Cannabis Health Science Studies Index

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EPILEPSY/ SEIZURES & Cannabis studies

Overview

Epilepsy is a common and diverse set of chronic neurological disorders characterized by seizure.
Some definitions of epilepsy require that seizures be recurrent and unprovoked, but others require only a single seizure combined with brain alterations which increase the chance of future seizures.

In many cases a cause cannot be identified; however, factors that are associated include brain trauma, strokes, brain cancer, and drug and alcohol misuse among others.

CBD (non- psychoactive) is a chemical composite of the cannabis plant that does not contain THC, and has been extensively researched to stop seizures from occurring. This is very beneficial to young children suffering from seizures whose parents are concerned about their children using traditional cannabis therapies.
Lab tested CBD oils are now readily available.

High CBD Cannabis Seed Strains

First Aid for all seizure types (Image)

Science & Research

Undated - Anecdotal ~ Marijuana and Epilepsy.

1949 - Study ~ Anti-epileptic Action of Marijuana-Active Substances.

1980 - Study - Chronic administration of cannabidiol to healthy volunteers and epileptic patients.

1981 - Study - Hypnotic and Antiepileptic Effects of Cannabidiol.

1981 - Study ~ Antiepileptic potential of cannabidiol analogs.

1981 - Study ~ The cannabinoids as potential antiepileptics.

1982 - Study ~ Anticonvulsant effects of the (-) and (+)isomers of cannabidiol and their dimethylheptyl homologs.

1982 - Study ~ Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice.

1990 - Study ~ ILLICIT DRUG USE AND THE RISK OF NEW-ONSET SEIZURES.

1992 - Study ~ Marijuana use and the risk of new onset seizures.

1999 - Study - Therapeutic Aspects of Cannabis and Cannabinoids.

2001 - Study ~ Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

2001 - Study ~ Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy.

2003 - Study ~ The Endogenous Cannabinoid System Regulates Seizure Frequency and Duration in a Model of Temporal Lobe Epilepsy.

2003 - Study ~ On the application of cannabis in paediatrics and epileptology.

2003 - Study - Experiences with THC-treatment in children and adolescents.

2003 - Article - Marijuana and Epilepsy.

2003 - News - Marijuana Use More Prevalent With Epilepsy.

2003 - News - Cannabis may help epileptics.

2004 - Study - Endocannabinoids and Their Implications for Epileps.

2004 - Study ~ Cannabinoids: Defending the Epileptic Brain.

2004 - Study ~ Marijuana use and epilepsy - Prevalence in patients of a tertiary care epilepsy center.

2004 - News - Epilepsy patients are smoking pot.

2005 - Study ~ Selective antiepileptic effects of N-palmitoylethanolamide, a putative endocannabinoid.

2005 - Study - Treatment with CBD in oily solution of drug-resistant paediatric epilepsies.

2005 - Study ~ Cannabinoids as potential anti-epileptic drugs.

2006 - Study ~ Not Too Excited? Thank Your Endocannabinoids.

2006 - Study ~ Forebrain-Specific Inactivation of Gq/G11 Family G Proteins Results in Age-Dependent Epilepsy and Impaired Endocannabinoid Formation.

2006 - Study ~ The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus.

2006 - Study ~ Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy.

2006 - Study ~ Activation of the Cannabinoid Type-1 Receptor Mediates the Anticonvulsant Properties of Cannabinoids in the Hippocampal Neuronal Culture Models of Acquired Epilepsy and Status Epilepticus.

2006 - Study ~ Cannabinoids In Medicine: A Review Of Their Therapeutic Potential.

2006 - Study ~ Arachidonyl-2'-chloroethylamide, a highly selective cannabinoid CB1 receptor agonist, enhances the anticonvulsant action of valproate in the mouse maximal electroshock-induced seizure model.

2006 - News ~ Brain's Cannabinoid System 'Mellows' Seizures.

2006 - News ~ Brain's cannabinoid system fights seizures.

2007 - Study - Marijuana: an effective antiepileptic treatment in partial epilepsy?

2007 - Study ~ Development of pharmacoresistance to benzodiazepines but not cannabinoids in the hippocampal neuronal culture model of status epilepticus.

2007 - Study ~ Endocannabinoids block status epilepticus in cultured hippocampal neurons.

2007 - Study ~ Downregulation of the CB1 Cannabinoid Receptor and Related Molecular Elements of the Endocannabinoid System in Epileptic Human Hippocampus.

2007 - Study ~ Ultra-low dose cannabinoid antagonist AM251 enhances cannabinoid anticonvulsant effects in the pentylenetetrazole-induced seizure in mice.

2007 - News ~ Rimonabant: safety issues.

2008 - Study ~ The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum.

2008 - Study ~ The cannabinoid anticonvulsant effect on pentylenetetrazole-induced seizure is potentiated by ultra-low dose naltrexone in mice.

2009 - Study ~ The effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats.

2009 - Study ~ Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy.

2009 - Study ~ Effect of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the protective action of the various antiepileptic drugs in the mouse maximal electroshock-induced seizure model.

2009 - Study ~ Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB(1) agonist ACEA in the pentylenetetrazole-induced seizure in mice.

2009 - News ~ Medical Marijuana and Epilepsy.

2010 - Study ~ Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo.

2010 - Study ~ Cannabinoid-mediated inhibition of recurrent excitatory circuitry in the dentate gyrus in a mouse model of temporal lobe epilepsy.

2010 - Study ~ AAV vector-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects against seizure-induced excitoxicity.

2010 - Study ~ Delta-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats.

