Monday, February 25, 2019

Cannabis and Seizure Disorders





Cannabis and Seizure Disorders


“Epilepsy refers to a spectrum of chronic neurological disorders in which clusters of neurons in the brain sometimes signal abnormally and cause seizures (NINDS, 2016a). 
Epilepsy disorder affects an estimated 2.75 million Americans, across all age ranges and ethnicities (NINDS, 2016a). 
Although there are many antiepileptic medications currently on the market, about one-third of persons with epilepsy will continue to have seizures even when treated (Mohanraj and Brodie, 2006). 
Both THC and CBD can prevent seizures in animal models (Devinsky et al., 2014).”


Epilepsies are the third most common class of neurological disorders.

Cannabinoids THC and CBD bind themselves to endocannabinoid receptors, which are located throughout the brain, and body. When cannabis, high in CBD, is consumed – these cannabinoids go to work in halting the seizure activity within the brain.
Some parents turned to cannabis, only after trying multiple anti-epilepsy drugs (AED) that have failed for their children’s epilepsy, because they were frustrated by little to no results from the AEDs. High CBD cannabis was given to some of these children who were suffering from hundreds of seizures per week. CBD oil halted these seizures.
Parents moved to legal states, like Colorado, where they could get access to this high CBD oil. Companies started cultivating these high CBD strains and developed products to help adults and children with neurological disorders, such as seizures. 


History of Cannabis and Seizure Disorder
The earliest descriptions of cannabis use to treat epilepsies are from medieval Arabic medical texts. As early as the 10th century, the Persian medical writer al-Majusi recommended that the juice of hemp leaves be poured into the nose to prevent seizures.  https://www.tandfonline.com/doi/abs/10.1300/J175v01n01_05
In the 15th century, the polymath al-Badri claimed that the epilepsy of a son of the caliph’s chamberlain was successfully treated with cannabis resin, although modern scholars question the veracity of this account.
in The Herb: Hashish Versus Medieval Muslim Society 

Cannabis and Seizure Disorder used Today
Anti-epilepsy drugs (AEDs) are the primary treatment option for seizure disorders. Some patients experienced little to no help at all from these AEDs. 30 percent of epilepsies do not respond to currently available drug treatments, over 20 million people worldwide have drug-resistant epilepsies. https://www.ncbi.nlm.nih.gov/pubmed/17874969
These facts underscore the pressing need for new, effective AEDs. There is potential use in cannabis medicine. Researchers have long known that both THC and CBD can cause and prevent seizures.
https://www.ncbi.nlm.nih.gov/pubmed/24854329
Cannabis has been used to treat several severe childhood epilepsies, including Dravet Syndrome, which strikes very young children with catastrophic results and can be life-threatening.
https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0037-1598109.pdf


Reviews and Studies on Cannabis and Epilepsy
“We identified two systematic reviews of randomized trials assessing the efficacy of cannabis or cannabinoids, used either as monotherapy or in addition to other therapies, in reducing seizure frequency in persons with epilepsy. Gloss and Vickrey (2014) published a systematic review of randomized controlled trials. They identified four reports (including one conference abstract and one letter to the editor) of cannabinoid trials, all of which they considered to be of low quality. Combined, the trials included a total of 48 patients. The systematic review's primary prespecified outcome was freedom from seizures for either 12 months or three times the longest previous seizure-free interval. None of the four trials assessed this endpoint. Accordingly, Gloss and Vickrey asserted that no reliable conclusions could be drawn regarding the efficacy of cannabinoids for epilepsy.
Koppel et al. (2014) published a fair-quality systematic review. They identified no high-quality randomized trials and concluded that the existing data were insufficient to support or refute the efficacy of cannabinoids for reducing seizure frequency.
Recent systematic reviews were unable to identify any randomized controlled trials evaluating the efficacy of cannabinoids for the treatment of epilepsy. Currently available clinical data therefore consist solely of uncontrolled case series, which do not provide high-quality evidence of efficacy. Randomized trials of the efficacy of cannabidiol for different forms of epilepsy have been completed and await publication.”
-The Health Effects of Cannabis and Cannabinoids: assessments on therapeutic efficacy of CBD in epilepsy 
https://www.ncbi.nlm.nih.gov/books/NBK425767/

The anti-epilepsy effects of cannabinoids have been studied since the mid-1970s. 
Fried and McIntyre 1973
Research focus has been primarily on CBD as an AED, with other cannabinoids, CBDV and THCV, in early human trails. 
Cannabidiol (CBD) reliably delivers a range of anticonvulsant effects with few known adverse results and no intoxication. 
Cannabidivarin (CBDV) is a non-psychoactive cannabinoid that will not cause the euphoric feeling of being “high.” It is found more prevalently in indica strains, specifically landrace indica strains, and strains that are lower in THC. Like CBD, CBDV significantly reduces the frequency and severity of seizures. It also reduces or even eliminates nausea associated with several conditions, and helps to reduce inflammation throughout the body. CBDV is also beneficial in the treatment of pain and mood disorders.
Tetrahydrocannabivarin (THCV) is a marijuana compound that potentially provides people with an array of benefits and unique effects. THCV was discovered in 1973 and is an extremely well-studied cannabinoid. THCV is only psychoactive in high doses. In low doses, THCV acts as an antagonist of the CB1 receptor, which means you won’t experience a ‘high’. When you increase the dose THCV switches behavior and acts as a CB agonist, like THC, which means you WILL get a ‘high’ feeling. There is evidence that THCV reduces seizures and since it is non-intoxicating in smaller doses, could be a useful way to treat children with epilepsy. 
https://www.marijuanabreak.com/thcv-tetrahydrocannabivarin

