Les épilepsies - Cannabis, potential for improving life comfort

Worldwide, nearly twenty million people withepilepsy are drug-resistant to antiepileptic drugs, which represents three out of ten cases of chronic epilepsy.(1)

Numerous clinical studies have been conducted with phytocannabinoids on childhood diseases such as Dravet syndrome, Lennox Gastaut syndrome, Angelman syndrome and FIRES syndrome (Febrile Epilepsy Infection Related Syndrome).

What is the status of research on phytocannabinoids and what are their actions on epilepsy?

The different epilepsies

Epilepsy is a group of about fifty chronic neurological diseases that can occur at any age. They are the third most common neurological diseases, after migraines and Parkinson's disease, affecting sixty million people worldwide. Half of them are children.(2)

Long considered as curses or psychiatric disorders, epilepsies are considered as a disease from 400 BC by the famous Greek physician Hippocrates. Moreover, the term epilepsy comes from the Greek " επιλαμβανειν " (epilambanein), meaning "to attack by surprise ".(3)

Epilepsies are most commonly characterized by convulsive seizures, absences and muscle stiffness, leading to disorders of cognition,mood, sleep,appetite... The symptoms of these different epilepsy syndromes are complex and currently lack further research.

The common feature of these syndromes is theepileptic seizure due to a coordinated and abnormal excitation of groups of neurons in the cerebral cortex, which can lead to a dysfunction of other parts of the brain. Epileptic seizures are characterized by two types(4) :

• Generalized seizures, linked to discharges that extend throughout the brain, cause transient loss of consciousness (absences) and motor signs that may be tonic (muscle contractions), myoclonic (muscle jerks), tonic-clonic (muscle contractions and jerks) or atonic (loss of muscle tone)
• Partial seizures, linked to discharges targeted on a part of the brain, generate, according to their localization, disorders of motor skills, sensitivity, sensory processing (anxiety, hyperactivity, inattention) and behavior. These partial seizures represent two out of three cases of epilepsy and can develop into generalized seizures

Phytocannabinoids and epilepsy

The story

The cannabis would be used to relieve epilepsy since 2900 years BC, in Mesopotamia(5).
In the 10th century, Ali ibn Abbas al-Majusi, a famous Persian physician, psychologist and writer, advised his patients toinhale cannabis juice to reduce epileptic seizures.(6)

In 1890, Sir John Russell Reynolds, neurologist and physician to Queen Victoria of the United Kingdom, wrote in the British scientific journal The Lancet, " There are many cases of so-called epilepsy in adults...for which Indian hemp is the most useful agent with which I am familiar...and the seizures may be stopped at once by a whole dose of hemp.(7)

The first modern study on the anti-epileptic properties of cannabinoids took place in 1973, with delta-9-tetrahydrocannibinol (THC).(8)
In 1980, researchers conducted a study on eight volunteer patients with cannabidiol (CBD), while continuing their usual anti-epileptic treatments. During the experimentation, half of the patients declared not to have had epileptic seizures, the state of three patients was partially improved, while in only one person the treatment was ineffective.(9)

Although these two previous studies were promising, clinical trials on the anti-epileptic properties of phytocannabinoids have reappeared in the early 2010s thanks to the media coverage on the internet of rare cases ofchildhood epilepsy (Dravet syndrome, Lennox Gastaut syndrome, ...). Because of its non-psychoactivity, research then focused on the cannabidiol (CBD).

The numbers

A study carried out on rodents showed a significant effectiveness of cannabidiol (CBD) on the reduction of epileptic syndromes.
This study concludes on the high potential of this phytocannabinoid This study concludes on the high potential of CBD to relieve human epilepsy which are diverse and for which antiepileptic drugs are no longer effective in certain cases of drug resistance.(10)

An investigation was conducted on a hundred epileptic children with cannabidiol (CBD) treatment, notably for infantile spasms and Lennox Gastaut syndrome.
The results are encouraging with an eighty-five percent reduction in epileptic seizures and a fourteen percent seizure-free period during the treatment, which lasted about six months.
In addition, more than one child out of two improved their sleep, seven out of ten improved their alertness and six out of ten improved theirmood. (11)

In 2016, Israeli clinical trials were conducted on seventy-four incurable epileptic patients between the ages of one and eighteen, using a cannabidiol (CBD) and a low dose of delta-9-tetrahydrocannibinol (THC).