2010 - Study ~ Anticonvulsant effects of GWP42006 in vitro and in vivo in rat.

2010 - Study ~ Dynamic changes of CB1-receptor expression in hippocampi of epileptic mice and humans.

2011 - Study ~ Endocannabinoid system protects against cryptogenic seizures.

2011 - Study ~ Convulsions Associated with the Use of a Synthetic Cannabinoid Product.

2011 - Study ~ Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model of audiogenic epilepsy.

2011 - Study ~ Synthetic cannabinoid WIN 55,212-2 mesylate enhances the protective action of four classical antiepileptic drugs against maximal electroshock-induced seizures in mice.

2011 - Study ~ Protective effects of CB1 receptor agonist WIN 55.212-2 in seizure activity in the model of temporal lobe epilepsy.

2011 - Study ~ L-Type Calcium Channel Mediates Anticonvulsant Effect of Cannabinoids in Acute and Chronic Murine Models of Seizure.

2011 - Study ~ Changes in the cannabinoid (CB1) receptor expression level and G-protein activation in kainic acid induced seizures.

2011 - Study ~ Marijuana, endocannabinoids, and epilepsy: Potential and challenges for improved therapeutic intervention.

2011 - News ~ Cannabis could help treat epilepsy.

2011 - News ~ Cannabis could be used to treat epilepsy.

2011 - News ~ New research provides hope for those with epilepsy.

2012 - Patent Application ~ Use of the phytocannabinoid cannabidivarin (cbdv) in the treatment of epilepsy: Patent Application 20120004251

2012 - Study ~ Inverse relationship of cannabimimetic (R+)WIN 55, 212 on behavior and seizure threshold during the juvenile period.

2012 - Study ~ Equipotent Inhibition of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase - Dual Targets of the Endocannabinoid System to Protect against Seizure Pathology.

2012 - Study ~ Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ-aminobutyric acid type B receptor activity.

2012 - Study ~ Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

2012 - Study ~ Statistical parametric mapping reveals regional alterations in cannabinoid CB1 receptor distribution and G-protein activation in the 3D reconstructed epileptic rat brain.

2012 - Study ~ Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

2012 - Study ~ Internet Highs-Seizures After Consumption of Synthetic Cannabinoids Purchased Online.

2012 - Study ~ Cannabinoid receptor 1 inhibition causes seizures during anesthesia induction in experimental sepsis.

2012 - Study ~ Effect of ACEA-a selective cannabinoid CB1 receptor agonist on the protective action of different antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model.

2012 - News ~ Hammer Head' 'incense' blamed for seizure of youth in Le Roy.

2012 - News ~ How Medical Marijuana Is Giving a Six-Year-Old Boy New Life

2013 - Study ~ Alterations of endocannabinoids in cerebrospinal fluid of dogs with epileptic seizure disorder.

2013 - Study ~ Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression

2013 - Study (article) ~ Medical Marijuana Coverage Still Lost in the Legal Weeds

2013 - Study ~ Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment- resistant epilepsy

2013 - Study ~ Cannabis and other illicit drug use in epilepsy patients.

2013 - Study ~ The Role of CB1-Receptors in the Proconvulsant Effect of Leptin on Penicillin-Induced Epileptiform Activity in Rats.

2013 - Study ~ The role of potassium BK channels in anticonvulsant effect of cannabidiol in
pentylenetetrazole and maximal electroshock models of seizure in mice.

2013 - Study ~ Cannabinoid 1 receptor as therapeutic target in preventing chronic epilepsy

2013 - Study ~ The du2J mouse model of ataxia and absence epilepsy has deficient cannabinoid CB1 receptor-mediated signalling.

2013 - Study ~ The role of α2-adrenoceptors in the anti-convulsant effects of cannabinoids on
pentylenetetrazole-induced seizure threshold in mice.

2013 - Study ~ CB1 agonists, locally applied to the cortico-thalamic circuit of rats with genetic absence epilepsy, reduce epileptic manifestations.

2013 - Study ~ The secret "spice": an undetectable toxic cause of seizure.

2013 - Study ~ Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine,
oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures
in mice.

2013 - Study ~ Therapeutic potential of cannabinoid medicines.

2013 - Study ~ Cannabidivarin-rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor-independent mechanism.

2013 - Study ~ Epidiolex - GW Pharmaceuticals (drug development page)

2013 - News ~ Science/Animal: CBD inhibits the activity of a certain liver enzyme

2013 - News ~ Cannabis Anti-Convulsant Shakes up Epilepsy Treatment

2013 - News ~ New cannabis discovery could lead to better treatments for epilepsy

2013 - News ~ Parents of epileptic N.J. tot lament medical marijuana delays

2013 - News ~ Medical Marijuana for Kids? Some Praise Results While Others Worry About Risks

2013 - News ~ New therapy for fragile X chromosome syndrome discovered

2013 - News ~ Charlotte’s Web Of Suffering: Six-Year-Old Colorado Girl With Dravet Syndrome Finds Relief From Marijuana High In CBD

2013 - News ~ Toronto family hopes for access to controversial treatment to cure baby’s rare epilepsy

2013 - News ~ New Study: Cannabinoids Protect the Brain and Heart From Injury

2013 - News ~ Families of children with epilepsy moving to Colorado, drawn by success of marijuana oil

2013 - Study ~ Families migrate to Colorado for marijuana miracle

2013 - Study ~ Comes Now Epidiolex (FDA approves IND studies of CBD

2013 - Study ~ Pharmaceuticals Provides Update on Orphan Program in Childhood Epilepsy for
Epidiolex®

2013 - Study ~ Endogenous Signaling by Omega-3 Docosahexaenoic Acid-derived Mediators Sustains Homeostatic Synaptic and Circuitry Integrity.

