THC

Marijuana for the treatment of epilepsy: A review

/in , , /by

By: Lauren Hammond

Leticia Shea, PharmD, BCACP

Robin Wackernah, PharmD, BCPP

Matt Fete, PhD

 

Abstract

The use of Cannabis is extensive and dynamic, dependent not only on the strain of the plant, but also on the formulation and the vehicle used for administration. Several different constituents of the plant, known as phytocannabinoids, have been studied for numerous conditions, including amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia, anxiety disorders and for the use in pain management.1,2,3 This article aims to provide a review of the research findings for the use of marijuana in epilepsy, including the phytocannabinoids with the most evidence shown to inhibit or diminish seizure propagation. In addition, the pathways that determine formulations for administration and a review of drug resistant epilepsy will be discussed.

Introduction

There are numerous medications and treatment options for epilepsy that have been researched in clinical trials and brought to the market in the standard, evidenced-based medicine format. Regardless, many patients with epilepsy remain resistant to treatment options and seek additional therapies for better management of their condition. In the United States it is determined that of the 3 million people that live with epilepsy, 1 million are resistant to treatment and present with uncontrolled seizures regardless of their current medication therapy.4 Many medications approved for epilepsy come with intolerable side effects that may hinder patient compliance. Marijuana research is lacking well designed clinical trials as a result of local and federal regulation.  This, however, has not stopped in-vitro and in-vivo studies. In the 1980’s two double-blinded studies with small samples sizes examined the  use the phytocannabinoid cannabidiol (CBD), in the treatment of epilepsy.5,6 Although CBD has demonstrated anticonvulsant properties, conflicting studies suggest  that other phytocannabinoids in Cannabis provide a synergistic antiepileptic benefit that cannot be achieved with CBD alone. Much of the data to support the use of marijuana in the treatment of epilepsy is based on research examining signaling pathways where different active moieties of Cannabis target, modulate and interfere with signaling responsible for seizure propagation. These initial findings provide foundational support for continued research to further determine and examine potential therapeutic benefits of marijuana in the treatment of epilepsy.

Epilepsy

Epilepsy is a broad term encompassing numerous syndromes that feature unprovoked seizure activity. The type of seizure, origination and progression can vary and the exact mechanism(s) are not fully understood. It is generally accepted that seizures occur as a result of excessive cerebral neuron discharge.7 Oscillations in excitatory activity within the brain have also been determined to be a likely factor in particular types of seizure induction.8 Phytocannabinoids such as delta (9)-tetrahydrocannabinol (THC) and CBD interact with receptors that may inhibit excitatory activity and also prevent the breakdown of endogenous cannabinoids, (endocannabinoids), which may further prevent excessive activity.

Drug Resistant Epilepsy

Drug resistant epilepsy (DRE) is defined as the inability to achieve complete seizure elimination after an adequate trial of two AEDs at therapeutic doses when used as either monotherapy or in conjunction with other anti-epileptic drugs (AEDs).9 In accordance with this definition, approximately 30-35% of patients meet the criteria for DRE.10 A population based study in Singapore reported 21.5% of patients having DRE.11

While the exact cause of DRE has not been fully elucidated, there several mechanisms proposed.  Theories include increased p-glycoprotein expression12, alterations in gamma-aminobutyric acid A (GABA) expression13, genetic polymorphisms14 and cell death secondary to mitochondrial dysfunction.15

DRE impacts a patient’s quality of life, specifically; it is associated with reduced cognition, reduced energy, altered social functioning and an overall lowered emotional well-being.16 Additionally, patients with DRE may have an increased risk of death.  High seizure frequency, multiple AEDs and years with epilepsy are potential theories that may clarify the causes of sudden unexplained death in epilepsy.17 Although not strongly demonstrated, death secondary to cardiac conduction abnormalities in DRE has also been reported.18 This reduced quality of life and increased chance of mortality emphasizes the need for medications that utilize novel mechanistic targets.   Currently, the primary mechanisms for AEDs focus on sodium or calcium channels and enhancement of GABA or inhibition of glutamate. In addition to Cannabis, glial cells19, brain derived neurotrophic factor20 interleukin-1 beta receptor caspase 1 inhibitors21 are all potential targets for the treatment of DRE.

