An Introduction to CBD
Cannabidiol (CBD) is a natural compound found in the sticky flower of cannabis. This plant has a rich history as medicine going back thousands of years. Today the therapeutic attributes of CBD are tested and endorsed by scientists and doctors around the world.
A safe, non-addictive material, CBD is one of more than a hundred phytocannabinoids. These phytocannabinoids are unique to cannabis and endow the plant with its strong therapeutic profile.
CBD associates closely with another critical medicinally active phytocannabinoid: tetrahydrocannabinol (THC). THC is the compound that causes the high from cannabis. These are the two elements of cannabis that scientists have most studied.
Both CBD and THC have notable therapeutic attributes. But unlike THC, CBD does not make you feel “stoned” or intoxicated. That’s because CBD and THC behave in different ways on different receptors in the brain and body.
CBD can decrease or neutralize the psychoactive effects of THC, depending on how much of each compound you use. Many people want the health advantages of cannabis minus the high – or with less of a high. CBD is therapeutically effective as well as non-intoxicating. It is also simple to take as an oil. This makes it an appealing method option for those cautious about trying cannabis for the first time.
A molecule with many advantages
Many people explore alternatives to pharmaceuticals with severe side effects – medicine more in synch with natural methods. By tapping into how we operate biologically, CBD can relieve chronic pain, anxiety, inflammation, depression, and many other conditions.
Comprehensive scientific research highlight CBD’s potential as a treatment for a wide range of disorders, including (but not limited to):
- Autoimmune illnesses (inflammation, rheumatoid arthritis)
- Neurological diseases (Alzheimer’s, dementia, Parkinson’s, multiple sclerosis, epilepsy, Huntington’s chorea, stroke, traumatic brain injury)
- Metabolic syndrome (diabetes, obesity)
- Neuropsychiatric sickness (autism, ADHD, PTSD, alcoholism)
- Gut disorders (colitis, Crohn’s)
- Cardiovascular dysfunction (atherosclerosis, arrhythmia)
- Skin conditions (acne, dermatitis, psoriasis)
CBD has possible neuroprotective effects, and its anti-cancer features are under examination at numerous research hubs in the U.S. A 2010 brain cancer investigation by California scientists found that CBD potentially improves the inhibitory results of THC on human glioblastoma cell-reproduction and survival. CBD makes THC even more effective as an anti-cancer substance. In 2010, German researchers reported that CBD excites neurogenesis, new brain cells, and adult mammals.
How Does CBD Work?
CBD and THC communicate with our bodies in a variety of ways. One of the main ways is copying and augmenting the compounds’ effects in our bodies called endogenous cannabinoids. Named so because they resemble compounds found in the cannabis plant, these “endocannabinoids” are part of what scientists note as the “endocannabinoid system.”
The discovery of the endocannabinoid system has significantly improved our understanding of health and disease. It has significant meanings for almost every area of medical science. It helps clarify how and why CBD and THC are such versatile compounds. Also why cannabis is such a widely used plant, despite its illegal status.
The endocannabinoid system performs a crucial role in managing a broad range of physiological processes. These processes influence our everyday experience, mood, energy level, intestinal fortitude, immune activity, blood pressure, bone density, and glucose metabolism. It also affects how we feel stress, pain, hunger, and more.
What occurs if the endocannabinoid system doesn’t function correctly? What are the issues of a chronically deficient or overactive endocannabinoid system?
Sickness and disease.
Cutting-edge science shows that the ECS malfunctions in almost all unhealthy conditions. Thus, it’s safe to say that modulating endocannabinoid system activity may possess therapeutic potential in nearly all diseases affecting humans.
By adjusting the endocannabinoid system and enhancing endocannabinoid tone, CBD and THC can delay or stop disease progression.
There’s a lot of enthusiasm about the healing potential of CBD.
Not until June 25, 2018, that the FDA recognized cannabidiol as medicine by approving Epidiolex. An almost pure pharmaceutical CBD formulation treatment for two severe pediatric seizure disorders, Lennox-Gastaut Dravet syndrome.
For the first time since the peak of the reefer madness era 80 years ago, the federal government had given an official go-ahead for a cannabis-derived product.
In acknowledging the FDA’s historic decision, the Drug Enforcement Administration (DEA) declared in September 2018 that it had withdrawn Epidiolex from Schedule I classification. A classification reserved for unsafe drugs with no medical benefit. Henceforth, Epidiolex became a Schedule V drug, the least threatening classification under the Controlled Substances Act. The DEA later discharged Epidiolex from the federal government’s account of controlled substances.
But the DEA held cannabis and CBD (when acquired from a cannabis plant with over 0.3 % THC) as illegal narcotics. According to the U.S. Government, pharmaceutical CBD is formally the only medicinally beneficial cannabinoid while the remainder of the plant remains an illegal drug.
