WHAT WE KNOW, DON’T KNOW & THINGS IN THE MIDDLE

WHAT IS IN THE BOTTLE?

We believe it is critically important for the consumer to know, and hence trust the manufacturer and distributor of their chosen CBD products.  Accordingly, we have seed to bottle oversight, 3rd party lab testing, and QR codes on all products that link to Certificates of Authenticity (COA’s).  As a function of the lack of Federal oversight and FDA regulation, there are multiple reports that demonstrate the frequency of mislabeling.

The most widely cited article is from the Journal of the American Medical Association (JAMA, 11/7/2017) in which a Penn Medicine researcher, Marcel Bonn-Miller Ph.D. found that 69% of all CBD products sold online were either over or under labeled, creating particular confusion on what dose was actually being taken.  Some of the 84 undercover purchases that the researchers made had little or no CBD.  Of more significant concern, however, was the fact that 21% of the products had >.3% THC, above the legal limit to be considered hemp, and creating the potential for a failed drug test.  While this study is over 4 years old, and predates the 2018 Farm Bill, there remains essentially no federal oversight of manufacturing.  In addition, a study by the Clean Label Project in 2020 found more recent and equally disturbing results:  45% of CBD products tested were found to have detectable levels of THC despite claims to be THC-free;  CBD content was not consistent with the label, ranging from 0 CBD content to 700%; and average lead content for the products tested was quite high.  (CleanLabelProject.org.  CBD:  The New Hot and Totally Unregulated Supplement. July 7,2020)

BEWARE:  HEMP OIL & HEMP SEED OIL CONTAIN NO CBD

The vast majority of Federal activity in the CBD market has focused on the prevention of fraudulent marketing claims of medicinal value for any illness or chronic medical disease.  False claims the FDA has identified include statements that advise using CBD to treat:  alcoholism, Alzheimer’s disease, arthritis, autism, blood pressure and heart rate, cancer, chronic traumatic encephalopathy, cardiovascular disease, colitis, concussions, depression, diabetes, leukemia, liver inflammation, lupus, Lyme disease, neurologic damage, Parkinson’s, stroke, schizophrenia, Traumatic Brain Injury and tumors.  (FDA and FTC:  CBD Warning letters.  2019)

ABSORPTION

We do know that absorption for tinctures far surpasses that for edibles (gummies, capsules, pills), and is the primary reason we are producing CBD and CBN for oral use only as a tincture.  Our cream and aerosol formulations are for local effect only and dependent solely on transcutaneous absorption.  It is critically important to understand the term Bioavailability in order to grasp some of the decisions we have made regarding our products and their concentrations, and to guide your choice of formulation.  Bioavailability is the proportion of a drug or other substance which enters the circulation when introduced into the body and is thereby able to have an active clinical effect.  More simply, it is  the fraction of an administered substance that reaches the circulation.  By definition, when a medication is administered intravenously, its bioavailability is 100%.  If a formulation has low bioavailability, as for instance edibles (gummies and capsules), the CBD will need to be taken in larger mg amounts to be considered potentially effective.  This low absorption is a function of the fact that orally ingested CBD is first absorbed through the GI tract, and then passes through the liver (first pass metabolism) before entering the circulation.  Tinctures on the other hand, when placed under the tongue, are absorbed through the oral lining (mucosa) directly into the bloodstream, generating considerably higher bioavailability.  Accordingly, lower mg doses are required to be taken as a tincture, and Medium Chain Triglycerides (MCT) as the carrier, enhances tincture absorption.

Based on the above, a 20 mg gummie, assuming an absorption of 20%, would only deliver 4 mg of CBD to the circulation for effect.

Primarily due to the fact that CBD and minor cannabinoids were illegal until the passage of the 2018 Farm Bill, there has been, and there remains very little scientific research on the clinical utility and effects of their use.  There are few, if any randomized, double-blinded, placebo controlled trials (the standard for drug research) and accordingly, it is impossible to make clinical claims for the use of any cannabinoid except for the only FDA approved, cannabis derived plant product, Epidiolex®, for resistant pediatric seizure disorders.