Endocannabinoid system

The endocannabinoid system (ECS) is comprised of endogenous lipid ligands, endocannabinoids, and their receptors. It has numerous effects on the body and there remains opportunity for discovery of additional biological effects.  The main receptors of interest are G-protein-coupled cannabinoid-1 (CB1R) and cannabinoid-2 (CB2R). Our review focuses on CB1R due to its effects on neuronal transmission and how this may play a role in the prevention of seizure induction and/or propagation. CB2R is generally associated with immune function and expressed only in the periphery.22,23

CB1R is the most predominant of the two receptors and is largely expressed in the brain (substantia nigra, globus pallidus, hippocampus, cerebral cortex, putamen, caudate, cerebellum, and amygdala), with limited expression in adipose and hepatocyte tissue.22 CB1R can be activated by endogenous or exogenous cannabinoids.24 Endogenous cannabinoids, known as endocannabinoids, include anandamide (AEA) and 2-arachidonoyl glycerol (2-AG).  AEA and 2-AG are responsible for the regulation of the endocannabinoid system. They are made on demand, from increased neuronal excitability.25 Fatty acid amide hydrolase (FAAH) catabolizes AEA and monacylglycerol lipase degrades 2-AG. These are all important modulators of regulation in the ECS.22 Neuronal excitability triggers the release of endocannabinoids into the synaptic cleft from the postsynaptic neuron where they bind to presynaptic neuron CB1R resulting in inhibition of neurotransmitter release at both excitatory and inhibitory synapses.26,27  This inhibits the release of either glutamate or GABA.28 Evidence suggests that activation of CB1R on glutamatergic rather than GABAergic terminals is required for antiepileptic action of endogenous cannabinoids.29 This brief discussion of the ECS highlights the complexity of these poorly understood pathways. Research has shown that exogenous cannabinoids that interact at these receptors, including THC and CBD, provide distinctly different responses, and yet both have been shown to provide benefit in inhibiting or slowing seizure propagation. It is beyond the scope of this review to analyze all of the mechanisms responsible for Cannabis ’activity. Our goal is to highlight the complexity of the various cannabinoids found within Cannabis and summarize what research has been done with these cannabinoids in relation it their use in epilepsy.

Endocannabinoids Studied for the Use in Epilepsy

The two most common phytocannabinoids in marijuana are THC and CBD.  Both compounds, which can be derived from either strain of marijuana, Cannabis sativa or Cannabis indica, have been shown to have anticonvulsant and antiepileptic properties.22 Of the many phytocannabinoids present in Cannabis, THC and CBD are the 2 constituents with research to support their use in epilepsy. THC is the major psychoactive component of marijuana whereas CBD is the primary nonpsychoactive component. The interaction and effect when THC binds to CB1R (and CB2R) is dramatically different than that of CBD.30 THC binds to both CB1R and CB2R with relatively high affinity but lower than known synthetic CB1/CB2 receptor agonist WIN 55,212-2. WIN 55, 212-2 is a synthetic CB1/CB2 agonist which has been studied to evaluate the numerous effects of binding to cannabinoid receptors.28 THC resembles AEA affinity for CB1R but has lower efficacy than the synthetic agonists, suggesting THC to be a partial agonist.28 There is evidence to support that CBD acts as an antagonist at CB1R and CB2R. Although CBD has been determined to have low affinity for both of these receptors, it has exhibited high potency.30  The fact that THC exhibits partial agonist activity at CB1R whereas CBD exhibits antagonist activity at this receptor exemplifies the distinct differences involved with these two phytocannabinoids and their activities on receptors in the brain. Considering that THC and CBD both possess antiepileptic properties while exerting different effects on neuronal activity creates additional questions related to their clinical use in epilepsy. It may be that when THC and CBD are both used together they may provide benefit, however the ratios in relation to each other and dosing parameters are not clearly defined. Additionally, both cannabinoids have activity beyond CB1R and CB2R. It has been suggested that CBD may exhibit anti-epileptic properties as a result of multiple interactions with other receptors and ion channels.27, 31 CBD is speculated to have effects on receptors such as transient receptor potential channels, PPARϒ, GPR55, GPR18, 5HT1A and VDAC1.31, 32 When GPR55 is agonized in the brain, it mobilizes intracellular calcium elevating the presynaptic amount of calcium resulting in glutamate release.27  Interestingly, CBD is a GPR55 antagonist which would aid in glutamate release inhibition, thus decreasing the rate of the neuronal action potentials and seizure activity.27  The voltage-dependent anion channel protein (VDAC1) is a major component of the mitochondria membrane that regulates ion exchange.32 Studies propose that CBD helps to regulate the homeostasis of calcium in the mitochondria, which prevents calcium fluctuations under high excitability conditions.31, 33  It has also been suggested that CBD inhibits the reuptake and degradation of AEA by inhibiting FAAH and therefore increasing AEA’s agonistic effects on CB1R.31, 34, 35    Studies have shown that CBD works in a bi-phasic fashion demonstrating that its actions are heavily dose dependent.31  The possible synergistic or inhibitory activity with other phytocannabinoids found in marijuana such as THC are also important considerations. The inhibitory action produced by THC at CB1R offers a mechanism to diminish neuronal excitability, but at the cost of psychoactive properties and cognitive impairment. CBD’s actions provide a possible mechanism for inhibition of excitatory neurons (through different pathways involving GPR55 and resulting increased levels of AEA), but without the adverse effects mentioned above. Although there is supportive research that analyzes specific pathways for neuronal activity modulation using endocannabinoids, the full extent of each phytocannabinoid’s role is not clear.  Additional studies are needed that focus on the variety of constituents and various concentrations from different Cannabis plants, strains and formulations.