2013 - Study ~ OBTAINING EPIDIOLEXTM IN THE U.S.


Experiences with THC-treatment in children and adolescents

TitleExperiences with THC-treatment in children and adolescents
Author(s)Lorenz R
Journal, Volume, IssueAbstract, IACM 2nd Conference on Cannabinoids in Medicine, September 12-13, 2003, Cologne
Major outcome(s)Positive effects of THC in children with severe neurological disorders
 
IndicationSpasticity;Dystonia;Epilepsy;AnxietyAbstract
MedicationDelta-9-THC

8 patients – children or adolescents aged 3 to 14 years – have been treated with Ä9-THC, dosages ranged from 0.04 mg/kg body weight to 0.14 mg/kg body weight.


In an 8 year-old-boy with NCL Jansky-Bielschowsky spasticity was diminished, he became more alert and his mood improved.


In a 12 year-old-girl, who had suffered from severe hypoxia during birth, mood improved, awareness was increased and focal seizures (presenting as nystagmus and versive movement) but not tonic-clonic seizures were reduced.


A 12 year-old-girl with PDHC-deficiency became more interested in her surroundings and society. Nodding spasms and tonic seizures decreased.


In a 14 year-old-girl with marked dystonia due to NCL Spielmeyer-Vogt a reduction of abnormal movement patterns was observed. In addition the girl had more initiative.


In a 13 year-old-boy presenting with spasticity, athetosis, myoclonic movements and epileptic seizures of unknown cause interest in his surroundings was improved, myoclonic movements were less intense but of similar frequency.

Frequency and duration of his focal and generalized seizures were not influenced.


In an 11 year-old-girl with a traumatic paraplegia a significant improvement of symptoms of a posttraumatic reaction presenting as an eating disorder and negative behaviour was observed.

Taking higher doses the girl started to develop side effects including inappropriate language (concerning sexual content) and very associative thinking.

Therapy was discontinued without signs of withdrawal.


In a 3 10/12 year-old-boy with a traumatic paraplegia a significant improvement in his behaviour and eating disorder was observed.


In a 14 year-old-boy suffering from intractable epilepsy and severe mental retardation appetite and mood improved.

Frequency of seizures seemed not to be influenced, but clear assessment was not possible because antiepileptic drugs were changed.


Conclusion: In severly disabled children and adolescents Ä9-THC-medication can have positive psychotropic effects, influences the degree of spasticity and dystonia

and-occasionally-seems to have an anticonvulsant action.


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Route(s)Oral
Dose(s)0.04 - 0.14 mg/kg body weight
Duration (days) 
Participants8 children with different neurological disorders
DesignUncontrolled case report
Type of publicationMeeting abstract
Address of author(s)Paediatrician, Brunnenstrasse 54, 34537 Bad Wildungen, Germany
Full text

Chronic administration of cannabidiol to healthy volunteers and epileptic patients

TitleChronic administration of cannabidiol to healthy volunteers and epileptic patients.
Author(s)Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R, Sanvito WL, Lander N, Mechoulam R
Journal, Volume, IssuePharmacology 1980;21(3):175-185
Major outcome(s)4 of the 8 CBD subjects remained almost free of convulsive crises and 3 other patients demonstrated partial improvement
 
IndicationEpilepsyAbstract
MedicationCannabidiol

In phase 1 of the study, 3 mg/kg daily of cannabidiol (CBD) was given for 30 days to 8 health human volunteers.

Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting.

Neurological and physical examinations, blood and urine analysis, ECG and EEG were performed at weekly intervals.

In phase 2 of the study, 15 patients suffering from secondary generalized epilepsy with temporal focus were randomly divided into two groups.

Each patient received, in a double-blind procedure, 200-300 mg daily of CBD or placebo.

The drugs were administered for along as 4 1/2 months. Clinical and laboratory examinations, EEG and ECG were performed at 15- or 30-day intervals.

Throughout the experiment the patients continued to take the antiepileptic drugs prescribed before the experiment, although these drugs no longer controlled the signs of the disease.

All patients and volunteers tolerated CBD very well and no signs of toxicity or serious side effects were detected on examination.

4 of the 8 CBD subjects remained almost free of convulsive crises throughout the experiment and 3 other patients demonstrated partial improvement in their clinical condition. CBD was ineffective in 1 patient.

The clinical condition of 7 placebo patients remained unchanged whereas the condition of 1 patient clearly improved.

The potential use of CBD as an antiepileptic drug and its possible potentiating effect on other antiepileptic drugs are discussed.


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Route(s)Oral
Dose(s)200-300 mg per day plus standard medication
Duration (days)4.5 months
Participants15 patients with epilepsy
DesignControlled study
Type of publication 
Address of author(s) 
Full text

Anticonvulsant nature of marihuana smoking

TitleAnticonvulsant nature of marihuana smoking.
Author(s)Consroe PF, Wood GC, Buchsbaum H
Journal, Volume, IssueJournal of the American Medical Association 1975;234(3):306-307
Major outcome(s)Cannabis was able to control seizures in conjunction with phenobarbital and diphenylhydantoin.
 
IndicationEpilepsyAbstract
MedicationCannabis

Marihuana smoking, in conjunction with therapeutic doses of phenobarbital and diphenylhydantoin, was apparently necessary for controlling seizures in one 24-year-old epileptic patient.


