Thursday, September 27 marks a historic day. Today the DEA (United States Drug Enforcement Administration) scheduled the first marijuana based medication.
Epidiolex(r) is a FDA approved medication that is made up of highly-purified, plant-derived cannabidiol (CBD) in a proprietary oral solution of pure plant-derived cannabidiol or CBD and was scheduled today at a “V”. Epidiolex(R) will be used for, early-onset, treatment-resistant epilepsy syndromes including Dravet syndrome, Lennox-Gastaut syndrome (LGS) and Tuberous Sclerosis Complex (TSC). The release of the drug will mark the first time that such a prescription drug has been made available to the U.S. public and now is available for sale in the U.S. The company needs to finalize the product label for the drug and expects to have it ready for customers in six weeks. Greenwich Biosciences, GWPH’s U.S. subsidiary, will be marketing the drug in America.
This scheduling is historic in that level V is reserved for drugs, substances, or chemicals defined as drugs with lower potential for abuse than other schedules. Example: Schedule V drugs are generally used for antidiarrheal, antitussive, and analgesic purposes. Some examples of Schedule V drugs are cough preparations with less than 200 milligrams of codeine or per 100 milliliters (Robitussin AC), Lomotil, Motofen, Lyrica, Parepectolin.
We also hope this will open the door on how marajuania is schedule. Currently it is a “Level I”, consistent with heroin and other addictive drugs. This scheduling has made it very restrictive to nearly impossible to gain access to it for valid medical research. Example, Epidiolex(r) was developed in the UK prior to U.S. FDA approved medical trials.
For more on understanding scheduling read on.
What is Drug Scheduling
Drugs, substances, and certain chemicals used to make drugs are classified into five (5) distinct categories or schedules depending upon the drug’s acceptable medical use and the drug’s abuse or dependency potential. The abuse rate is a determinate factor in the scheduling of the drug; for example, Schedule I drugs have a high potential for abuse and the potential to create severe psychological and/or physical dependence. As the drug schedule changes– Schedule II, Schedule III, etc., so does the abuse potential– Schedule V drugs represents the least potential for abuse. A Listing of drugs and their schedule are located at Controlled Substance Act (CSA) Scheduling or CSA Scheduling by Alphabetical Order. These lists describes the basic or parent chemical and do not necessarily describe the salts, isomers and salts of isomers, esters, ethers and derivatives which may also be classified as controlled substances. These lists are intended as general references and are not comprehensive listings of all controlled substances.
Please note that a substance need not be listed as a controlled substance to be treated as a Schedule I substance for criminal prosecution. A controlled substance analogue is a substance which is intended for human consumption and is structurally or pharmacologically substantially similar to or is represented as being similar to a Schedule I or Schedule II substance and is not an approved medication in the United States. (See 21 U.S.C. §802(32)(A) for the definition of a controlled substance analogue and 21 U.S.C. §813 for the schedule.)
Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. Some examples of Schedule I drugs are:
heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote
Schedule II drugs, substances, or chemicals are defined as drugs with a high potential for abuse, with use potentially leading to severe psychological or physical dependence. These drugs are also considered dangerous. Some examples of Schedule II drugs are:
Combination products with less than 15 milligrams of hydrocodone per dosage unit (Vicodin), cocaine, methamphetamine, methadone, hydromorphone (Dilaudid), meperidine (Demerol), oxycodone (OxyContin), fentanyl, Dexedrine, Adderall, and Ritalin
Schedule III drugs, substances, or chemicals are defined as drugs with a moderate to low potential for physical and psychological dependence. Schedule III drugs abuse potential is less than Schedule I and Schedule II drugs but more than Schedule IV. Some examples of Schedule III drugs are:
Products containing less than 90 milligrams of codeine per dosage unit (Tylenol with codeine), ketamine, anabolic steroids, testosterone
Schedule IV drugs, substances, or chemicals are defined as drugs with a low potential for abuse and low risk of dependence. Some examples of Schedule IV drugs are:
Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Ambien, Tramadol
Schedule V drugs, substances, or chemicals are defined as drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics. Schedule V drugs are generally used for antidiarrheal, antitussive, and analgesic purposes. Some examples of Schedule V drugs are:
cough preparations with less than 200 milligrams of codeine or per 100 milliliters (Robitussin AC), Lomotil, Motofen, Lyrica, Parepectolin
Cannabidiol, or CBD, is a non-intoxicating chemical compound that comes from the cannabis sativa plant. CBD is one of over 100 such compounds, known as cannabinoids, which are found in the plant.
Unlike THC — or tetrahydrocannabinol, another cannabinoid — CBD is non-euphoric.
