Cannabinoids in pain management

Cannabis-based drugs

Prescribing

• only specialists, and they will be expected to get approval from the chair of their hospital's drug and therapeutics committee, or the medical director, on a named patient basis. GPs cannot prescribe

Indications:

• NHS England lists just two:
  • children with rare forms of epilepsy and adults with nausea or vomiting caused by chemotherapy (1)
  • "Very few people in England are likely to get a prescription for medical cannabis," its guidance to patients says
  • rare forms of epilespsy
    • Deb Pal, professor of paediatric epilepsy at the Institute of Psychiatry, Psychology and Neuroscience at King's College London
      • states there is good evidence from clinical trials that drugs based on cannabidiol are effective against two types of severe childhood epilepsy:
        • Dravet syndrome and Lennox-Gastaut syndrome
      • Epidiolex, an oral solution of cannabidiol, has been licensed in the US for these two indications - however at present not licensed for these indications in Europe (3)
  • use in chronic neuropathic pain
    • a Cochrane review states "potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes" (4)
    • a systematic review and meta-analysis concluded that
      • cannabinoids have a role in treating chronic neuropathic pain as evidenced by significant improvements in sleep quality, pain intensity, and patients' global impression of change (PGIC) (7)
    • in comparison to use of opioids for non-cancer related pain (8)
      • cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain
  • nausea and vomiting after chemotherapy
    • a systematic review by Allan et al concluded that "... reasonable evidence that cannabinoids improve nausea and vomiting after chemotherapy. They might improve spasticity (primarily in multiple sclerosis). There is some uncertainty about whether cannabinoids improve pain, but if they do, it is neuropathic pain and the benefit is likely small. Adverse effects are very common, meaning benefits would need to be considerable to warrant trials of therapy." (5)

Licensed cannabis-based drugs:

• nabiximols (sold in the UK as Sativex) has been licensed since 2010 as a treatment for spasticity in multiple sclerosis (3)
  • contains cannabidiol and tetrahydrocannabinol (THC)

NICE (6):

• Chronic pain:
  • do not offer the following to manage chronic pain in adults:
    • nabilone
    • dronabinol THC (delta-9-tetrahydrocannabinol)
    • a combination of cannabidiol (CBD) with THC
• Spasticity:
  • offer a 4-week trial of THC:CBD spray to treat moderate to severe spasticity in adults with multiple sclerosis, if: other pharmacological treatments for spasticity are not effective
  • the company provides THC:CBD spray according to its pay-for-responders scheme
  • after the 4-week trial, continue THC:CBD spray if the person has had at least a 20% reduction in spasticity-related symptoms on a 0 to 10 patient-reported numeric rating scale
  • treatment with THC:CBD spray should be initiated and supervised by a physician with specialist expertise in treating spasticity due to multiple sclerosis, in line with its marketing authorisation
• Severe treatment-resistant epilepsy:
  • Cannabidiol with clobazam is recommended as an option for treating seizures associated with Dravet syndrome in people aged 2 years and older, only if:
    • the frequency of convulsive seizures is checked every 6 months, and
    • cannabidiol is stopped if the frequency has not fallen by at least 30% compared with the 6 months before starting treatment
  • Cannabidiol with clobazam is recommended as an option for treating seizures associated with Lennox-Gastaut syndrome in people aged 2 years and older, only if:
    • the frequency of drop seizures is checked every 6 months,
    • and cannabidiol is stopped if the frequency has not fallen by at least 30% compared with the 6 months before starting treatment

Adverse effects associated with cannabis-based drugs:

• Epidiolex use has reported adverse effects such as sleepiness, sedation, and lethargy; elevated liver enzymes; decreased appetite; diarrhoea; rash; fatigue, malaise, and weakness; insomnia, sleep disorder, and poor quality sleep; and infections
• medication containing THC may have additional risks
  • the Royal College of Physicians lists psychosis, dependency, hallucination, and suicidal thoughts as possible side effects
  • the Royal College of Paediatrics and Child Health warns that THC may affect the developing brain and cause alterations to IQ and mental health
    • however, the long-term adverse effects of cannabis-based drugs as therapeutic agents are unknown because they have not previously been encouraged

References:

1. NHS England. Cannabis-based products for medicinal use [letter]. 31 Oct 2018. https://www.england.nhs.uk/wp-content/uploads/2018/10/letter-guidance-on-cannabis-based-products-for-medicinal-use.pdf.
2. NHS. Medical cannabis (and cannabis oils). https://www.nhs.uk/conditions/medical-cannabis.
3. Hawkes Nigel. Cannabis based drugs: how will they be used in practice? BMJ 2018; 363:4665.
4. Mucke M et al. Cannabis-based medicines for chronic neuropathic pain in adults.Cochrane Database Syst Rev. 2018 Mar 7;3:CD012182. doi: 10.1002/14651858.CD012182.pub2.
5. Allan GM et al. Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms.Can Fam Physician. 2018 Feb;64(2):e78-e94.
6. NICE (November 2019). Cannabis-based medicinal products.
7. McParland AL, Bhatia A, Matelski J, Tian C, Diep C, Clarke H, Kapustin D, Triveda A, Brull R, Singh M. Evaluating the impact of cannabinoids on sleep health and pain in patients with chronic neuropathic pain: a systematic review and meta-analysis of randomized controlled trials. Reg Anesth Pain Med. 2023 Apr;48(4):180-190. doi: 10.1136/rapm-2021-103431. Epub 2022 Dec 5. PMID: 36598058.
8. Jeddi HM, Busse JW, Sadeghirad B, et al. Cannabis for medical use versus opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised clinical trials. BMJ Open 2024;14:e068182.
9. NICE (December 2019). Cannabidiol with clobazam for treating seizures associated with Dravet syndrome.