This article is about the therapeutic potential of cannabinoids for pain.
Treatment of chronic pain is the number one main reason why people in the United States are interested in the therapeutic potential of cannabinoids. As such, there has been an increasing number of clinical trials to assess how cannabinoids might help fight chronic pain.
In addition, a number of researchers have reviewed and summarized prior research conducted on cannabinoids and pain and have concluded that there is ample evidence to suggest that cannabinoids for pain are effective.
We will discuss the following topics:
Many scientific reviews have concluded that evidence for the efficacy of medical cannabinoids in fighting pain is “moderate” and “substantial”. As a matter of fact, the National Academies of Science, Engineering and Medicine (NASEM) came to the official conclusion that there is overwhelming evidence that cannabis is an effective therapeutic option for chronic pain in adults.
This conclusion, however, is mostly based on studies among people with neuropathic pain or patients with cancer-related pain. NASEM also concluded that scientists should conduct more research into different types of pain, since treatment conditions might be very different depending on the type of chronic pain.
Other scientists have also agreed that one cannot generalize the use of medical marijuana and cannabinoids for all pain conditions. Therefore, doctors should be careful about prescribing to different types of pain.
Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system (meaning: part of the nervous system that monitors the surface and the inside of the body). Most pain studies have focused on this type of pain.
In the majority of these scientific studies, patients reported moderate to large decreases in their pain levels. A small number of studies, though, found only little or no benefit for pain of cannabinoids.
While those studies that found a benefit of pain reduction, also found some side effects, such as dizziness, drowsiness, and confusion. The reason might be that these studies evaluated Sativex, which is a combination of THC and CBD. As such, little is known about using only CBD oil for pain or using other cannabis-based medicines or cannabinoids.
Latest research-informed guidelines in Canada and Europe suggest that only those patients use cannabis-based therapies who are resistant to standard pain medications, and only as a third-line therapy (meaning: two treatments have already failed).
Watch this 3:45 minute video by Transdermal Therapeutics, Inc.: “Neuropathic Pain”
Pain in MS might occur because of MS-related neuropathic pain, or because of painful muscle cramps. Using cannabinoids for MS-related pain is also a very frequently researched pain therapeutic area.
A systematic review of the scientific literature identified 32 studies using cannabinoids for pain. Of these, 10 found moderate to high quality randomized controlled trials (meaning: neither the patients nor the doctors knew who was getting the medication or placebo). These studies concluded that either THC alone or THC in combination with CBD was effective in controlling pain or painful muscle cramps in people with MS.
Other studies, however, found that cannabinoids were helpful in pain control only for MS related neuropathic pain, but not for MS-related musculoskeletal pain. Unfortunately, people who took cannabinoids, were more likely to experience adverse side effects than those who took placebo.
Visceral pain is a type of pain that is felt inside the body, such as in the heart, lungs, and organs of the abdomen and pelvis. This type of pain is associated with gallstones and a number of gastrointestinal conditions, such as Crohn’s disease, ulcerative colitis, and inflammatory bowel disease.
People with visceral pain are more likely to use medical cannabinoids. There is, however, very little research that would provide evidence of using cannabinoids or CBD for visceral pain. As such, no hard conclusion exists.
Pain conditions other than the ones described above include fibromyalgia, rheumatoid arthritis, and back and neck pain. There have been, however, not enough studies that investigated the effect of cannabinoids, such as CBD oil for pain for these conditions.
In addition, the sample size of these studies was also too small, meaning that the studies were not powerful enough to detect differences between placebo and control, and conclude that the results were not due to chance but due to the therapeutic effect of the cannabinoids.
Despite this, they suggest that there might be a benefit for people with other pain conditions from using cannabinoids to reduce their pain. Unfortunately, to our knowledge no controlled clinical trial has examined the effect of cannabinoids on migraine-related pain.
Watch this 3:21 minute video by Alila Medical Media: “Physiology of Pain, Animation”
A higher percentage of people who used cannabinoids for pain than those who used placebo reported adverse side effects. Strangely, while 81% of people who reported taking cannabinoids reported side effects, this was also very high: 66% (!) among those who were taking placebo.
The side effects were: dizziness, drowsiness, confusion, and depressive thoughts. However, it appears that the adverse side effects are more common among those that are heavy cannabis users, especially of products with very high THC content.
