rohit Sharma, Robyn Whitney, Katia Sinopoli and O. Carter Snead III  (August 2018)

Despite the expansion of available antiepileptic drugs (AED), dietary, and surgical therapies in the last 20 years, up to 30% of children with epilepsy continue to have seizures, termed drug‐resistant epilepsy. Twenty children received add‐on therapy with TIL‐TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC. Twenty children received add‐on therapy with TIL‐TC150. The dose ranged from 2 to 16 mg/kg/day of CBD and 0.04 to 0.32 mg/kg/day of THC.

Investigating the mechanisms of action of phytocannabinoids and a novel cognitive enhancer to target the comorbidity of temporal lobe epilepsy

Khan, Archie Arunima  (July 2018)

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Temporal lobe epilepsy (TLE) is the most common type of epilepsy and exists with memory loss as a comorbidity. The conventional therapy available to treat these disorders achieves only modest therapeutic efficacy at best. This study investigates two potential treatments: phytocannabinoids to alleviate seizures, and a novel cognitive enhancer to restore/halt memory deficits.

Cannabidiol in Pediatric Epilepsy

Dallas Armstrong and Eric Marsh  (January 2018)

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Cannabidiol has been well-tolerated in pediatric patients and may be an effective treatment for medically intractable epilepsy. Future studies that control for concomitant administration of clobazam and/or valproic acid are necessary.

Cannabinoids for epilepsy: What do we know and where do we go?

Martin J. Brodie and Elinor Ben-Menachem  (Dember 2017)

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Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients. The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use.

Cannabinoids in Pediatrics

Christopher T. CampbellPharmDMarjorie Shaw PhillipsMS; and Kalen ManascoPharmD  (June 2017)

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Many providers have started encountering patients experimenting with cannabis products for a wide range of conditions. While the debate continues regarding these agents for both medicinal and recreational use in the general population, special consideration needs to be made for pediatric use. This review will deliver the history of marijuana use and legislation in the United States in addition to the currently available medical literature to equip pediatric health care providers with resources to provide patients and their parents the best recommendation for safe and appropriate use of cannabis-containing compounds.

Cannabinoids for Epilepsy — Real Data, at Last

Samuel F. Berkovic  (May 2017)

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Medicinal cannabis is a hot-button issue in the treatment of epilepsy. The issue of its use is frequently raised in medical consultations, in the lay press, in social media, and at scientific meetings where the lack of hard data is disheartening. Anecdotal media reports of spectacular results, coupled with the allure of using a “natural” compound and long-held beliefs surrounding its recreational use, plus the fact that medicinal cannabis remains illegal in many jurisdictions, have conspired to make it extremely difficult for physicians to provide advice in this area.

Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?

Mauro Maccarrone, Rafael MaldonadoMiguel Casas, Thomas Henze and Diego Centonze  (February 2017)

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 From the different therapeutic possibilities, THC/CBD oromucosal spray has been in clinical use for approximately five years in numerous countries world-wide for the management of multiple sclerosis (MS)-related moderate to severe resistant spasticity. Clinical trials have confirmed its efficacy and tolerability. Other diseases in which different cannabinoids are currently being investigated include various pain states, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and epilepsy. The continued characterization of individual cannabinoids in different diseases remains important.

The Utility of Cannabidiol in the Treatment of Refractory Epilepsy

DS Reddy  (August 2016)

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Cannabis‐derived cannabinoids such as cannabidiol (CBD) have anticonvulsant properties. Recently, there has been an emerging interest in the use of CBD‐enriched products for treatment of drug‐resistant epilepsy. Some pilot trials of CBD have proved beneficial for refractory epilepsy, but its efficacy is yet to be confirmed by standard placebo‐controlled trials. However, the mechanisms underlying the seizure protection efficacy claims of CBD remain unclear. This review briefly describes the clinical utility of CBD in the treatment of refractory epilepsy.

Cannabinoids in the Treatment of Epilepsy

Daniel Friedman, M.D. and Orrin Devinsky, M.D.  (September 2015)

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The pharmacologic and biochemical features of cannabinoids make them candidates for antiseizure medications. At this time, anecdotes have outstripped controlled clinical trials as sources of support for their clinical value.