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Route(s)Inhalation
Dose(s)2-5 cannabis cigarettes per day plus standard medication
Duration (days)years
Participants1 patient with epilepsy
DesignUncontrolled case report
Type of publication 
Address of author(s) 
Full text 

Cannabis may help epileptic seizures

Article Date: 04 Oct 2003

Public Health

 Further evidence has emerged that an ingredient of cannabis could help prevent epileptic seizures.

Some experts are now calling for fresh research into the potential of cannabis-like compounds to help alleviate the condition.

Researchers from Germany found that natural brain chemicals which resemble cannabis extracts can interrupt a process which can trigger a seizure.

There have been trials of cannabis compounds in MS and cancer patients.

There are reports dating from the 15th century talking about the use of cannabis to ease the symptoms of epilepsy.

However, there have been few organised trials in humans in recent years, even though cannabis or its extracts are being evaluated in trials against several other illness types illness.

Brain chemicals

The researchers, from the Max-Planck Institut in Munich studies mice bred to suffer a key feature of epilepsy in humans.

This is 'excitotoxicity' - abnormal stimulation of brain cells by an excessive quantity of a chemical called glutamate.

In the mutant mice, a substance called kainic acid works in a very similar way, and the researchers used this to find out if cannabinoid chemicals could somehow interrupt the process or protect the brain cells involved.

They found, in the mouse brain at least, that key receptors on the surface of the brain cell, which normally respond to contact with cannabinoid-like chemicals produced naturally in the body, appeared to protect against these acid-induced seizures.

However, while the same receptors are found in the human brain, there is no evidence that seizures could be stopped by applying similar cannabinoids in a therapy.

'Promising'

The researchers describe their finding as a 'promising therapeutic target' for epilepsy drug research.

Professor Roger Pertwee, an researcher into cannabinoids at Aberdeen University, told BBC News Online that fresh studies into their promise against epilepsy were overdue.

He said: 'There is always a need for new drugs to treat epilepsy, and there have now been sufficient animal studies to justify research in humans with epilepsy.'

 

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Hypnotic and Antiepileptic Effects of Cannabidiol

J Clin Pharmacol. 1981 Aug-Sep;21(8-9 Suppl):417S-427S.

Carlini EA, Cunha JM.

Abstract

Clinical trials with cannabidiol (CBD) in healthy volunteers, isomniacs, and epileptic patients conducted in the authors' laboratory from 1972 up to the present are reviewed.

Acute doses of cannabidiol ranging from 10 to 600 mg and chronic administration of 10 mg for 20 days or 3 mg/kg/day for 30 days did not induce psychologic or physical symptoms suggestive of psychotropic or toxic effects; however, several volunteers complained of somnolence.

Complementary laboratory tests (EKG, blood pressure, and blood and urine analysis) revealed no sign of toxicity.

Doses of 40, 80, and 160 mg cannabidiol were compared to placebo and 5 mg nitrazepam in 15 insomniac volunteers.

Subjects receiving 160 mg cannabidiol reported having slept significantly more than those receiving placebo; the volunteers also reported significantly less dream recall; with the three doses of cannabidiol than with placebo.

Fifteen patients suffering from secondary generalized epilepsy refractory to known antiepileptic drugs received either 200 to 300 mg cannabidiol daily or placebo for as long as 4.5 months. Seven out of the eight epileptics receiving cannabidiol had improvement of their disease state, whereas only one placebo patient improved.

 

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Marijuana: an effective antiepileptic treatment in partial epilepsy?

TitleMarijuana: an effective antiepileptic treatment in partial epilepsy? A case report and review of the literature.
Author(s)Mortati K, Dworetzky B, Devinsky O.
Journal, Volume, IssueRev Neurol Dis. 2007 Spring;4(2):103-6.
Major outcome(s)Significant improvement of epilepsy with the use of cannabis.
 
IndicationEpilepsyAbstract
MedicationCannabis

Although more data are needed, animal studies and clinical experience suggest that marijuana or its active constituents may have a place in the treatment of partial epilepsy.

Here we present the case of a 45-year-old man with cerebral palsy and epilepsy who showed marked improvement with the use of marijuana.

This case supports other anecdotal data suggesting that marijuana use may be a beneficial adjunctive treatment in some patients with epilepsy.

Although challenging because of current federal regulations, further studies are needed to examine the role of marijuana in the treatment of this disorder.


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Route(s)Inhalation
Dose(s) 
Duration (days) 
Participants1 patient with cerebral palsy and epilepsy
DesignUncontrolled case report
Type of publicationMedical journal
Address of author(s)Departments of Neurology, New York University School of Medicine, New York, NY.
Full text 

Marijuana and Epilepsy

Dec. 12, 2003 (Boston) — People with epilepsy are more than twice as likely to use marijuana as the general population, according to a telephone survey conducted by researchers at the University of Alberta in Edmonton, Canada.

Donald W. Gross, MD, said about 21% of patients who answered the survey had used marijuana during the previous year, and 8% had used it every other day or more. In comparison, he quoted data from the National Household Survey on Drug Abuse and a Canadian survey, which put use during the previous year at 8.9% in the general population.

He and Daphne Quigley, BScN, nurse coordinator of the Adult Epilepsy Program at the University of Alberta Hospital, presented the study in a poster here at the 57th annual meeting of the American Epilepsy Society.

More surprising, he said, was that 24% of 136 respondents — including those who did not use marijuana — contended that marijuana is effective in the treatment of seizures. Despite studies showing cannabinoids can help control seizures in animals, no clinical studies have been conducted in humans, according to Dr. Gross.

