Posts Tagged cannabis
The three-pound organ that serves as command central for the human organism is certainly a marvel, just by virtue of the fact that the brain can appreciate its own awesomeness, even if it hasn’t quite perfected the flying car or even self-driving cars. Yet. Companies developing brain-computer interface technology are enabling humans to do things like send commands to computers by just flexing a bit of muscle. Still, there is much we don’t know about ourselves, no matter how much telepsychiatry we do. And that applies especially to medical conditions that affect the brain like epilepsy, a neurological condition for which there is no cure.
What is Epilepsy?
While most of us are probably familiar with some Hollywood-ized version of epilepsy in which someone starts flailing around after being hit by strobe lights on the disco floor, the reality is that epilepsy refers to a large group of neurological disorders that generally involve chronic, spontaneous seizures that vary greatly in how they manifest. The causes of epilepsy are also all over the place, from traumatic brain injuries and stroke to viral and bacterial infections to genetics.
It is considered a brain disorder, according to the U.S. Centers for Disease Control (CDC), though some researchers have suggested it could be classified as a neurodegenerative disease like Parkinson’s or Alzheimer’s. In fact, there is research that suggests a genetic link between epilepsy and neurodegenerative diseases.
Not surprisingly, many of the companies developing therapies for neurodegenerative diseases are also working on treatments for epilepsy and vice versa. For example, a new, well-funded joint venture involving Pfizer (PFE) and Bain Capital called Cerevel, which we profiled in our piece on Parkinson’s disease, is also in advanced clinical trials for an epileptic drug. Its GABA A positive modulator drug candidate targets GABA (Gamma-Aminobutyric Acid) neurotransmitters that block impulses between nerve cells in the brain, helping keep the nervous system chill.
Impacts of Epilepsy
More than 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally, according to the World Health Organization (WHO). The CDC estimates about 3.4 million Americans live with the condition. Globally, an estimated 2.4 million people are diagnosed with epilepsy each year. Interestingly, the disorder seems to target those who can least afford it: WHO said nearly 80% of people with epilepsy live in low- and middle-income countries.
A 2015 study of a bunch of other studies that estimated the cost of epilepsy in the United States found that epilepsy-specific costs probably average out to about $10,000 based on the variety of ranges, which means epilepsy costs the United States healthcare system about $34 billion, though the numbers are widely debated. Conversely, WHO says low-cost treatments are available, with daily medication coming as cheaply as $5 per year, so another win for the U.S. healthcare system.
Treatments for Epilepsy
There are more than 20 antiepileptic drugs used to treat epilepsy, usually to help prevent or slow the occurrence of seizures. Other therapies include surgery and electroceutical treatment in which electrical stimulation is applied, usually to the vagus nerve, the longest cranial nerve in the body. While many find relief from one or more of these options, a third of those who suffer from epilepsy are not able to manage their seizures, according to the U.S. National Institutes of Health (NIH). Below we take a look at a range of innovative therapies designed to detect, stop, or find a cure for epilepsy.
Brain Stimulation Therapies
In our article on electroceutical treatments, we highlighted a London company called LivaNova (LIVN) that offers an implantable Vagus Nerve Stimulation (VNS) therapy that has been approved by the U.S. Food and Drug Administration (FDA) to help treat those with partial seizures who do not respond to seizure medications. A medical device company with a lengthy track record of returning value to investors, Medtronic (MDT) got FDA pre-market approval last year for its Deep Brain Stimulation (DBS) therapy for use in reducing partial-onset seizure for those who have proven to not respond to three or more antiepileptic medications. DBS therapy delivers controlled electrical pulses to an area in the brain called the anterior nucleus of the thalamus, which is part of a network involved in seizures. Yet another company offering a variation of brain stimulation therapy is NeuroPace, which markets its responsive neurostimulation device, or RNS system, as “the first and only brain-responsive neurostimulation system designed to prevent epileptic seizures at their source.”
Artificial Intelligence to Detect, Predict, and Control Epilepsy
The NIH is funding further research into implantable devices that can detect, predict, and stop a seizure before it happens, “working closely with industry partners to develop pattern-recognition algorithms,” which sounds an awful lot like artificial intelligence and machine learning will be at the forefront of some future diagnostics and treatment. AI in healthcare has been an ongoing theme around here, with a recent dive into AI and mental health. Back to AI and epilepsy: A group of neurologists at the Medical University of South Carolina developed a new method based on artificial intelligence to predict which patients will see success with surgical procedures designed to stop seizures. Sounds like a great idea to learn beforehand if it’s necessary to crack open your skull.