Given CBD’s status as a successful, artisanal treatment, one would think that Epidiolex would hold a lot of “off-label” attention. After all, physicians frequently prescribe pharmaceuticals off-label to manage conditions that were not the clinical trials’ initial focus. But the expensive price tag for Epidiolex (higher than $30,000 annually) hinders off-label prescribing as well as reasonable access for tens of millions of Americans without health insurance.
Not everyone can afford or acquire pharmaceutical CBD. There are copious amounts of coffee shops, health clubs, chiropractic offices, upscale boutiques, internet storefronts, community markets, and gas stations that retail various hemp-derived CBD oil products, including pure CBD, isolates comparable in chemical make-up to Epidiolex.
CBD oil products and flowers with varying THC and CBD levels are available for smoking or vaping at cannabis dispensaries in states that legalize marijuana and CBD for therapeutic use.
In response to massive consumer demand, a vast, uncontrolled exchange in CBD oil goods reached a critical size in 2018. A wave of consumer attention in all things CBD was suddenly newsworthy. CBD garnered tons of approval from soccer moms, athletes, film stars, and parents of desperately ill children.
Users describe CBD oil as a curative for the sick and a preventive for the healthy. It is regarded as an all-purpose palliative for pets and people of all ages. But along with a growing awareness of cannabidiol as a potential health aide, there is a proliferation of misunderstandings about CBD and cannabis therapeutics.
The CBD Challenge
CBD is a molecule, not a miracle. Many people could benefit significantly from legal access to a wide range of cannabis remedies. Not just low-THC or no-THC products. CBD alone may not always do the trick. There is compelling evidence that CBD works best combined with THC and the full spectrum of additional cannabis elements.
Figuring out how to maximize one’s therapeutic use of cannabis is the main drive behind the excellent laboratory test in government. Known as medical marijuana, this test occurs state-by-state and country-by-country in current years.
The arrival of powerful cannabis oil concentrates, non-intoxicating CBD-rich products and revolutionary, smokeless delivery methods have changed the therapeutic landscape. This also modifies the public discussion about cannabis.
It’s no longer a matter of arguing whether cannabis has value as an herbal medication. Today, the critical challenge is discerning how to utilize cannabis for maximum therapeutic benefit. Given its low-risk profile, many people use CBD as an add-on therapy to their existing treatment plans.
However, most health professionals know little about CBD or cannabis therapeutics. They lack sufficient expertise to adequately counsel patients regarding dosage, modes of administration, CBD/THC synergies, and any risk factors, including interactions with other drugs.
Instead, the onus has been on a loose-knit community of self-reliant patients, supportive families, and a few pioneer physicians. They’ve learned a lot through trial and error and shared information about how to navigate promising avenues of cannabis therapy.
What About CBD from Hemp?
What began as a grassroots populist rebellion against cannabis prohibition has morphed into a multibillion-dollar market catalyzed by the rediscovery of CBD as a wellness option. CBD oil is red hot these days, and it seems that everyone – do-gooders and profiteers – wants a slice of the pie.
CBD has also sparked the rebirth of the U.S. hemp industry. The Hemp industry was dormant for decades because of drug war politics. The 2018 Farm Bill introduces a provision that sanctions the cultivation of hemp (cannabis with no more than 0.3 % THC). This is in part because of the demand and driving economic strength of CBD.
Growing hemp is now a legal agricultural industry in the United States. But obtaining CBD-rich oil from hemp biomass and selling CBD oil extracts and isolates for ingestion and inhalation steps on Big Pharma’s toes. It is also looked down upon by the DEA and FDA.
Legalities aside, hemp-derived cannabidiol is just a click or call away for anyone prepared to roll the dice and buy CBD oil products that have limited administrative oversight.
The bright side to all of this is easy access to CBD oil; the downside is variable quality.
Many hemp-derived CBD oil products do not have correct labels as to CBD and THC content. And farmers may spoil crudely processed CBD oil with toxic solvent sediments, pesticides, corn syrup, unnatural flavors and colors, and other contaminants.
Fortunately, high-grade quality CBD oil products are also ready for conscientious consumers who recognize that cannabis and CBD are the best part of a healthy lifestyle.
Is CBD Legal?
The verdict is in: Cannabis regulation is a lot more complicated than marijuana.
On June 25, 2018, the U.S. Food and Drug Administration (FDA) announced its first-ever support of a marijuana-derived pharmaceutical drug. Epidiolex (cannabidiol or CBD) passed to treat two rare pediatric seizure ailments, Lennox-Gastaut syndrome and Dravet syndrome. On September 27, 2018, the Drug Enforcement Administration (DEA) announced its scheduling of Epidiolex – and future drug products containing CBD derived from marijuana with no more than 0.1 percent tetrahydrocannabinol – in Schedule V of the Controlled Substances Act (CSA). These results represent historical milestones in the journey of cannabis from the origin of textiles and medicines in the early nineteenth century to an illicit drug and now an FDA-approved drug.