In an interview at the poster session, Dr. Gross said his group undertook the survey because patients often told him marijuana was effective in controlling seizures or asked about reports that the drug could be helpful.

In the study, about two thirds of 28 active users said it helped control their seizures: 19 reported improvement in seizure severity, and 15 in seizure frequency. No one said that seizures worsened, but nine respondents said marijuana had no effect on severity of seizures and 13 said it did not help reduce frequency.

Analysis of the responses showed that marijuana use in the study population did not correlate to most factors usually associated with recreational drug use: male sex, youth, and unemployment, according to Dr. Gross. The exception was use of other illicit drugs.

Marijuana use did correlate with more frequent seizures and longer history of epilepsy. "So from our perspective we felt marijuana use in our population was more consistent with a nonconventional healthcare choice than recreational drug use," he said, calling for clinical studies to evaluate whether marijuana is effective in seizure control.

This study received no external funding.

AES 57th Annual Meeting: Abstract 2.314. Presented Dec. 9, 2003.

 

 

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Therapeutic Aspects of Cannabis and Cannabinoids

PHILIP ROBSON, FRCPsych, Consultant Psychiatrist and Senior Clinical Lecturer, Warneford Hospital, Oxford OX3 7JX

22 July 1999, final revision 14 March 2000, accepted 15 March 2000)

Abstract

Background: Review commissioned in 1996 by the Department of Health (DOH).

Aims: Assess therapeutic profile of cannabis and cannabinoids.

Method: Medline search, references supplied by DOH and others, and personal communications.

Results and Conclusions: Cannabis and some cannabinoids are effective antiemetics and analgesics and reduce intraocular pressure.

There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification.

Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate.

The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

Declaration of interest: Funding from DOH. Between writing this paper and its acceptance for publication, P.R. was appointed Medical Director of GW Pharmaceuticals.

 


In 1996 I was commissioned by the Department of Health (DOH) to review the scientific literature regarding the potential therapeutic utility of cannabis and its derivatives.

The review was based upon primary sources (identified from a Medline literature search, reference lists supplied by the DOH and the Institute for the Study of Drug Dependence, and personal communications with relevant academics and clinicians). This paper is a greatly shortened version of the review.

The 4 years which have elapsed have seen little in the way of new clinical results but considerable advances in cannabinoid basic science (Institute of Medicine, 1999). Government licences have recently been granted for several controlled trials of both synthetic and plant-derived cannabinoids in multiple sclerosis and chronic pain. In January 2000, I was appointed Medical Director of GW Pharmaceuticals, a company established to derive medicinal extracts from standardised cannabis plants.

HISTORY OF THERAPEUTIC USE
The first formal report of cannabis as a medicine appeared in China nearly 5000 years ago when it was recommended for malaria, constipation, rheumatic pains and childbirth and, mixed with wine, as a surgical analgesic (Mechoulam, 1986). There are subsequent records of its use throughout Asia, the Middle East, Southern Africa and South America. Accounts by Pliny, Dioscorides and Galen remained influential in European medicine for 16 centuries.

It was not until the 19th century that cannabis became a mainstream medicine in Britain. W. B. O'Shaughnessy, an Irish scientist and physician, observed its use in India as an analgesic, anticonvulsant, antispasmodic, anti-emetic and hypnotic. After toxicity experiments on goats and dogs, he gave it to patients and was impressed with its muscle-relaxant, anticonvulsant and analgesic properties, and recorded its usefulness as an anti-emetic.

After these observations were published in 1842, medicinal use of cannabis expanded rapidly. It soon became available 'over the counter' in pharmacies and by 1854 it had found its way into the United States Dispensatory. The American market became flooded with dozens of cannabis-containing home remedies.

Queen Victoria's personal physician wrote (Reynolds, 1890), on the basis of more than 30 years' experience, that "Indian hemp, when pure and administered carefully, is one of the most valuable medicines we possess".

He found it incomparable for "senile insomnia", "night restlessness" and "temper disease" in both children and adults, but not helpful in melancholia, "very uncertain" in alcoholic delirium, and "worse than useless" in mania. It was very effective in neuralgia, period pains, migraine, "lightning pain of the ataxic patient" and gout, but useless in sciatica and "hysteric pains".

He found it impressive in clonic spasms and certain epileptiform convulsions related to brain damage, but no good at all in petit mal or "chronic epilepsy", tetanus, chorea or paralysis agitans. It effectively relieved nocturnal cramps, asthma and dysmenorrhoea.

Reynolds was writing at a time when the zenith of cannabis as prescribed medicine and home remedy was already past.

Although Sir William Osler was still recommending it for migraine sufferers in 1913, it was by then in steep decline because of variable potency of herbal preparations, poor storage stability, unpredictable response to oral administration, increasing enthusiasm for parenteral medicines and availability of potent synthetic alternatives, commercial pressures and American concern about recreational use.

Cannabis was outlawed in 1928 by ratification of the 1925 Geneva Convention on the manufacture, sale and movement of dangerous drugs. Prescription remained possible until final prohibition under the 1971 Misuse of Drugs Act, against the advice of the Advisory Committee on Drug Dependence.

In the USA, medical use was effectively ruled out by the Marijuana Tax Act 1937. This ruling has been under almost constant legal challenge and many special dispensations were made between 1976 and 1992 for individuals to receive 'compassionate reefers'. Although this loophole has been closed, a 1996 California state law permits cultivation or consumption of cannabis for medical purposes, if a doctor provides a written endorsement. Similar arrangements apply in Italy and Canberra, Australia.