A Boston area startup called Empatica, spun out from MIT in 2011, has raised $7.8 million for a smartwatch that detects possible seizures by monitoring subtle electrical changes across the surface of the skin. Other methods normally rely on electrical activity in the brain that tracks and records brain wave patterns called an electroencephalogram. Empatica’s seizure detection algorithm, on the other hand, can detect complex physiological patterns from electrodermal activity that is most likely to accompany a convulsive seizure. Psychology Today reportedthat the device, Embrace Watch, received FDA approval earlier this year for seizure control in children after getting the green light for the technology for adults in 2018.
AI and drug discovery for better epileptic drug candidates is yet another application that we would expect to see grow in the coming years. Silicon Valley-based startup System1 Biosciences raised $25 million last year, which included Pfizer among its dozen investors. System1 builds a sort of brain model for testing drug candidates using stem cell lines derived from patients with brain disease. The company uses robotic automation to develop these three-dimensional cerebral organoids, allowing it to generate huge datasets in a relatively short amount of time, then applying “advanced data analysis” (also AI?) to detect patterns that might match the characteristics of a neurological disease (what it refers to as deep phenotypes) such as epilepsy with novel treatments.
Cannabis for Controlling Seizures
We’ve written extensively about the suddenly booming hemp CBD market, noting that the FDA approved a CBD-based drug for epilepsy last year in our recent article on the best certified CBD oils on the market. However, we’ve only briefly profiled the company behind Epidiolex for treating rare forms of epilepsy, GW Pharmaceuticals (GWPH). Sporting a market cap just south of $5 billion, GW Pharmaceuticals has taken in about $300 million in post-IPO equity since our article, bringing total post-IPO equity funding to about $568 million. Aside from its successful epileptic drug, GW also developed the world’s first cannabis-based prescription medicine for the treatment of spasticity due to multiple sclerosis that is available in 25 countries outside the United States.
Back on the epilepsy side, Epidiolex has been approved for two rare forms of epilepsy, with clinical trials underway for two more rare neurological disorders associated with seizures – tuberous sclerosis complex and Rett syndrome. Also in the pipeline is a drug dubbed CBDV (GWP42006) that’s also for treating epileptic seizures, though the results of a trial last year were not encouraging. The same compound is also being investigated for autism. Be sure to check out our article on Charlotte’s Web, a CBD company that came about because of epilepsy.
Helping Cells Get Their Vitamin K
Neuroene Therapeutics is a small startup spun out of the Medical University of South Carolina that recently picked up $1.5 million in funding to tests its lead drug compounds, which are analogous to the naturally occurring form of vitamin K that is essential for brain health. In particular, the lab-developed vitamin K protects the integrity of the cell’s mitochondria, which serves as a sort of power plant for brain cells, helping the neural circuit fire better. Unfortunately, you can’t get the effect from simply eating a bowl of Special K each morning covered in an organic sugar substitute, so the company is developing a method to deliver the effects directly to the brain.
A Nasal Spray to Stop Seizures
Founded in 2007 near San Diego, Neurelis licenses, develops, and commercializes treatments for epilepsy and other neurological diseases. It has raised $44.8 million in disclosed funding, most coming in a $40.5 million venture round last November. The company’s flagship product is called Valtoco, a formulation that incorporates diazepam, an existing drug used to control seizures and alcohol withdrawal, with a vitamin E-based solution that is delivered using a nasal spray when a sudden seizure episode occurs. The product uses an absorption enhancement technology called Intravail developed by another San Diego area company called Aegis Therapeutics that Neurelis acquired in December last year. Neurelis submitted Valtoco to the FDA for approval in September.
While many people with epileptic conditions can control their seizures with many of the current medications or other therapies available now, there’s a big chunk of the population that is living with uncertainty. Considering the strong link between neurological disorders like epilepsy and certain neurodegenerative disorders, expect to see some good synergies in the next five to 10 years, especially as automation and advanced analytics using AI start connecting the dots between genetics, biochemistry, and brain disorders.
