Clinical question What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes? Current practice Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly...
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Dosing should be individualised and informed by titration, after starting at the lowest plausible therapeutic dose. For example, daily oral doses range from 2.5 mg to 40 mg for dronabinol, from 0.2 mg to 6 mg/day for nabilone, from 1 to 16 oral sprays for nabiximols (dronabinol/cannabidiol), and from 5 to 20 mg/kg/day for Epidiolex (an oil based extract of cannabis containing 98% CBD). Upper limits of dosages may vary between countries. Topical preparations theoretically require lower doses and stay local, therefore reducing harms associated with ingested forms of cannabis; however, commercial products typically lack pharmacokinetic data establishing their ability to cross the aqueous layer and remain localised.
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The opioid sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.
22 Clinicians may, however, consider medical cannabis as part of an approach to help facilitate opioid tapering among consenting patients. Importantly, forced opioid tapering is ineffective and may cause harm.
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Advertised content of medical cannabis products may not be accurate. One US analysis of 84 products found that 26% contained less CBD than labelled, which could negate any potential clinical effect.
111 Furthermore, with the exception of Epidiolex and Sativex, non-synthetic cannabinoids lack a drug identification number and cannot be prescribed by physicians, only authorised.
The bioavailability of oral preparations of medical cannabis or cannabinoids ranges from 13% to 19% and can take up to four hours to reach peak concentrations.
107 Dronabinol, THC, and CBD are metabolised in the liver, via cytochromes P450 (CYP) 2C9 and CYP3A, and about a third of the molecules and metabolites are eliminated in the urine (remaining metabolites are eliminated in the faeces). Several metabolites of THC are considered psychoactive. The elimination half-life of dronabinol ranges from 25 to 36 hours, and its main metabolite (11-hydroxy-delta-9-tetrahydrocannabinol) is 44-59 hours; the half-life of CBD is 56-61 hours. The effects of medical cannabis or cannabinoids may be enhanced in patients with renal or liver impairment.
Costs and resources
The panel focused on the perspectives of people living with chronic pain rather than those of society or payers when formulating their recommendation. As identified in our review of patient values and preferences, both legal availability of medical cannabis or cannabinoids and costs are likely to influence decision making.
Uncertainties for future research
Key research questions to inform decision makers and future guidelines include:
- Are there systematic differences in treatment effects of medical cannabis or cannabinoids for chronic cancer pain versus chronic non-cancer pain and for nociceptive versus neuropathic versus nociplastic pain?
- Are there systematic differences in treatment effects of different formulations and types of medical cannabis or cannabinoids, including CBD, CBD:THC, THC, and PEA?
- Does medical cannabis or cannabinoids reduce opioid use for chronic pain?
- Are the effects of medical cannabis or cannabinoids consistent among adolescents and young adults with chronic pain?
- What is the optimal dose, formulation, and method of administration of medical cannabis or cannabinoids for chronic pain?
- What are the benefits and harms of inhaled medical cannabis?
- What are the benefits and harms of prolonged medical cannabis or cannabinoid use?