What is the history of CBD?
CBD was first discovered in the 1940’s by Roger Adams, the former head of the chemistry department at University of Illinois at Champaign-Urbana. In his research, Adams isolated CBD from hemp but couldn’t determine what exactly he’d found. In addition to CBD, Adams also synthesized analogs of THC and another cannabinoid, showing their relationship to CBD.
In the 1960’s, Israeli chemist Raphael Mechoulam and his team took the research further, eventually synthesizing cannabinoids — including CBD, THC and others — and describing their chemical structures for future research. Mechoulam, a professor at Hebrew University of Jerusalem, still studies cannabis to this day.
Is CBD legal?
Much confusion exist around CBD due to current murky legal status.
The Federal DEA still list hemp and marijuana as dangerous Schedule I drugs, along with heroin and ecstasy, CBD remains illegal under federal law. Congress is now is considering the 2018 Farm Bill, which would legalize industrial hemp across the country.
Despite some confusion, the Agriculture Act of 2014 didn’t legalize hemp-based CBD products nationwide, but only allowed for states and universities to grow hemp. Nevertheless, hemp-based CBD is already widely and freely available throughout most of the country.
At this time, 37 states that have legalized marijuana-based CBD for medical use, while nine other states have fully legalized marijuana and its derivatives. Four other states — Idaho, Kansas, Nebraska and South Dakota still prohibit the medical use of marijuana-based CBD.
What is CBD used to treat?
In a study released last year, the World Health Organization’s Expert Committee on Drug Dependence said CBD may benefit people diagnosed with:
- Alzheimer’s disease
- Parkinson’s disease
- Multiple sclerosis
- Huntington’s disease
- Inflammatory diseases
- Rheumatoid arthritis
- Inflammatory bowel and Crohn’s disease
- Cardiovascular diseases
- Diabetic complications
In the report, the committee noted that “CBD exhibits no effects indicative of any abuse or dependence potential.” Other health care professionals are also using CBD to treat other medical issues, like autism, sleep problems and other mental health conditions.
CBD started gaining national exposure when media outlets began profiling Charlotte Figi, an 11-year-old girl from Colorado with Dravet syndrome, a severe form of intractable epilepsy.
At age 5, Figi’s parents, Matt and Paige Figi, had exhausted all traditional options in their quest to control the hundreds of grand mal seizures their young daughter was experiencing every day. They ultimately turned to the Stanleys, a group of brothers who grow marijuana in Colorado, who then developed a groundbreaking CBD oil they called “Charlotte’s Web.”
Since she began taking the oil, Charlotte has experienced far fewer seizures and is able to enjoy a more normal childhood. However, evidence from cases like Figi’s remains largely anecdotal as researchers continue to pin down CBD’s exact scientific effects.
What are the effects of CBD?
Unlike THC, CBD doesn’t get users high, an important distinction that has helped drive the popularity of the drug compound.
Traditional medications tend to target the symptoms of a specific condition, but CBD goes after the cause of those symptoms, according to Ronald Aung-Din, M.D., a renowned Florida neurologist.
Pharmaceuticals generally stimulate or block receptors to provide their function, but CBD and other cannabis-based treatments interact with the body’s endocannabinoid system, which naturally binds to chemicals like CBD and THC. This biological effect reportedly enables CBD to treat such a wide range of medical conditions.
A European study published last year by the National Center for Biotechnical Information listed tiredness, diarrhea and changes in weight and appetite as possible side effects of CBD. Most of the research was conducted on patients with epilepsy or psychotic disorders.
Are there different types of CBD?
Yes, there are several different types including:
CBD products that come from the marijuana plant tend to have higher amounts of THC, a combination that some experts claim increases the CBD’s healing effects. As a result, CBD strains with higher amounts of THC can cause both euphoria and stony side effects, like anxiety, paranoia and dizziness.
Hemp-based CBD products can be bought over-the-counter (OTC) in many states and some internet sales. A trend lately in some states is to “confiscate” over the counter/internet CBD due to the lack of control on content, quality, contaminants, etc.
Some OTC product may contain a full range of hundreds of cannabinoids, including cannabinol (CBN), cannabigerol (CBG) and tetrahydrocannabivarin (THCV), as well as CBD and a minuscule amount of THC.
All the different chemicals found in the cannabis plant are said to have various healing effects. For example, non-intoxicating CDG apparently helps with sleep and inflammation and kills bacteria.
In June, the U.S. Food and Drug Administration approved the first prescription CBD drug, a move that will almost undoubtedly spur more research into what else it can treat.
