Study: Oral Cannabis Extracts Associated With Seizure Control In Children With Treatment-Resistant EpilepsyApril 21, 2015
The administration of oral cannabis extracts is associated with the mitigation of seizures in adolescents with epilepsy, according to clinical data published this month in the journal Epilepsy & Behavior.
Researchers from the Colorado Children’s Hospital in Denver performed a retrospective chart review of 75 children provided cannabis extracts. Authors reported that 57 percent of subjects showed some level of improvement in seizure control while 33 percent reported a greater than 50 percent reduction in seizure frequency.
Researchers also reported “improved behavior/alertness” in one-third of subjects and improved motor skills in ten percent of treated patients. Adverse events were reported in 44 percent of subjects, 13 percent of which reported increased seizure activity. Overall, however, authors concluded that the extracts were “well tolerated by children.”
Separate clinical trial results publicized last week at the 67th Annual Meeting of the American Academy of Neurology reported that the administration of a proprietary form of CBD (cannabidiol) extracts decreased seizure frequency by 54 percent over a 12-week period in children with treatment-resistant epilepsy.
Survey data compiled by Stanford University in 2013 reported that the administration of cannabidiol-enriched cannabis decreased seizures in 16 of 19 patients with pediatric epilepsy.
Last February, the Epilepsy Foundation of America enacted a resolution in support of the “rights of patients and families living with seizures and epilepsy to access physician directed care, including medical marijuana.”
An abstract of the study, “Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy,” appears online here.
On Monday, I published a rebuttal of these claims in a commentary published on the website Alternet.org — an excerpt of which appears below.
Debunking the Latest Pathetic Fear Smear Campaign Against Marijuana
[excerpt] [N]umerous (though far less publicized) studies have come to light downplaying the likelihood that cannabis use is a direct cause of psychiatric disorders like schizophrenia. Specifically, a 2009 paper in the journal Schizophrenia Research compared trends in marijuana use and incidences of schizophrenia in the United Kingdom from 1996 to 2005. Authors reported that “incidence and prevalence of schizophrenia and psychoses were either stable or declining” during this period, even though pot use among the general population was rising. They concluded: “This study does not therefore support the specific causal link between cannabis use and incidence of psychotic disorders. … This concurs with other reports indicating that increases in population cannabis use have not been followed by increases in psychotic incidence.”
Similarly, a 2010 review paper published by a pair of British scientists in the journal Addiction reported that clinical evidence indicating that use of he herb may be casually linked to incidences of schizophrenia or other psychological harms is not persuasive. Authors wrote: “We continue to take the view that the evidence that cannabis use causes schizophrenia is neither very new, nor by normal criteria, particularly compelling. … For example, our recent modeling suggests that we would need to prevent between 3000 and 5000 cases of heavy cannabis use among young men and women to prevent one case of schizophrenia, and that four or five times more young people would need to avoid light cannabis use to prevent a single schizophrenia case. … We conclude that the strongest evidence of a possible causal relation between cannabis use and schizophrenia emerged more than 20 years ago and that the strength of more recent evidence may have been overstated.”
More recently, researchers at Harvard University released a study further rebutting this allegation. Writing in 2013 in Schizophrenia Research, investigators compared the family histories of 108 schizophrenia patients and 171 individuals without schizophrenia to assess whether youth cannabis consumption was an independent factor in developing the disorder. Researchers reported that a family history of schizophrenia increased the risk of developing the disease, regardless of whether or not subjects consumed weed as adolescents. They concluded: “The results of the current study, both when analyzed using morbid risk and family frequency calculations, suggest that having an increased familial risk for schizophrenia is the underlying basis for schizophrenia in these samples and not the cannabis use. While cannabis may have an effect on the age of onset of schizophrenia it is unlikely to be the cause of illness.”
In fact, some researchers speculate that specific cannabinoids, such as cannabidiol (CBD), may even be efficacious in treating symptoms of psychosis. According to a review published in the January 2014 issue of the journal Neuropsychopharmacology: “CBD has some potential as an antipsychotic treatment. … Given the high tolerability and superior cost-effectiveness, CBD may prove to be an attractive alternative to current antipsychotic treatment.” Specifically, a 2012 double-blind, randomized placebo-controlled trial assessing the administration of CBD versus the prescription anti-psychotic drug amisulpride in 42 subjects with schizophrenia and acute paranoia concluded that two substances provided similar levels of improvement, but that cannabidiol did so with far fewer adverse side effects.
Case reports in the scientific literature also indicate that some patients turn to cannabis for subjective benefits, though other studies indicate that pot use may exacerbate certain symptoms in patients with psychiatric disorders. Nonetheless, even a recent paper summarizing the “adverse health effects of recreational cannabis use” acknowledges, “It is difficult to decide whether cannabis use has had any effects on psychosis incidence, because even if a relationship were to be causal, cannabis use would produce a very modest increase in incidence.”
You can read my full commentary here.
You can also watch my discussion with Thom Hartmann of The Big Picture (air date: February 23) here.
Study: CBD Administration Associated With Improved Quality Of Life In Patients With Parkinson’s DiseaseSeptember 25, 2014
The administration of cannabidiol (CBD), a nonpsychotropic cannabinoid, is associated with improved quality of life in patients with Parkinson’s disease, according clinical trial data published online ahead of print in the Journal of Psychopharmacology.
Investigators at the University of São Paulo in Brazil assessed the efficacy of CBD versus placebo in 21 subjects with Parkinson’s. Authors reported that the administration of 300 mg doses of CBD per day was associated with “significantly different mean total scores” in subjects’ well-being and quality of life compared to placebo.
Separate assessments of CBD versus placebo reported that the cannabinoid did not appear to mitigate general symptoms of the disease, nor was it shown to be neuroprotective.
“This study points to a possible effect of CBD in improving measures related to the quality of life of PD patients without psychiatric comorbidities,” investigators concluded. They added, “We found no statistically significant differences concerning the motor symptoms of PD; however, studies involving larger samples and with systematic assessment of specific symptoms of PD are necessary in order to provide stronger conclusions regarding the action of CBD in PD.”
Clinical reports have previously indicated that both CBD and/or whole-plant cannabis may address various symptom’s of Parkinson’s disease, including improvement in motor symptoms, pain reduction, improved sleep, and a reduction in the severity of psychotic episodes.
Survey data of patients with PD indicates that almost half of all subjects who try cannabis report experiencing subjective relief from the plant.
The abstract of the study, “Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial,” appears online here.
Most of us were caught off-guard by the rush of states this year that approved the limited use of CBD-only marijuana extracts because these traditionally conservative states had heretofore rejected the medical use of marijuana. So it seems worth a moment to consider how this occurred, and what it means on a grander scale.
But first, a little recent history.
Throughout this year’s state legislative season, a total of 10 states enacted laws seeking to provide limited access to medical marijuana products that contain high levels of CBD and virtually no THC for qualified, typically pediatric patients suffering from severe and disabling seizures: Alabama, Florida, Iowa, Kentucky, Mississippi, Missouri, South Carolina, Tennessee, Utah and Wisconsin.
On one level, this unexpected embrace of the medicinal qualities of marijuana by states that previously rejected the concept must be seen as a favorable development. These serendipitous adoptions reflect a degree of compassion not obvious in the previous legislative debates in those states.
But it is far from certain that these laws will actually help the young patients they are intended to help.
First, such products are primarily only available in a handful of states like California and Colorado and none of these new state laws create a viable in-state supply source for such products. Further, even if a patient from out-of-state could find these products in California or Colorado, it would be a violation of federal law (and also likely state law) to take the medicine back to their home state.
And while some of these laws attempt to establish CBD research projects at their major universities or research hospitals, recent experience demonstrates that few universities or research hospitals are willing to enter this confusing field while marijuana remains a federal crime, and those that may be willing to take the bait will face a steep and long learning curve before the first patient will have high-CBD extracts available.
This legislative rush to CBD-only extracts also suggests (1) the degree to which elected officials are influenced by popular media, (2) their willingness to pick and choose the science they like (while ignoring the science they do not), and (3) the strong puritanical impulse that remains a factor with many elected officials.
And it all relates to the “Gupta Effect”. When CNN’s Dr. Sanjay Gupta’s report highlighting how high-CBD marijuana products control debilitating seizures among children suffering from Dravet’s syndrome (the most severe form of childhood epilepsy) went public, few Americans had even heard of cannabidiol. Most people were familiar with THC (tetrahydrocannabinol), the primary psychoactive ingredient in marijuana that principally accounts for the “high” that marijuana smokers enjoy, but had zero idea that CBD even existed.
Dr. Gupta, who had previously uncritically accepted the federal government’s consistent claim that marijuana had no legitimate medical use, when confronted with actual children whose lives had been transformed following their use of high-CBD marijuana extracts, understandably felt misled by the government’s anti-marijuana propaganda, and went public with two special programs introducing the importance of high-CBD extracts in reducing or eliminating seizures in these children.
In the second program Dr. Gupta made it clear that while CBD appeared to be the primary therapeutic ingredient for this class of patients, he also made the point that some level of THC was also required, because of what he termed the “entourage effect.” Without the THC, the CBD would either be less effective, or in some instances ineffective.
It’s embarrassing that so many of our elected officials would get their scientific understanding of the medical properties of marijuana from a popular television doctor, instead of conducting their own research into the available science, before moving legislation forward. But better they be motivated by a celebrity doctor than continue to ignore the benefits of medical marijuana altogether.
Of which there are a myriad.
The marijuana plant is one of the most studied biologically active substances of modern times. A search on PubMed, the repository for all peer-reviewed scientific papers, using the term “marijuana” yields nearly 20,000 scientific papers referencing the plant and/or its constituents, nearly half of which have been published just within the past decade. In addition, more than 100 controlled trials, involving thousands of subjects, have evaluated the safety and efficacy of cannabis and/or individual cannabinoids.
Most recently, a review of FDA-approved marijuana plant trials conducted by various California universities concluded, “Based on evidence currently available the Schedule I classification (for cannabis) is not tenable; it is not accurate that cannabis has no medical value, or that information on safety is lacking.” The best summary of this research can be found in the publication Emerging Clinical Applications for Cannabis and Cannabinoids, available on the NORML website. So the basic research is available for all who care to learn.
But few elected officials appear to be aware of this considerable body of science. Rather, the common refrain is to claim they cannot support the medical use of marijuana because the only evidence is “anecdotal”. These officials prefer to remain ignorant because it reinforces their preconceived notion that medical marijuana is a hoax perpetuated by those who simply wish to get “high”.
So what this latest rush to approve CBD-only marijuana products demonstrates, more than anything else, is the degree to which our public policy can frequently be influenced by a strong strain of puritanism that remains alive among our elected officials. If it feels good, it must be bad!
These many state legislators were willing to show some compassion by allowing the medical use of marijuana by these poor children suffering from multiple, disabling seizures, so long as the marijuana did not make them feel “high” (i.e., feel better!). These legislators are against pleasure, and if the use medical marijuana includes the feeling of pleasure, then it cannot be approved.
Excuse me, but is that not the purpose of using medicine when one is ill – to feel better?
Admittedly, for some of these puritans, the association of the word “high” with the use of marijuana may lie at the heart of the problem for them. Marijuana has long been demonized by conservatives, law enforcement, and many in the medical community, and that has spilled-over to the marijuana “high”.
If they understood that the marijuana “high” makes the user feel better, and that seriously ill patients almost always want (and need) to feel better, perhaps they could overcome their fear of medical marijuana. But for now at least, it is clear that in their view the marijuana “high”, like marijuana itself, is something to be avoided by responsible Americans, even if that precludes the use of medical marijuana by seriously ill patients.
It is time we moved beyond the notion that pleasure is bad, and stopped treating the marijuana “high” as something to be avoided, when it makes patient feel better. For them, feeling better and feeling high is often the same.
Lawmakers in Alabama and Utah recently approved legislation seeking to authorize the physician-supervised use of varieties of cannabis and/or extracts high in the non-psychotropic cannabinoid cannabidiol (CBD). Both measures, which I previously summarized as ‘largely unworkable,‘ have now been signed into law.
In recent days, lawmakers in three additional states — Kentucky, Mississippi, and Wisconsin — have similarly signed off on CBD-explicit legislation. These measures are now awaiting signatures from each states’ respective Governors.
Similar to Alabama’s SB 174 (aka ‘Carley’s Law), which only permits the use of CBD by prescription during the course of an FDA-approved clinical trial, the pending Kentucky and Wisconsin bills may also be classified as ‘research-centric’ measures. Kentucky’s SB 124 permits physicians “practicing at a hospital or associated clinic affiliated with a Kentucky public university” to “dispense” cannabidiol during the course of an FDA-approved clinical trial. Wisconsin’s AB 726 similarly limits those who may legally dispense CBD to only include those physicians who have obtained an FDA-issued investigational drug permit to prescribe it. In Tennessee, lawmakers are also close to finalizing similar language (included in HB 2461 and SB 2531) that seeks to allow university clinical researchers to “manufacture” and “dispense” high-CBD cannabis oil “as part of a clinical research study on the treatment of intractable seizures.” (By contrast, separate, broader medical cannabis measures seeking to authorize the use of the whole plant failed this year in all three states.)
As I’ve previously written here and here, it is unlikely that specific changes in state law will stimulate these type of proposed clinical trials from taking place in these states any time soon. Because CBD is acknowledged by federal regulators to be classified as a schedule I prohibited substance, multiple federal agencies — including the FDA, DEA, NIDA (US National Institute of Drug Abuse), and PHS (Public Health Service) must all sign off on any clinical investigation of the cannabinoid — a process that typically takes several years. A keyword search of FDA-approved clinical trials using the terms “cannabidiol” and “United States” yields fewer than ten ongoing human trials involving CBD — less than half of which are assessing its potential therapeutic application. (Two additional safety trials assessing the use of GW Pharmaceutical’s patented high-CBD formulation Epidiolex in children with severe epilepsy are also ongoing.)
Unlike the above-mentioned measures, Mississippi’s HB 1231, does not seek to encourage state-sponsored clinical trials. Rather, the measure exempts specific high-CBD formulated oils “that contain more than fifteen percent cannabidiol [and] … no more than one-half of one percent of tetrahydrocannabinol” from the state’s definition of a schedule I prohibited substance. However, like Utah’s HB 105 (aka ‘Charlee’s Law), Mississippi’s pending law does not provide guidance as to where patients could legally obtain such extracts. Though such high-CBD products are presently available in a limited number of medical cannabis states (such as in California and Colorado), these extracts are typically only available to in-state residents who possess authorization from a physician licensed to practice in that state. (Although Colorado state law also allows for a recreational cannabis market, which may be legally accessed by out-of-state residents, at present time such high-CBD concentrates are seldom available at retail outlets.)
Additional cannabidiol-specific measures also remain pending in Florida and South Carolina, among other states. NORML will report on these measures as they progress and we will continue to express caution in regards to their practical utility for those patients who require immediate access to whole-plant cannabis and its variety of naturally-occurring compounds.