Cannabidiol (CBD) is one of more than a hundred cannabinoids discovered in Cannabis sativa L. (Cannabis spp. or cannabis), a plant more recognized colloquially as “marijuana” or hemp. CBD was first isolated in 1940 and characterized structurally in 1963. Forecasted retail sales of CBD products -hemp, marijuana, and pharmaceutical – as high as $1.9 billion by 2020. CBD is poised to become the darling of the medical Cannabis campaign.
Despite its rapidly growing demand and practice, the regulatory status of CBD in the United States remains convoluted, even after the approval and scheduling of Epidiolex. The source of CBD is critically essential in determining its legal status. The most common source, botanically speaking, is the plant Cannabis sativa L. (Cannabis), which encompasses both marijuana and hemp. Various schema for differentiating marijuana from hemp (e.g., Genotype, phenotype, Drug-type Cannabis v. fiber-type cannabis, etc.).
Still, from a regulatory standpoint, the difference between marijuana and hemp is based on chemical composition. Specifically, to the concentration of delta-9 Tetrahydrocannabinol (THC). This is the primary intoxicating compound found in cannabis.
Hemp is a cultivar of Cannabis sativa with low concentrations of THC. Although restrictions on THC concentrations for hemp differ internationally, THC concentrations cannot exceed three-tenths of one percent (0.3%) in the United States. Hemp-derived and marijuana-derived CBD each have their novel regulatory status and consequent legal implications.
CBD From Marijuana is Still a Schedule 1 Substance
Despite the scheduling of Epidiolex, CBD from marijuana is still deemed a Schedule I controlled substance by the DEA under the 1970 Controlled Substances Act. As such, CBD from marijuana has no accepted medical use, a lack of accepted safety for use under medical supervision, and a high potential for abuse. While the scheduling of Epidiolex represents the first time that the DEA has acknowledged that marijuana has a “currently accepted medical use,” it did not change the regulatory status of CBD itself.
On May 22, 2018, the DEA issued an internal directive which stated, “Products and materials made from the Cannabis plant and which fall outside the CSA definition of marijuana (such as sterilized seeds, oil or cake made from the seeds, and mature stalks) do not fall under the CSA.” Although these statements clarified that CBD derived from a source other than marijuana was not a controlled substance, they did not expressly state that CBD from industrial hemp was lawful. Furthermore, these parts of the plant are not viable sources of CBD. As a result, confusion remains.
CBD also comes from some hemp cultivars. Historically, hemp was bred as an industrial crop to produce fabrics, rope, and other textiles from its long stalks. Despite not being explicitly defined or mentioned in the CSA, it is a controlled substance by the DEA since the CSA passage in 1970.
The Hemp Farming Act of 2018
On December 20, 2018, The Hemp Farming Act of 2018, S. 2667 (2018 Hemp Bill) became law and formally and definitively removed hemp from the list of controlled substances. The 2018 Hemp Bill redefines hemp as all parts of the Cannabis Sativa plant that do not exceed 0.3% delta-9 THC by dry weight, including “derivatives,” “extracts,” and “cannabinoids.” Notably, the 2018 Hemp Bill explicitly removes popular hemp products, including hemp-derived CBD, from the CSA purview.
Before the 2018 Hemp Bill passage, domestically cultivated hemp was only federally lawful when grown under a state-sanctioned pilot program. In 2017, a total of 23,343 acres of hemp grew across 19 states. As of this writing, 41 states have passed legislation to allow them to take advantage of hemp pilot programs under the 2014 Farm Bill. Today, only a minority of the hemp-derived CBD products available in the U.S. come from domestically cultivated hemp. As the 2018 Hemp Bill fosters more significant investment in this area, this will change.
In addition to industrial hemp, CBD may also be lawful if it comes from “non-psychoactive hemp” imported into the United States. The Ninth Circuit Court of Appeals uses Non-psychoactive hemp in a pair of companion cases filed against the DEA by a national trade organization, the Hemp Industries Association (HIA). This case is regarding a DEA rule, which would have made it illegal to import any hemp products that contained any THC, including trace amounts. In a February 6, 2004 ruling, the Court found that the DEA had exceeded its authority in enacting the rule and struck it down as void and unenforceable.
