By Jeffrey Leman, MD
Cannabidiol (CBD): Since December 2018, you have seen it sold in gas stations, shopping mall kiosks, video stores and countless other places. What is behind this CBD explosion, and what are we to think about it?
Congress passed the 2018 Farm Bill by a wide majority across party lines and, in December 2018, President Trump signed this bill into Law. This bill removed hemp and hemp products containing less than 0.3% tetrahydrocannabinol (THC) as well as CBD that is derived from such hemp from Schedule I classification. Prior to that, in December 2017, a proclamation from WHO Expert Committee on Drug Dependence (ECDD) concluded that, “In its pure state, cannabidiol does not appear to have abuse potential or cause harm.” These two events have contributed to a surge of retail sales of CBD related products.
What is hemp? How is it different from marijuana?
Both are plants of the same species, cannabis sativa, but hemp is a subspecies with much lower concentrations of THC. Hemp typically contains less than 0.3% THC and has 3-4% CBD, compared with marijuana which often has THC contents higher than 10%, with less than 1% CBD.
THC is a psychoactive substance, which works specifically on CB1 and CB2 receptors and is structurally similar to the endogenous cannabinoid anandamide. It is a Schedule I controlled substance.
By contrast, CBD is not psychoactive, and works through a wide range of other mechanisms of which scientists have conclusively identified only a few. CBD is the second most abundant of the 107 different non-THC cannabinoids (of which only six are psychoactive).
CBD studies
CBD has received FDA approval under the trade name Epidiolex for two less common pediatric seizure disorders (Dravet Syndrome and Lennox-Gastault). Several other studies of CBD have shown laboratory action against pain receptors and have demonstrated potential antioxidant and anti-inflammatory properties. It works also on pathways related to anxiety and sleep. Two rat studies have shown that topical application of CBD oil over inflamed joints reduced both inflammatory cytokines and pain associated behaviors. For these reasons and for other suspected mechanisms, the sale and marketing of CBD is booming.
CBD oil is only starting to be robustly studied. Currently PubMed lists only 22 completed clinicals trials of CBD, for a wide range of conditions, such as anxiety, psychosis, movement disorders, PTSD, palliative care uses, substance use disorders, as well as diabetes, Crohn’s, ocular HTN, fatty liver disease, chronic pain. The studies to date have all been small and of low (and very low) quality. Current evidence shows it may provide some relief of anxiety, psychosis, sleep, PTSD, and substance use disorders, but the effect size is small and the results to date are less than overwhelming. Looking forward however, a search of clinicaltrials.gov in October 2019, showed 164 human clinical interventional trials are currently registered and underway for the above listed and many other conditions, most of them for pain or inflammation.
Uses for CBD
Many physicians and pharmacists are using CBD with reported success, including pain specialists, orthopedic surgeons, sports medicine physicians, as well as primary care providers. Topical preparations are very commonly used for musculoskeletal or inflammatory pain and reportedly have an effect for 2-3 hours. The ingested oil preparations have been used for pain, sleep and anxiety with some individually reported success. There are even preparations available for the use in hyperactive or anxious pets!
With respect to safety and adverse effects, topical products may be safer than ingested ones as the common side effects of somnolence and diarrhea are more common in users ingesting the product. It should be used with caution in patients taking anti-seizure medications. Any patient who is taking multiple medications should be aware of potential for drug-drug interactions and should seek the advice of a knowledgeable pharmacist or physician.
Quality control
Other than the prescription form Epidiolex, CBD is not FDA approved for any clinical uses and is considered a dietary or herbal product. Therefore, there is no regulation of its extraction from hemp nor its formulation into it various forms, which include oils for ingestion (tincture and capsules), topical balms and formulations for vaping. An alarming 2017 study in JAMA showed that only 30% of the CBD preparations available online were accurately labelled as to how much CBD they contained. The other 70% were divided equally between those that were under-labeled and those over-labeled. Even more alarming, however, was that 21% contained THC — many with enough THC to cause a positive urine drug screen for marijuana. The presence of heavy metals and pesticides in less quality preparations have also been noted.
So, while CBD is widely available over the counter, the quality of these unregulated projects is a concern. It is important to know where and how the hemp was raised, if the preparations are tested by an independent lab for consistency of dose and purity from contaminants. Also, considering current epidemic of vaping induced lung injury having some association with THC and CBD oils, vaping or inhaling of CBD should be avoided.
Going forward
So, miracle drug — or hoax? Time will tell and, meanwhile, we await further solid clinical evidence. Be sure to ask your patients about the use of these products. And if your patients want to use CBD, be sure they are using a quality product and using in recommended doses. A trial of topical balms might be a good starting point depending on the indication.
The interest in CBD and subsequent demand will not be waning anytime soon, so the coming research on CBD should be watched carefully.