Key messages
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Due to a lack of robust evidence, the benefits and harms of cannabis-based medicines are unclear.
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Larger, well-designed studies including people with serious internal diseases (e.g. heart, kidney) and mental disorders are needed to give better estimates of the benefits and harms of cannabis-based medicines.
Introduction to the review topic
What is neuropathic pain?
Neuropathic pain is nerve pain coming from malfunctions of or damage to the nervous system (brain, spinal cord, peripheral nerves). It is different from pain messages that are carried along healthy nerves from damaged tissue (for example, a fall, cut, or arthritic knee).
How is the condition treated?
Neuropathic pain is treated with different types of medicines. Only a minority of people with neuropathic pain experience sufficient pain relief with the medications available.
Several products based on the cannabis plant have been suggested as treatments for neuropathic pain. These products include inhaled herbal cannabis and various medications (sprays, tablets, creams, transdermal patch (a medicated patch stuck to the skin)) containing active cannabis ingredients obtained from the plant, or made synthetically.
Cannabis-based products may contain: mainly tetrahydrocannabinol (THC), one main component of the cannabis flower; mainly cannabidiol (CBD), another main component of the cannabis flower; or a balanced ratio of THC and CBD.
Some people with neuropathic pain claim that cannabis-based products are effective for them. These claims are often highlighted in the media.
What did we want to find out?
We wanted to find out:
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which components of the cannabis flower (if any) help reduce neuropathic pain;
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if cannabis-based medicines cause any unwanted or harmful effects.
What did we do?
We searched for studies that compared different types of cannabis-based medicines (products including mainly THC or CBD and products including a balanced ratio of THC and CBD) against an inactive, fake medication, known as a 'placebo'.
We compared and summarised their results, and rated our confidence in the evidence, based on factors such as study methods and sizes. We analysed three comparisons:
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THC-dominant medicines versus placebo;
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THC/CBD-balanced medicines versus placebo;
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CBD-dominant medicines versus placebo.
What did we find?
We found 21 studies that involved 2187 people with different types of neuropathic pain. The studies were conducted in Asia, Europe, and North America. The smallest study had 18 participants; the largest, 339 participants. Participants' average age ranged from 34 to 70 years. The proportion of women ranged from 0% to 90%. Studies lasted between two and 26 weeks. Pharmaceutical companies funded 14 (or two-thirds) of the studies.
Main results
THC-dominant medicines versus placebo
It is unclear if medicines with mainly THC make any difference to the number of people who:
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experience pain relief of at least 30% or at least 50%;
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rate their condition to be much or very much improved;
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stop the medication due to unwanted effects;
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experience serious unwanted or harmful effects;
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experience unwanted psychological effects (e.g. confusion).
THC-dominant medicines may slightly increase the number of unwanted effects of the nervous system (e.g. dizziness) compared to placebo.
THC/CBD-balanced medicines versus placebo
It is unclear if medicines with a balanced THC/CBD ratio make any difference to the number of people who experience:
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pain relief of at least 50%;
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serious unwanted or harmful effects;
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unwanted effects of the nervous system (e.g. dizziness); and
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unwanted psychological effects (e.g. confusion).
They may increase the number of people who rate their condition to be much or very much improved, experience pain relief of at least 30%, and stop the medication due to unwanted effects.
CBD-dominant medicines versus placebo
It is unclear if medicines with mainly CBD make any difference to the number of people who experience pain relief of at least 50%.
We do not know whether CBD-dominant medicines increase or decrease the number of people who:
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rate their condition to be much or very much improved;
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stop the medication due to unwanted effects;
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experience serious unwanted or harmful effects;
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experience pain relief of at least 30%;
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experience unwanted psychological or nervous system-related effects.
This is because the evidence is limited, and the results vary between studies.
What are the limitations of the evidence?
Our confidence in the evidence is low to very low, and the results of further research could differ from the results of this review. Four main factors reduced our confidence in the evidence. Some studies did not clearly report how they were conducted. The results for many outcomes differed between studies. The results were also often not precise enough to draw firm conclusions. People with serious internal diseases (e.g. of the heart or liver) were excluded from the studies.
How current is the evidence?
The evidence is current to 29 January 2025.
Read the full abstract
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.
Objectives
To assess the benefits and harms of cannabis-based medicines (herbal, plant-based, synthetic) compared to placebo or conventional drugs for chronic neuropathic pain conditions in adults.
Search strategy
We searched CENTRAL, MEDLINE, Embase, and three trial registries, together with reference checking. The latest search date was 29 January 2025.
Selection criteria
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.
Data collection and analysis
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.
Main results
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.
Primary outcomes
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).
Secondary outcomes
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.
Subgroup analyses
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).
Authors' conclusions
There is no clear evidence for an effect of THC-dominant medicines on pain relief of 50% or greater, PGIC ratings of 'much' or 'very much' improved, withdrawals due to adverse events, and serious adverse events (very low-certainty evidence).
There is no clear evidence for an effect of THC/CBD-balanced medicines on pain relief of 50% or greater and serious adverse events (very low-certainty evidence). They may increase PGIC ratings of 'much' or 'very much' improved, and withdrawals due to adverse events (low-certainty evidence).
There is no clear evidence for an effect of CBD-dominant medicines on pain relief of 50% or greater (very low-certainty evidence). They may increase or decrease PGIC ratings of 'much' or 'very much' improved, serious adverse events, and withdrawals due to adverse events (low-certainty evidence).
Funding
No funding.
Registration
DOI 2018 review: 10.1002/14651858.CD012182.pub2