CANNABINOID PHARMACOLOGY RELEVANT TO THERAPEUTICS
Cannabinol was isolated in 1895 and cannabidiol in 1934, but the most significant discovery was that of [DELTA]9-tetrahydrocannabinol (THC) in 1964. Chromatographic and spectroscopic methods subsequently uncovered many closely related compounds.

Capsules of synthetic THC (dronabinol) have been available for restricted medical use in the USA since 1985. Nabilone, a synthetic THC analogue, was marketed in 1983 and is the only cannabinoid licensed for prescription in the UK, restricted to treatment of nausea and vomiting caused by cytotoxic chemotherapy unresponsive to conventional anti-emetics. Use in other indications is only possible on a 'named patient' basis if the drug is supplied by a hospital pharmacy.

In 1988, a specific protein receptor (known as CB1) for THC was discovered in mouse nerve cells. This mediates most of the central nervous system (CNS) responses to cannabinoids, and is abundant in basal ganglia, hippocampus and cerebellum, globus pallidus, substantia nigra and cerebral cortex. An endogenous ligand was identified in 1992 and labelled anandamide (ananda: 'bliss' in Sanskrit). Anandamide has analgesic and tranquillising effects in animals, is involved in muscle coordination and affects the secretion and function of certain hormones. Other endogenous agonists almost certainly exist.

In 1993, a second receptor (CB2) was identified in rat spleen macrophages, and this occurs only outside the CNS. There is scope for chemical manipulation of cannabinoids to maximise selectivity for CB2 and so avoid psychoactive effects. It is thought this receptor has relevance for anti-inflammatory and immunosuppressive activity.

Pertwee (1995) has suggested that the anandamide system might be concerned with mood, memory and cognition, perception, movement, coordination, posture and skeletal muscle tone, sleep, thermoregulation, appetite and immune response.

CLINICAL APPLICATIONS
Nausea and vomiting
Many cytotoxic drugs are powerful emetics, and this is the major limiting factor in patients' acceptance of cancer chemotherapy (see Table 1 and Appendix).

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Treatment with CBD in oily solution of drug-resistant paediatric epilepsies

TitleTreatment with CBD in oily solution of drug-resistant paediatric epilepsies.
Author(s)Pelliccia A, Grassi G, Romano A, Crocchialo P
Journal, Volume, Issue2005 Congress on Cannabis and the Cannabinoids, Leiden, The Netherlands: International Association for Cannabis as Medicine, p. 14.
Major outcome(s)Improvement of EPILEPSY without side effects
 
IndicationEpilepsyAbstract
MedicationCannabidiol

Introduction: As shown by Turkanis et al. (EPILEPSY, 1979), cannabidiol (CBD), similarly to d9- tetrahydrocannabinol (d9-THC) and Phenytoin (PHT) increases the “afterdischarge” and seizures threshold, mainly at the limbic level, without exhibiting the side effects induced by drugs such as PHT.

Studies on rats were conducted that confirmed the anticonvulsant effects of both CBD (Chiu et al., 1979) and of d 9-THC (Cosroe and Mechoulam, 1987).

However, in spite of other studies having confirmed the anticonvulsant effect of cannabinoids, up to date no trials were conducted on man and, the less so, on the child.

Methods: We collected data on a population of children who presented with traditional antiepileptic drugs-resistant seizures, treated with a 2.5% corn oily solution of CBD as part of an open study, by modulating administration and titration schedules on a case by case basis, according to clinical response.

Results: On June 2002 we started to treat an eleven year-old girl affected with a
highly drug-resistant Lennox-Gastaut syndrome, with CBD, a substance not included in
the list of illicit drugs, in a 2.5% corn oily solution, administered at gradually increasing doses up to the present 20 drops daily.

Results have been encouraging: the girl, since she assumes CBD, did not need any longer to be admitted to hospital for her epileptic seizures, while her attacks decreased both in frequency and intensity, in addition her awareness, postural tone and speaking ability improved, as to allow us to gradually decrease her barbiturate intake.

Along the same line, CBD was proposed to another patient, a 17 year-old boy with an equally drug-resistant Lennox-Gastaut syndrome: although he reached the dose of only 30 drops daily, he also exhibited a slight improvement of the crises and, first and foremost, a clear-cut attention-behavioural improvement, and even in his case a suspension of the barbiturate treatment was initiated.

During the last year, 16 more children were started on CBD, all of them affected with symptomatic drug-resistant EPILEPSY; however, only 9 out of these are currently on treatment, since the parents of the remaining children, although appreciating the improvement of their offspring, not only concerning the fits but also the awareness and the muscular tone, preferred to discontinue due to the economic overcharge induced by the treatment (approximately 300 EURos per month).

Conclusions: So far obtained results in our open study appear encouraging for various reasons:

1) no side effects of such a severity were observed as to require CBD discontinuation;

2) in most of the treated children an improvement of the crises was obtained equal to, or higher than, 25% in spite of the low CBD doses administered;

3) in all CBD- treated children a clear improvement of consciousness and spasticity (whenever present) was observed.

 

 


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Marijuana Use More Prevalent With Epilepsy

From Medscape Medical News

Jane Salodof MacNeil

Dec. 12, 2003 (Boston) — People with epilepsy are more than twice as likely to use marijuana as the general population, according to a telephone survey conducted by researchers at the University of Alberta in Edmonton, Canada.

Donald W. Gross, MD, said about 21% of patients who answered the survey had used marijuana during the previous year, and 8% had used it every other day or more. In comparison, he quoted data from the National Household Survey on Drug Abuse and a Canadian survey, which put use during the previous year at 8.9% in the general population.

