What Doctors Need to Know About Help
The general public usually turns to physicians to consult about medi- cal treatments and therapies. Yet when it comes to medical cannabis and hemp, a recent study found that fewer than one in five patients thought their doctor was a good source of information.
A physician’s understanding of hemp and CBD, and their ability to discuss therapeutic uses, dosing, and drug interactions, can be the difference between compliance and failure. And with so many hemp and CBD products available over the counter, it is crucial that those conversations between practitioner and patient take place.
The following is an introduction to hemp and CBD for physicians and healthcare professionals
What is Hemp?
Hemp is a name for cannabis varieties that have no or extremely low levels of THC, the main psychotropic chemical responsible for the euphoric and intoxicating effects most commonly associated with the plant. While there are over 550 distinct chemical compounds in the cannabis plant, federal law in the United States defines hemp as containing less than 0.03% THC, and it generally has much higher levels of cannabidiol (CBD). Hence, the terms hemp and CBD are often used interchangeably.
The hemp plant’s flowers are used for medicinal purposes, its stalks and stems are used for fiber, and its seeds as food and nutritional supplements.
How Hemp Interacts with the Body
How Hemp Interacts with the Body
Attached to cells throughout the human body are cannabinoid receptors. While the body produces endogenous cannabinoid receptor ligands like Narachidonoylethanolamine (“Anandamide”) and 2-Ara- chidonoylglycerol (“2-AG”), phyto-cannabinoids present in hemp and other cannabis plants (like THC and CBD) also act as partial agonists or antagonists of these receptors, respectively.
There are two main cannabinoid receptors. CB1 receptors, G-protein coupled receptors (GCPR), are most abundant in the central and peripheral nervous systems, and they are actually the most abundant GCPR in the brain. CB2 receptors are also a part of the GCPR family and are more commonly found in the tissues and cells of the immune system, as well as in some liver and nerve cells.
- CB1 receptors in the hypothalamus help regulate metabolism, while those in the amygdala help regulate emotional responses.
- CB2 receptors modulate many autonomic processes, and in the immune, system by inhibiting cytokine/chemokine release.
CBD, the main ingredient in hemp, is a very weak antagonist of both CB1 and CB2, though it does appear to serve as a non-competitive negative allosteric modulator of CB1 receptors. CBD also operates through other targets such as ion channels, receptors, and enzymes. In addition, CBD can also increase anandamide levels by blocking FAAH activity, act as an antioxidant, and act as a positive allosteric modulator of glycine receptors. Much of the activity of THC, on the other hand, is mediated through its function as a partial agonist of both CB1 and CB2 receptors.
The endocannabinoid system has been found to interact with various basic functions and body systems, including: memory and learning, appetite regulation, thermoregulation, immune system function, fe- male reproductive processes, sleep and sleep cycles, pain perception, blood pressure, and digestion. CBD in particular is associated with alagesic, anti-ischemic, anti-epileptic, anxiolytic, anti-nausea, and anti-inflammatory effects.
It is important to note that most of the available published research has been based on trials that used cannabis with higher THC concen- trations and not on hemp-derived products.
A growing body of clinical and preclinical studies has shown the therapeutic uses of hemp and CBD. Cannabis-derived CBD (Epidi- olex) has been approved by the FDA for the treatment of treatment-re- sistant pediatric epilepsy, particularly Lennox-Gastaut Syndrome and Dravet Syndrome. Research indicates that CBD and hemp are promis- ing therapies for other indications and symptoms, including:
- Anxiety — pre-clinical evidence, limited clinical evidence
- Autism Spectrum Disorder — retrospective and open-label studies, shown to improve behavioral issues
- Autoimmune disorders & inflammation — pre-clinical evidence
- Insomnia — preliminary research, mixed results
- Neuropathic pain — some trials
CBD Isolates vs Whole-Plant Extracts
In addition to CBD, there are many other active ingredients in the hemp plant — primarily terpenes and other minor cannabinoids. When administered as a whole-plant extract, the benefits of all those compounds combined are theorized to work synergistically — known as the entourage effect.
In particular, the terpenes in hemp and other cannabis products
are suggested to be responsible for many of its therapeutic effects, specifically its antibacterial, anti-inflammatory, anti-anxiety, and antioxidant effects. A number of clinical and preclinical studies have shown that CBD can be more effective treating pain, epilepsy, and inflammation as a whole-plant extract than isolates but there is no specific clinical evidence of the entourage effect as a more general phenomenon.
Today, many hemp and CBD products on the market, such as tinc- tures and oils, are whole-plant extracts seeking to take advantage of the entourage effect. Others are CBD isolates that deliver only one active ingredient more akin to a traditional “one-molecule, one-tar- get” pharmaceutical approach.
There are several methods of administering hemp and CBD products. Orally, tinctures and oils can be ingested or taken sublingually. Topi- cally, creams and balms are available for localized treatment. Hemp flower, which can be inhaled or vaporized, is also available in some states.
Delivery methods significantly affect how a hemp product is ab- sorbed, its onset time, and the chemical or metabolite that enters the bloodstream. (Most of the available information about delivery meth- ods is based on research into cannabis products containing THC.)
There are no specific dosing guidelines for hemp and CBD products. One systematic review found that in clinical studies where CBD had a positive effect, the dosing ranged from 1-50mg per kilogram per day. Efficacy can vary from person to person and according to the indication. Dosing for Epidiolex, the only FDA approved CBD medi- cation, recommends between 10-20 mg/kg/day.
CBD is generally well-tolerated. The most commonly reported side effects associated with CBD use include changes in weight/appetite, nausea, fatigue, and diarrhea, although these are rare and most data comes from studies looking at already sick populations. There is no known lethal dose of CBD.
CBD is a known CYP3A4 & CYP2D6 inhibitor. It increases serum concentrations of benzodiazepines, cyclosporine, macrolides, calci- um channel blockers, sildenafil (and other PDE5 inhibitors), antihista- mines, haloperidol, antiretrovirals, atorvastatin, simvastatin and war- farin, SSRIs, tricyclic antidepressants, antipsychotics, beta blockers and opioids. It significantly increases concentration of clobazam.
Some medications may inhibit the enzyme that metabolizes cannabi- diol, leading to an accumulation of excess CBD in the body. Some of those drugs include ketoconazole, itraconazole, ritonavir, and clari- thromycin. Other medicines — including phenobarbital, rifampicin, carbamazepine, and phenytoin — do the opposite, speeding up the metabolism of CBD, resulting in reduced CBD bioavailability.
CBD may increase levels of blood thinners like Warfarin due to Cyto- chrome P450 inhibition.
Product Quality and Testing
Because the regulation around hemp and CBD products is still nascent, there are legitimate concerns about quality and labeling ac- curacy with many retail products. When in early 2020 the FDA tested nearly 150 CBD products, fewer than half contained levels within 20 percent of the amount indicated on the label. Dozens more didn’t specify doses at all.
Furthermore, most CBD products are treated as dietary supplements, which are only loosely regulated in comparison to pharmaceuticals in most jurisdictions. “ It is difficult to regulate products that are steeped in culture and are promoted by industry in a vacuum away from public health imperatives,” wrote the authors of one review.
Therefore, transparency, lab testing, and accurate labeling is in- valuable for being able to find the right dose and expect consistent results. When choosing a CBD product, one should look for reputable companies that provide information about their testing and ideally are GMP compliant. All Alethiah products come with a QR code to view the certificate of analysis provided by our independent testing lab.