One limitation of these studies is that they did not differentiate between patients with past or present history of recreational (or other) cannabis use and those who had never used any whole cannabis or cannabis-based products.
One review study found that over half of clinical trials involved cannabis medicine, as opposed to medical cannabis (the whole plant, or THC or CBD extract) – 59 vs 42 studies.
As it is well known, there are over 100 natural cannabinoids and other compounds in the cannabis plant, and their respective components vary significantly. As such, it is very difficult to establish the most effective combination, type, and dose.
Therefore, it is not surprising that both European and North American (Canadian and US) guidelines would recommend the use of approved medications before the use of non-medicine medical cannabis and its products.
One main problem with research studies in the field of cannabis medicines is that the gold standard of scientific proof is randomized controlled clinical trials (RCT).
The first problem with RCTs is that it is very difficult to conduct RCTs with medications that are not single-ingredient (meaning: plant-based).
In addition, to also control for other factors, it is very typical that RCTs exclude patients with complex comorbidities (meaning: they have several serious health conditions as opposed to just one condition of interest) and people who have a substance abuse disorder. In a way this is biased discrimination, since a lot of people with chronic non-cancer pain belong to these categories.
As such, it is exactly those people that would benefit most from clinical trials that are excluded from clinical trials because of the nature of design of these trials.
Several studies have shown that people with chronic pain are more likely to have psychiatric comorbidities (meaning: in addition to their pain, they also have anxiety, depression, and other mental health issues). Furthermore, they are more likely to have a history of substance abuse, especially heavy cannabis use.
To better understand the medical use of cannabis, cannabinoids, and cannabis-based products, people with complex comorbidities should also be regularly involved in clinical trials – and currently they are not.
Another problem with clinical trials is that they usually last for only a short time (8-12 weeks). Since chronic pain is a long-term disability, studies with much longer time frames would be needed.
This would be especially necessary because the body will get used to cannabinoids after some time, and therefore a dosage adjustment might be necessary. This, however, is not standard protocol in RTCs. As such, it is suspected that this might be the reason why longer-term clinical studies are less likely than shorter-term studies to find a beneficial effect of cannabis-based medications and cannabinoids for pain.
Moreover, a little-mentioned but nevertheless important aspect is that studies assessing the effect of cannabinoids for pain involve relatively few patients. What this means is that the fewer people the less likely it is to find a strong effect of the medications.
Watch this 24:42 minute video by Michigan Medicine: “The Use of Cannabinoids to Treat Pain”
One study assessing the burden of different types of pain found that the most common types of pain were these, in the following order:
Still, most research has assessed the role of cannabinoids for neuropathic pain, and there is also a relatively large body of studies assessing fibromyalgia and visceral pain.
This leaves a big gap in knowledge and also underserved populations of those people that make up the largest proportion of pain sufferers. It is doubtful whether knowledge gained from a study assessing the effect of cannabinoids for one pain can be transferred to the management of another type of pain (e.g. visceral pain vs migraines).
There are also other factors that might vary among pain patients, including:
Therefore, studies assessing the effect of cannabinoids for pain should also evaluate the effect on other comorbidities of pain patients.
It is very difficult to draw conclusions about the effect of “cannabinoids” (in general terms) and medical marijuana, because of the diversity of these two. Stepping one further, these are also big differences in:
Moreover, some study participants might use recreational cannabis while also using cannabinoids for pain, which make the evaluation of these studies very difficult.
Scientists need to consider that the studies aimed at the assessment of cannabinoids and medical cannabis will most definitely involve participants/patients who are not homogenous. As such, studies need to assess real-world situations with real-world people and real-world cannabinoids and cannabis products.
Knowing the benefits of cannabinoids for pain is very important given the pain-medication driven prescription opioid epidemic in the United States and Canada. Preliminary evidence suggests that the use of cannabinoids for pain reduces reliance on strong opioid medications.
Therefore, using cannabinoids for pain has the potential to reduce opioid overdoses and curb the North American opioid epidemic. This public health potential should also increase interest in the medicinal potential of cannabinoids.
Campbell G, Stockings E, Nielsen S. Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. Eur Arch Psychiatry Clin Neurosci. 2019 Feb;269(1):135-144.