The results of a GW trial in Dravet syndrome released in December 2016, for their Epidiolex product containing CBD dissolved in sesame oil showed at a dose of 20 mg of CBD per kilogram of patient weight, 43 percent of CBD patients had a greater than 50 percent reduction in convulsive seizures compared to 27 percent of patients taking placebos.
An additional four CBD patients achieved convulsive seizure freedom during maintenance. 93 percent of patients were on multiple AEDs during the CBD trial. The effect of these AEDs on efficacy will be explored more in the future.
THCV in cell and animal models of epilepsies produces contradictory results. https://www.ncbi.nlm.nih.gov/pubmed/20196794
Following promising animal studies, clinical trials of CBDV for treatment of seizure disorders could begin soon.
https://www.ncbi.nlm.nih.gov/pubmed/22970845

CBG is another cannabinoid that may exhibit anti-seizure properties. Synthetic cannabinoids that target the CB1 receptor have so far demonstrated significant anti-seizure activity in animal models of chronic epilepsy.
https://www.fasebj.org/doi/abs/10.1096/fasebj.27.1_supplement.660.2
Reports in 2016-2017 have shown that the concentration of linalool in particular cannabis cultivars exhibited anticonvulsant activity in human patients.
https://www.ncbi.nlm.nih.gov/pubmed/28254350

How Cannabis Helps Seizure Disorder
The mechanism by which cannabinoids inhibit seizure activity is still not understood, but certainly extends beyond interaction with the cannabinoid receptors CB1 and CB2 to other receptor systems within the body.
A cannabinoid might modulate neural circuitry to gain control over seizure activity, here are the different receptors and ion channels in the nervous system that have been linked to the THC’s limited anti-seizure activity: CB1, CB2, TRPA1, TPRV2, TRPM8, GPR55, 5-HT3A, PPARy, u- and delta-opioid receptors, the beta-adrenoreceptors, and calcium, potassium, and sodium ion channels.
CBD doesn’t activate CB receptors, but it does activate the TRPV1 receptor, calcium and sodium ion channels, the 5-HT1A and 5-HT2A receptors, the GPR55 and the adenosine receptors A1 and A2, and more.
Linalool, a terpene found in some cannabis strains, has anticonvulsant effects.
https://www.ncbi.nlm.nih.gov/pubmed/20452289
https://www.ncbi.nlm.nih.gov/pubmed/20655301
It will likely take some time to sort out incredibly complex potential receptor interactions to determine the cannabinoid mechanisms of action for the dozens of different seizure disorders.

Dosing with Cannabis
Dosage guidance depends upon the type of disorder and the cannabinoid being used. Consultation with a physician is highly recommended to help determine appropriate guidelines. Daily doses are important to help keep seizure activity at bay.
Typically, a CBD protocol begins with a dose of 10 mg twice a day, then this dose is doubled every 3 days until seizure control or the daily dose equals 20 mg per kilogram of the patient’s body weight.
Conventional oral use is typical, since doses tend to be large, up to 1200 mg per day, for patients who have been treating with cannabis for some time.

Some Adults use herbal cannabis in combination with conventional AEDs. Some adults achieve seizure control with herbal cannabis alone, that they smoke or vaporize.

Chemotypes of medicinal cannabis to look for are CBD varieties, such as ACDC, Harlequin, Dance World, Sour Tsunami, and Ringo’s Gift, have become popular among adult patients with seizure disorders.

CBDV and THCV varieties are very rare, however, some local dispensaries may carry special medications such as oil, or edibles highlighting these specific cannabinoids.

You can use Leafly.com to find a dispensary near you that offers specific products with a high CBD cannabinoid content, or Linalool terpene content. It is easy to find medical marijuana with high CBD oil, just make sure to purchase from a reputable source. Talk to a trusted physician who knows and understands your medical condition and cannabis and the endocannabinoid system. Finding the best dose, or medication, that works for you may take some time and patience.

If you are looking for a Medical Marijuana Doctor near you, who can help you find the right cannabis medicine for your specific seizure disorder, you may visit MarijuanaDoctors.com



Information about Cannabis and Seizure Disorder was taken from the amazing book:

Cannabis Pharmacy – The Practical Guide to Medical Marijuana by Michael Backes, Andrew Weil, M.D. and Jack D. McCue, M.D., medical editor



More Articles for research on Cannabis and Seizure Disorder
The Epilepsy Foundation: Medical Marijuana and Epilepsy

Epilepsy Society: Cannabis Oil for Epilepsy

Cannabinoids in the Treatment of Epilepsy

WebMD: Low Dose of CBD Liquid Eases Epilepsy Seizures

Project CBD: Epilepsy and Seizure Disorders