Epilepsy is considered to be one of the most common non-communicable neurological diseases especially in low to middle-income countries. Approximately one-third of patients with epilepsy have seizures that are resistant to antiepileptic medications. Clinical trials for the treatment of medically refractory epilepsy have mostly focused on new drug treatments, and result in a significant portion of subjects whose seizures remain refractory to medication. The off-label use of cannabis sativa plant in treating seizures is known since ancient times. The active ingredients of this plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the latter considered safer and more effective in treating seizures, and with less adverse psychotropic effects.
Clinical trials prior to two years ago have shown little to no significant effects of cannabis in reducing seizures. These trials seem to be underpowered, with a sample size less than 15. In contrast, more recent studies that have included over 100 participants showed that CBD use resulted in a significant reduction in seizure frequency. Adverse effects of CBD overall appear to be benign, while more concerning adverse effects (e.g., elevated liver enzymes) improve with continued CBD use or dose reduction.
In most of the trials, CBD is used in adjunct with epilepsy medication, therefore it remains to be determined whether CBD is itself antiepileptic or a potentiator of traditional antiepileptic medications. Future trials may evaluate the efficacy of CBD in treating seizures due to specific etiologies (e.g., post-traumatic, post-stroke, idiopathic).[…]
Epilepsy drugs don’t work well, or at all, for about one-third of people with the condition. Unfortunately, these hard-to-treat epilepsies are associated with an increased risk of premature death.
Anecdotal evidence suggests that cannabis oil may help some of these people control their seizures and potentially save their lives. A small number of studies have shown that adding cannabis oil to existing medication may be effective in devastating, hard-to-treat epilepsy in children and adolescents.
One of those people is 12-year-old Billy Caldwell. Billy was in the UK news recently after the cannabis oil prescribed for him was confiscated at Heathrow airport by the authorities. Billy’s mother, Charlotte, was attempting to bring the cannabis oil into the UK from Canada, where cannabis oil is legal.
Billy was seizure-free for more than 250 days when taking the oil, but his seizures started again when his cannabis oil was withdrawn. The home secretary, Sajid Javid, was persuaded to intervene and one of the seven bottles of cannabis oil was returned, with a 20-day licence to administer the medicine.
In a similar case, six-year-old Alfie Dingle, who suffers from severe epilepsy, had been successful[ly] treated with cannabis oil in the Netherlands. Alfie’s mother, Hannah Deacon, has been campaigning to allow her son to be provided with cannabis oil in the UK.
The government has now also relented in Alfie’s case following the concerns raised around the confiscation and return of Billy Caldwell’s medicine.
What the evidence shows
So what do we know about cannabis oil and its effects on epilepsy seizures?
The two main constituents of cannabis oil are THC (tetrahydrocannabinol) and CBD (cannabidiol). Oil containing CBD alone (CBD oil) can be legally bought in the UK without a prescription because it contains only very low quantities of THC. But cannabis oil that contains THC at higher levels (more than 0.3%) is illegal. THC is a schedule 1 drug, that is to say, it is deemed to have no medicinal value.
The reason that Billy’s cannabis oil was seized at Heathrow airport was that it didn’t just contain CBD, it also contained THC at higher levels than legally permitted.
There is good evidence in robust human clinical trials that CBD is of benefit for specific epilepsies, such as Dravet syndrome and Lennox Gastaut syndrome. An advantage for the pharmaceutical industry is that these rare diseases with no cure can be fast-tracked for drug development. On this basis, the US Food and Drug Administration is widely expected to grant a licence for CBD (under the tradename Epidiolex) to treat these epilepsies. If so, Epidiolex is likely to be available in US by late 2018. European approval is likely to follow.
It should be noted that Epidiolex is designed as standardised oral solution of pure plant-derived CBD. It is not the same as the non-standardised, viscous CBD oils that contain varying amounts of CBD and can be purchased in health food shops. There is currently no good evidence that formulations of CBD oil (or indeed cannabis oil) are as effective on epilepsy seizures. Equally, there is no robust evidence – just anecdotal reports – that THC helps reduce epilepsy seizures human.