The structures of cannabinoids present in Cannabis (Figures 1 and 2) as well as the endogenous ligands of CB1R and CB2R (Figures 3 and 4) are provided. The structures of the Cannabis cannabinoids are quite similar to each other and this is also true of the endogenous cannabinoids.  Interesting, however, is that the two separate families of cannabinoids lack structural similarity to one another.  Structure is a key determinant of binding affinity, pharmacodynamics and pharmacokinetic profiles and this highlights the importance of emphasizing research that establishes ADME profiles, efficacy, potency, and clearance parameters under a variety of conditions and strategies of formulation.

THC

Figure 1. Delta (9)-tetrahydrocannabinol (THC)

CBD

Figure 2. Cannabidiol (CBD)

 

anandamide

Figure 3. Anandamide

arachidonoylglycerol

Figure 4. 2-arachidonoylglycerol

 

Currently available formulation of marijuana utilized for the treatment of epilepsy

Cannabis can be administered by inhalation, oral ingestion and topically. There is large variation in pharmacokinetic parameters depending on the route of administration. The inhalation route, either by smoking or vaporization provides the fastest onset, however lung administration burns lung tissue via direct smoke or increased temperatures with vaporization. Oral administration is associated with inconsistent absorption and onset of action. Gastric contents and first pass metabolism affect systemic absorption and dosing adjustments are recommended in the presence of food. Onset after oral administration can vary from 30 minutes to 2 hours or longer, with duration of action ranging from 5 to 8 hours.36 Little data is available on the pharmacokinetics of topical administration of cannabinoids and, to date, there are not any studies researching this formulation strategy for the use in epilepsy.36

In the state of Colorado an oil based formulation, known as Charlotte’s WebTM, is available from a non-profit organization “Realm of Caring” for the treatment of seizures in addition to other medical conditions.37 There is currently a waitlist for this formulation and patients and caregivers are required to move to Colorado in order to obtain this medical formulation of Cannabis. The formulation is stated to be highly concentrated in CBD, with less than 0.3% of THC, providing a formulation not likely to cause psychoactive activity as result of the low concentration of THC.37 Currently there are not any clinical trials evaluating the efficacy of this product, however this non-profit organization is currently working on observation trials.37

Conclusion

It is exciting to consider the possibilities that Cannabis may provide for treatment options in epilepsy. It is also evident that additional studies are needed to better understand the dynamic way in which different components of marijuana may play a role in preventing seizure activity in patients diagnosed with epilepsy. In addition, the pharmacokinetic parameters most likely to achieve therapeutic benefit without adverse effects and drug interactions require further investigation. Research is also needed to evaluate the specific metabolism of CBD and the optimization of patient centered dosing of these highly concentrated CBD formulations. Despite the need for additional research, current and ongoing clinical trials provide strong evidence to support the use of Cannabis formulations in epilepsy. This is especially true for those that are unable to achieve therapeutic success with currently available AED medications.

 

 

