Worldwide, 20% of the population lives with chronic pain, in some areas one in four people suffer from it. Chronic pain often co-occurs with depression, insomnia, post-traumatic stress disorder (PTSD), anxiety and substance use disorders such as opioids or alcohol. Chronic pain is also the most common indication for which medical cannabis has been recently prescribed in countries that allow this type of treatment.
The use of cannabis for pain has been documented as far back as 5,000 years ago. Early Chinese physicians used it to treat pain associated with giving birth, rheumatism and even constipation. Over the past 30 years or so, countless studies have been conducted on the effectiveness of cannabis preparations in treating and managing chronic pain.
For example, a study from 2017 looked into the perspective of chronic pain patients and their views on cannabinoid treatment. The research included 984 subjects, among them patients with neuropathic pain, back pain, arthritis, post-surgical pain, headache and abdominal pain. The authors noted that two-thirds of patients reported subjective pain relief as the main benefit of cannabis therapy. The second most commonly reported benefit was improved sleep – a fact corelating also with many other studies.
Opioids and medical cannabis: Friends or foes?
Another earlier study from 2016 reported that patients with chronic pain who used medical cannabis managed to reduce their opioid use by up to whooping 64%. These patients subsequently talked about fewer side effects and a significantly improved quality of life. There was also a 2021 study from the United States, which was analysing the impact of the existence of ‘cannabis dispensaries’ (places where patients buy medical cannabis upon prescription from their doctor) on adverse effects due to opioid use. The researchers found there was a 17% reduction in the number of deaths related to opioid use. The presence of medical cannabis dispensaries also had a positive impact on the number of patients recovering from opioid dependence at official treatment centers.
A different study from Florida in 2018 highlighted the effectiveness of medical cannabis in treating chronic non-cancer pain, neuropathic pain, medication-induced headaches and allodynia. However, it turned out that cannabis did not prove to have the same efficacy as non-opioid analgesics in the treatment of acute pain. Nor was medical cannabis more effective than placebo in treating visceral pain in this particular study. Moreover, it provided only a minimal analgesic effect in cancer pain.
Multinational pain studies on dosage
Researchers from various parts of the world conducted several randomised controlled trials investigating the dosage and administration of medical cannabis. In one interesting study, experts from nine different countries developed three different treatment protocols for the dosing and administration of cannabis in the treatment of patients suffering from chronic pain. In the standard protocol, the initial dose was set to be 5 mg of CBD twice daily (given the safety profile of this cannabinoid). At the point where a dose of 40 milligrams of CBD per day does not provide sufficient pain relief, an initial dose of 2.5 milligrams of THC is next in line.
According to the consensus of the study authors, THC can then be slowly titrated up to 2.5 milligrams every two to seven days until the maximum dose of 40 milligrams per day is reached. If even this maximum dosage does not provide sufficient pain relief, the physicians and authors of this research recommend consulting an experienced medical cannabis healthcare provider.
For the record, the conservative protocol looked like this: The starting dose is 5 milligrams of CBD once or twice a day up to a maximum dose of 40 milligrams per day, followed by a starting dose of 1 milligram of THC if the maximum dose of CBD did not result in sufficient pain relief. The THC dose could then be titrated by 1 milligram every seven days until the maximum dose of 40 milligrams per day was reached. Finally, the “fast” protocol included a balanced ratio of CBD and THC from the beginning, starting with 2.5 to 5 milligrams of each cannabinoid once or twice daily. The dose could be titrated up by 2.5 to 5 milligrams every two to three days once or twice a day until a maximum dose of 40 milligrams of THC was reached (no upper limit was considered for CBD).
The two main cannabinoids THC and CBD are mainly metabolised in the liver by the cytochrome P450 system. Few clinical studies are available on the effect of cannabinoids on this enzyme system, but in vitro studies suggest that THC inhibits CYP3A4, CYP3A5, CYP2C9 and CYP2C19, while CBD inhibits CYP2C19, CYP3A4 and CYP3A5. Due to the weak inhibitory effect of these cannabinoids, higher concentrations than those used in clinical practice would be probably needed for a clinical inhibitory effect.
Nonetheless, the co-administration of cannabinoids with medications which have the so-called narrow therapeutic window and are also metabolised by these enzymes, such as direct-acting oral anticoagulants metabolised via CYP3A4 and clopidogrel requiring conversion to an active metabolite via CYP2C19, may be a cause for concern. For example, significantly elevated levels of the antiepileptic clobazam and its metabolite n-desmethylclobazam have been observed when very high doses of CBD were administered simultaneously, probably due to co-metabolism via CYP2C19 and CYP3A4.
Lack of relevant data
In conclusion, many of the studies analysing the potential benefits of medical cannabis in the treatment of chronic pain are unfortunately based on small groups of participants. That said, as more and more countries legalise medical cannabis, there will surely be more relevant studies with larger samples in the future. Although preliminary data support the use of medical cannabis in the treatment of chronic pain, it is clear that more extensive research is needed before generally valid conclusions can be drawn.
*The above text was written by an independent contributor and does not reflect the official views of Motagon or the guidelines for the use of Motagon products.