The drug, a strawberry-flavored syrup called Epidiolex, is used to treat two rare forms of childhood epilepsy. During their research, FDA officials found that Epidiolex reduced seizures when it was combined with other epilepsy drugs.
FDA Commissioner Scott Gottlieb said his agency had supported research on cannabis-derived products for “many years,” but warned against the use of CBD products with “unproven medical claims.”
“The promotion and use of these unapproved products may keep some patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases,” Gottlieb said.
Before Epidiolex can go to market, the Drug Enforcement Administration must formally reclassify CBD into a federal drug category with medical approval. The FDA has previously approved synthetic cannabinoids to treat severe weight loss in patients with HIV.
Source: Most of the content from an article by T. Schuba for the Chicago Sun Times
Treating epilepsy presents a variety of challenges for patients and their families. Sometimes, it takes time to find the right medication and dosing to properly manage seizures and other epilepsy-related health issues. Or it may be necessary to adjust the medication so that it doesn’t cause side effects that impact quality of life. This is especially true for patients with two rare forms of severe childhood-onset epilepsy: Lennox-Gastaut syndrome and Dravet syndrome.
In the search for new treatments for these rare forms of epilepsy, researchers have been studying marijuana-based drugs for their potential seizure-controlling benefits. In June, the FDA approved cannabidiol (CBD), a marijuana-based medication, for the treatment of seizures in patients (age 2 and older) who have been diagnosed with Lennox-Gastaut syndrome or Dravet syndrome.
Here, epilepsy expert Elaine Wyllie, MD, explains the science behind the new treatment, common side effects and guidance for use.
Q: How is CBD different from marijuana?
A: Unlike marijuana, CBD does not contain tetrahydrocannabinol (THC), the chemical that causes users to feel high. Since the THC has been removed, researchers believe that CBD treatment is likely to involve a low risk of abuse or addiction. The U.S. Drug Enforcement Administration will soon reclassify CBD in a medication category among other drugs that have received federal approval for medical use.
Q: What research was used to evaluate CBD?
A: The FDA reviewed the results from three clinical trials involving more than 500 children and adults with either Lennox-Gastaut syndrome or Dravet syndrome. The researchers conducted randomized, placebo-controlled, double-blind studies that followed strict guidelines to ensure accurate and reliable results.
The following results demonstrate the efficacy of CBD:
Patients with Lennox-Gastaut syndrome who received CBD experienced a 37 percent to 42 percent reduction in drop seizures (involving muscle stiffening or limpness in the body, trunk or head, which can cause a patient to fall).
About 43 percent of patients with Dravet syndrome who were treated with CBD had a 50 percent or greater reduction in convulsive seizures — compared with 27 percent of placebo patients.
Q: What are the side effects of CBD?
A: The most common side effects were sleepiness and lethargy. A few patients reported diarrhea, vomiting, unsteadiness or decreased appetite.
During the study, some patients experienced mild liver abnormalities — especially if they were also taking the seizure drug valproate (Depakote®). Once CBD was discontinued, however, their liver function readings on blood tests returned to normal.
Q: Is CBD known to interact with other medications?
A: Some patients who took CBD experienced interactions with other seizure medications. For example, CBD increased the level of one of the components of the seizure drug clobazam (Onfi®) in the bloodstream, which caused some patients to feel sleepy. During the clinical trials, CBD mildly affected some other seizure drugs; however, the impact was inconsequential.
Q: What is the approved dosing schedule for CBD?
A: CBD will be available as a twice-daily oral solution — under the brand name Epidiolex®.
Q: When will CBD be available by prescription, and what is the FDA guidance for use?
A: By fall 2018, pharmacies anticipate CBD’s availability by prescription only. At that time, the manufacturer will provide physicians and families with comprehensive information and guidance that details the safe use of CBD. This is unlike other marijuana-based products, which have not been subjected to a stringent FDA approval and quality-controlled manufacturing method.
Q: What about using CBD to treat other forms of epilepsy?
A: You may ask your doctor about taking CBD for epilepsy conditions other than Dravet syndrome or Lennox-Gastaut syndrome. While physicians can legally prescribe FDA-approved drugs for conditions other than those involved in the clinical trials, such “off-label” use of medications mandates thoughtful analysis and specialized medical expertise. Additional research is needed to clearly define the range of patients who may benefit from CBD treatment.
Q: How do I know if this new treatment is right for me?
A: Talk to your epilepsy specialist to discuss whether you may benefit from CBD.
Source: Cleveland Clinic
Note: EpilepsyU will be hosting s seminar on Facebook Live on November 3, 2018 on CBD. Be watching for announcements.