References

  1. Amtmann D, Weydt P, Johnson KL, Jensen MP, and Canter GT. Survey of cannabis in use in patients with amyotrophic lateral sclerosis (ALS). American Journal Hospital Palliative Care.2004;21(2): 95-104.
  2. Koppel BS, Brust JC, Bronstein J, Youssof S, Gronseth G and Gloss D. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology.Neurology.2014;82(17): 1556-63.
  3. Syed YY, McKeage K, and Scott LJ. Delta-9-tetrahydrocannabinol/cannabidiol (sativex(®)): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis.Drugs.2014;74(5): 563-78.
  4. Institute of Medicine. 2012. Epilepsy across the spectrum. March 30. Accessed July 16, 2014. http://www.iom.edu/Reports/2012/Epilepsy-Across-the-Spectrum.aspx.
  5. Cunha JM, Carlini EA, and et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients.Pharmacology.1980;21(3):175-85.
  6. Ames FR, and Cridland S. Anticonvulsant effect of cannabidiol. S Afr Med J.1986;4(1):14.
  7. Elger CE, Schmidt D. Modern management of epilepsy: A practical approach. Epilepsy & Behavior.2008;12(4):501-39.
  8. Jefferys, JG. Models and mechanisms of experimental epilepsies. Epilepsia.2003;(12): 44-50.
  9. Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on therapeutic strategies. Epilepsia. 2010;51(6):1069-1077.
  10. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-319.
  11. Kong ST, Ho CS, Ho PC, Lim SH. Prevalence of drug resistant epilepsy in adults with epilepsy attending a neurology clinic of a tertiary referral hospital in Singapore. Epilepsy Res. 2014;108(7):1253-1262.
  12. Feldmann M, Asselin MC, Liu MC, Wang S, McMahon A, Anton-Rodriguez J, Walker M, Symms M, Brown G, Hinz R, Matthews J, Bauer M, Langer O, Thom M, Jones T, Vollmar C, Duncan JS, Sisodiya SM, Koepp MH. P-glycoprotein expression and function in patients with temporal lobe epilepsy: a case-control study. Lancet Neurol. 2013;12(8):777-785.
  13. Loup F, Picard F, Yonekawa Y, Wieser HG, fritschy JM. Selective changes in GABAA receptor subtypes in white matter neurons of patients with focal epilepsy. Brain.2009;132(pt 9):2449-2463.
  14. He X, Li Y, Liu Z, Yue X, Zhao P, Hu J, Wu G, Mao B, Sun D, Zhang H, Song X, Wang Y, Shao J. The association between CCL2 polymorphisms and drug-resistant epilepsy in Chinese children. Epileptic Disord. 2013;15(3):272-277.
  15. Kudin AP, Zsurka G, Elger CE, Kunz WS. Mitochondrial involvement in temporal lobe epilepsy. Exp Neurol. 2009;218(2):326-332.
  16. Alonso-Vanegas MA, Cisneros-Franco JM, Castillo-Montoya C, Martínez-Rosas AR, Gómez-Pérez ME, Rubio-Donnadieu F. Self-reported quality of life in pharmacoresistant temporal lobe epilepsy: correlation with clinical variables and memory evaluation. Epileptic Disord. 2013;15(3):263-271.
  17. Tellez-Zenteno JF, Ronquillo LH, Wiebe S. Sudden unexpected death in epilepsy: evidence-based analysis of incidence and risk factors. Epilepsy Res. 2005;65(1-2):101-115.
  18. Surges R, Adjei P, Kallis C, Erhuero J, Scott CA, Bell GS, Sander JW, Walker MC. Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study. Epilepsia. 2010;51(2):233-242.
  19. Heuser K, Szokol K, Taubøll E. The role of glial cells in epilepsy. Tidsskr Nor Laegeforen. 2014;134(1):37-41.
  20. Liu X, Liu J, Liu J, Liu XL, Jin LY, Fan W, Ding J, Peng LC, Wang Y, Wang X. BDNF-TrkB signaling pathway is involved in pentylenetetrazole-evoked progression of epileptiform activity in hippocampal neurons in anesthetized rats. Neurosci Bull. 2013;29(5):565-575.
  21. Vezzani A, Balosso S, Maroso M, Zardoni D, Noé F, Ravizza T. ICE/caspase 1 inhibitors and IL-beta receptor antagonists as potential therapeutics in epilepsy. Curr Opin Investig Drugs. 2010;11(1):43-50.
  22. McPartland JM, Guy GW, Di Marzo V. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.” PLOS ONE.2014;9(3): e89566.
  23. Fezza F,Marrone MC, Avvisati R, Di Tommaso M, Lanuti M, Rapino C, Mercuri NB,  Maccarrone M, and Marinelli S. Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting. Molecular and Cellular Neuroscience.2014;62C:1-9.
  24. Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists. Philos Trans R Soc Lond B Biol Sci.2012;367(1607):3353-63.
  25. Dlugos A, Childs E, Stuhr KL, Hillard CJ, and de Wit H. Acute stress increases circulating anandamide and other N-Acylethanolamines in healthy humans. Neuropsychopharmacology.2012;37(11): 2416-2427.
  26. Skaper SD, Di Marzo V. Endocannabinoids in nervous system health and disease: the big picture in a nutshell. Philos Trans R Soc Lond B Biol Sci.2012;367(1607):3193-200.
  27. Sylantyev S, Jensen TP,  Ross RA, and Rusakov DA. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci U S A.2013;110(13): 5193-5198.
  28. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology.2008;153(2): 199-215.
  29. Hofmann ME, Frazier CJ. Marijuana, endocannabinoids, and epilepsy; potential and challenges for improved therapeutic intervention. Experimental Neurology.2013;244: 43-50.
  30. Thomas A., Baillie GL, Phillips AM, Razdan RK, Ross RA, and RG Pertwee. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro.Br J Pharmacol. 2007;150(5):613-23.
  31. Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia. 2014;55(6):787-90.
  32. Rimmerman, N., D. Ben-Hail, Z. Porat, A. Juknat, E. Kozela, MP. Daniels, PS. Connelly, E. Leishman, HB. Bradshaw, V. Shoshan-Barmatz, and Z. Vogel. 2013. Direct modulation of the outer mitochondria membrane channel, voltage-dependent anion channel 1 (VDAC1) by cannabidiol: A novel mechanism for cannabinoid-induced cell death.” Cell Death Dis. 20135;4:e949.
  33. Ryan D, Drysdale AJ, Lafourcade C, Pertwee RG, Platt B. Cannabidiol targets mitochondria to regulate intracellular Ca2+ levels. J Neurosci. 2009;18;29(7):2053-63.
  34. Ryan D, Drysdale AJ, Pertwee RG, Platt B. Interactions of cannabidiol with endocannabinoid signaling in hippocampal tissue. Eur J Neurosci. 2007;25(7):2093-102.
  35.  Fernandez-Ruiz J, Sagredo O, Pazos MR, Garcia C, Pertwee R, Mechoulam R, Martinez-Orgado J. Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid? Br J Clin Pharmacol. 2013;75(2):323-33.
  36. Aggarwal SK. Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Clin J Pain. 2013;29(2):162-71.
  37. Realm of Caring. 2014. FAQ General: Realm of Caring. Accessed September 13, 2014. http://theroc.us/index.php?option=com_content&view=article&id=77&Itemid=427.