He and Daphne Quigley, BScN, nurse coordinator of the Adult Epilepsy Program at the University of Alberta Hospital, presented the study in a poster here at the 57th annual meeting of the American Epilepsy Society.

More surprising, he said, was that 24% of 136 respondents — including those who did not use marijuana — contended that marijuana is effective in the treatment of seizures. Despite studies showing cannabinoids can help control seizures in animals, no clinical studies have been conducted in humans, according to Dr. Gross.

In an interview at the poster session, Dr. Gross said his group undertook the survey because patients often told him marijuana was effective in controlling seizures or asked about reports that the drug could be helpful.

In the study, about two thirds of 28 active users said it helped control their seizures: 19 reported improvement in seizure severity, and 15 in seizure frequency. No one said that seizures worsened, but nine respondents said marijuana had no effect on severity of seizures and 13 said it did not help reduce frequency.

Analysis of the responses showed that marijuana use in the study population did not correlate to most factors usually associated with recreational drug use: male sex, youth, and unemployment, according to Dr. Gross. The exception was use of other illicit drugs.

Marijuana use did correlate with more frequent seizures and longer history of epilepsy. "So from our perspective we felt marijuana use in our population was more consistent with a nonconventional healthcare choice than recreational drug use," he said, calling for clinical studies to evaluate whether marijuana is effective in seizure control.

This study received no external funding.

AES 57th Annual Meeting: Abstract 2.314. Presented Dec. 9, 2003.

Reviewed by Gary D. Vogin, MD

 

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Endocannabinoids and Their Implications for Epilepsy

Endocannabinoids and Their Implications for Epilepsy
Bradley E. Alger, Ph.D.
 
 
Abstract
This review covers the main features of a newly discovered intercellular signaling system in which endogenous ligands of the brain's cannabinoid receptors, or endocannabinoids, serve as retrograde messengers that enable a cell to control the strength of its own synaptic inputs. Endocannabinoids are released by bursts of action potentials, including events resembling interictal spikes, and probably by seizures as well.
 
Activation of cannabinoid receptors has been implicated in neuroprotection against excitotoxicity and can help explain the anticonvulsant properties of cannabinoids that have been known since antiquity.

Cannabis in its various forms, including marijuana and hashish, is produced from the flowers and leaves of the hemp plant, Cannabis sativa. Through their primary psychoactive ingredient, Δ9-tetrahydrocannabinol (THC), these drugs affect the central nervous system by activating specific membrane-bound receptors.

The primary brain receptors, cannabinoid receptors type 1 (CB1), are G protein–coupled, seven-transmembrane domain proteins that share numerous similarities with heterotrimeric G protein–coupled receptors for conventional neurotransmitters such as γ-aminobutyric acid (GABA) and glutamate.

The CB1s bind THC with a high degree of selectivity and are heterogeneously distributed throughout the brain. Inasmuch as THC is a plant-derived compound not produced in mammals, endogenous ligands must exist for the cannabinoid receptor, that is, endocannabinoids. Indeed, several endogenous ligands for CB1 have been discovered...read entire case study here

 

 

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first aid for all seizure types

Epileptic seizures can be divided into two main types: focal seizures and generalised seizures. Seizures can vary from one person to another and how people are affected and how they recover after seizures varies. How you can best help someone during a seizure depends on what type of seizure they have and how it affects them.

Focal seizures

Woman comforting another woman

Focal seizures start in, and affect, part of the brain: either a large part or just one small area. What happens during the seizure depends on where in the brain the seizure happens and what this part of the brain normally does.

Simple focal seizures

In a simple focal seizure (SFS) a small part of the brain is affected. The person is conscious (aware and alert) and usually knows that the seizure is happening. A SFS could be an unusual smell or taste, a twitching of an arm or hand, a strange feeling such as a ‘rising’ feeling in the stomach or a sudden feeling of joy or fear.

How to help:

  • as the person might feel strange or be upset, reassuring them might be helpful.

Complex focal seizures

Complex focal seizures (CFS) affect more of the brain than simple focal seizures. The person’s consciousness is affected and they may be confused and not know what they are doing. They might wander around, behave strangely, pick up objects or make chewing movements with their mouth. Afterwards, they be confused for a while or need to sleep. CFS can last a few seconds or a few minutes.

How to help:

  • do not restrain the person as this may upset or confuse them
  • gently guide them away from any danger for example from walking into the road
  • speak gently and calmly as they may be confused. If you speak loudly or grab them they might not understand and get upset or respond aggressively.

After the seizure:

  • they may feel tired and want to sleep. It might be helpful to remind them where they are.
  • stay with them until they recover and can safely return to what they had been doing before. Some people recover quickly but others may take longer to feel back to normal again.

Secondarily generalised seizures

Sometimes a focal seizure spreads to affect both sides of the brain. This is called a secondarily generalised seizure as it starts as a focal seizure and then becomes generalised. Some people call these seizures ‘auras’ or ‘warnings’ as it warns them that another seizure may follow. When this happens the person will usually have a tonic clonic seizure.

How to help:

  • if the person is aware of a warning, they may need help to get to a safe place before the generalised seizure happens.

Generalised seizures

Generalised seizures affect both sides of the brain at once and happen without warning. The person usually becomes unconscious and will not remember the seizure afterwards.

Absences (sometimes called petit mal)

During an absence the person becomes unconscious for a short time. They may look blank and stare and will not respond to what is happening around them. If they are walking they may carry on walking, but will not be aware of what they are doing.

How to help:

  • stay with the person and gently guide them away from any danger.