In [animal studies], THC has weak overall effects in reducing seizures and has also been shown to be a less effective anticonvulsant than CBD. THC, being a psychoactive substance, also has a number of side effects, including the well-known euphoric “high” associated with recreational use – which is a significant disincentive for the pharmaceutical industry to develop a medicine containing this compound.
We now need to decide if we should expand human trials with better defined THC-containing cannabis oil, or if we should focus on CBD. The fact that Epidiolex has progressed towards approval in the US may encourage the latter course. CBD lacks psychoactive effects associated with THC and, in general, is regarded as a safe compound.
If Epidiolex is granted regulatory approval, it will also need to be monitored in a larger number of patients – in what’s known as “phase 4 post-marketing surveillance” – to ensure that it is safe and effective in a broader population. For any cannabis-based product, only large-scale clinical trials can provide definitive answers about effectiveness and safety.
WEBINAR ON CANNABIS FOR SEIZURES
An advisory panel from the United States Food and Drug Administration (FDA) has recommended the approval of a novel epilepsy drug that is made up of ingredients from marijuana. The agency normally follows the recommendations of the advisory panels regarding approvals and rejections of applications of new drugs. The recommendation statement came yesterday (19th April 2018).
If this drug gets a green light, it is expected to become the first cannabis-derived prescription medicine to be available in the US. The drug is named Epidiolex and is made by GW Pharmaceuticals from Britain. It contains cannabidiol or CBD that is derived from cannabis. However the drug is not seen to cause any intoxication among the users.
The use of only one of the components of cannabis also makes it different from medical marijuana that is approved for pain management and other conditions around the world and in the United States. Synthetic forms of chemicals in the cannabis plant are also used to treat nausea among cancer patients and in AIDS patients to prevent weight loss.
Dr. Igor Grant, director of the Center for Medicinal Cannabis Research at the University of California San Diego welcomed this new recommendation from the panel saying, “This is a very good development, and it basically underscores that there are medicinal properties to some of the cannabinoids… I think there could well be other cannabinoids that are of therapeutic use, but there is just not enough research on them to say.”
As of now the panel has recommended the use of this new drug for two types of epilepsy only – Lennox-Gastaut syndrome and Dravet syndrome. These are notoriously difficult to treat and most people continue to have seizures despite treatment. Multiple seizures may occur in a day and this makes the children with these conditions vulnerable for developmental and intellectual disabilities. Lennox-Gastaut syndrome can appear in toddlers at around ages 3 to 5 and Dravet syndrome is usually diagnosed earlier. Nearly 30,000 children and adults suffer from Lennox-Gastaut syndrome and similar numbers of people are diagnosed with Dravet syndrome. Due to the small population of diagnosed patients Epidiolex was filed and classified under orphan drug status.
An orphan drug is one that is developed for a relatively rare disease condition. The FDA provides special subsidies and support for development of orphan drugs and often speed tracks their approval process.
The recommendation from the advisory panel is based on the results of three randomized, double-blind, placebo-controlled trials that included patients of both these disease conditions. The agency statement says, “The statistically significant and clinically meaningful results from these three studies provide substantial evidence of the effectiveness of CBD for the treatment of seizures associated with LGS and DS.” They drug causes liver damage but the report says that this could be managed effectively.
The FDA will conduct a final vote for approval of this drug in June. Oral solution of the drug for a small group of patients with these conditions would be allowed.
[REVIEW] Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence – Full Text
Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.
The International League Against Epilepsy (ILAE) defines epilepsy as a disease of the brain, diagnosis of which requires: (a) at least two unprovoked seizures occurring >24 hours apart; (b) one unprovoked seizure and a probability for further seizures of at least 60%, occurring over the next 10 years or (c) the diagnosis of an epilepsy syndrome.1 Between 70% and 80% of patients with new-onset epilepsy achieve complete seizure control using antiepileptic drugs such as valproate or carbamazepine.2 In 20%–30% who are drug-resistant,3 4 there is great interest in investigating novel agents to reduce seizure frequency and severity. For the purposes of this review, the ILAE’s definition of drug-resistant epilepsy—the failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs (AEDs) schedules (as either monotherapies or in combination) to achieve seizure freedom5—is used. For the 30% of patients who experience drug-resistant epilepsy, the efficacy of alternative and adjunctive therapies is likely to be of great interest.