 

 

 

 

 

 

 

 

PuraMed BioScience

PuraMed BioScience Develops a Cannabis-Based Epilepsy Drug

/in , , /by

Today, PuraMed Bioscience, Inc. announced its plans to initiate testing of a new hemp-based epilepsy medication this year.

PuraMed, a researcher, developer and marketer of over-the-counter (OTC) medicinal and healthcare products, said that it plans to begin testing a new hemp-based medication for treatment of epilepsy in the fourth quarter of 2014.

According to an article in Seizure, the prevalence of migraine in people who experience epilepsy is 8.4 to 20 percent. Additionally, an estimated 64 percent of epilepsy sufferers also experience seizure-related (ictal) headaches, of which 20 percent experience headache prior to the seizure (pre-ictal) and 44 percent experience headache after the seizure (post-ictal).

“As we looked at the similarities between migraine and epilepsy the treatment path became obvious,” said Russell Mitchell, CEO and Chairman of PuraMed BioScience. “Epilepsy and migraine seem to be triggered by the same cortical spreading depression (CSD) in the brain; the difference is the rate of reaction. This may be why many migraineurs are prescribed epileptic medications.”

Epilepsy is the third most common neurological disorder in the US, affecting approximately 2.7 million people, with children and older adults being most susceptible. Epilepsy also causes up to 50,000 sudden deaths each year. The condition often affects veterans wounded in combat. According to Citizens United to Cure Epilepsy, approximately 22 percent of the 440,000 military service men and women who experienced traumatic brain injury are expected to develop post-traumatic epilepsy.

Mitchell said that the company has developed a formula and is ready to start setting up trials. As an natural extension to PuraMed’s product line, key researchers have expressed interest in working with the company on CBD-based products.

“Standardization is key to creating a quality sublingual formula,” said Mitchell. “Sublingual delivery offers the distinct advantages of faster delivery and efficiency while avoiding the ‘first pass effect’ that often degrades oral medications. Our goal is to build medicines that withstand scientific scrutiny and perform well in double-blind, placebo controlled clinical trials. We believe that the efficacy of our formulations will be proven by scientific trials. This type of testing lends credibility to our line of natural medications which often work faster, more effectively, and have fewer side effects than their chemical-based counterparts.”

Source: PuraMed BioScience, Inc.

Last updated: 8/5/14; 3:50pm EST

Cuomo

Gov. Cuomo Requests for a Speedy Medical Cannabis Implementation for Children with Epilepsy in New York

/in , , , , /by

On Wednesday, Governor Andrew Cuomo called for a swift implementation of New York’s recently passed medical marijuana law.

In a letter to the Acting State Health Commissioner Dr. Howard Zucker, Cuomo cited the deaths of two children from complications of seizure disorders which could have been treated with medical cannabis. This month, nine year-old Anna Conte and three year-old Olivia Marie Newton of Western New York died from their epilepsy. Their deaths serve as reminders of the urgent help that children with seizure disorders need.

New York’s Compassionate Care Act was passed last month to provide relief for children suffering from epilepsy across the state. Under the state law, the DOH has 18 months to implement the program, which allows patients with serious conditions and illnesses to access cannabis for therapeutic purposes.

In Cuomo’s letter, he asks Dr. Zucker to determine if there is a way to accelerate the process and shorten the 18 month implementation timeline for children with epilepsy.

“Striking the right balance to ensure public safety and public health are protected is crucial. That said, I ask that you review the eighteen month implementation timeline to determine if there is any way to accelerate the process for this specific dire population,” Cuomo wrote in the letter.

Medical cannabis advocates in New York agree, claiming that the law needs to be implemented immediately. Several families suffering from diseases that would benefit from medical cannabis have moved to states like Colorado, where medical cannabis is legal. Advocates express their concern of many patients dying before the law is implemented.

“Families with children struggling from epilepsy have fought for years for the passage of the Compassionate Care Act. Now that it is finally law, the children struggling with this condition deserve every condition we can make that could potentially ease their pain and suffering,” said Cuomo.

Read the letter here.

Last updated: 7/31/14; 12:00pm EST

 

Perry Scott

US Rep Introduces Bill for National Legalization of Marijuana-Based Oil for Seizures

/in , , , , /by

On Monday, US Representative Scott Perry introduced legislation to nationally legalize a marijuana-based oil that has shown to reduce the amount and duration of seizures in children suffering from epilepsy and other seizure disorders.

