Medical Cannabis for the treatment of Pain

Pain is the number one indication treated by medical cannabis, with over 70% of prescriptions made for pain-related symptoms.

Now that patients can legally access medical cannabis in New Zealand, it’s more important than ever for doctors to understand how cannabis works for pain.

Here’s everything you need to know.

What is medical cannabis?

The term “medical cannabis” refers to cannabis products containing the cannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of both, specifically used for the management of medical conditions. Medical cannabis can also refer to synthetic cannabinoids and “minor cannabinoids” such as cannabigerol (CBG) and cannabinol (CBN).

Cannabis sativa contains around 113 chemical compounds known as cannabinoids. The most commonly known and studied of these are THC and CBD. THC is responsible for, among other effects, the intoxicating and psychoactive effects of cannabis. CBD does not have the same intoxicating “high” like THC. When taken together at suitable ratios, CBD may mitigate some of the intoxicating effects of THC.

Although this article primarily looks at medical cannabis to alleviate pain, it has been widely studied and has shown to be effective in helping with a wide range of other medical conditions as well.

How medical cannabis works to alleviate pain

Extensive preclinical and a few clinical studies suggest promising pain-relieving properties of THC and CBD. Until recently, studies assessing the use of medical cannabis were limited due to legal and accessibility issues surrounding medical cannabis. As the use of medicinal cannabis is legalised and becomes more widespread, more extensive clinical trials will likely be performed. These will help to determine the efficacy and safety of medical cannabis.

Animal models show medical cannabis has significant analgesic (pain-relieving) effects on inflammatory, neuropathic and arthritis-related pain. Many of these studies have investigated the mechanism of action of THC and CBD in pain relief.

Researchers believe it is primarily through the interaction with the endocannabinoid system (ECS) that medical cannabis works to reduce pain.

The ECS is a complex biological system comprised of cannabinoid receptors (CB1 and CB2) that regulates many physiological processes, including immunity, appetite, metabolism, and more.

How THC can alleviate pain

THC acts in a similar way to endogenous endocannabinoids to activate the CB1 and CB2 receptors, which is how it’s thought to affect pain.

Activation of the endocannabinoid system by THC causes the inhibition of ascending nociceptive transmission (pain perception). It also causes the activation of the inhibitory descending pain pathways and the modulation of the emotional component of pain. This happens through the activation of CB1 receptors in the limbic and cortical areas of the brain. The overall effect is to decrease the patient’s sensation of pain.

In chronic pain conditions, there is often increased sensitisation to pain. The increased sensitisation means that the more pain individuals experience, the more sensitised they become to feeling pain. This becomes a pain cycle that is hard to break.

Activation of peripheral and central CB2 receptors modulate immune and inflammatory responses, leading to neuronal sensitisation inhibition in chronic pain. THC can intercept the cycle of increased pain sensitisation.

How CBD can alleviate pain

The interaction of CBD on the endocannabinoid system is not as straightforward.

CBD is an allosteric inhibitor of THC binding to CB1. That means CBD modifies how THC binds to CB1 receptors to lessen THC’s stimulatory effect on the receptors. Through this mechanism of action, CBD, when combined with THC in medical cannabis, alleviates the psychoactive effects of THC; lessening the “high” patients might feel.

CBD is an inverse agonist of CB1 and CB2. This means that when CBD binds to CB1 and CB2 receptors, it inhibits rather than activates them.

Typically, activation of CB2 leads to cytokine release, which causes the migration of immune cells to target sites. This is part of the normal inflammatory pathway and is necessary for normal immune function, wound healing, and more.

However, it becomes problematic when the inflammatory response is exaggerated, as it is in certain pain conditions such as arthritis. CBD binding to the CB2 receptor inhibits the inflammatory response, decreasing inflammation.

There are secondary pathways by which CBD can decrease pain. Some of the analgesic effects of CBD are mediated by the activation of the serotonergic 5HT1a receptors, key mediators in anxiety and depression. This pathway is important when considering the link between pain and depression.

