Is Cannabis Effective in Cancer Pain Management?
Cancer pain is one of the most debilitating symptoms in those with cancer and those who have survived cancer. This type of pain is caused by the cancer itself and/or by various anticancer treatments such as chemotherapy, radiation and surgery. Up to 60% of those receiving anticancer therapy experience cancer pain and in those with advanced cancers, the percentage is even higher – up to 80-90%. At this time, opioids remain the treatment of choice for moderate to severe cancer pain but is there a role for cannabis or cannabinoids? Are they effective and how do they compare to opioids?
To be fair, there is no painkiller out there that works 100% of the time. There is significant individual variation in response to all the analgesics so as expected, cannabis-based medicines can be helpful in some individuals and not in others. Cannabis remains a third-line or adjuvant option for pain in most pain guidelines but that doesn’t mean you cannot experiment and do your own individual therapeutic trial to see if it works. My recommendation is to find a healthcare provider who is knowledgeable in cannabis and have them make sure that it is indeed safe for you to take as there could be drug interactions and other precautions to be aware of. As a pharmacist and medical cannabis educator, I have been helping my patients safely use cannabis and navigate how to dose and titrate it since 2019. And as expected, I have seen some individuals who benefit from it and some who do not.
So why are some healthcare providers against recommending cannabis? It’s not uncommon to find a provider who doesn’t want to have anything to do with cannabis or who says there’s no evidence. Actually, it’s not that we don’t have data or evidence on cannabis-based medicines – in fact, there’s a lot data because it’s a plant-based medicine that’s basically been used for thousands of years. It’s just that we don’t currently have a lot of high quality data and evidence to support its use as a first-line therapy. The gold standard that measures the effectiveness of an intervention or treatment is the Randomized Controlled Trial (RCT) and unfortunately, we don’t have a ton of this form of data. Cannabis being a schedule I drug in the US makes it difficult to conduct large-scale clinical trials and restricts its investigation as a potential medicine. However, RCTs (on a smaller scale) for cannabis in cancer pain have been conducted since at least 1975 and the trials have reported results ranging from moderate improvement to small improvement to inconclusive to no difference between cannabis and placebo. So there’s a lot of data – it’s just not exactly consistent. And perhaps the efficacy of cannabis depends on the type of pain– we don’t know at the moment and there are so many types in cancer - bone pain, soft tissue pain, nerve pain, mixed types of pain, etc. All types of cancer pain were generally included in the clinical trials. What we do know though is that there are a number of trials that did find efficacy. In fact, one study found that 10mg of THC was comparable to about 60mg of codeine in pain relief and produced about the same amount of sedation as 120mg of codeine. For reference, Tylenol No. 3 contains 30mg of codeine per tablet and single entity codeine products start at 15mg per tablet. And in another study in 1975, they found that 15mg THC oil and 20mg THC oil produced more pain relief than placebo.
Generally speaking, cannabis products that worked well for cancer pain in these trials were a high THC product or a ~1:1 THC:CBD product (that is, roughly equivalent THC and CBD in concentration). The 1:1 product was oftentimes an oral spray known as nabiximols - a whole plant cannabis sativa extract known as the prescription drug, Sativex, available in over 25 countries. It is officially indicated for the adjunctive treatment of spasticity in multiple sclerosis and is an oromucosal spray that contains 2.7mg THC and 2.5mg CBD per spray. Since it is a whole plant extract, it contains other minor cannabinoids, terpenes, flavonoids and sterols that may help the CBD and THC work better via an “entourage effect”. There is some postulation that full-spectrum or whole plant cannabis products (that is, those that contain not just CBD and THC, but other cannabinoids, terpenes, etc.) work better than purified CBD and THC because the terpenes in cannabis work synergistically with CBD and THC to produce effects greater than the sum of its contributing parts.