Scott Perry has introduced the “Charlotte’s Web Medical Hemp Act of 2014” to ensure that children and individuals with epilepsy and other debilitating seizure disorders have access to life-changing Cannabidiol (CBD) Oil and therapeutic hemp. Currently, more than 300,000 children in America suffer from some form of epilepsy, many of which experience more than 100 violent seizures a day. These violent seizures could be fatal without proper care. If passed, this legislation would allow individuals to access this potentially life-saving supplement, without having to move to alternate geographic regions to receive treatment.

“Earlier this year I was approached by three local families whose children suffer from severe epilepsy,” said Rep. Perry. “As a father, I can’t imagine how helpless and crestfallen I’d feel to be essentially out of options, without any significant way to help my child; and these families live with this circumstance every single day. Their heartbreaking situations compelled me to act at the federal level to enable their access to a supplement that literally has changed lives – not only in the form of relief for the individual who suffers from this condition, but subsequently for their families and loved ones as well. Unfortunately, this plant and its derivatives and extracts are currently banned for medical use at the federal level and are unavailable to the citizens of Pennsylvania; this legislation would remedy that. This bill in no way changes my stance on marijuana – I still disagree with the recreational use of marijuana; however, these children and individuals like them deserve a chance to lead a healthy and productive life and our government shouldn’t stand in the way.”

The bill is an incremental approach to providing relief to those suffering from ailments that could benefit from CBD oil and therapeutic hemp. The bill would remove CBD oil and therapeutic hemp from the federal definition of marijuana in the Controlled Substances Act. Therapeutic hemp is that which has no more than .3 percent tetrahydrocannabinol (THC), the psychoactive chemical responsible for the ‘high’ from marijuana. The plants used in the oil are grown to be high in CBD, which is credited for the reduction in seizures, but low in THC.

“We applaud Congressman Perry and his leadership in creating access to this treatment for Americans with epilepsy who have run out of options,” said the Epilepsy Foundation’s President & CEO Philip M. Gattone, MEd. “As a parent of a child with epilepsy, I know how difficult it can be to stand by as your child has a seizure that you are helpless to stop. The Epilepsy Foundation has supported access to CBD oil – which is showing dramatic results for some patients. Access to a lifesaving treatment should not be determined or limited by a zip code. It is time for Congress to enact this sensible bill that could help save lives.”

The Charlotte’s Web strain of marijuana is named after seven-year-old Charlotte Figi, who suffers from Dravet Syndrome, a rare and catastrophic form of epilepsy. Charlotte was having up to 300 seizures per week, some of which lasted for hours, to having as few as two per month after treatment with Charlotte’s Web, which contains minimal traces of THC and high levels of CBD.

Perry’s bill will be assigned to a committee, where a passing vote will be required before it can be forwarded for consideration by the entire House.

 

Illinois Patients with Epilepsy

Illinois Expands Medical Cannabis Program to Include Use for Children and Seizures

/in , , , /by

On Sunday, Illinois Governor Pat Quinn signed legislation that will expand access to the state’s medical marijuana pilot program.

With Quinn’s signature, Illinois children and adults with epilepsy will soon be allowed to use medical marijuana to ease their symptoms.

Senate Bill 2636, sponsored by State Senator Iris Martinez (D- Chicago) and State Representative Lou Lang (D-Skokie),amends the Compassionate Use of Medical Cannabis Act to allow children under 18, with parent’s consent, to be treated with non-smokable forms of medical marijuana for the same range of conditions now available to adults. Additionally, the bill adds seizures, including those characteristic of epilepsy, to the list of medical conditions that qualify for legal treatment with medical marijuana.

“This new law will help alleviate the suffering of many adults and children across the state,” said Governor Quinn. “Epilepsy is a debilitation condition, and this much needed relief will help to reduce some of its symptoms for those who endure seizures. The Compassionate Use of Medical Cannabis Act is now designed to help our fellow citizens of all ages by allowing its strictly controlled use for specific medical conditions.”

The Illinois Department of Public Health (IDPH) will create rules for children using medical marijuana for treatment of their condition. The legislation will go into effect on January 1, 2015.

“The legislation was really an initiative by scores of families in Illinois with children that experience literally hundreds of seizures a day,” said Kurt Florian, President and CEO, Epilepsy Foundation of Greater Chicago. “Many of these families have uprooted for treatment in Colorado and have experienced dramatic reductions in seizures from oil based, low to zero THC medical cannabis. We are thankful to our sponsors and applaud Governor Quinn for signing this legislation which will help hundreds of children and families.”

Illinois became the 21st state to enact a medical cannabis legislation. The Compassionate Use of Medical Cannabis Act was originally signed into law by Governor Quinn in 2013, and includes one of the nation’s strongest restrictions on the cultivation, dispensing and use of medical marijuana. In September, residents will be formally allowed to apply for permission to use the drug to treat seizures.

