Chronic Pain and Cannabis
Written by Dr Stephanie Davies Dr Max Majedi
Wednesday, 29 November 2017
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Our concern over the rush and push for Medicinal Marijuana (MM) (Inside WA’s Cannabis Story, November is that investors discuss the blue sky potential benefits without discussion of the negatives. As a profession we’ve seen the effects of other industries that ignored or released selective information on potential harms, the tobacco industry for one, Purdue Pharma another.

201712-Davies-Stephanie-Dr Oct15Dr Stephanie DaviesThe aim of pain management is to improve pain and function – to give a patient the pain-reduced freedom to do what they want to do. The reduction in the use of opioids for chronic non-cancer pain is due to the lack of benefit over the short-to-medium term, and the significant harms. It is also because we have many more better pain options than we had 20 years ago. 

MM is outdated for treatment of chronic non-cancer pain (CNCP) and has significant harms, such as inability to drive, to work, reduction of ability to function, and medium-to-long term potential harms to mental health disorders and addiction.  

We now have a wide range of behavioural and low-risk medical options that are cheap, accessible, evidence-based and can be matched to the individual’s pain condition(s). Good physiotherapy, OT, psychology interventions, combined with interventional pain procedures are options for many people with spinal, regional, joint, or widespread pain(s).

More options available

Excitingly, two novel low-risk compounds are available, both of which are emerging as having additional CBD receptor actions without the harms of MM. They have minimal side-effects, are non-addictive, cheap, and available from compounding chemists today. We have used them in our clinical practice since 2015. Specifically, we are talking about PEA and LDN, which are glial modulators (important in neuropathic and plastic pain), and reduce inflammation (important in inflammatory pain).

Palmitoylethanolamide (PEA) is a naturally occurring anandamide in food, it is an endogenous lipid modulator in animals and humans, and has been evaluated since the 1970s as an anti-inflammatory and analgesic drug in more than 30 clinical trials, in a total of ~6000 patients. These include eight clinical trials for nerve entrapment.

In one pivotal, double blind, placebo controlled trial in 636 sciatic pain patients, the number needed to treat (NNT) to reach 50% pain reduction compared to placebo was NNT=1.5 after three weeks of treatment. This emerging evidence is of interest as no drug interactions or troublesome side effects have been described so far.

Low-dose naltrexone (LDN) improves symptoms in fibromyalgia (NNT=5), Crohn's disease, multiple sclerosis,complex regional pain syndrome, and insomnia. LDN works as an anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and are independent from naltrexone's activity on opioid receptors.

These both fit the bill of a cannabinoid-like option (not called cannabis because they aren't as the CEO of AusCann was hoping for). In addition, they do not interfere with driving (patients can't drive for about eight hours (no clear data) after having medical cannabis), don't increase mental health disorders, and don't require state or federal processes.

Benefit:Risk inadequate

201712-Majedi-Payam-Max-Dr-Feb14Dr Max MajediWe have both attended several Faculty of Pain Medicine (FPM) roundtable discussions and in WA with key stakeholders. The overwhelming medical view is that data of the risk-benefit ratio in the use of MM for CNCP is lacking. The gap is not that doctors ‘need to get with the program’; the issue is the cart is before the horse.

A 2015 systematic review (Deshpande A) where five of six randomised controlled studies using smoked or vapourised cannabinoids (non-synthetic) as an adjunct to other agents including opioids for neuropathic pain (the sixth was for MS). The study duration was up to five days and all studies lacked adequate masking of the active treatment (possible reporting bias). The NNT to reach 30% pain reduction compared to placebo was NNT=4 after five days of treatment. All trials excluded individuals with a history of psychotic disorders and previous history of cannabis abuse or dependence.

Each study found statistically significant pain reduction with cannabinoid use. However, physical function did not improve or was not reported. Adverse events included psychosis, psychiatric issues, increased heart rate, impaired learning and memory.

Concern exists about mental health, especially in youth or people with concurrent mental health conditions, which are more common in people attending pain clinics than mental health clinics. A greater proportion of individuals with persistent pain develop mental health clinical syndromes (generalised anxiety disorder, somatisation disorder, and major depressive disorder) and that the prevalence of these disorders was significantly higher (55%) than those in a matched control group (24%). Studies have also reported an increased prevalence of Borderline Personality Disorder in people with persistent pain (30%) compared to those admitted to psychiatric services (20%).

Long-term uncertainties

A recent meta-analysis raised concerns that long-term cannabis use may cause neurotoxicity especially in brain areas enriched with cannabinoid receptors such as the hippocampus.

We agree with Zelda Therapeutics and Little Green Pharma that if MM is to be trialled by patients in Australia for pain, then this should be within targeted research projects. These would then provide data to determine if there is a subset of patients that may benefit after all the lower risk options have been trialled. These trials would need to reflect the proposed use, and not be limited to the short five-day trials that have been done on MM in the past.

The Faculty of Pain Medicine (FPM) has a position statement on the use of cannabinoids in patients with chronic non-cancer pain. http://fpm.anzca.edu.au/documents/pm10-april-2015.pdf . We strongly recommend it be read in full, including the references.

ED: Full references available