There is a lack of good evidence that any cannabis-derived product works for any chronic neuropathic pain.
Neuropathic pain is pain coming from damaged nerves. It is different from pain messages that are carried along healthy nerves from damaged tissue (for example, a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines to those used for pain from damaged tissue.
Several products based on the cannabis plant have been suggested as treatment for pain, including neuropathic pain. These products include inhaled herbal cannabis, and various sprays or tablets containing active cannabis ingredients obtained from the plant, or made synthetically.
Some people with neuropathic pain claim that cannabis-based products are effective for them, and that is often highlighted in the media.
In November 2017 we searched for clinical trials that used cannabis products to treat conditions with chronic neuropathic pain in adults. We found 16 studies involving 1750 people. Studies lasted 2 to 26 weeks. Studies compared different cannabis-based medicines. Ten studies compared an oromucosal (mouth) spray with a plant-derived combination of tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, and cannabidiol (CBD), an anti-inflammatory ingredient of cannabis, against a fake medication (placebo). Two studies each compared inhaled herbal cannabis and cannabis plant-derived THC with placebo, and one study compared a man-made cannabinoid mimicking the effects of THC (nabilone) with placebo. One study compared nabilone with a pain killer (dihydrocodeine).
Key results and quality of the evidence
We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results.
There was no high-quality evidence.
All cannabis-based medicines pooled together were better than placebo for the outcomes substantial and moderate pain relief and global improvement. All cannabis-based medicines pooled together were better than placebo in reducing pain intensity, sleep problems and psychological distress (very low- to moderate-quality evidence).
There was no difference between all cannabis-based medicines pooled together and placebo in improving health-related quality of life, stopping the medication because it was not effective, and in the frequency of serious side effects (low-quality evidence).
More people reported sleepiness, dizziness and mental problems (e.g. confusion) with all cannabis-based medicines pooled together than with placebo (low-quality evidence). There was moderate-quality evidence that more people dropped out due to side effects with cannabis-based medicines than with placebo.
Herbal cannabis was not different from placebo in reducing pain and the number of people who dropped out due to side effects (very low-quality evidence).
The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.
This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain.
To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults.
In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles.
We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm.
Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient’s global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a ‘Summary of findings’ table.
We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane ‘Risk of bias’ tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.
Cannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).
Cannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).
We found no information about long-term risks in the studies analysed.
We are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence).
Cochrane Bottom line There is a lack of good evidence that any cannabis-derived product works for any chronic neuropathic pain. Background Neuropathic pain is pain coming from
Cannabis for nerve pain studied
Tuesday 31 August 2010
“Smoking cannabis from a pipe can significantly reduce chronic pain in patients with damaged nerves,” reported the BBC. It added that improvements in sleep and anxiety were seen.
This news story is based on a small randomised controlled trial in 23 people, which found that a low dose of inhaled cannabis (lower than that needed to cause euphoria or a “high”) modestly improved reported pain in patients who had neuropathic pain.
This is a well-conducted study, but its small size means that it is not possible to tell whether the results demonstrate a real association between cannabis and pain relief, or if they are due to chance.
More research in larger groups of people over a longer period of time is needed to see if the effects of cannabis for this type of pain can be replicated. In addition, there are health concerns related to the use of smoked cannabis, including mental health problems and lung damage.
It is important to point out that cannabis is a class B drug, which is illegal to possess or supply, and is not licensed in any form for medical use.
Where did the story come from?
The study was carried out by researchers from McGill University, Canada, and was funded by The Canadian Institutes of Health. The study was published in the (peer-reviewed) Canadian Medical Association Journal.
This research was covered well by _The Daily Telegraph and the BBC, though the study did not find any evidence for effects on anxiety or depression, as the Telegraph headline suggests.
What kind of research was this?
This randomised controlled trial investigated whether cannabis can relieve neuropathic pain (neuralgia) – severe pain caused by the abnormal activity of nerve cells. Various events can set off neuropathic pain, including surgery, trauma or shingles.
The researchers say that although there are drug treatments for neuropathic pain, such as anticonvulsants, antidepressants, opioids and local anaesthetics, their effectiveness varies between patients. Some patients are put off taking them because of unpleasant side effects. They say there is anecdotal evidence that cannabis relieves chronic neuropathic pain and improves sleep. The researchers wanted to investigate whether these reported effects could be replicated under controlled experimental conditions.