“My family is grateful to the Illinois Legislature and Governor for their sensible addition of those with seizure conditions to the Compassionate Care Act,” said Randy Gross, parent of a child with epilepsy. “We admire their particular courage in explicitly including children with seizures, and in giving an option to children with other chronic conditions to petition for relief. On behalf of all patients of those with epilepsy, we would also like to thank the Epilepsy Foundation of Greater Chicago for their support and guidance of this effort as well. Finally, for those of us who left Illinois to pursue this treatment, we are overjoyed and anxious to come home soon.”

Source: Illinois Government News Network

Last updated: 7/21/14; 5:20pm EST

CBD oil

Missouri Governor Signs Cannabis Extract Legislation

/in , , , , /by

Individuals with epilepsy that cannot be effectively treated with conventional means will now be able to use a cannabis extract under legislation signed into law in Missouri.

On the last possible day to do so, Gov. Jay Nixon signed Missouri legislation that will allow the use of hemp oil containing the chemical cannabidiol (CBD) for consumption by people who have tried other treatments for epilepsy without success. The legislation was sponsored by St. Louis County Republican Eric Schmitt, a state senator whose nine year old son has the disorder.

The legislation went to Nixon’s desk in May, and he had until Monday, July 14th to sign or veto it.  Under the new Missouri law, patients wanting to use the CBD will be required to register with Missouri’s health department. Additionally, a neurologist will have to vouch that the patient’s epilepsy has not responded to at least three other treatments. The CBD extract is low in THC, the compound which gives users a “high”, and therefore would not be favored for recreational use.

The law allows for two nonprofit agencies to be licensed to grow the marijuana plants and produce the oil. The two cannabis centers will be overseen by the Missouri Department of Agriculture. Currently, there has been no timeline set for opening these centers.

In a separate action, Nixon also signed legislation allowing terminally ill patients to use investigational drugs that have not been approved by the Food and Drug Administration (FDA).

Last updated: 7/15/14; 3:20pm EST

Nathan Deal

Georgia Governor Pushes for Medical Cannabis Trials

/in , , , , /by

Earlier this week, Georgia Governor Nathan Deal and the chairman of GW Pharmaceuticals, Dr Geoffrey Guy, met at Georgia Regents University (GRU) to discuss conducting clinical trials with GW’s marijuana-derived drug in children with epilepsy.

Deal said that Dr. Guy has agreed to launch expanded clinical trials that would allow a wider range of children suffering from debilitating seizures to participate in studies on the use of cannabis oil.

After Georgia lawmakers failed to pass a bill this year that would allow clinical trials with cannabis oil, many families and advocates expressed their anger. The failure to pass the bill prompted Deal to take action to coordinate clinical trial programs in the state. Currently, there is no determined timeframe of when the trials will start, but Deal has said that he’s hopeful they will get regulatory approval by early next year.

Deal said that under Georgia’s plan, the state through GRU in Augusta will be partnering with London-based GW Pharmaceuticals for an expanded clinical trial. In addition to Georgia, GW has a research partnership with New York and is conducting trials in various other states.

The cannabis oils being tested in kids with epilepsy do not have TCH in them and therefore do not make users feel high. GW has already received approval from the US Food and Drug Administration (FDA) to conduct clinical trials in the US. Additionally, Deal announced a separate effort by GRU to launch a clinical trial using cannabis oil obtained from federal regulators in Mississippi.

Last updated: 7/10/14; 3:55pm EST

Charlee's Law

Starting Today Cannabis Oil Available for Treatment of Children with Epilepsy in Utah

/in , , , , /by

Today, Charlee’s Law takes effect in Utah, allowing children suffering from severe epileptic seizures to be legally prescribed a marijuana extract for medicinal purposes.

Utah Gov. Gary Herbert signed the bill, also called HB105, in late March. The bill is known as Charlee’s Law, named after six-year-old Charlee Nelson, who suffered from severe seizures due to Batten Disease.

Batten disease is the most common form of a group or disorders called Neuronal Ceroid Lipofuscinoses (NCL). The various forms of NCL are classified by age of onset and have the same basic cause, progression and outcome, but are the result of a different gene, according to the Batten Disease Support and Research Association (BDSRA). Over time, children with the disease suffer mental impairment, worsening seizures and progressive loss of vision and motor skills. Children with Batten disease eventually become blind, bedridden and unable to communicate. Currently, there is no specific treatment available that can stop or reverse the symptoms of the disease, and therefore it is always fatal.

Charlee died right after the legislation was passed. Although the use of cannabis oil might not have been able to save her life, it could have improved her quality of life and given her a longer future.

“The hemp extract that Charlee’s Law allows Utah parents to administer to their children might have helped improve Charlee’s quality of life and prolong her time with her parents, Jeff and Catrina Nelson. The Legislature dedicates Charlee’s law to Charlee, her family, and all of the sick Utah children searching for a cure,” said Rep. Froerer

The Law allows for the possession of a marijuana that is high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC) oil for use in intractable epilepsy. The oil, which has been used for over two years in Colorado, has seen an 80 percent efficacy rate in reducing seizures by 50 percent on average. Individuals will not be allowed to get the cannabis oil in the state of Utah, but they will be allowed to obtain the oil from another state, such as Colorado, and legally bring it back. There are over 50 families in Utah that are on a waiting list to get cannabis oil from Colorado.

