Part VIII: CBD Oil… Hype, Harm, or Heck Yeah!
We are now arriving at the conclusion of my CBD (cannabidiol) oil series with the much-awaited review of the current and most pertinent research on this “magical” medical elixir. Before continuing with this article, if you have not yet done so, for your safety, please read “An Important Review of the Factors to Consider When Determining if CBD Oil is Right for You!” It reviews the topics already covered in this series and important caveats and potential side effects of using CBD oil.
Now, onto the promised review on CBD oil uses and its efficacy.
Digging into the Data on CBD and Its Fellow Cannabinoids: Understanding Effects of CBD and the Full Spectrum of the Cannabis Compounds
In determining the effects of CBD, I’ve previously discussed the benefits of what happens when the synergy of the other components of the cannabis plant are included in a full-spectrum hemp product. This is referred to as the “entourage effect” of cannabis, and it is similar to the concept of synergy in relation to the inclusion of all the compounds found in essential oils.
This hour interview with Cal Germano and Dr. Mercola is one of the best summaries on the benefits of full spectrum hemp. Here’s the story at a glance:
- Cannabinoid receptors in the human body were discovered in the 1990s, which in turn led to the realization that we make compounds in our body — endogenous cannabinoids — that influence these receptors
- Endocannabinoid deficiency has been identified in people who have migraines, fibromyalgia, irritable bowel syndrome, inflammatory and neurological conditions and a variety of treatment-resistant conditions
- While CBD has gained the most attention, CBD alone cannot fully support your body’s endocannabinoid system (ECS). You need the other phytocannabinoids and terpenes as well
- Hemp has been outlawed in the U.S. since 1938. The latest Farm Bill, signed into law at the end of 2018, makes it legal again; hemp oil with full-spectrum phytocannabinoids may benefit a wide range of health problems
- There’s an intimate relationship between your ECS and your omega-3 status. Omega-3 fats make your cannabinoid receptors more active, and are used as backbone structures to produce cannabinoids in your body
In the article, Full Spectrum Cannabis – Benefits Beyond THC & CBD, the author provides an example of the intricate actions of the vast number of cannabinoids and terpenes (from the essential oil) found in full spectrum cannabis. The following excerpts demonstrate the multiple effects on these compounds, how they may work in synergy, and their far-reaching actions on various biochemical pathways. The author’s state the following on the substances in cannabis:
With over 140 cannabinoids identified in cultivars of the cannabis plant, clinical application of THCV, CBC and CBG needs to be recognized for their beneficial therapeutic effects. Delta-9 tetrahydrocannabivan (THCV) has been shown to work with CBD to modulate the effects of THC via a blockade of CB1 receptors. THCV also has a high affinity for CB2 receptors which differs from CBD activity (22). More recent findings show that THCV at low concentrations has potential for management of chronic liver diseases and inflammation-associated obesity (23)…
Cannabichromene is a non-psychotropic plant cannabinoid with anti-inflammatory and analgesic properties described in the 1980s. Both CBC and cannabigerol (CBG) have been shown to have anti-fungal properties and anti-depressant activity (25).
Terpenoids form the largest group of plant chemicals numbering between 15,000 to 20,000 (7) with over 200 reported in cannabis but only a few have been studied (8). Terpenoids are essential for the viability of plants and have a variety of functions within the plant by acting as growth regulators, insect defense secretors and pollinator attractants (9). In human nutrition, they have provided flavors and scents and have GRAS (Generally Recognized As Safe) status by the U.S. Food and Drug Administration (10). As essential oil components they provide the aroma of cannabis despite their yield being less than 1 percent of the total product weight (11) in addition to having significant pharmacological interest.
Monoterpenes- limonene, myrcene, pinene- dominate. Sesquiterpenoids like beta-caryophyllene are found in higher proportion. Myrcene displays opioid-like analgesic effect (12) while beta-caryophyllene demonstrates anti-inflammatory activity (13) and both pinene and linalool have been found to inhibit PGE-1 as an anesthetic (14). D-limonene found in lemons and other citrus fruits is the second most widely distributed terpenoid in nature (15) and other studies (16,17) suggest it is a powerful anxiolytic agent. Komari et al. in 1995 described a hospital study of depressed patients who were exposed to citrus fragrance in ambient air who discontinued anti-depressant medication in 9 out of 12 patients with normalization of Hamilton Depression scores (18).
One Compound with Different Mechanisms on Multiple Receptors Means Many Actions…
By including all the substances found within the plant in a full spectrum product of cannabis, it is believed that a more harmonious outcome on the body will be achieved. To demonstrate this, consider the difference between an isolated caffeine supplement and drinking an organic cup of coffee or tea.
Caffeine alone has multiple actions and multiple metabolites and there exist many factors that impact its effects. As the author of this article review states:
In conclusion, there are significant inter-individual differences in the metabolism, clearance, and elimination of caffeine and its metabolites. Several extrinsic factors influence metabolic and excretion rates, such as smoking, food intake, gastric emptying speed, pregnancy, hepatic and cardiovascular diseases, viral infections, and concomitant drug use.
