By Dr Emma Stone for Helius Therapeutics
Diverse cultures have long nurtured an understanding of cannabis as a form of pain relief. Historians have dated the use of cannabis for pain as far back as 2700 BC, but regulatory changes ushered in during the twentieth century banned its prescription.
However, clinical interest in cannabis for the management of various forms of pain has recently been reignited. In the face of burgeoning global opioid dependence, cannabis may represent a safer or more effective alternative. Indeed, evidence strongly suggests that cannabis can replace or lower opioid use.
One in five New Zealanders report living with chronic pain. Globally, lower back pain represents the leading cause of disability. Individuals living with chronic pain often experience a profound impact on their quality of life and may suffer insomnia, anxiety or depression. The nature of pain is complex, encompassing biomedical, psychological, and social dimensions.
Could cannabis help render the experience of pain more manageable?
How does medicinal cannabis work?
The endocannabinoid system (ECS) represents the key to understanding how cannabis acts on the body. The endocannabinoid system is a critical regulatory force within the body, helping to maintain homeostasis in response to environmental factors. The ECS is composed of two central cannabinoid receptors (CB1 and CB2) and endocannabinoids that are manufactured by the body.
The ECS is one of the most influential systems regulating pain sensation, with modulatory actions at all levels of the processing pathway.
Endocannabinoids and cannabinoid receptors both play a role in the transmission and modulation of pain signals. CB1 receptors are found throughout the peripheral and central nervous systems, while the CB2 receptors are more commonly found on peripheral tissues such as immune cells. The CB2 receptors may also contribute to pain relief by modulating dopamine release.
Cannabis consists of many cannabinoids, which exert their effects, in part, by mimicking endocannabinoids. Both endocannabinoids and cannabinoids exert anti-inflammatory effects and can activate the cannabinoid receptors in response to pain. The two major cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been shown to modulate pain. The anti-inflammatory effect of CBD has been calculated to be several hundred times more potent than aspirin. THC functions in synergy with the anti-inflammatory actions of CBD.
Is there evidence that cannabis can ease pain?
Pain is generally categorised in two ways. It can be due to tissue injury (nociceptive), or neuropathic, where changes in the nervous system is the source of pain. Pain is also conceptualised according to duration and thus identified as acute or chronic. Evidence suggests that cannabis can help ease diverse expressions and experiences of pain, with studies investigating its efficacy in alleviating arthritis, postoperative discomfort, multiple sclerosis, glaucoma, cancer, fibromyalgia, HIV, and migraines.
According to Dr. Rick Acland, a pain management specialist in New Zealand who has worked extensively in the field of spinal cord injury (SCI), medicinal cannabis is a potent alternative to existing analgesics. He says, "Medicinal cannabis offers another dimension in achieving pain relief.”
“It is safe, well-tolerated and unlike paracetamol or opioids, you can’t die of overdose. When you listen to patients, you realise how effective cannabis can be in managing many aspects of pain," says Dr Acland.
A major report, Cannabis: The Evidence for Medical Use, an in-depth review commissioned by the UK Parliament in 2016, examined a number of randomised controlled trials investigating cannabis and pain and found that there was ‘good evidence for the efficacy of cannabis for pain relief’. This review is informally known as The Barnes Report after it's author Professor Michael Barnes MD FRCP, who led New Zealand's first RNZCGP endorsed Masterclass in Medical Cannabis for healthcare professionals in 2019.
Similarly, in the US, a 2017 review of more than 10,000 peer-reviewed abstracts by the National Academies of Sciences, Engineering, and Medicine (NASEM) determined that ‘there was conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of pain in adults’.
So, while there appears to be a clinical consensus that cannabis can alleviate pain, where do its specific strengths lie? Current findings suggest that it seems most helpful in the short-term alleviation of neuropathic and nociceptive pain, commonly experienced by multiple sclerosis patients. Another study has also indicated that cannabis is clinically meaningful to one in five patients for immediate, short-term relief from chronic neuropathic pain. It also reported that cannabis is as potent as gabapentin in easing neuropathic pain.
The jury is still out, however, regarding the effects of cannabis on acute pain. One review has questioned its efficacy; however, another study suggests it may be helpful for acute nociceptive pain when delivered as an oral extract containing THC.
Insomnia, and compromised quality of life are frequently interlocked with the pain experience. Cannabis has been linked to significant improvements in sleep and enhanced quality of life, thus rendering the experience of pain more manageable.
Which cannabis formulations are most effective?
Cannabis is available as a whole-plant extract containing the full complement of cannabinoids, as well as substances called terpenes and flavonoids. It can also be consumed as an extract containing one or other cannabinoids, or in a synthetic format such as nabilone. Research indicates that the formulation may influence efficacy in alleviating pain.
According to the 2017 NASEM review, whole-plant cannabis extracts appear to reduce pain more successfully than their synthetic counterparts, although synthetic formulations still reduce pain more effectively than placebo.
New Zealand’s leading medicinal cannabis firm, Helius Therapeutics, is already engaged in the research and development of a novel solution for the treatment of pain. The company is working on next-generation, targeted dose forms that improve bioavailability and enhance the therapeutic potential of cannabis as a medicine.
Should any pain patients avoid cannabis?
At present, there are no clinical reviews that recommend the use of cannabis for pain management in children. Most studies consider THC-dominant medications inappropriate for use in children and adolescents due to the cannabinoid’s psychoactive properties, and uncertainties regarding the effects on adolescent brain development.
Experts recommend that patients taking medications for neurological, psychiatric, or respiratory conditions should be monitored for potential drug-on-drug interactions, such as those who are taking medications which are metabolised by cytochrome P450.
Are there any side effects?
In most studies investigating cannabis as a treatment for pain, adverse events experienced by participants were generally mild, transient, and well-tolerated. The most commonly experienced side effects include drowsiness, dizziness, disorientation, difficulty concentrating, dry eyes, dry mouth, and mild anxiety.
The side effects associated with cannabis are dose-dependent, so they can be reduced or avoided by gradual titration and low-maintenance doses. Care should be taken with higher doses of THC (7% or greater), as these have been associated with acute psychosis, increased anxiety, and short-term declines in attention, memory, learning, and psychomotor activity.
What does the future hold for cannabis as a treatment for pain?
The recent global shift towards the legalisation of medical cannabis has been accompanied by a rise in randomised controlled trials (the gold standard in clinical research).
As of July 2020, there were more than 80 clinical trials for pain registered at ClinicalTrials.gov. Both acute pain and chronic pain are under study, with a specific focus on conditions such as multiple sclerosis, diabetes, HIV, spinal cord injury, traumatic brain injury, arthritic conditions, inflammatory bowel disease, glaucoma, cancer, and others.
Some of the cannabis medicines that are under assessment include novel ratios of CBD and THC, with delivery methods that include inhalation, oral and topical gels. A number of these studies are also using active comparison conditions, comparing the efficacy and safety of cannabis to opioids, benzodiazepines, and anti-inflammatory medications.
Multiple studies are also considering cannabis as a treatment for pain in conjunction with significant secondary outcomes such as insomnia, anxiety, mood, and quality of life. As these high-quality research findings are released, expect current knowledge of cannabis as a treatment for pain to become more nuanced and comprehensive.
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