This type of study design is the most appropriate way of determining whether a drug is effective. However, this was a very small trial in only 23 people, so it is not possible to conclude that the results are due to chance alone.
What did the research involve?
The study recruited people who had experienced neuropathic pain for at least three months as a result of trauma or surgery. The participants ranked their current level of pain on a 10-point scale, and patients reporting pain intensity greater than four were included. Excluded from the study was anyone whose pain was due to cancer, anyone who had heart or lung disease, and those who had any type of substance abuse, a history of psychiatric disorders, or who were pregnant. In total, 23 people were eligible to participate in the study.
The effect of smoking cannabis with the active ingredient tetrahydrocannabinol (THC) was compared to smoking cannabis in which the THC had been removed (the control). Different potencies of THC were also compared to each other. Participants were not told which treatment they were given.
The control cannabis that had the THC removed was provided to the researchers by the US National Institute of Drug Abuse. The cannabis doses were prepared by blending the flowers and leaves of the plant to make three different potencies of the active drug (2.5%, 6.0% and 9.4% of THC).
Cannabis doses were delivered as single smoked inhalations taken through a pipe. The participants were instructed to inhale for five seconds as the cannabis was lit, hold the smoke in their lungs for 10 seconds, then exhale. The patients were observed taking the first dose. They then took subsequent doses at home, three times daily for five days. After 14 days, the participants swapped treatments so that those who had received the cannabis without THC then received cannabis containing the active drug. And those who had received active cannabis then received the placebo or a different dose of cannabis treatment.
In total, participants had four cycles of treatment where they received doses of 0%, 2.5%, 6% and 9.4% THC. Throughout the trial, the participants continued any routine medications that they were taking.
On the first day of each treatment period, the participants were asked about their feelings of pain, and how relaxed, stressed or happy they were. Their heart rate was also measured and a blood sample taken. During the five days of treatment or placebo, the participants were contacted by telephone and asked about their pain, how they were sleeping, their medication, and whether they were having any side effects. A urine sample was taken every day. On the fifth day of each treatment, a blood sample was taken and the participants were asked more questions about their pain, mood and quality of life.
What were the basic results?
The study had screened 113 participants but only 23 were eligible. Out of these, 21 completed all four cycles.
The researchers found that the average pain intensity was significantly lower on 9.4% THC cannabis (score 5.4 out of 10) than on 0% THC cannabis (6.1 out of 10) (p=0.023). However, no other comparisons between the different doses were found to be statistically significant.
Participants using 9.4% THC cannabis reported finding it easier to fall asleep and had better quality of sleep than those taking 0% THC. No differences in mood or quality of life were seen with the different THC potencies.
Of the reported side effects, none were serious or unexpected. The most frequent side effects reported by participants when taking 9.4% THC cannabis were headache, dry eyes, burning sensation, dizziness, numbness and cough. Feeling “high” and euphoric was reported once in the 2.5%, 6% and 9.4% THC cannabis treatment periods.
How did the researchers interpret the results?
The researchers said that the 25mg herbal cannabis with 9.4% THC, administered as a single smoked inhalation three times a day for five days, significantly reduced average pain intensity compared to placebo in adults with chronic post-traumatic or post-surgical neuropathic pain. They also said that there were improvements in measures of sleep quality, but that long-term safety and efficacy studies are needed.
This placebo-controlled trial found that cannabis containing 9.4% THC could reduce neuropathic pain compared to the placebo. However, this was a small trial with only 23 participants, so it is difficult to tell whether these results demonstrate a real association, or if they are due to chance. A much larger trial would be needed for a longer period to assess the long-term outcomes of such a treatment. Additionally, there are health concerns related to the use of smoked cannabis, including mental health problems and lung damage. Further research is needed to assess such potential side effects over the long term.
The researchers say that their study provides a way of looking at the short-term effects of smoked cannabis in a placebo-controlled trial. It is important to point out that cannabis is a class B drug, which is illegal to possess or supply, and is not licensed in any form for medical use.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 30 August 2010
BBC News, 30 August 2010
Links to the science
Ware MA, Wang T, Shapiro S et al.
Canadian Medical Association Journal 2010, Published online ahead of print August 30
“Smoking cannabis from a pipe can significantly reduce chronic pain in patients with damaged nerves,” reported the BBC. It added that improvements in sleep and anxiety were also seen.