CBD has also been shown to have sleep-promoting effects, which also plays a role in pain reduction and increases the quality of life of people suffering from painful conditions.

Conditions medical cannabis may treat

Multiple Sclerosis

Multiple Sclerosis (MS) is a degenerative disease that affects the central nervous system, especially the brain, the spinal cord, and the optic nerves. Symptoms can range from mild visual loss and weakness to severe, debilitating muscle spasms, loss of mobility, and paralysis.

Many clinical trials support medicinal cannabis in the treatment of the pain and spasticity associated with MS. A 2020 review of over 33 studies and 7500 patients found adequate data to support the safe and effective use of medical cannabis at a THC to CBD ratio of 1:1 for alleviating pain and spasticity in MS patients.

Neuropathic pain

Neuropathic pain is pain resulting from nerve damage. Often described as a severe burning sensation, it can result from trauma, diseases (e.g. diabetes, thyroid disease), or medication. It is also largely intractable pain and is notoriously unresponsive to standard pain medication.

A 2020 review of the use of medicinal cannabis in the management of pain found the most evidence to support its use in chronic neuropathic pain. Medical cannabis could be a welcome option for many who are unable to treat chronic neuropathic pain.

Arthritis-related pain

The pain from arthritis is a combination of inflammatory, nociceptive, and neuropathic pain. The articular cartilage of joints breaks down in patients with rheumatoid arthritis and osteoarthritis (primarily mediated by proinflammatory cytokines). Animal models have shown cannabinoids are effective in reducing joint damage from the breakdown of cartilage.

A 2019 review found a potential for the use of cannabinoids in managing rheumatoid arthritis by using a targeted receptor approach. Further clinical trials are required in this area to understand its full potential.

Cancer pain

A 2020 review of cannabinoid use in cancer patients showed promise for medical cannabis in the management of cancer pain. The results showed improved pain scores in patients with advanced-stage cancer when medical cannabis with a THC:CBD ratio of 1:1 was added to opioid treatment. An observational study also showed an improvement in pain and the quality of life. However, it was also mentioned that there is a need for further high-quality randomised controlled trials to adequately define the role of medical cannabis in managing pain in cancer patients.

Medical cannabis has not only been used directly for cancer pain but has also been used successfully in alleviating the side effects of chemotherapy. There is good evidence to show that medical cannabis can reduce nausea and vomiting associated with certain chemotherapy treatments. It can also help counteract the loss of appetite and wasting (cachexia) that many cancer patients suffer from.

Importantly, across all reviewed studies in patients with cancer-related and non-malignant pain who were using daily THC:CBD for an extended period, there were no new safety concerns identified. There was also no evidence of the development of tolerance to the medication i.e. the dose did not have to be increased with extended periods of use in order to have the same effect.

Opioid-sparing effect of medical cannabis

Opioids are usually the drug of choice for chronic, severe pain when first-line pain options (paracetamol and non-steroidal anti-inflammatories) have proved ineffective. Although opioids are effective, they come with a host of risks and side-effects. Most concerning, is their addictive potential, with up to 1 in 4 patients in primary care who have been prescribed opiates developing dependence.

Even without addiction, opiates have many unwanted and intolerable side-effects such as constipation, nausea, drowsiness, itching, depression and tolerance (meaning that with time, you need a continually higher dose to achieve the same level of pain control).

Medical cannabis has been shown to be opioid-sparing. This means that if a patient is already on opioid medication, by adding medical cannabis the patient is able to decrease their dose of opioids. This decreases both side-effects and the risk of dependence.

The bottom line

There is a growing body of evidence to support the use of medical cannabis in the management of pain. This is only likely to increase going forward as further legal restrictions on the use of medicinal cannabis are lifted.

Traditional methods of pain management come with many unwanted risks and side-effects and can often be lacking in efficacy. Medical cannabis could well fill the gap in pain management left by existing pain medications.

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