Cannabis and the endocannabinoid system

Using cannabis to manage pain was written into the earliest known book of Traditional Chinese Medicine about two thousand years ago, and even earlier into India’s ancient Ayurvedic texts. Today, pain relief is the most common reason patients turn to medical cannabis. As scientists look to verify the plant’s ability to ease soreness, discomfort and inflammation, mounting  research reveals cannabis as a promising tool to manage many types of pain—just as the ancients suspected long ago. 

How does cannabis help manage pain and inflammation? 

To understand how cannabis eases pain, we first need to understand the endocannabinoid system, the most extensive receptor system in the human body. You may have heard of dopamine, serotonin or histamine receptors, but because the endocannabinoid system was only discovered in 1988, most people are unfamiliar with cannabinoid receptors. 

As you can guess by the name, cannabinoid receptors respond to chemicals called cannabinoids that naturally occur within cannabis, including THC and CBD and, to a lesser extent, minor cannabinoids such as CBG, CBN and CBC. Our bodies contain these receptors because because we manufacture our own endocannabinoids—endo meaning they come from within the body. 

One of these endocannabinoids is called anandamide, named after the Sanskrit word ananda, meaning “bliss”. Anandamide is produced on demand by the body to help regulate pain and other fluctuating states of being such as mood and appetite. (Although present in very low doses, anandamide has also been detected in chocolate and may be responsible for the feel-good response some people get from eating the candy.) 

Researchers discovered anandamide after they came across receptors that respond to the cannabinoid THC. They went on to find concentrations of THC-friendly receptors in the brain’s cortex, cerebellum, hippocampus and basal ganglia, which also happen to be areas that control the sensation of pain. It turns out THC has a similar molecular structure to anandamide, which is why this intoxicating cannabinoid easily binds to endocannabinoid receptors that have an affinity for anandamide. Researchers named these receptors CB1. 

Soon after anandamide and CB1 receptors were found, researchers came across an expansive collection of different receptors that respond to the cannabinoid CBD. Sure enough, there is an endocannabinoid with a similar molecular structure to CBD called 2-Arachidonoylglycerol, or 2-AG, which is also produced by the body in response to pain, especially when tissues are under acute stress. 

These widespread receptors that respond to CBD are more readily found in the body’s immune system: organs, glands, immune cells and connective tissues. Scientists named these receptors CB2, and together with CB1 receptors, they make up the endocannabinoid system. Researchers have since found five cannabinoid receptors within the endocannabinoid system, but CB1 and CB2 make up the vast majority. 

The endocannabinoid system and pain 

When your body experiences tissue damage, it manufactures both endocannabinoids anandamide and 2-AG as a first response. Because CB1 receptors are located along pain pathways in both the peripheral nervous system (limbs, glands and organs) and central nervous system (spinal cord and brain), activating these receptors with cannabis can help modulate the sensation of pain. Research has shown that when activated by THC—and to a lesser extent CBD and the minor cannabinoids—CB1 receptors appear to reduce pain sensitivity. 

Inflammation, which is the immune system’s healthy response to infection and injury, can be exacerbated by stress and other factors. Stimulating CB2 receptors, which are found throughout the immune system, appear to instruct cells to slow or stop the release of inflammation-causing cytokines. Research has shown the cannabinoid CBD can inhibit cytokine production, although there are no published studies to date that verify CBD for pain management. 

When it comes to cannabis medicine, it is good to remember that CBD and THC aren’t the only molecules at play. There are also terpenes, flavonoids and hundreds of other components that all work together synergistically, known as the entourage effect. For example, the aromatic terpene Myrcene, also found in mango and celery, has a mild sedative effect on its own and is thought to boost the felt effects of THC through other mechanisms in the body. 

Cannabis may also boost the felt effects of other medications. There is growing evidence to suggest patients using traditional pain-relieving medications, such as opioids, have been able to reduce their intake when used in combination with cannabis therapy. Further evidence suggests cannabis can mitigate the flu-like symptoms of opioid withdrawal. However, keep in mind that combining pain medications can be dangerous and should only be done under your healthcare provider’s supervision. 

Which cannabis forms are best for pain relief

CBD or THC for pain relief? 

Because of growing public interest in CBD-only products, it can be tempting to think of cannabis therapy in terms of either CBD or THC. But the reality is these cannabis chemicals work better together, a concept known as the entourage effect, which is why many cannabis medications often contain both—even if in small amounts. 

Studies to date have mostly concentrated on cannabis that contains THC that may or may not contain CBD. Of these studies, evidence points to THC-rich cannabis as effective in easing chronic pain, especially chronic neuropathic pain. In terms of acute pain, a handful of smaller studies showed cannabis as having little to no role in pain management, although research is still ongoing. 

While the study of pure CBD is still in early stages, evidence suggests it has its own pain-relieving properties in addition to its ability to ease inflammation. CBD is showing promise in reducing the symptoms of retinal inflammation and intestinal inflammation. Preclinical trials also show CBD may also help manage neuropathic pain and osteoarthritis. 

