How does CBD work? The Endocannabinoid System and The Entourage Effect
The Endocannabinoid System
A brief history
In 1970, scientists discovered neurotransmitters. Neurotransmitters are “the messengers that relay information between neurons throughout the entirety of the nervous system.” Neuroreceptors are specialized protein molecules present in cell membranes and activated by a neurotransmitter, allowing communication through chemical signals.
By 1973, researchers had identified receptor sites in the brain capable of binding with opioids. CBD: A Patient’s Guide to Medicinal Cannabis¹ suggests they may have discovered similar receptors for cannabis soon after, had their efforts not been stunted by a politicized agenda.
In 1992, it was discovered that animal bodies naturally produce what he called endocannabinoids, which are compounds similar to the plant-based phytocannabinoids present in hemp and cannabis. ¹
What does the endocannabinoid system do?
Researchers have determined that two main receptors in the body (CB1 and CB2) respond similarly to endocannabinoids produced in the body as they do to plant-based phytocannabinoids.
The endocannabinoid system is responsible for two main activities: modulating pleasure, energy, and well-being; and slowly nudging the body “back to health in the face of injury and disease.”¹
Healthline writes that research has linked the endocannabinoid system a wide range of bodily functions, all of which contribute to homeostasis, which refers to stability of your internal environment. “For example, if an outside force, such as pain from an injury or a fever, throws off your body’s homeostasis, your ECS kicks in to help your body return to its ideal operation.” (Healthline)
What happens when we consume CBD?
“All cannabinoids produce effects in the body by interacting with cannabinoid receptors, which form part of the endocannabinoid system.” (medicalnewstoday.com)
Our current understanding of the endocannabinoid system is that it consists of the following:
Two receptors (CB1: coordinates movement, pain, emotion, mood, thinking, appetite, memories, and other functions; & CB2: affects inflammation and pain.)
Two signaling molecules: Arachidonoyl Ethanolamide (AEA or anandamide) & 2-arachidonoyl glycerol (2-AG)
Five enzymes: DGLα (for synthesis of 2-AG), DGLβ (for synthesis of 2-AG), NAPE selective phospholipase-D (for synthesis of AEA), MAGL (for breakdown of 2-AG), FAAH (for breakdown of AEA).¹
“According to an article published in the British Journal of Pharmacology, THC is a CB1 and CB2 agonist. That means that THC binds to cannabinoid receptors in your body and mimics the function and role of endocannabinoids.” (weedmaps.com)
In contrast, CBD is an “antagonist”; it stimulates the receptors so that the body produces more of its own cannabinoids, known as endocannabinoids. “It blocks cannabinoid receptors rather than activating them, which is why CBD is thought to counteract some of the effects produced by THC.” (weedmaps.com)
This difference in how THC and CBD each interact with our receptors helps us begin to understand how it makes us feel. THC has a more psychoactive effect because it attaches to cannabinoid receptors. CBD can be psychoactive in the sense that it may help regulate bodily functions, but it is non-inhibiting and does not produce the feeling of being “high”.
Can you take too much CBD?
Exactly 0 deaths that have occurred from either THC or CBD. Research leads us to believe that it’s impossible to overdose on cannabis because “cannabinoid receptors are not located in the brainstem, it cannot alter key functionalities like breathing.” (potguide.com)
In a separate article, potguide.com elaborates: “Preliminary studies show that marijuana has a therapeutic index (the ratio that compare the blood concentration at which a drug becomes toxic versus effective) of 40,000:1.” Comparatively, Morphine has a therapeutic index of 70:1.
The Entourage Effect
One of the primary features of phytocannabinoids (plant-based cannabinoids which are unique to cannabis) is that they work better in the whole plant or as plant-based extracts than they do as isolated, refined and synthesized products.
CBD: A Patient’s Guide To Medical Cannabis¹ explains:
“THC has psychotropic effects that are partially modified and significantly decreased when paired with CBD. A study² regarding the use of cannabis in patients with moderate to sever spasticity due to multiple sclerosis suggests that 1:1 THC/CBD is more effective than either isolated CBD or isolated THC. In another study,³ ‘high THC in a plant extract reversed the actual disease progression of multiple sclerosis, but CBD in a plant extract did not do so.’ In a third study,⁴ isolated CBD was consistently shown to have a narrow dose range, below which or above which it was ineffective for the treatment of pain and inflammation. Meanwhile, CBD-enriched whole-plant extract with very low levels of THC, CBC, CBG, CBN and CBDV improved as a pain reliever and anti-inflammatory as the dose was increased and was farm more effective than pure CBD. ‘In effect, THC acts as a catalyst that makes CBD work better.’”
This is why it is recommended that most people use Full Spectrum CBD products as long as they don’t have to worry about being drug tested. It is also why a lot of medicinal cannabis literature will recommend using CBD & THC in conjunction with each other. There are many ways to use both CBD and THC, so there’s something for everyone!
Terms:
Psychotropic: “Denotes a pharmacotherapeutic agent that affects brain function, usually used in the context of drugs.” (thefreedictionary.com)
Endocannabinoid System: “The endocannabinoid system (ECS) is a widespread neuromodulatory system that plays important roles in central nervous system (CNS) development, synaptic plasticity, and the response to endogenous and environmental insults… The most abundant cannabinoid receptor is the CB1 cannabinoid receptors, however CB2 cannabinoid receptors, transient receptor potential (TRP) channels, and peroxisome proliferator activated receptors (PPAR’s) are also engaged by some cannabinoids.” (ncbi.nlm.nih.gov)
Endocannabinoids: “a naturally occurring neuromodulatory lipid in the body involved in the regulation of numerous physical systems”¹
Phytocannabinoids: cannabinoids which are unique to cannabis plants¹
CB1 (cannabinoid-1) receptor: “believed to be located primarily in the central and peripheral nervous system, activated by all types of cannabinoids and largely responsible for the efficacy of THC”¹
CB2 (cannabinoid-2) receptor: “believed to be located primarily in the peripheral tissues of the immune system, the gastrointestinal system, the peripheral nervous system, and to a lesser degree in the central nervous system.”¹
Sources:
Leinow, Leonard, Juliana Birnbaum, and Michael H. Moskowitz, “CBD: A Patient's Guide to Medicinal Cannabis,” North Atlantic, 2017.
Y. Y. Syed, K. McKeage, and L. J. Scott, “Delta-9-tetrahydrocannabinol/cannabidiol (Sativex): A Review of Its Use in Patients with Moderate to Severe Spasticity Due to Multiple Sclerosis,” Drugs 74, no. 5 (April 2014): 563-578.
M. Moreno-Martet, A. Feliu, F. Espejo-Porras, M. Mecha, F.J. Carrillo-Salinas, J. Fernandez-Ruiz, C. Guaza, and E. de Lago, “The Disease-Modifying Effects of a Sativex-Like Combination of Phytocannabinoids in Mice with Experimental Autoimmume Encephalomyelitis Are Preferentially Due to Delta-9-tetrahydrocannabinol Acting through CB1,” Multiple Sclerosis Related Disorders 6 (November 4, 2015): 505-511.
R. Gallily, Z. Yekhtin, and L. O. Hanus, “Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol.” Pharmacology & Pharmacy 6 (2015): 75-85.
