Friday, March 27, 2020

CBD Series -- Part 2

The Endocannabinoid System-- How CBD Actually Works

Hang with me on this post.  It is going to be a brief lesson in neuroscience. It is a bit dry, but it gives you the mechanism of action for how CBD actually works.

Decades ago as a young scientist in Israel, Raphael Mechoulam longed to make an impact in research, but he acknowledged that he was in a small country with limited capital.  He decided to focus his interest on readily available materials that were not being studied by other major nations. Dr. Mechoulam surveyed his resources and ended up at the local police department.  He requested the hashish that had been confiscated during drug raids. This began the journey of the man who would become the father of modern cannabinoid research.

Dr. Mechoulam separated the components of hashish (compressed resin of the cannabis plant) and initially identified only one active component, tetrahydrocannabinol (THC).  He noted that THC seemed to have anti-anxiety and sedating effects in animal models.

In the mid 1980s, Dr. Allyn Howlett in the United States continued this research and identified the first specific receptor in the brain for cannabinoids.  She named it the CB(1) receptor. The CB(1) receptor had a specific affinity for THC, and CB(1) was found to be prevalent in the brain and the central nervous system.  This was the first momentous discovery of the endocannabinoid system because we now had identified a specific receptor for THC.

The next logical question was why would a receptor exist for an element of the cannabis plant in our bodies?  The answer had to be that we were already producing a form of THC internally. Dr. Mechoulam gathered his research team, and an American, Bill Devane, discovered the ligand anandamide.  This was the first isolated naturally occurring internally produced cannabinoid. So now we have both the receptor CB(1) which we can view as the lock on the membrane of the cell and we have the key--the endocannabinoid anandamide.  This was followed by the identification of the CB(2) receptor as well as other cannabinoid isolates.

Brain cells (neurons) communicate with the body and with each other by releasing chemicals called neurotransmitters to send messages from one cell to the next.  The neurotransmitter latches on to a receptor much like a runner passing a baton in a relay race, and the message jumps from cell to cell in this fashion. The endocannabinoid system (ECS) is different in that it communicates backwards.  When the neurotransmitter “hands the baton” to the next cell, cannabinoids are made on demand to act almost as a dimmer switch in the body, limiting the amount of neurotransmitters like dopamine and serotonin that are released. This has a significant impact on how messages are sent and received in the body.

The identification of the ECS shows that we truly are fearfully and wonderfully made.  We have an entire system designed to maintain biological harmony in response to changes in the environment, and this system is in all mammals.*  Cannabinoid receptors are found throughout the body. CB(1) receptors, primarily associated with THC, are found mainly in the brain and central nervous system while CB(2) receptors are found throughout the body: in skin, immune cells, bone, fat tissue, liver, pancreas, skeletal muscle, heart, blood vessels, kidney, and the gastrointestinal tract.

The clinical implications of this system are almost overwhelming.  In our next session, we will be discussing what this means from a treatment standpoint.

Bottom line:  We do have an understanding of the science behind CBD.  The endocannabinoid system has been found throughout the body, and CBD can act as a “key” for the cannabinoid receptor on the cell membrane.  For this reason, studies are being conducted with CBD on a number of disease states from anxiety and sleep disorders to the immune response of the body.  THC works on the CB(1) receptors and CBD targets the CB(2).  This is why the full spectrum CBD with the legal limits of THC will provide the maximum benefit.  More on specific diseases in next post! Stay healthy!

*De Laurentis A, Araujo HA, Rettori V.  Role of the endocannabinoid system in the neuroendocrine responses to inflammation.  Curr.Pharm Des. 2014; 20(29);4697-4706

Mackie K. Cannabinoid receptors:  where they are and what they do. J Neuroendocrinol.2008;20 Suppl 1:10-14.

Tuesday, February 18, 2020

CBD Series -- Part 1

Cannabidiol (CBD):  What is the real story?