Tonic and atonic seizures

In a tonic seizure the person’s muscles suddenly become stiff. If they are standing they often fall backwards and may injure the back of their head. In an atonic seizure (or 'drop attack') the person’s muscles suddenly relax and become floppy. If they are standing they often fall forwards and may injure their face or head. Both seizures are brief and happen without warning. Most people usually recover quickly.

How to help:

  • reassuring them may be helpful
  • if they are injured they may need medical help.

Myoclonic seizures

Myoclonic means 'muscle jerk', and these seizures involve jerking of a limb or part of a limb. They often happen shortly after waking up, and are brief and can happen in clusters (many happening close together in time).

How to help:

  • you don't need to do anything to help during the seizure other than make sure that the person has not hurt themselves.

Tonic clonic and clonic (convulsive) seizures

During a tonic clonic seizure the person goes stiff ('tonic' phase), usually falls to the ground, and shakes or makes jerking movements (convulsions or 'clonic' phase). Their breathing may be affected and they may go pale or blue, particularly around their mouth. They may also bite their tongue. Some people have clonic seizures without going stiff to start with.

Although it can be frightening to see, this is not usually a medical emergency. Usually, once the convulsions have stopped, the person recovers and their breathing goes back to normal.

How to help:

  • try to stay calm
  • check the time to see how long the seizure goes on for (because there may be a risk of status epilepticus - see below)
  • only move the person is they are in a dangerous place, for example in the road. Instead, move any objects, such as furniture, away from them so that they don't hurt themselves
  • put something soft (such as a jumper) under their head, or cup their head in your hands, to stop it hitting the ground
  • do not restrain them or hold them down - allow the seizure to happen
  • do not put anything in their mouth - they will not swallow their tongue
  • try to stop other people crowding around.

How to help once the shaking stops:

  • roll them on to their side into the recovery position
  • if their breathing sounds difficult or noisy, gently open their mouth to check that nothing is blocking their airway
  • wipe away any spit from their mouth
  • try to minimise any embarrassment. If they have wet themselves deal with this as privately as possible (for example, put a coat over them).
  • stay with them until they have fully recovered. They may need some gentle reassurance.

Some people recover quickly from a tonic clonic seizure but often they will be very tired, want to sleep and may not feel back to normal for several hours or sometimes days.

Most people's seizures will stop on their own and the person will not need any medical help. However, if you are not sure whether someone is recovering from a seizure, they have hurt themselves during the seizure, or you have any concerns about them, you might want to think about when to call for an ambulance.

Some people might injure themselves during a seizure. Dental injuries can be common.

Status epilepticus

A person's seizures usually last the same length of time each time they happen, and stop by themselves. However, sometimes seizures do not stop, or one seizure follows another without the person recovering in between. If this goes on for 30 minutes or more it is called status epilepticus, or 'status'.

Status is not common, but can happen in any type of seizure and the person may need to see a doctor.

Status in a tonic clonic (convulsive) seizure is a medical emergency and the person will need urgent medical help. It is important to call for an ambulance before the seizure goes on too long. Do not wait until it has lasted 30 minutes before calling for an ambulance. See when to dial 999.

Some people are prescribed emergency medication, either buccal midazolam or rectal diazepam, to stop their seizures. Carers need training in giving emergency medication. It is important to have an individualised written protocol (plan) about when to give it, for the carer to follow.

How else can I help?

Checking the length of a seizure is essential in avoiding status (see above).  Another important reason to check the time and note the length of a seizure is so that you can pass this information on afterwards to the person who has had the seizure.  Many people keep a record of their seizures, and a description of the seizure and how long it lasted can be vital information for them to record, and pass on to their specialist.

More information about recording information about seizures.

 

 

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Epilepsy patients are smoking pot

by Helen FieldsU.S. News & World Report
December 6th, 2004

Even though there's not a lot of evidence that it helps, many patients with epilepsy use marijuana, hoping it will reduce their seizures. Researchers in Alberta, Canada, asked epilepsy patients if they were smoking pot.

What the researchers wanted to know: How common is marijuana use among epilepsy patients?

What they did: Patients seen at the University of Alberta Epilepsy Clinic were called and asked about their condition and whether they use medical marijuana.

What they found: Of 136 subjects, 48 (35 percent) had used marijuana in the past month. Nearly half had used it at some time in their lives, and four were determined to be dependent on the drug. People with frequent seizures or who'd had the disease longer were more likely to use marijuana frequently—which could mean that using marijuana makes seizures happen more often but could also mean that patients whose disease was worse were more likely to try alternative treatments. Not surprisingly, people who used other illicit drugs were also more likely to smoke marijuana.

What the study means to you: Many people with epilepsy seem to think marijuana helps. Animal studies have come up with conflicting results—in some, marijuana increases convulsions, while in others it has an anticonvulsant (somewhat more desirable) effect. In any case, if many patients are using marijuana, it seems worth studying more.

Caveats: This is one clinic in Canada, so the findings probably don't apply to everyone with epilepsy, especially if they live in places with stricter marijuana laws. (Medical use of marijuana is legal in Canada under certain conditions.)

Find out more: The people who run the website the Science of Medical Marijuana are—no surprise—in favor of medical marijuana.

Go to the National Institute of Neurological Disorders and Stroke for information and resources about epilepsy.

Read the article: Gross, D.W., et al. "Marijuana Use and Epilepsy: Prevalence in Patients of a Tertiary Care Epilepsy Center." Neurology. June 8, 2004, Vol. 62, No. 11, pp. 2095–2097

 

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