The results show that in eighty-nine percent of the patients the seizures were reduced. But for seven percent, the seizures increased, leading to the discontinuation of the treatment.
The researchers also noted an improvement in behavior, alertness, language, communication, motor skills and sleep.

Although this study shows some adverse effects such as drowsiness, fatigue, gastrointestinal disorders and irritability. Practitioners conclude that they wish to continue their research and justify the likelihood of using cannabidiol (CBD) to treat some forms ofepilepsy.(12)

In Mexico, clinical trials with cannabidiol (CBD) have been conducted on patients aged nine months to eighteen years with Lennox Gastau syndrome,unspecified refractory epilepsy, West syndrome and Ohtahara syndrome.
In more than eight out of ten patients, the treatment reduced seizures, and sixteen percent were seizure-free.(13)

Due to its non-psychoactivity, research shows that cannabidiol (CBD) has antiepileptic properties suitable for drug-resistant children and young adults.(14)

The receptors CB1 of endocannabinoid system receptors would be affiliated with seizure activity, depending on how they are activated.
The cannabidivarin (CBDV) also has anti-epileptic properties. In synergy with the cannabidiol (CBD), it would increase their common anti-epileptic properties.
Other phytocannabinoids are currently being tested, such as cannabigerol (CBG) and the tetrahydrocannabivarin (THCV).

Report

On February 28, the French public channel, France 2, broadcast a report entitled " The other face of cannabis ".
This report is centered on the case of a 9 year old girl named Kaylah suffering from Dravet syndrome.

Dravet syndrome is a rare genetic disease, causing severe myoclonic (muscle twitching) seizures, as well as various disorders and alterations:

• Psychomotor and language delays
• Walking,balance and fine motor skills (hands and fingers)
• Behavioral disorder (hyperactivity/autism)
• Eating disorders
• Sleep disorders
• Chronic conditions of the upper respiratory tract
• Disorder of body temperature regulation and sweating

Dravet syndrome is now a drug-resistant disease requiring a cocktail of heavy medication. Studies are underway to determine the genes involved.

The cannabidiol (CBD) could reduce, or even eliminate, the need to take certain treatments and the number of daily attacks. It does not cure this disease but allows toimprove the comfort of life: sleep,appetite,learning,mood...

Sources

Michael Backes: Medical Cannabis - What you need to know...

Franjo Grotenhermen - CBD - A cannabinoid with broad therapeutic potential

1 : P Kwan, MJ Brodie - Emerging drugs for epilepsy

2 : INSERM - Epilepsy, A complex disease

3 : LFCE - Where does the term epilepsy come from?

4 : FFN - What is epilepsy? 

5 : EC Rosenberg, RW Tsien, BJ Whalley, O Devinsky - Cannabinoids and Epilepsy

6 : I Lozano - The Therapeutic Use of Cannabis sativa (L.) in Arabic Medicine

7 : J Russell Reynolds - On the Therapeutical Uses and Toxic Effects of Cannabis Indica

8 : PA Fried, DC McIntyre. Electrical and behavioral attenuation of the anti-convulsant properties of delta 9-THC following chronic administrations.

9 : JM Cunha, EA Carlini, AE Pereira, OL Ramos, C Pimentel, R Gagliardi, WL Sanvito, N Lander, R Mechoulam - Chronic administration of cannabidiol to healthy volunteers and epileptic patients

10 : NA Jones, SE Glyn, S Akiyama, TD Hill, AJ Hill, SE Weston, MD Burnett, Y Yamasaki, GJ Stephens, BJ Whalley, CM Williams - Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures

11 : SA Hussain, R Zhou , C Jacobson, J Weng, E Cheng, J Lay, P Hung, JT Lerner, R Sankar - Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome

12 : M Tzadok, S Uliel-Siboni, I Linder, U Kramer, O Epstein, S Menascu, A Nissenkorn, OB Yosef, E Hyman, D Granot, M Dor, T Lerman-Sagie, B Ben-Zeev - CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience

13 : CG Aguirre-Velázquez - Report from a Survey of Parents Regarding the Use of Cannabidiol (Medicinal cannabis) in Mexican Children with Refractory Epilepsy

14 : O Devinsky, E Marsh, D Friedman, E Thiele, L Laux, J Sullivan, I Miller, R Flamini, A Wilfong, F Filloux, M Wong, N Tilton, P Bruno, J Bluvstein, J Hedlund, R Kamens, J Maclean, S Nangia, NS Singhal, CA Wilson, A Patel, MR Cilio - Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial