A Reality Check for CBD Oil

By Roger Chriss, PNN Columnist

The Food and Drug Administration’s recent approval of the anti-seizure medication Epidiolex has attracted a lot of new attention for CBD (cannabidiol). But enthusiasm was already on the rise. CBD is being promoted as a “new medical elixir” and marketed in everything from cosmetics to bottled water.

CBD was isolated in marijuana in 1940 and its chemical structure was characterized in 1963. It does not have euphoric effects and is increasingly being used in oils, edibles and other forms to treat medical conditions such as pain.

Last November the World Health Organization released its “Cannabidiol Pre-Preview Report”) stating that “CBD is generally well tolerated with a good safety profile.” The WHO report found “no evidence of recreational use of CBD or any public health related problems associated with the use of pure CBD.”

Last month the FDA approved Epidiolex, a CBD-based drug, to treat seizures caused by two rare forms of childhood epilepsy, Dravet syndrome and Lennox-Gestaut syndrome.  It was the first -- and so far only -- marijuana-based drug to be approved by the agency.

“In terms of solid evidence, the one thing we really know about CBD is that it can be helpful for rare childhood seizure disorders,” Ryan Vandrey, PhD, a cannabis researcher and associate professor of psychiatry at Johns Hopkins University, told Health.com. “There’s not yet sufficient evidence to support its use for any other reason.”

This is not for lack of effort. Zynebra Pharmaceuticals recently tested a topical CBD product for osteoarthritis knee pain with mixed results. The Phase 2 clinical study did not meet its primary endpoint of reducing the average pain score, although there were some indications it improved function and reduced pain severity.

A small clinical trial of CBD for Crohn’s disease in Israel in 2017 was also negative, finding “CBD was safe but had no beneficial effects.”

GW Pharmaceuticals, the manufacturer of Epidiolex and Sativex, conducted a clinical trial in 2012 on CBD oil for pain due to spinal cord injury. The outcome was disappointing. The treatment arm of the study (55 subjects) and placebo arm (59 subjects) showed essentially the same level of improvement in neuropathic pain.

A 2015 study on CBD extracts for childhood epilepsy had puzzling results. Researchers reported in the journal Epilepsy & Behavior that “relocating to Colorado had a significant effect on response rates.” Drugs are not normally affected by zip code or time zone.

A recent review of studies on CBD oil and other forms of cannabis for the management of neurologic disorders was more positive, finding “there is strongest evidence to indicate benefits in treatment of spasticity and neuropathic pain in multiple sclerosis.”

CBD Safety Questions

But there are also cautions. Thorsten Rudroff, PhD, a professor of Health and Exercise Science at Colorado State University, told Neurology Advisor that more studies of CBD were needed.

“While cannabis seems to be effective for the treatment of MS symptoms like pain and spasticity, there are so many unknowns. For example, we don't know much about interactions with other drugs. Also, based on my own research, it seems that cannabis may further impair cognitive function in people with MS, especially in older adults,” Rudroff said.

There are safety issues as well. CBD oil has a good safety profile, but according to Food Safety Magazine, CBD oil products have problems with labeling accuracy, product quality and contaminants.

People with serious medical problems who want to use CBD oil need to reliably source a quality product. Medical users may have allergies, chemical sensitivities and, in the case of cancer patients or people with autoimmune disorders, a compromised immune system. For such people, purity and dose matter.

In addition, there are drug interactions to be aware of. Medline lists nearly a dozen medications that potentially interact with CBD, such as amitriptyline, ibuprofen and meloxicam, which are frequently used by people with health problems.

The decision to use CBD oil for medical purposes needs to be based on science, not marketing. As David Cassaret, MD, notes in his book, Stoned: A Doctor’s Case for Medical Marijuana: “Medical marijuana is becoming too widespread, and the risks are too great, to leave the patient to fend for himself, and to let the buyer beware.”

At present, however, CBD oil is very much a buyer beware world. And the current hype is not helping.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

FDA Approves First Marijuana-Based Prescription Drug

By Pat Anson, Editor

The U.S. Food and Drug Administration has approved the use of Epidiolex, the first drug derived directly from marijuana, to treat seizures caused by two rare and severe forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.

Epidiolex is the first FDA-approved medication that contains cannabidiol (CBD), one of the active ingredients in marijuana. It does not contain tetrahydrocannabinol (THC), the chemical compound in marijuana that makes people high.

“This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition,” FDA commissioner Scott Gottlieb, MD, said in a statement.

FDA approval of Epidiolex is a major milestone for GW Pharmaceuticals, a British company focused on developing CBD-based medications. The company said Epidiolex would be available in the fall, but did not disclose the price. Some analysts have predicted it could cost as much as $25,000 a year.

Many oils and tinctures containing CBD are already sold online and in states were medical marijuana is legal, but the FDA has not approved any of them. The agency has only approved a handful of synthetic cannabinoids such as Marinol (dronabinol) to treat loss of appetite and nausea.