Add this complexity of caffeine and individual alterations in metabolism to the different mechanisms that the many components found in green tea will exert and the result is a very intricate and comprehensive profile that science has yet to duplicate. As this article states:
The chemical composition of green tea is complex: proteins (15-20% dry weight), whose enzymes constitute an important fraction; amino acids (1-4% dry weight) such as theanine or 5-N-ethylglutamine, glutamic acid, tryptophan, glycine, serine, aspartic acid, tyrosine, valine, leucine, threonine, arginine, and lysine; carbohydrates (5-7% dry weight) such as cellulose, pectins, glucose, fructose, and sucrose; minerals and trace elements (5% dry weight) such as calcium, magnesium, chromium, manganese, iron, copper, zinc, molybdenum, selenium, sodium, phosphorus, cobalt, strontium, nickel, potassium, fluorine, and aluminum; and trace amounts of lipids (linoleic and ?-linolenic acids), sterols (stigmasterol), vitamins (B, C, E), xanthic bases (caffeine, theophylline), pigments (chlorophyll, carotenoids), and volatile compounds (aldehydes, alcohols, esters, lactones, hydrocarbons). Due to the great importance of the mineral presence in tea, many studies have determined their levels in tea leaves and their infusions (Table ?(Table1)1) . Fresh leaves contain, on average, 3-4% of alkaloids known as methylxanthines, such as caffeine, theobromine, and theophylline . In addition, there are phenolic acids such as gallic acids and characteristic amino acid such as theanine present .
How CBD works is just as complicated, even or more so.
As with caffeine, CBD oil has different mechanisms of actions as an isolate alone. Below is a peak of some of the various receptors CBD oil has been found to “hit” in the body from various sources.
Imagine, all that impact with one tiny molecule!
5-HT, 5-hydroxytryptamine; AEA, N-arachidonoylethanolamine; CB1 and CB2, cannabinoid receptor type 1 and 2; eCB, endocannabinoid; FAAH, fatty acid amide hydrolase; PPAR?, peroxisome proliferator-activated receptor gamma; modulation of THC, ?9-tetrahydrocannabinol; TRPA1, transient receptor potential cation channel A1; TRPM8, transient receptor potential cation channel M8; TRPV1 and TRPV2, transient receptor potential cation channel V1 and V2.
CBD acts as agonist of the receptors TRPV1, PPARy, and 5-HT1A, and as antagonist of the receptor GPR55. CBD is an inverse agonist of the receptors GPR3, GPR6, and GPR12. Moreover, CBD antagonizes the action of CB1 and CB2 receptors agonists, and is suggested to act as an inverse agonist and a negative allosteric modulator of these receptors. CBD also inhibits FAAH, which results in increased anandamide levels. Anandamide activates CB1, CB2, and TRPV1 receptors. By acting on mitochondria, CBD increases the activity of mitochondrial complexes. In addition, CBD displays antioxidant and anti-inflammatory effects—that are partially mediated by CBD’s actions on TRPV1, mitochondria and PPAR?. 5-HT1A, serotonin receptor 1A; CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2; FAAH, fatty acid amide hydrolase; GPR3, G-protein-coupled receptor 3; GPR6, G-protein-coupled receptor 6; GPR12, G-protein-coupled receptor 12; GPR55, G-protein-coupled receptor 55; PPARy, peroxisome proliferator-activated receptor gamma; ROS, reactive oxygen species; TRPV1, transient receptor potential vanilloid type 1.
Another review demonstrates multiple effects of CBD, and the authors also give us a glance at the difference between it and another cannabis compound, THC (delta9-tetrahydrocannabinol):
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with delta9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington’s disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like delta9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.
Then, There’s Your Own…Endogenous Cannabinoids Actions
Add this complexity of CBD’s actions to the fact that CBD modulates the use of our own endocannabinoids (eCBs), and now you’ve multiplied its multifactorial effects. This article states:
“In addition to CB1 and CB2, cannabinoids and eCBs can exert their effects engaging other non-CB receptors, including the transient receptor potential vanilloid 1 (TRPV1) channel, expressed mainly in peripheral tissues, including peripheral sensory neurons, epithelial and endothelial cells as well as immune cells (Xia et al., 2011). Other targets are peroxisome proliferator-activated receptors (PPAR) a and y (Pistis and Melis, 2010) that belong to a family of nuclear receptors whose role is mainly to control lipid metabolism; and orphan G protein-coupled receptor GPR55 (Moriconi et al., 2010).”(source)
Summary on CBD and Full Spectrum Products… So Far
As a whole, cannabis and its extracts have been deemed overall safe when used properly. Still, research and long-term reports are far from complete and have limitations. Many may respond to the “hit” of isolated CBD from cannabis; however, many may not and experience neutral or irritating side effects.
For these reasons, many of my colleagues are advocating ingestion of more than just the isolate of CBD and prescribing the full spectrum cannabinoids in the form of hemp extracts.
In the FINAL article, I will review two more limitations of safety and conclusions on CBD from non-clinical trials. Then, I will provide a summary on the studies on its effects on mood, pain, and the brain and neurological system.
Hang in there… we are crossing the finish line!