Preclinical studies suggest that naturally occurring cannabinoids (phytocannabinoids) have anticonvulsant effects which are mediated by the endocannabinoid system.6 Cannabidiol (CBD) and cannabidivarin have shown antiseizure effects in both in vivo and in vitro models. In contrast to tetrahydrocannabinol (THC), CBD does not produce euphoric or intrusive psychoactive side effects when used to treat seizures.7 Cannabinoids have been proposed as an adjunctive treatment for epilepsy7 and parents of children with epilepsy report using CBD products.8–10 There are a number of phase III human trials underway of CBD as an adjunctive therapy for treatment resistant paediatric and adult epilepsies.11 12
Recently Israel, the Netherlands, Germany and Canada have legislated to allow the use of cannabinoids for medicinal purposes. In Australia, Federal and state legislation that allows doctors to prescribe cannabinoids is being implemented. Systematic reviews are required to synthesise the evidence for individual conditions for which cannabinoids may be used to inform clinical practice and patient guidance.
This review considers evidence on the safety and efficacy of cannabinoids as adjunctive treatments for drug-resistant epilepsy. As previous reviews noted a lack of controlled studies,13 14 we synthesised evidence from randomised controlled trials (RCTs) and observational studies.[…]
The interest in cannabis-based products for the treatment of refractory epilepsy has skyrocketed in recent years. Marijuana and other cannabis products with high content in Δ(9) –tetrahydrocannabinol (THC), utilized primarily for recreational purposes, are generally unsuitable for this indication, primarily because THC is associated with many undesired effects. Compared with THC, cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models and is largely devoid of adverse psychoactive effects and abuse liability. Over the years, this has led to an increasing use of CBD-enriched extracts in seizure disorders, particularly in children. Although improvement in seizure control and other benefits on sleep and behavior have been often reported, interpretation of the data is made difficult by the uncontrolled nature of these observations. Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a turning point in the last 12 months, with the completion of three high-quality placebo-controlled adjunctive-therapy trials of a purified CBD product in patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD was found to be superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome. For the first time, there is now class 1 evidence that adjunctive use of CBD improves seizure control in patients with specific epilepsy syndromes. Based on currently available information, however, it is unclear whether the improved seizure control described in these trials was related to a direct action of CBD, or was mediated by drug interactions with concomitant medications, particularly a marked increased in plasma levels of N-desmethylclobazam, the active metabolite of clobazam. Clarification of the relative contribution of CBD to improved seizure outcome requires re-assessment of trial data for the subgroup of patients not comedicated with clobazam, or the conduction of further studies controlling for the confounding effect of this interaction. (2017;7:61-76) […]
Traumatic Brain Injury, or TBI, is a serious condition usually caused by an external blow to the head that can cause severe and often chronic symptoms. These symptoms can be cognitive, behavioral, movement related, speech and visual impairing, mood altering, involve painful headaches, and even cause gastrointestinal issues.
Each year in just the U.S., nearly 52,000 people die from TBI and 80,000 sustain severe disabilities. Compare that to car fatalities (32,675) and homicides (14,196), which combined claim fewer lives. Moreover, 5.3 million people in the U.S. live with TBI-related disabilities, a number comparable to those living with Alzheimer’s disease.
How Cannabis Can Slow Traumatic Brain Injury Damage
While effective therapies to treat ongoing TBI symptoms have been difficult to come by, thanks to researchers like Prof. Yosef Sarne of Tel Aviv University, we’ve discovered that cannabis may prevent long-term brain damage by administering THC before or shortly after the injury. In fact, Israel Defense Force (IDF) practitioners administer CBD or low-dose THC as a first-line treatment to IDF soldiers – and even enemy combatants – who suffer brain trauma.
Sarne and his team published their results in 2013, where they demonstrated that administering just a fraction of the amount of THC that would be found in a typical cannabis joint anywhere from one to seven days prior to, or one to three days after an injury, induces the biochemical processes necessary to protect critical brain cells while preserving long-term cognitive function.
Can Cannabis Help People Currently Suffering From TBI?
Given the success found in Israel utilizing cannabis to halt TBI in its tracks, it begs the question: can cannabis help persistent TBI symptoms?
