As explained by Martin Lee, “cannabinoid receptors function as subtle sensing devices, tiny vibrating scanners perpetually primed to pick up biochemical cues that flow through fluids surrounding each cell.”
As we’ve mentioned, the ECS is equipped with specialized receptors to pick up cannabinoids (endo-, phyto-, and synthetic varieties). These receptors, called CB1 and CB2 receptors, are located all over the body. Lee continues to explain: “Marijuana does so much and is such a versatile medicine because it acts everywhere, not just in the brain.”
The CB1 receptors are most abundant in the central nervous system, connective tissues, glands, and organs like the uterus, cardiovascular system, GI tract, pancreas, bones, and liver, with the brain containing most of these receptors. CB2 receptors are more often found on immune cells, in the gastrointestinal tract, and in the peripheral nervous system. CB2 receptors are also present in the brain, gut, spleen, liver, heart, kidneys, bones, blood vessels, lymph cells, endocrine glands, and reproductive organs.
Many tissues contain both CB1 and CB2 receptors, where they carry out different actions. Cannabinoid receptors are the most plentiful receptors in the body, more numerous than any other receptor system.
Location of CB1 Receptors in the Brain and Physiological Effects
- Hippocampus: Learning, memory, stress related to memories
- Hypothalamus: Appetite
- Cerebellum: Motor coordination
- Limbic system: Anxiety
- Cerebral cortex: Pain, higher cognitive function
- Nucleus accumbens: Reward and addiction
- Basal ganglia: Sleep and movement
- Medulla: Nausea and vomiting
Our endocannabinoids, anandamide and 2-AG, interact with both receptors; however, anandamide interacts primarily with the CB1 receptors while 2-AG interacts primarily with CB2 receptors.
The list of brain functions that are impacted by the endocannabinoid system is quite long! Decision making, cognition, emotions, learning, memory, regulation of movement, anxiety, stress, fear, appetite, and sense of reward are all affected. When CB1 receptors are activated in the brain, it provides pain and anxiety relief, mood stabilization, and feelings of pleasure and well-being. When CB2 receptors are activated in the brain, it creates a localized anti-inflammatory effect, which is noteworthy because we now know that many neurodegenerative diseases like Alzheimer’s and Parkinson’s, post-traumatic stress disorder, multiple sclerosis, depression, autoimmune disorders, and cancer have been linked to chronic brain inflammation. The CB2 receptor is also particularly vital to the ECS’s ability to generate new nerve cells in the adult brain, crucial to maintaining adult neuroplasticity throughout life.
Outside the brain, anandamide and 2-AG function more as immune system activators than neurotransmitters, focused on stopping inflammation. A 2016 study by K. A. Sharkey and J. W. Wiley concluded that virtually all major GI function is controlled by the ECS. Most of the CB2 receptor actions in the immune system (where they are most plentiful) are involved in reducing inflammation, and tempering immune response, reducing swelling, along with influencing cell migration and programmed cell death.
Cannabis Science Deep Dive
The science behind how cannabis works with our own natural endocannabinoid system is fascinating and complex. Because cannabis has such widespread effects throughout the body at the cellular level, it can provide a level of deep healing that is, according to Martin Lee, “way beyond symptom relief, it’s deep healing.” For a deep dive on the science of cannabis and CBD, check out Green Flower Media’s CBD Summit, an online video resource where Lee explains the mechanisms at work and how cannabis heals at the cellular level.
So in summary, we know that the endocannabinoid system (with the help of cannabinoids and their receptors) impacts:
- Appetite, digestion, hunger
- Motor control
- Immune function
- Reproduction and fertility
- Pleasure and reward
- Pain and inflammation
- Temperature regulation
- Neurogenesis (growth and development of nervous tissue)
One point to underscore here, is that cannabis medicine is not a one-size-fits-all solution: not all the medicinal effects of cannabis are desirable or appropriate for every medical use.
Cannabis and the Opioid Crisis
Cannabis has gained traction as a natural and nonaddictive source of pain relief in the face of a growing opioid crisis. The Centers for Disease Control announced that more than 42,000 people died from opioid overdose in 2016. Within the brain, there are 10 times as many CB1 cannabinoid receptors (which modulate pain response) as there are the “mu” opioid receptors (responsible for the effects of morphine, for example). Research has shown that THC can enhance the efficacy of opioids, meaning that less opioid is needed to provide the same effect. In addition to this, cannabinoids affect the nucleus accumbens region of the brain, which modulates the reward circuit and is involved in addiction. Cannabis has been approved in several state medical programs to treat the symptoms of opioid withdrawal, and research is showing that CBD is particularly effective for this.