What is Chemotherapy-Induced Peripheral Neuropathy?
Chemotherapy-induced peripheral neuropathy (CIPN) is nerve damage caused by some chemotherapy drugs, as part of cancer treatment. It is one of the most common side effects of cancer treatment. Up to 85% of people having chemotherapy may experience some form of CIPN.
CIPN tends to affect the nerves in the hands and feet first, on both sides of the body. Common symptoms include:
- Numbness
- Tingling or “pins and needles” (also called paraesthesia)
- Increased sensitivity to cold
- Burning or shooting pain
- In more severe cases, weakness or problems with balance, digestion, or bladder control
For many people, symptoms improve after chemotherapy ends. But for around 1 in 3 people, the symptoms continue for a year or more. In some cancer survivors, nerve symptoms can last for many years.
Why does CIPN matter for cancer treatment?
The chemotherapy drugs most often linked with CIPN are some of the most effective treatments available for common cancers, including breast, bowel, ovarian, and lung cancer. When CIPN becomes severe, some people need a lower dose of chemotherapy. In some cases, treatment has to stop early.
This means that managing CIPN well is not only important for comfort and quality of life. It can also affect how well someone can complete their cancer treatment.
How is CIPN usually treated?
There is no single treatment that works well for everyone with CIPN. Standard pharmacological options that doctors may consider include certain antidepressants and certain anti-seizure medicines that are also used for nerve pain.
Of these, only one (duloxetine) has shown a clear benefit in large clinical trials, and even then, it does not help everyone.
Because current treatments are limited, researchers are looking at other possible options. Cannabinoids — the active compounds found in the cannabis plant — are one of the areas being studied.
A recent systematic review, published in the Journal of Pain & Palliative Care Pharmacotherapy, analysed the results of existing clinical trials to assess the potential of cannabinoids for chemotherapy-induced peripheral neuropathy.
Cannabinoids for Chemotherapy-Induced Peripheral Neuropathy
The body has its own natural system called the endocannabinoid system. This system is involved in how we experience pain and inflammation. Cannabinoids found in the cannabis plant, including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), can interact with this system in different ways.
In laboratory studies, cannabinoids appear to influence pain signals and reduce inflammation in the nervous system. This has led researchers to ask whether they might be useful for chronic pain conditions, including CIPN.
It is important to be clear, though, that laboratory and animal studies do not always translate into a benefit for patients. That is why randomised controlled trials in people are so important.
What did the new systematic review look at?
The new systematic review brings a focus on randomised controlled trials of cannabis-based medicinal products in adults with CIPN.
The researchers searched three large medical databases and clinical trial registers. They found 1,115 records, of which only three completed randomised trials met the strict inclusion criteria. A further three trials are ongoing.
Across the three completed trials, 68 adults with CIPN took part. The trials tested three different types of cannabinoid product:
- An oral capsule containing CBD and a smaller amount of THC, taken daily for 8 weeks
- A mouth spray containing balanced amounts of THC and CBD, used over a 6-week period
- A topical CBD cream applied to affected areas twice daily for 2 weeks
All three trials compared the cannabinoid product with a placebo. A placebo looks, tastes, or feels like the active treatment but contains no active medicine. This allows researchers to see whether any benefit is from the cannabinoid itself.
What did the trials find about pain?
The most important question for patients is usually whether a treatment reduces pain. Across the three trials, none of the cannabinoid products produced a statistically significant reduction in pain compared with placebo.
In more detail:
- In the mouth spray trial, average pain scores improved slightly over time. However, the improvement with the active spray was not significantly greater than with placebo. A smaller group within the trial, around 1 in 3 participants, did experience a clinically meaningful reduction in pain while using the spray. This may suggest that some people respond better than others, but the numbers were too small to draw firm conclusions.
- In the oral capsule trial, pain scores improved over the 8-week study. Again, there was no significant difference between the active capsule and placebo.
- In the topical cream trial, sensory symptoms improved slightly, but improvements were similar in both the cream and placebo groups.
What did the trials find about quality of life and function?
The results for day-to-day functioning and quality of life were mixed:
- In the mouth spray trial, physical functioning scores were actually slightly higher in the placebo group than in the active treatment group.
- In the oral capsule trial, sleep quality scores were worse in the cannabinoid group. Some measures of nerve symptoms and well-being also favoured the placebo group.
- In the topical cream trial, some short-term improvements were reported — for example, with everyday tasks like writing, dressing, and household chores. However, these improvements also occurred in the placebo group, and there was no overall difference between the two.
About half of the people who used the cream said they would recommend it. Around the same proportion of people using the placebo cream said the same.
How well were the cannabinoid products tolerated?
Across all three trials, cannabinoid products were generally well tolerated. No serious side effects were reported, and no one stopped taking part because of side effects from the active treatment.
The most common side effects reported included:
- Tiredness or daytime sleepiness
- Dizziness
- Nausea
- Dry mouth
In the topical cream trial, no side effects were reported in the active treatment group. One person in the placebo group developed skin irritation.
It is worth remembering that these are small studies. With small numbers of participants, less common or longer-term side effects may not be detected.
What about real-world observational evidence?
Randomised controlled trials are considered the most reliable way to test whether a treatment works. However, they are not the only source of information.
Observational studies, including data from the UK Medical Cannabis Registry, record what happens when patients use medical cannabis in everyday clinical practice. Some of this observational data has suggested possible improvements in chronic pain symptoms for some patients. However, observational studies cannot prove cause and effect. Patients in observational studies are not randomly allocated to a treatment, and there is no placebo group for comparison. This means we cannot tell whether any improvement is due to the treatment itself, the natural course of the condition, or other factors.
For this reason, observational evidence and randomised trial evidence should be considered together, not as alternatives.
Important limitations to note
The findings of this systematic review must be read with caution. Several important limitations apply:
- Very small sample sizes. Only 68 people took part across all three trials combined.
- Pilot studies. All three trials were early-phase or pilot studies, designed mainly to test whether a larger trial would be feasible. They do not to give a definitive answer on whether cannabinoids work for CIPN.
- Different products, different doses. The trials tested very different products, at different doses, by different routes (capsule, spray, cream). This makes it difficult to combine or compare the results.
- Different ways of measuring pain. Each trial used different pain and quality-of-life scales, which made a combined statistical analysis (meta-analysis) impossible.
- Short follow-up. None of the trials followed participants for long enough to assess long-term benefit or delayed side effects.
- Highly selected patients. People in these trials may not represent the wider population living with CIPN.
What could these findings mean for the future?
This review found no strong evidence from randomised trials that the cannabinoid products tested help reduce pain, improve quality of life, or improve function in people with CIPN, compared with placebo.
However, this does not necessarily mean that cannabinoids have no role to play. The trials were small, the products differed, and the follow-up was short. Importantly, none of the trials tested formulations with higher amounts of THC, which some researchers believe may be more relevant for nerve pain than CBD alone.
The authors of the review also note that future trials should consider whether cannabinoids might be useful alongside chemotherapy, to try to prevent CIPN developing in the first place, rather than only to treat established symptoms.
Several larger ongoing trials are expected to report over the next few years. These should provide a clearer picture.
Speak to a specialist
If you are living with chemotherapy-induced peripheral neuropathy and your current treatments are not providing enough relief, it is important to speak to a healthcare professional. Treatment options should always be considered carefully on an individual basis, taking your medical history and other treatments into account.
If you would like to find out whether a specialist consultation may be appropriate for you, you can complete our online eligibility check here.