DOSE WILL DEPEND ON FORMULATION TYPE, INTENDED USE AND BODY WEIGHT

With the lack of clinical studies, and specifically the lack of pharmacokinetic data (amount absorbed from various formulations, and the duration of activity), dose and dosing interval is  unknown for any usage.  An appropriate dose, defined as one that provides the intended therapeutic effect and is well tolerated is thus unknown.  We do know, however, that CBD has a low toxicity and therefore a wide margin of safety for doses.  The vast majority of studies that have been done have used oral capsules or liquids and, for instance in the Epidiolex® trials, oral doses of 1200 to 1500 mg/day were well tolerated.  In general,

Side effects, while uncommon, can include drowsiness, diarrhea, diminished appetite, fatigue and change in mood or irritability.  Furthermore, it must be realized that any substance can have different effects on different people.  A common example of this is Benadryl®, capable of making some sleepy and others wide-awake.

POSSIBLE INTERACTIONS WITH PRESCRIPTION DRUGS

 CBD and the minor cannabinoids are metabolized (broken down) by the liver and they can affect the activity of various enzyme systems in the liver that also are responsible for the metabolism and inactivation of many drugs and supplements.  The most studied liver enzyme system is the P450 cytochrome family, and in vitro (in an artificial environment) and animal studies confirm that cannabinoids generally inhibit the activity of these enzymes.  As such, if a medication is inactivated by this family of enzymes, the concurrent use of CBD can cause the blood stream levels of the other medications to increase (i.e., inhibiting the inhibitor), enhancing its clinical effects and/or the chance of side effects.  This interaction is potentially most significant for blood thinners (e.g., Coumadin®, Eliquis®).  While it is not necessarily contraindicated to use CBD while on blood thinners, it is essential that their use be monitored by a physician for the possible need to, at minimal, change the dose of the medication  Similarly, there are many medications that are inactivated by the P450 family of enzymes, including but not limited to:  SSRI anti-depressants (e.g., Zoloft®, Celexa®), sedatives or benzodiazepams (e.g. Valium®), anti-arrhythmics (e.g. Amiodarone) and calcium channel blockers (e.g. Diltiazem).

In general, avoid the use of CBD if any of your prescribed medications have a GRAPEFRUIT WARNING on the label, or at minimum, consult with your physician before initiating use.  Grapefruit juice is a known inhibitor of the P450 enzyme system, similar to CBD.

To further complicate matters, there is some evidence that CBD can also stimulate other enzymes in the P450 family, potentially causing a previous satisfactory dose of medication (anti-platelet agent Plavix®) to now be inadequate (stimulating the inhibitor).

Concomitant use of Central Nervous System depressants and/or alcohol could create a potential enhanced sedative effect, and perhaps require lowering your CBD or CBN dose.

Avoid the use of CBD if you have glaucoma.  There is evidence that CBD can increase intra-ocular pressure.

While this section in particular, and the website generally has been researched and written by Michael J. Cohen MD, none of the statements should be considered nor interpreted as medical advice.  Throughout, great care has been taken to point out the widespread lack of scientific research that exists and precludes any definitive statements.  It is likely, however that scientific research for CBD etc. will greatly increase over the next several years.  The final arbiter of potential benefit versus safety is YOUR physician. 

Cannabidiol (CBD)- what we know and what we don’t. Peter Grinspoon MD, Harvard Health Publishing, Harvard Med School. 6/2019

www.medicalnewstoday.com/articles/327518.  1/17/2020

A systematic review of cannabidiol dosing in clinical populations, S. A. Millar et. al., Br J Clin Pharm. 2019;85:1888-1900.

Dosage, Efficacy and Safety of Cannabidiol Administration in Adults:  A Systematic Review of Human Trials; Christian Larsen,

Jorida Shahinas;  J Clin Med Res. 2020;12(3):129-141