A review of the evidence on cannabinoids and pain finds that cannabis compounds, when given by injection, generate a small but significant reduction in acute pain.

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There is some evidence that cannabinoids may reduce acute pain, but the quality of the evidence remains questionable.

The new paper, a meta-analysis of existing studies, appears in the specialist journal Cannabis and Cannabinoid Research.

Cannabinoids are a group of substances in the cannabis plant, including tetrahydrocannabinol (THC), which is the psychoactive element, and cannabidiol (CBD), which is widely available as an oil and has purported benefits for anxiety, depression, and a range of other conditions.

Both compounds act to reduce inflammation and pain, and there is good evidence that cannabis can help people who live with chronic pain. For this reason, medical marijuana is available by prescription throughout much of the world.

There is much less evidence, however, of cannabinoids’ potential for treating short-term, or acute, pain, such as that which can follow surgery.

In fact, a review published in 2017 suggests that cannabinoids have “no role” in managing acute pain.

However, the team behind the current research wanted to reassess the available evidence and include more recent investigations into the potential benefits of cannabinoids for postsurgical pain.

The researchers, from McMaster University and the Northern Ontario School of Medicine, both in Canada, where cannabis has been legal since 2018, included only robust clinical trials in their analysis.

They looked at six trials in total, five of which involved cannabinoids taken orally, as in tablet form, and one of which involved intramuscular injections of cannabinoids in the arm.

The team found no difference in pain relief after comparing the effects of oral cannabinoids and placebos.

However, the researchers determined that cannabinoids administered by injection led to a small but significant reduction in acute pain.

They conclude that intramuscular injection is likely to be a more effective approach; the body absorbs cannabinoids taken by mouth more slowly, and they can be broken down by the liver.

Injection into muscle bypasses these effects and leads to faster absorption and higher levels of the compounds in the bloodstream.

In terms of safety, the researchers found that no significant increase in serious side effects was associated with cannabinoids.

Study participants who received these compounds were more likely to experience dizziness and low blood pressure, but those who received placebos instead also reported side effects, including headaches and nausea.

If cannabinoids could be used clinically to treat acute pain — which might otherwise be treated with potent and addictive opioids — this could have significant implications for the opioid crisis in the United States, which claims an estimated 128 lives every day.

Already, studies are showing that states with legalized marijuana have reduced hospitalizations due to opioid dependence by 23% and opioid-related overdoses by 13%.

Researchers involved are particularly hopeful about the capacity of CBD to relieve pain; the compound has anti-inflammatory and analgesic effects without the harmful side effects associated with THC.

The authors of the present review note that researchers are currently using animal models to investigate whether CBD can help treat neuropathic pain — which can affect, for example, people with multiple sclerosis — and pain associated with arthritis.

They write, “Given the promising animal studies and favorable safety profile, further human trials examining the efficacy of CBD for the management of acute pain and inflammation are warranted.”

It is important to note that, although this review represents the most recent and reliable evidence on the subject, it is based on limited data: only one study involving intramuscular administration.

The authors acknowledge that the evidence that cannabinoids can reduce acute pain is of “low quality,” adding:

“Our review highlights the need for further research to investigate the optimal route and composition of cannabinoids in the acute pain setting, including large, high-quality randomized clinical trials to better understand the risks and benefits of cannabinoids in this patient population.”

This echoes a comment from the journal’s editor in chief, Daniele Piomelli, Ph.D.

“The usefulness of cannabis-derived medicines in the treatment of pain, both acute and chronic, is still vigorously debated. The meta-analysis conducted in this study reinforces the need for more rigorous studies to assess whether cannabis might be effective in the treatment of acute pain conditions,” he concludes.