Anecdotally, many patients and their families report success. The daughter of one patient wrote in a Reddit forum:
“My father suffered severe TBI for years. He used to sit around hating his life all day. Once he started using marijuana, he changed a lot. He was able to get off some of his meds, start eating more, go outside, enjoy music, laugh at a movie, sleep at night, less anxiety in the day, less body pain. The list goes on and on.”
We hear many success stories like this, but these are, of course, anecdotal. Thus far, there aren’t any notable clinical trials demonstrating the efficacy of cannabis to treat ongoing symptoms in TBI patients. Unfortunately, even outside of cannabis research, phase II/III clinical trials of potential treatments haven’t demonstrated any consistent improvements in outcomes.
The lack of cannabinoid-focused trials is likely due in part to the federal government’s long-standing position that cannabis is a “substance [with] no currently accepted medical use” and “a high potential for abuse” – a position that has long frustrated scientists who are forced to navigate significant bureaucratic obstacles to conduct high-quality rigorous studies.
Nonetheless, despite the federal government’s position, there is some evidence that at least lends support to speculation that cannabis-derived treatments may be beneficial:
“Effect of Marijuana Use on Outcomes in Traumatic Brain Injury” (UCLA Medical Center, 2014):
In a three-year retrospective review of 446 separate cases of similarly injured patients, researchers found traumatic brain injury (TBI) patients who had a history of cannabis consumption possessed increased survival rates compared to non-consumers (97.6 percent survived surgery, versus 88.5% of those who didn’t consume cannabis).
“[O]ur data suggest an important link between the presence of a positive THC screen and improved survival after TBI,” the researchers concluded. “With continued research, more information will be uncovered regarding the therapeutic potential of THC, and further therapeutic interventions may be established.”
“Endocannabinoids and Traumatic Brain Injury” (Mechoulam, 2007):
This Israeli study points to research that demonstrates:
“…the [endocannabinoid] system…has the ability to [positively] affect the functional outcome after TBI by a variety of mechanisms.”
“The Therapeutic Potential of the Cannabinoids in Neuroprotection” (Grundy RI, 2002):
This review shows that in experimental models:
“…various cannabinoids rescue dying neurons in experimental forms of acute neuronal injury, such as cerebral ischaemia and traumatic brain injury.”
Positive results in experimental models don’t always translate to human subjects, hence the desperate need for more research. But, as early research shows promise and we know cannabinoids demonstrate neuroprotective effects in a variety of neurological conditions, there’s no excuse not to prioritize further research.
Further, because TBI is a condition affecting a highly complex, intricate system like the brain, successful strategies will likely involve more than a single “magic bullet.”
CBD Can Be Remarkably Effective for TBI
In the meantime, as we continue to learn more about THC and other cannabinoids to treat traumatic brain injury, many physicians believe CBD can be a safe and effective treatment. CBD, a largely non-psychoactive cannabinoid that possesses neuroprotective, anti-inflammatory, and anti-anxiety properties, could be as close to a “magic bullet” as we have right now. In fact, CBD may be more beneficial than THC. Japanese researchers found cannabidiol (CBD) exhibited stronger antioxidative power than THC without creating tolerance to its neuroprotective effect.
Dr. Allan Frankel, of GreenBridge Medical in Santa Monica, California, believes incorporating small amounts of CBD as a daily nutritional supplement is a safe and sensible adjunct to therapy. “I had a patient recently, a 45 year mother who was in a bad car accident. She experienced memory loss, and hadn’t been making any progress. I suggested CBD,” recounts Frankel. “Within four to six weeks, she made significant progress – her cognitive function improved and her memory returned to normal.” Frankel notes that this is just one of many patients he’s had who have experienced successful recoveries.
While clearly there’s lots of promise in the limited research to date and anecdotal reports, we need to continue developing our understanding of cannabinoid neurobiology in order to most effectively exploit the numerous therapeutic properties of cannabis. We can then, hopefully, unleash the full spectrum of potential benefits cannabis may be able to provide and discover innovative new treatments that could quite possibly help the millions of people who continue to suffer.
Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study that will be presented at the American Academy of Neurology’s 69th Annual Meeting in Boston, April 22 to 28, 2017. Cannabidiol is a molecule from the cannabis plant that does not have the psychoactive properties that create a “high.”