Depending on the kind of pain and inflammation you’re trying to manage, your healthcare provider may suggest high-CBD cannabis, or high-THC cannabis, or a combination of both, depending on the situation and your symptoms. 

Are cannabis oils better for pain? 

For patients seeking longer-lasting pain management or those who don’t wish to inhale, ingesting cannabis oils can be a good option. Rapid-acting oil sprays can start to work within 15 minutes, as can cannabis oil products with titrated or built-in droppers to administer the oil under the tongue and held there before swallowing. If swallowed directly, cannabis oil will take effect within 90 minutes. Patients can expect the effects of cannabis oils to last anywhere between two to eight hours. 

Cannabis edibles and beverages also have similar onset, within 15 minutes for beverages or 90 minutes for foods, and last two to eight hours. 

For immediate effects, however, inhalation through vaping or smoking is a better route. Onset is felt within seconds or minutes, with the full impact felt within 10 to 30 minutes. Symptom management will typically last three to four hours and up to six hours. 

What kinds of pain can cannabis help with? 

While mounting preliminary studies demonstrate cannabis can ease pain and inflammation, published double-blind, randomized controlled human trials (the gold standard of research) are still lacking for many conditions. Here are some of the latest findings: 

Back pain: A recent preclinical trial of 46 patients with chronic back pain, who didn’t find opioids or other pain relief medication helpful, reported cannabis was effective in managing their pain along with overall improved quality of life. 

Menstrual pain and endometriosis: There is a high concentration of CB1 receptors in the ovaries and uterus, along with some CB2 receptors. In five clinical studies on endometriosis, including two randomized controlled trials, cannabis was found to significantly ease painful periods and general pelvic pain associated with endometriosis. 

Arthritis pain: Numerous studies on classic arthritis, which is a loss of collagen around joints, have shown CBD as having an anti-inflammatory effect on these areas. Studies have also shown activation of CB2 receptors may decrease further joint damage. One randomized controlled trial for rheumatoid arthritis pain demonstrated a synthetic form of cannabis, nabiximol, helped manage pain during movement, at rest, along with improved quality of sleep compared to placebo. 

Migraine and headache pain: While one preliminary study showed cannabis was no better for pain management than amitriptyline for migraines and cluster headaches, a subset of this same study—adults who suffered migraines since childhood—experienced decreased pain when using cannabis as abortive therapy during a migraine attack. However, there have been no randomized controlled trials to confirm. 

Fibromyalgia: In one observational study of 367 fibromyalgia patients, most reported a reduction in pain with cannabis therapy, and over 80 percent had improved symptoms after six months. One randomized controlled trial with a synthetic cannabis drug, nabilone, showed consistent pain management and improved quality of life after six months. 

Inflammatory Bowel Disease: It is known that CB1 receptors help to modulate and control gastrointestinal function. One randomized controlled trial and subsequent review could not conclude whether cannabis managed the pain and other symptoms associated with inflammatory bowel disease. However, a more recent pilot study demonstrated improvement in IBD patients’ symptoms after three months of cannabis therapy. 

Traumatic Brain Injury: Animal trials have shown synthetic cannabis as having neuroprotective properties in traumatic brain injury treatment. While there is anecdotal evidence of cannabis easing headaches and other traumatic brain injury symptoms, randomized controlled trials have yet to confirm. 

What if I take too much cannabis for my pain? 

Taking too much cannabis can result in a very uncomfortable experience, but it will not directly result in death. Because there are no known cannabinoid receptors in the brain stem’s cardiac and respiratory centers, an excess of cannabis will not cause the heart and lungs to shut down, which can happen in an opioid overdose. The best thing to do in the event of cannabis poisoning is to find a comfortable place to rest, stay hydrated, and wait until the cannabinoids work their way out of your system. If you’re concerned about your symptoms after consuming cannabis, contact your local poison control centre, or call our Shoppers Cannabis Care team at 1-844-633-2627 Monday to Friday 9 a.m. to 9 p.m. EST, or Saturday 9 a.m. to 5 p.m. EST.

Do I need to be “high” for cannabis to work? 

Your cannabis medication should never make you feel uncomfortable, nor should it significantly interfere with everyday activities such as work or school. If your symptom management regimen includes THC, your healthcare provider may suggest taking less THC in the daytime and more at night, allowing you to sleep through any potential intoxicating effects. 

A high-CBD regimen is usually well tolerated by patients without generating feelings of euphoria, although it does affect the brain. Anecdotally, some people find a low dose of CBD taken at night can interfere with sleep. Talk to your pharmacist or healthcare provider about how to keep potential intoxication to a minimum while ensuring you get enough rest at night. 

Omega-3 and inflammation

The omega-3 connection  

It is well documented that omega-3 fatty acids, found in foods such as fish oil and flax seeds, have a positive effect on bodily inflammation. These fatty acids may also play a supporting role in cannabis therapy: a recent study suggests they may help improve the body’s ability to access cannabinoids in the bloodstream and help the entire endocannabinoid system perform at optimal levels. Talk to your pharmacist about whether omega-3 fatty acid supplements could complement your cannabis medication.