“We’ll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products,” Gottlieb said.

“But, at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases.”

Some children in clinical trials experienced side effects from Epidiolex such as liver toxicity, anemia and drowsiness, but an FDA staff report said the risks were “mild to moderate” and could be managed with warning labels. The staff report also found there was low risk of the strawberry flavored Epidiolex being abused.

“Today’s approval of Epidiolex is a historic milestone, offering patients and their families the first and only FDA-approved CBD medicine to treat two severe, childhood-onset epilepsies,” Justin Gover, GW Pharmaceutical’s CEO, said in a statement.

“This approval is the culmination of GW’s many years of partnership with patients, their families, and physicians in the epilepsy community to develop a much needed, novel medicine. These patients deserve and will soon have access to a cannabinoid medicine that has been thoroughly studied in clinical trials, manufactured to assure quality and consistency, and available by prescription under a physician’s care.”

While Epidiolex is only approved for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, doctors will presumably be able to prescribe it “off label” for other conditions such as chronic pain.  

GW Pharmaceuticals also makes Sativex, an oral spray that contains both CBD and THC. Sativex has been approved in Europe, Canada, Australia, New Zealand and several other countries for the treatment of muscle spasticity caused by multiple sclerosis. In Israel, Sativex is also approved for the treatment of pain and chronic non-cancer pain.  

FDA Staff Recommends Approval of Marijuana Drug

By Pat Anson, Editor

The U.S. Food and Drug Administration may be on the verge of approving its first prescription drug derived directly from marijuana.

In a report posted online, FDA staff said there was “substantial evidence” that Epidiolex, a liquid formula containing cannabidiol (CBD), was effective in reducing seizures in children with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), two severe forms of childhood epilepsy.

GW PHARMACEUTICALS IMAGE

Epidiolex is made by GW Pharmaceuticals, a British drug maker that specializes in developing drugs from marijuana.

“The applicant has provided positive results from three randomized, double-blind, placebo-controlled studies conducted in patients with LGS and DS,” FDA staff reported.

“The studies are adequate and well-controlled. 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.”  

CBD is one of the active ingredients in marijuana. It does not contain THC (tetrahydrocannabinol), the chemical compound in marijuana that makes people high. Many oils and tinctures containing CBD are already sold online and in states were medical marijuana is legal, but the FDA has not approved any of them.  The agency has only approved a handful of synthetic cannabinoids such as Marinol (dronabinol) to treat loss of appetite and nausea.

Although some children in the clinical trials experienced side effects from Epidiolex such as liver toxicity, anemia and drowsiness, the FDA staff report said the risks were “mild to moderate” and could be managed with warning labels. The report also found there was low risk of the strawberry flavored Epidiolex being abused.

“Although the review is still ongoing, the risk-benefit profile established by the data in the application appears to support approval of cannabidiol for the treatment of seizures associated with LGS and DS,” the report concludes.

(4/18/18 Update: An FDA advisory committee unanimously recommended that the FDA accept the staff findings and approve Epidiolex) 

In a briefing paper for the committee, GW Pharmaceuticals said there were few effective treatment options for children with LGS and DS, who often have severe intellectual and developmental disabilities and a high risk of mortality.

A final decision by the FDA is expected this summer. There is no guarantee the agency will follow the advice of its staff or advisory committee. If Epidiolex is approved, it would only be for the treatment of childhood epilepsy. However, doctors would presumably be able to prescribe it “off label” for other conditions such as chronic pain.  

GW Pharmaceuticals also makes Sativex, an oral spray that contains both CBD and THC. Sativex has been approved in Europe, Canada, Australia, New Zealand and several other countries for the treatment of muscle spasticity caused by multiple sclerosis. In Israel, Sativex is also approved for the treatment of pain and chronic non-cancer pain.  

Marijuana Based Drug Effective in Treating Epilepsy

By Pat Anson, Editor

A British pharmaceutical company has released positive results from a Phase 3 clinical study of an experimental drug derived from marijuana.

GW Pharmaceuticals (NASDAQ: GWPH) reported that the drug – called Epidiolex – significantly reduced seizures in patients with Lennox-Gastaut syndrome, a rare form of childhood epilepsy. Epidiolex contains cannabidiol (CBD) a chemical compound found in marijuana that does not produce the “high” associated with cannabis plants.

“From a physician’s perspective, the positive outcome in this trial of Epidiolex in patients with Lennox-Gastaut syndrome is very exciting. Lennox-Gastaut syndrome begins in early childhood, is particularly difficult to treat, and the vast majority of patients do not obtain an adequate response from existing therapies,” said study investigator Linda Laux, MD, Director of the Comprehensive Epilepsy Center at Ann & Robert H. Lurie Children's Hospital of Chicago.

“I am excited about the prospect of Epidiolex being made available on prescription in the future and believe it has the potential to make an important difference to the lives of many patients.”

