An international team of researchers compared three cannabinoid therapies with six non-cannabis-based medicines. The drugs were assessed according to their risk-benefit ratio for the treatment of chronic nerve pain in adults. The result: although cannabinoids are inferior to the drugs amitriptyline, duloxetine and gabapentin in terms of pain relief, cannabis-based drugs improve quality of life more – and with a better side effect profile. If patients want to improve their quality of life, cannabis can be a good therapy option.
Compared to other medicines such as antidepressants, painkillers and antiepileptics, cannabis-based medicines have the best benefit-risk ratio: THC/CBD-balanced cannabis medicines achieved the most optimal result, followed by CBD-dominant and THC-dominant products. This was the result of a multicriteria decision analysis (MCDA) conducted in 2020.
Decision-making conference with pain clinics, neurologists, psychiatrists, scientists and patients
The drug treatment of chronic pain is a major challenge. Due to increasing scientific evidence and clinical experience, cannabinoids are becoming more and more important in pain therapy.
A multi-professional panel of experts gathered to develop the Multi-Criteria Decision Analysis (MCDA): pain clinics in England, Denmark, Israel and Germany, neurologists and psychiatrists as well as scientific experts took part. Cannabis patients also participated. A smaller group started work on the MCDA on 9 December 2019 and compiled a list of drug therapies for chronic nerve pain. The team compiled favourable and unfavourable side effects for the drugs. The positive effects on pain and quality of life were weighed against 15 negative effects.
In total, three cannabis-based medicines (THC-dominant, CBD-dominant and THC/CBD-balanced) were compared with nine non-cannabinoid medicines: the antidepressants amitriptyline and duloxetine, the anti-epileptic drug gabapentin, the opioid painkillers methadone, oxycodone, morphine and fentanyl, and the non-opioid painkiller ibuprofen.
Criteria for assessing the benefits and risks of medicines
The group set an arbitrary scale from 0 to 100 for each criterion: the best option for each criterion is given 100 points and the least preferable option is given 0 points, from which a total score was calculated. Higher scores mean a better risk-benefit ratio: favourable effects such as pain relief are stronger and if side effects occur, they are less dangerous. However, the scores are to be understood in relative terms. The non-opioid painkiller ibuprofen was given 0 points, which means that the drug has the weakest pain-relieving effect compared to the other drugs. 100 points for duloxetine, gabapentin and amitriptyline mean that these three agents provide the best pain relief.
Cannabinoids have better risk-benefit ratio than other painkillers
Finally, in January 2020, the full expert panel met and came to the following conclusion: Oral cannabis-based medicines are an important option for the treatment of chronic (lasting more than 3 months) neuropathic pain. Compared to other types of pain, medicinal cannabis currently has the best evidence for neuropathic pain. According to this, cannabis medications have the best benefit-risk ratio and the opiate-based painkillers morphine and fentanyl the least favourable.
The analysis showed that THC-dominant and THC/CBD-dominant cannabis medicines are both more effective and safer compared to other commonly prescribed medicines. Thus, no dangerous overdoses from the sole use of medicinal cannabis have been described so far. All 12 medicinal therapies and 17 criteria were examined in combination. Amitriptyline, duloxetine and gabapentin were found to be the most effective in terms of pain relief.
However, the best increase in quality of life was achieved with tetrahydrocannabinol (THC) alone or in combination with the non-psychotropic cannabidiol (CBD).
Even though cannabinoids were less analgesic than other medications, opiate-based analgesics were best saved by THC-dominant and THC/CBD-balanced cannabis medications.
Overall assessment of the risk-benefit ratio of the drug therapies studied:
Pain-relieving effect of tetrahydrocannabinol (THC)
THC exerts its analgesic effect by binding to cannabinoid-1 receptors (CB1 receptors), which are widely distributed in the central nervous system. Two clinical studies investigated, among other things, the influence of cannabinoids on the quality of life of patients with chronic nerve pain. A double-blind study published in 2012 showed that nabilone, a synthetic THC derivative, effectively relieved neuropathic pain in peripheral diabetic neuropathy. Sleep and overall quality of life also improved. In contrast, another study published in 2010 with 23 participants showed no significant improvement in quality of life by smoking THC-free or different doses of THC-containing cannabis flowers. However, the use of cannabis flowers with the highest THC content improved sleep.
No substitute for clinical trials
The results show that chronic pain is difficult to treat. Although a multi-criteria decision analysis cannot replace clinical trials, it enables the exchange of clinical experience and thus provides prescribers and patients with a guide to pain management with cannabinoids. Further studies are needed to improve the evidence base for cannabinoids in the treatment of chronic neuropathic pain. In addition, the systematic recording of clinical experience with cannabinoids is also important.
Nutt DJ, Phillips LD, Barnes MP, et al. A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products [published online ahead of print, 2021 Mar 17]. Cannabis Cannabinoid Res. 2021;10.1089/can.2020.0129. doi:10.1089/can.2020.0129