Recall that I said the data wasn’t entirely consistent. Some trials found a benefit and some did not but most trials that found efficacy in cancer pain used a high THC or a ~1:1 THC:CBD product. However, there was one RCT of 177 patients in 2010 that did not find any difference between high THC and placebo but did find an effect that was statistically significant with the ~1:1 product (nabiximols). In this study, the average dose in the 1:1 group was 23.6mg THC and 21.9mg CBD per day (about 8.75 sprays per day) and twice as many patients taking the 1:1 product experienced a 30% reduction in pain compared to placebo. Most of the patients in this trial had mixed types of pain, while others had bone pain, or neuropathic pain.
In 2013, a much smaller RCT of 18 patients with chemotherapy-induced neuropathic pain looked at the efficacy of nabiximols (again, the ~1:1 oromucosal spray) and found it effective in reducing pain significantly in 5 patients. The mean dose used in the treatment arm was 8 sprays per day which is about 21.6mg THC and 20mg CBD while the range used was 3 to 12 sprays a day (8.1mg THC + 7.5mg CBD per day to 32.mg THC + 30mg CBD per day). The study also reported a number-needed-to-treat (NNT) of 5 which means it takes treating 5 patients with nabiximols in order for 1 additional person to experience significant pain reduction. NNT is a number that is often reported in RCTs and in this case, is a useful measure in comparing the analgesic effectiveness across different analgesics. For reference, the NNT in neuropathic pain for tricyclic antidepressants (eg. amitriptyline, nortriptyline, etc.) is 2.1. For opioids, it is 2.6 and for gabapentin, it is 6.4. So a NNT of 5 is not exactly amazing but tells you there could be a role for cannabis in some cases.
One of the potential benefits of using cannabis in cancer pain as an adjunct therapy is that it may reduce the use or dose of opioids. Opioids are associated with a lot of side effects such as constipation, mental clouding, somnolence, respiratory depression, urinary retention, and the risk of developing physical dependence and addiction. Cannabis has side effects as well, which is discussed in the next section, but there’s less and it reduces the chance of dependence and eliminates the risk of fatal overdose compared to opioids. So if there is an adjunct therapy with a better side effect profile that can reduce the use of opioids, why would we not consider it? In an Israeli observational study of 3619 cancer patients offered various combinations of THC and CBD (high THC, 1:1 and high CBD), 36% of patients achieved opioid cessation, 9.9% used less opioids and 51.1% continued to take the same opioid dose after 6 months of cannabis use. At the 6-month follow-up, only 4.6% continued to experience severe pain (compared to 52.6% at baseline) and 69.5% reported a good quality of life (compared to 18.7% at baseline).
Like any other drug, cannabis has the potential for side effects. Not everyone will experience it and it is dose dependent so the higher the dose, the more likely that side effects will occur. In the trial with 177 patients described above that looked at high THC and ~1:1 THC:CBD, 60% of patients experienced mild to moderate side effects and they were mostly somnolence, dizziness and nausea. Common side effects reported in other trials were tiredness, confusion, disorientation, and dry mouth.
My patients generally take their cannabis at night before bed so unless they continue to stay awake for hours after their dose, they generally sleep off their side effects like somnolence, dizziness and disorientation. Dry mouth is the one side effect that probably cannot be slept off and may be experienced in the morning or during the day. Sometimes side effects can be controlled through dosage titration so I always start my patients on a low dose and gradually titrate them (every 3-5 days) as needed so that they tolerate the dose better.
So here are my takeaway points for using cannabis in the management of cancer pain:
find a provider who is knowledgeable in cannabis and have them help you with dosage titration and optimization (in addition to ensuring that it is safe for you to take and that any drug interactions are managed)
select a high THC or ~1:1 THC:CBD product (we know that high CBD is not likely to do anything in cancer pain– clinically, I observe this as well)
based on clinical trials, we know that the average dose that showed efficacy was about 20mg THC and 20mg CBD per day in the form of an oil or oromucosal spray
start with a low dose and titrate slowly to minimize side effects. It is best to start cannabis with once daily dosing at bedtime so that most side effects can be slept off
potentially, cannabis may help to reduce the use of opioids
lastly – there is significant individual variation in analgesic effectiveness across all analgesics so cannabis may work but it also may not work for you