John Hollis is an innovator.  He is always monitoring trends and new directions in pharmacy.  I am a perpetual clinical skeptic, always ready to question the latest brand new “thing.”  With CBD, we followed our patterns.  John began discussions with hemp farmers in Kentucky, one of the first states to legalize hemp production, back in 2015, long before CBD was introduced into the marketplace.  John drove out to hemp farms to watch the production and even critiqued the process by which CBD oil was produced, suggesting carrier oils that would provide the greatest bioavailability of the active ingredient.  John insisted on examining the source even before working with the product.  As CBD oil became available for use, John was ready to move forward.  I was, unsurprisingly, skeptical.  One afternoon, John was rushing out of the pharmacy, late for a meeting, and the lab was a mess of CBD soaked glassware.  I assured him that I would clean up and that he was free to charge forward.  During clean-up, I realized that CBD oil had spilled on my bare skin.  As a result, I could smell the CBD oil on my hands as I left the pharmacy, shaking my head, slightly irritated with myself (and John) as I knew it would be a long, aromatic drive home through Nashville rush hour traffic.  Much to my surprise, it was the easiest commute I had ever driven!  I was polite, even charming to other drivers.  The traffic was the same.  I, with the addition of CBD, was not.  This began my research into CBD.

While there is a huge amount of media attention devoted to CBD, the accuracy of information has been questionable.  New research has provided a clearer picture of how and why CBD works in the body.  We are beginning a new educational series on CBD, starting with understanding how CBD differs from marijuana, then moving to how CBD works on the Endocannabinoid system in the body, and finishing with information on using CBD in disease states.

To begin, CBD stands for Cannabidiol.  Like marijuana, the plant family is cannabis sativa; however, there are huge differences in CBD and marijuana.  CBD is derived from the hemp plant which is a cousin of the marijuana plant, and hemp contains lower levels of THC (tetrahydrocannabinol) which is the psycho-active ingredient in marijuana.  Hemp also contains higher levels of CBD than the marijuana plant, so the active levels of medication in the two plants are reversed:  hemp is high in CBD and low in THC, and marijuana is just the opposite.  By law, CBD oil has to have 0.3% or less THC.  CBD oil that contains THC is referred to as “Full Spectrum CBD.”  For reference, marijuana has from 5 to 28% THC, and the more THC, the more potent marijuana becomes.  Very importantly, CBD is legal in all 50 states. 

CBD oil is usually packaged in a 30 milliliter (or 1 ounce) bottle.  The amount of CBD listed on the label is the entire amount in the bottle.  It is not the amount per dropperful.  For example, if a 30 ml bottle of CBD has 2400 mg on the label, it means that there is 2400 mg per 30 ml or 80 mg per dropperful.  We will explore this at length along with dosing in a future post.

And now, does CBD work?  At this point, CBD has been promoted for an extensive variety of health conditions, and more research definitely needs to be completed.  CBD is being used to address anxiety and insomnia,* and may offer options for chronic pain and inflammation.**  We will address these disease states in upcoming posts.  The strongest evidence that CBD is effective comes from the FDA which recently approved the prescription drug Epidiolex (Cannabidiol) for the treatment of seizures in children.  

Side effects of CBD are mild and can include nausea, fatigue, and irritability.  The most important concern is that CBD does not currently fall under any regulatory agency, so evaluating the quality of CBD falls on the consumer.  Any reputable provider of CBD will have a Certificate of Analysis to prove that what you are buying contains actual CBD.  Each lot of CBD produced will have a certificate of analysis for that particular lot number.  The certificate of analysis is the official record that documents that a chemical contains what it is supposed to contain.  We always have our certificate of analysis per lot available and others should also.  Feel free to ask for this information when you purchase CBD oil.

The bottom line is that CBD is not marijuana.  CBD can potentially provide a safe and effective option for managing anxiety, insomnia and chronic pain.  It is important to read the labels carefully and to have information about the origin of the product, and to discuss CBD with your physician or pharmacist to make sure that it does not interfere with your current medication. 

Next time, we will discuss how CBD works in the body, so stay tuned!

*Cannabidiol as a Potential Treatment for Anxiety Disorders. Blessing EM, Steenkamp MM, Marmar CR. Neurotherapeutics 2015;12(4) 825-836.
**Cannabinoids and Pain:  Sites and Mechanisms of Action. Starowicz K, Finn DP, Adv Pharmacol. 2017; 80: 437-475.