The Court used the term “non-psychoactive hemp” and stated, “The non-psychoactive hemp used in Appellants’ products come from industrial hemp plants grown in Canada and Europe.” The flowers contain only a trace amount of the THC contained in marijuana varieties grown for psychoactive use. Confusion remains as to whether the Court, in effect, legalized the whole hemp plant for importation, including the “flowering tops,” so long as it contains no more than trace amounts of THC, or whether it simply reiterated the mature stalks exception in a different context. The Court never addressed that distinction. Cases addressing hemp, which both preceded and succeeded in this ruling, do not resolve the issue.
Despite the FDA and DEA’s confusion and stance, hemp-derived CBD products can currently be purchased online and over-the-counter (OTC) throughout most countries as if they were dietary supplements. In contrast, Qualifying patients in states with medical marijuana laws can only purchase marijuana-derived CBD products by qualifying patients in states with medical marijuana laws (30 states and the District of Columbia as of this writing) or by consumers in states with adult-use/recreational laws (9 states and the District of Columbia as of this writing).
Before the approval of Epidiolex, the FDA explicitly stated that “CBD products do not fall under the dietary supplement definition.” They excluded CBD because of its status as an Investigational New Drug (IND) under the Food, Drug, and Cosmetic Act (FD&C Act).20 CBD is no longer an Investigational New Drug (IND). It is an approved one. As a result, CBD cannot be part of a dietary supplement.
This preclusion is not entirely novel. Biostratum, a pharmaceutical company, requested the FDA take action against manufacturers of pyridoxamine-containing dietary supplements in a somewhat similar case. The reason that Biostratum submitted an IND application for pyridoxamine dihydrochloride. It took the FDA three and a half years to formally conclude that these products violated its regulations. Products containing pyridoxamine and sold as dietary supplements are not currently permitted.
There is another precedent that informs how the FDA might alter its enforcement approach in the future. In April 1997, Pharmanex, a dietary supplement manufacturer, was advised by the FDA that its mevinolin-containing dietary supplement, named Cholestin, was a drug, not a dietary supplement. Mevinolin, also known as monacolin K, is a constituent of red yeast rice and has lower elevated cholesterol levels.22 Mevinolin is chemically identical to lovastatin (brand name Mevacor), an FDA-approved drug manufactured by Merck. The FDA concluded that Cholestin contains lovastatin concentrations that exceeded traditional red yeast rice products. The product was thus more similar to a drug than any red yeast rice product available. While Cholestin is no longer available, many red yeast rice products remain on the market with naturally occurring lovastatin concentrations.
In the Cholestin case, the FDA’s argument hinged on lovastatin concentration in red yeast rice products exceeding some traditional standards. The vast majority of hemp-derived CBD oil products available today contain concentrations by weight of CBD below 5% compared to Epidiolex, which is ≥ 99% CBD. Given this precedent, it is possible, and perhaps even likely, that the FDA will restrict products enriched with isolated CBD but not hemp extracts that contain naturally occurring concentrations of CBD.
The FDA may restrict products containing isolated CBD but not hemp extracts containing naturally occurring CBD concentrations.
With the FDA approval of Epidiolex and the FDA’s public proclamation that CBD products do not fall under the statutory definition of a dietary ingredient, the future of online and over-the-counter CBD products is uncertain. The FDA has the authority to enforce the Federal Food, Drug, and Cosmetic Act (FD&C Act) against products with CBD. It is worth noting that the FDA is a public health agency with a myriad of competing priorities and a limited enforcement budget. When considering enforcement action, the FDA weighs multiple factors, including benefits and harms. To date, injuries associated with hemp-derived CBD products have been largely undocumented.
In the absence of strict FDA enforcement and oversight, widespread mislabeling of CBD products exists. Independent research has confirmed that the CBD content in almost 70% of CBD products available online are incorrectly labeled. The FDA sent warning letters to 25 companies in 2015-16 for violations of the FDA rule. The FDA has also sent cease and desist letters to companies for making drug claims about CBD products, including claims that they treat or even cure cancer.
The current legal and regulatory status of CBD is both complex and evolving, particularly its legal position vis-a-vis the CSA and its regulatory status under the FD&C Act. While these complexities’ implications are widespread, clinical research restrictions have hindered understanding important safety and efficacy considerations. As a result, individuals are currently using CBD products to treat medical conditions without informed healthcare providers.
Although the approval of Epidiolex has precipitated the scheduling of drug products containing CBD derived from marijuana with no more than 0.1 percent tetrahydrocannabinol, it is less clear how it will influence the FDA’s enforcement priorities relating to hemp-derived CBD products. Increased enforcement could result in decreased access.
On the other hand, the passage of the 2018 Hemp Bill could liberate the supply chain and prevent enforcement by creating a de facto legal market for hemp-derived CBD products that is separate and distinct from the medical need for Epidiolex. Or, perhaps products with low CBD concentrations will remain below FDA enforcement priorities, as in red yeast rice.