Nearly 40 percent of people with LGS, which starts in childhood, had at least a 50 percent reduction in drop seizures when taking a liquid form of cannabidiol compared to 15 percent taking a placebo.
When someone has a drop seizure, their muscle tone changes, causing them to collapse. Children and adults with LGS have multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which involve loss of consciousness and full-body convulsions. The seizures are hard to control and usually do not respond well to medications. Intellectual development is usually impaired in people with LGS.
Although the drop seizures of LGS are often very brief, they frequently lead to injury and trips to the hospital emergency room, so any reduction in drop seizure frequency is a benefit.
“Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control,” said study author Anup Patel, MD, of Nationwide Children’s Hospital and The Ohio State University College of Medicine in Columbus and a member of the American Academy of Neurology.
For the randomized, double-blind, placebo-controlled study, researchers followed 225 people with an average age of 16 for 14 weeks. The participants had an average of 85 drop seizures per month, had already tried an average of six epilepsy drugs that did not work for them and were taking an average of three epilepsy drugs during the study.
Participants were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol or placebo as an add-on to their current medications for 14 weeks.
Those taking the higher dose had a 42 percent reduction in drop seizures overall, and for 40 percent, their seizures were reduced by half or more.
Those taking the lower dose had a 37 percent reduction in drop seizures overall, and for 36 percent, seizures were reduced by half or more.
Those taking the placebo had a 17 percent reduction in drop seizures, and for 15 percent, seizures were reduced by half or more.
There were side effects for 94 percent of those taking the higher dose, 84 percent of those taking the lower dose and 72 percent of those taking placebo, but most side effects were reported as mild to moderate. The two most common were decreased appetite and sleepiness.
Those receiving cannabidiol were up to 2.6 times more likely to say their overall condition had improved than those receiving the placebo, with up to 66 percent reporting improvement compared to 44 percent of those receiving the placebo.
“Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures,” said Patel. “This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients.”
There is currently a plan to submit a New Drug Application to the FDA later this year.
People with epilepsy resort to cannabis products when antiepileptic drug side-effects are intolerable and epilepsy uncontrolled.
The first Australian nationwide survey on the experiences and opinions of medicinal cannabis use in people with epilepsy has revealed that 14 per cent of people with epilepsy have used cannabis products as a way to manage seizures.
The study showed that of those with a history of cannabis product use, 90 per cent of adults and 71 per cent of parents of children with epilepsy reported success in managing seizures after commencing using cannabis products.
Published in Epilepsy & Behaviour, the Epilepsy Action Australia study, in partnership with The Lambert Initiative at the University of Sydney, surveyed 976 respondents to examine cannabis use in people with epilepsy, reasons for use, and any perceived benefits self-reported by consumers (or their carers).
The survey revealed:
- 15 per cent of adults with epilepsy and 13 per cent of parents/guardians of children with epilepsy were currently using, or had previously used, cannabis products to treat epilepsy.
- Across all respondents, the main reasons for trying cannabis products were to manage treatment-resistant epilepsy and to obtain a more favourable side-effect profile compared to standard antiepileptic drugs.
The number of past antiepileptic drugs was a significant predictor of medicinal cannabis use in both adults and children with epilepsy.
“This survey provides insight into the use of cannabis products for epilepsy, in particular some of the likely factors influencing use, as well as novel insights into the experiences of and attitudes towards medicinal cannabis in people with epilepsy in the Australian community,” said lead author Anastasia Suraev from The Lambert Initiative.
“Despite the limitations of a retrospective online survey, we cannot ignore that a significant proportion of adults and children with epilepsy are using cannabis-based products in Australia, and many are self-reporting considerable benefits to their condition.
“More systematic clinical studies are urgently needed to help us better understand the role of cannabinoids in epilepsy,” she said.
Co-author of the paper Carol Ireland, CEO of Epilepsy Action Australia, who was recently appointed to the Australian Government’s new Australian Advisory Council on the Medicinal Use of Cannabis, said: “Cannabis products are often what people turn to when they have been unable to control their epilepsy with conventional medication.”
“This highlights a growing need to educate consumers and health professionals on the use of cannabis by people with epilepsy, and to provide safe and timely access to cannabinoid medicine in order to lessen people’s reliance on illicit black market products” she said.