The law requires parents to first get a letter of recommendation from a neurologist that suggests the oil would be beneficial for the children. To qualify, a patient must have previously received three other anti-epileptic drugs.

“The words of support from legislators, along with their affirmative votes on our behalf, show an immense understanding and compassion for the suffering of the children and families of Hope 4 Children With Epilepsy,” said Jennifer May, H4CE co-founder and mother to Stockton, who has Dravet syndrome. “We are grateful to Utah for stepping up and helping open the way for research into the possibilities behind this treatment option,” she commented on the passing of Charlee’s Law.

Sources: Utah.Gov; Hope 4 Children With Epilepsy

Last updated: 7/1/14; 10:40am EST

Insys Therapeutics

FDA Grants Orphan Drug Status to Insys’ CBD for Treatment of Lennox-Gastaut Syndrome

/in , , , /by

Specialty pharmaceutical company Insys Therapeutics, Inc. announced that the US Food and Drug Administration (FDA) has granted orphan drug status to its pharmaceutical cannabidiol (CBD) for treatment of a rare pediatric-onset epilepsy.

The company said that the agency granted Orphan Drug designation to its CBD for the treatment of Lennox-Gastaut Syndrome, a severe form of childhood-onset epilepsy that typically manifests in individuals between two and six years of age. Lennox-Gastaut Syndrome is characterized by several seizure types, moderate-to-severe cognitive impairment, and an abnormal EEG. The frequency and severity of seizure vary by individual. Currently, no cure exists for the syndrome. Individuals with Lennox-Gastaut Syndrome are often treated with various anti-seizure medications, which the syndrome has proved resistant to.

Insys said that it expects to file an application to the FDA seeking approval of the drug this year. Following the announcement, the company’s shares rose five percent.

“With no cure and persistence of seizure with current antiepileptic medications, the orphan drug designation recognizes the significant, unmet need that exists among children with this severe form of epilepsy and the teams who provide their care,” said Insys’ President and Chief Executive Officer Michael L. Babich. “We have the unique opportunity to test a controlled pharmaceutical CBD product for Lennox-Gastaut Syndrome, and our company is committed to advancing cannabinoid therapies that have the potential to provide significant medical benefits to patients across multiple indications. We expect to file an investigational New Drug Application (IND) for CBD in the second half of 2014.”

Insys has more than seven years of research and development experience in the pharmaceutical cannabinoid space. The company manufactures pharmaceutical dronabinol (THC) and pharmaceutical CBD, both of which are cannabinoids, at its Round Rock, Texas-based facility, which is FDA-inspected and Drug Enforcement Administration (DEA) approved. According to Insys, in addition to Lennox-Gastaut Syndrome, the company is evaluating the potential use of pharmaceutical CBD in several other indications including adult epilepsy; chemotherapy-induced peripheral neuropathy; addiction in cocaine, heroin and opioids; and glioblastoma.

Source: Insys Therapeutics, Inc.

Last updated: 6/26/14; 11:25am EST

FDA

FDA Reviewing the Classification of Marijuana as a Schedule 1 Substance

/in , , , , , , , , /by

The US Food and Drug Administration (FDA) is currently conducting research to determine if marijuana should continue to be classified as a Schedule 1 drug in the US, or if its classification should be downgraded, a step toward decriminalizing the drug at the federal level.

The agency is conducting the research at the Drug Enforcement Administration’s (DEA) request, according to a statement from Douglas Throckmorton, Deputy Director for Regulatory Programs at the FDA, at a congressional hearing. The study could lead to the removal of marijuana from the Schedule 1 category of the Controlled Substances Act.

Marijuana’s potential use for a range of medical conditions has gained significant interest over the last few decades. Recently, several states have passed laws that remove state restrictions on health care professionals using marijuana as a medical treatment for a variety of conditions.

Currently, 23 states and the District of Columbia have legalized use of marijuana for medical purposes. Additionally, several other states are considering similar legislation, regarding the use of medical marijuana. Although nearly half of the US states have legalized some form of marijuana, the drug is still classified as a Schedule 1 substance. Drugs that are classified as Schedule 1 drugs have the most restrictions and are considered substances with no medical benefit that are highly addictive.

The reclassification of marijuana could have a significant impact on the cannabis industry, and could help reconcile some of the differences between federal laws and less restrictive state laws.

The agency will make a recommendation after conducting an eight-factor analysis that evaluates marijuana’s abuse potential, its pharmacological effect and risk to public health, among other factors, according to Throckmorton. The FDA must first consult with the National Institute on Drug Abuse and send its recommendation through the Department of Health and Human Services before going to the DEA.

Last updated: 6/24/14; 2:40pm EST