A few years ago, I began to see children in my practice who seemingly responded to marijuana-derived extracts. And as a result, I grew cautiously optimistic that these extracts might be good treatments for the condition.
As a devout believer in evidence-based medicine, I still needed experimental data that could distinguish bona fide effectiveness from a deceptive impression of benefit — a placebo effect.
But my desire to study marijuana ran headlong into a seemingly immovable obstacle: the U.S. Drug Enforcement Agency (DEA). The agency’s illogical and stubborn stance makes it all but impossible for scientists to study cannabidiol. I persevered and eventually succeeded in launching a study, but no doubt many others give up, robbing us of valuable insight into marijuana’s potential benefits.
PLEASE BEWARE – DON’T SELF MEDICATE WITH OVER THE COUNTER CBD PRODUCTS/CLAIMS – EpilepsyU
The July 31 warning letter reflects FDA’s continuing concern over the marketing of CBD products—including supplements—to treat diseases like cancer and schizophrenia without agency drug approval.
For the fourth year in a row, FDA delivered at least one warning letter related to the sale of cannabidiol (CBD), reflecting the agency’s concerns that the cannabis-based compound features claims documenting an intent to treat diseases such as cancer and schizophrenia without necessary drug approval.
FDA also reiterated its position that CBD cannot be lawfully sold as a dietary supplement because, in part, it has been subject to substantial clinical investigations held by GW Pharmaceuticals plc.
A warning letter was sent to Signature Formulations LLC on July 31, 2018, a little over a month after FDA approved Epidiolex, a CBD drug manufactured by GW Pharmaceuticals used to treat seizures associated with rare forms of epilepsy typically occurring in early childhood.
In addition to raising concerns over the marketing of CBD products, FDA cited Signature Formulations for “significant violations of current good manufacturing practice (cGMP) regulations for finished pharmaceuticals.”
Based on a review of a product label for “CBD Muscle Gel” and a website where Signature Formulations markets various CBD products, FDA determined the claims established the products are unapproved new drugs.
Among the website claims quoted by FDA:
“For hundreds of years, people have used preparations made from C. Sativa, including CBD for a variety of disorders, including gout, rheumatism, malaria, pain, and fever.”
“[P]eople have reported reduced pain or positive results from taking CBD as a dietary supplement for ailments and neurological disorders such as . . . Alzheimer’s Disease . . . cancer . . . Crohn’s disease . . . diabetes . . . fibromyalgia . . . glaucoma . . . gout . . . HIV dementia . . .. . . Parkinson’s disease . . . rheumatism . . . schizophrenia . . . stress disorders like PTSD [post-traumatic stress disorder] . . .”
Signature Formulations did not immediately respond to an emailed request for comment.
In phone interviews, two lawyers who advise clients on FDA regulations said they were unaware of a warning letter sent to a company solely because it marketed CBD.
Previous letters, New York-based attorney Marc Ullman said, targeted “products making drug claims” and were consistent with a statement from FDA commissioner Scott Gottlieb, M.D., which “indicated the agency, at this point at least, is going to exercise enforcement discretion and act against the products that are making unapproved drug claims.”
Said Justin Prochnow, a partner in Denver with Greenberg Traurig LLP: “If you’re going to dip your toe into the CBD waters, at the top of the list should be, ‘Don’t make disease claims.’”
According to FDA, all CBD products sold as supplements are noncompliant, added Ullman, of counsel to Rivkin Radler LLP.
“But they [FDA officials] are using their discretion for now and acting only against the products making illegal drug claims,” the attorney said. “The thing about enforcement discretion is they could change their mind tomorrow and they are not required to give any advance notice. They can change their mind tomorrow. They can change their mind in five years.”
The warning letter, Prochnow suggested, serves as a reminder that FDA hasn’t changed its position that CBD is not a permissible ingredient in a dietary supplement. The lawyer also pointed out FDA hasn’t gone beyond warning letters in its enforcement strategy related to CBD.
“While the FDA has reiterated its position on the legality of CBD in various forums, the FDA has also emphasized that its focus is on safety issues and those companies making disease claims regarding their products,” Prochnow explained in a follow-up email. “To date, the FDA has not taken any further steps to enforce its position that CBD is not a permissible ingredient.”
The issuance of additional warning letters, Prochnow opined, is unlikely “to change the behavior of many companies selling products with CBD in them.”
That’s because he said many companies have interpreted FDA’s message as so “long as a company doesn’t make express disease claims, the FDA is unlikely to take action and, even if a company is making disease claims, the only repercussion is likely to be a warning letter in the file.”
SOURCE: Written by J. Long for Natural Products Insider