The placebo controlled study involved 171 patients with Lennox-Gastaut syndrome. Epidiolex reduced the number of seizures in a month by 44 percent, compared with those taking a placebo medication that reduced seizures by 22 percent.

In March, another Phase 3 trial of Epidiolex also showed positive results in children with Dravet syndrome, another form of childhood epilepsy. GW is also conducting a Phase 3 trial of Epidiolex in Tuberous Sclerosis Complex and expects to initiate a Phase 3 trial of Epidiolex in infantile spasms in the fourth quarter of this year.

If approved by the Food and Drug Administration, the drug would be the first cannabis derived drug to win approval for the treatment of childhood epilepsy. Epidiolex has both Orphan Drug Designation and Fast Track Designation from the FDA. GW plans to formally file for FDA approval later this year.

GW is already marketing a marijuana-based oral spray called Sativex that is being sold in Europe, Canada and Mexico to treat muscle tightness and contractions caused by multiple sclerosis. Canada also allows Sativex to be used for the treatment of neuropathic pain and advanced cancer pain.

Sativex is not currently approved for use in the U.S. for any condition. It is estimated that over 400,000 cancer patients in the U.S. suffer from pain that is not well controlled by opioid pain medications. However, two recent Phase 3 studies found that Sativex worked no better than a placebo in treating cancer pain.

Results of Cannabis Drug Study Cause Market Frenzy

By Pat Anson, Editor

A British pharmaceutical company has reported positive results from a Phase 3 clinical study of a marijuana-based medication for Dravet syndrome, a severe form of children’s epilepsy.

The study found that Epidiolex, a liquid formula containing a plant-derived cannabinoid (CBD), significantly reduced the number of seizures in children with Dravet syndrome. CBD is a compound in cannabis that does not produce the “high” caused by marijuana.

The study findings caused shares of GW Pharmaceuticals (NASDAQ: GWPH) to more than double in trading Monday, much of it fueled by speculation that the company’s cannabinoid products would eventually be approved by the Food and Drug Administration for pain relief.

“If they get this, doctors will say, here’s a cannabinoid prescription,” said CNBC’s Jim Cramer. “This will be the pure cannabis that a lot of people who have been waiting for, an actual painkiller that is not addictive. This will replace, I believe, the terrible, terrible wave of death that oxycodone has caused.

image courtesy gw pharmaceuticals

“If you want to prescribe actual medical marijuana, a real doctor is reluctant to do it because there are no uniform standards, and what you really want is the pure cannabinoid. There will be use of this galore.”

In a statement to CNBC, GW said it was not investigating Epidiolex for pain relief.

"Today's Phase 3 results of Epidiolex (cannabidiol) were not studying the medicine as a possible treatment for pain. Epidiolex is being investigated for Dravet syndrome, Lennox-Gastaut syndrome and Tuberous Sclerosis Complex (TSC), three rare, extremely debilitating epilepsy syndromes that begin in infancy or early childhood," the company said.

The Phase 3 placebo controlled study involved 120 children with Dravet syndrome, who were averaging about 13 seizures a month before the trial began. Seizures declined by over a third in patients treated with Epidiolex, with few side effects.

“The results of this Epidiolex pivotal trial are important and exciting as they represent the first placebo-controlled evidence to support the safety and efficacy of pharmaceutical cannabidiol in children with Dravet syndrome, one of the most severe and difficult-to-treat types of epilepsy,” said Orrin Devinsky, MD, of New York University Langone Medical Center’s Comprehensive Epilepsy Center.

“These data demonstrate that Epidiolex delivers clinically important reductions in seizure frequency together with an acceptable safety and tolerability profile, providing the epilepsy community with the prospect of an appropriately standardized and tested pharmaceutical formulation of cannabidiol being made available by prescription in the future.”

Epidiolex has both Orphan Drug Designation and Fast Track Designation from the U.S. Food and Drug Administration. There are currently no approved treatments for Dravet syndrome in the U.S.

“We are excited about the potential for Epidiolex to become the first FDA approved treatment option specifically for Dravet syndrome patients and their families,” said Justin Gover, GW’s CEO. “In light of this positive data, we will now request a pre-NDA (new drug application) meeting with the FDA to discuss our proposed regulatory submission.”

GW is recruiting 150 patients for a second Phase 3 trial of Epidiolex for Dravet syndrome and is currently conducting a Phase 3 study for Lennox-Gastaut syndrome. Another study of Epidiolex is scheduled to begin soon for a third form of epilepsy, Tuberous Sclerosis Complex.

The company is already marketing a marijuana-based oral spray called Sativex that is being sold in Europe, Canada and Mexico to treat muscle tightness and contractions caused by multiple sclerosis. Canada also allows Sativex to be used for the treatment of neuropathic pain and advanced cancer pain.

Sativex is not currently approved for use in the U.S. for any condition. It is estimated that over 400,000 cancer patients in the U.S. suffer from pain that is not well controlled by opioid pain medications. Two recent Phase 3 studies found that Sativex worked no better than a placebo in treating cancer pain.