More Evidence Needed to Support Medical Cannabis Use for Pain, Say Experts

Following a new systematic review and meta-analysis, the International Association for the Study of Pain (IASP) says it cannot currently endorse the general use of cannabis and cannabinoids for pain relief based on a lack of high-quality evidence.

In its position statement, the association says that it recognizes the medicinal use of cannabis for pain is already permitted in some jurisdictions. But without further research, the IASP itself cannot currently endorse cannabis for pain relief.

IASP review finds good preclinical evidence, but lack of other support

The IASP review and meta-analysis looked at a total of 171 different cannabinoids, cannabis-based medicines, and endocannabinoid system modulators that has been tested for antinociceptive (pain-blocking) properties in mice models of pain.

The findings from these preclinical studies “support the concept of cannabinoid-mediated analgesia” the IASP concluded. Several compounds, the reviewers note, demonstrated consistent efficacy in laboratory tests for models of neuropathic pain and mixed results for inflammatory pain models.

However, the conclusions drawn from the available body of clinical research were less promising. Fifty-seven self-declared systematic reviews that were looked at by the IASP were found to be either of “low” or “critically low” quality.

A new systematic review from the IASP using established quality standards found 36 randomized controlled trials covering over 7200 participants. These trials mainly focused on the use of nabiximols (also known by the trade name Sativex), synthetic THC, or cannabis for pain. All these trials were judged to be of “unclear” or “high” risk of bias, with poor quality data. The taskforce set up by the IASP to study the effectiveness of cannabis for pain reported that it “did not find any moderate- or high-quality evidence” from any clinical trial.

Based on this information, the IASP concluded that current scientific evidence “neither supports or refutes” the use of cannabis for pain, and that, as a result, the IASP cannot endorse its general use.

“While the IASP cannot endorse the general use of cannabinoids for treatment of pain at this time, we do not wish to dismiss the lived experiences of people with pain who have found benefit from their use,” commented Professor Andrew Rice, chair of the IASP’s Presidential Task Force on Cannabis and Cannabinoid Analgesia, in a press release.

“This is not a door closing on the topic, but rather a call for more rigorous and robust research to better understand any potential benefits and harms related to the possible use of medical cannabis, cannabis-based medicines and synthetic cannabinoids for pain relief, and to ensure the safety of patients and the public through regulatory standards and safeguards.”

Potential for harm needs further study

In addition to assessing the current state of research on cannabis for pain, the IASP position statement also commented on concerns over the potential for harm and the current state of the cannabis market.

Specifically, the IASP highlights a lack of high-quality data looking at the long-term effects of using cannabis. While current studies link cannabis use to various non-life-threatening adverse effects such as dizziness or fatigue, the IASP argues that lessons must be learned from the societal opioid epidemic and appropriate research into the long-term effects of any drug should be undertaken.

In the same vein, the IASP is concerned that jurisdictions that already allow for the marketing and use of medicinal cannabis might have done so with “insufficient regard for conventional and well-established regulatory safeguards and standards” for medicines. This is a concern because it means that people medicating with cannabis might be using products that fall short of pharmaceutical standards.

“The IASP statement is important and timely because we are concerned that in certain jurisdictions medical cannabis may have been introduced without reference to the conventional statutory regulatory procedures for approving marketing of medicines,” explained Rice.

“Furthermore, where ‘recreational’ use of cannabis is now permitted, there is a risk that patients could use cannabis for pain relief without the usual safeguard of a medical consultation and monitoring,” he added.

Medical cannabis and pain

The IASP statement concludes that “basic science advances are promising, but these are yet to be fully translated into efficacious and safe medicines.”

It is probably no surprise then that the existing literature on cannabis for pain presents a mixed picture.

A 2020 observational study involving the first 400 New Zealand patients to be prescribed cannabidiol (CBD) found evidence that the cannabinoid could be beneficial to patients reporting non-cancer pain. These patients reported statistically significant improvements to their mobility, ability to complete usual activities, and in feelings of pain, anxiety, and depression. In contrast, a recent systematic review published in the British Medical Journal found cannabinoids to be no different to placebos in tackling cancer-related pain.

“I think there is great interest in cannabinoid medicines from the general public at the moment,” Mike Bennett, a professor of palliative medicine at the University of Leeds and co-author of the BMJ review, told Analytical Cannabis at the time of the study’s publication. “But in cancer pain, using this particular product, we can't see a positive benefit.”

“In terms of the trial design, it may be that there are benefits but they’re not being picked up by the outcome we use, which is pain intensity,” Bennet added. “There may be small effects on pain, but we can’t detect those. And any effects come at the expense of more side effects.”

Speaking to Analytical Cannabis in 2019, cannabis-cancer researcher Dr David Meiri explained how cannabis’ effect on pain might be more complex than can be reasonably captured by the literature. Taking a more holistic approach to treatment and patient experience instead might be more suitable, he believes.

“If you look in [a] very specific and narrow window on pain, you would say it's not good,” he explained. “If you look how I think you should look on cannabis policy – more holistic and doing other things that are related to pain and depression, sleep, anxiety – now you're treating all of them and the patient is much, much better. If you look just to measure a very, very narrow question, then you will fail.”