Potluck? Might Cannabis reduce neuropathic pain?

The Journal of Pain’s 4th most downloaded article in 2013 (Wilsey ey al 2013) is a study of vaporised cannabis for the treatment of neuropathic pain.[1]  Thirty-nine patients, with various types of refractory neuropathic pain, participated in a double-blind crossover study, receiving low-dose (1.29%), medium dose (3.53%) or placebo cannabis in each of three 6-hour sessions.  The primary outcome was pain intensity (measured on visual analogue scale).  Data were collected on numerous other outcomes, the most pertinent of which were the psychoactive and neurocognitive side-effects of the treatments.

If you have neuropathic pain, your first concern is probably going to be pain relief.  A 30% reduction in pain intensity was reported by 26% of participants after placebo treatment, by 57% after low-dose cannabis treatment, and by 61% after medium dose cannabis treatment.  Allodynia and heat pain threshold were unaffected.

Your next cry will probably be, “It’s a recreational drug!  Am I going to lose touch with reality?  Will I even know what’s going on around me?”  Participants did report more psychoactive side-effects with cannabis than with placebo, but none of these effects was strong enough to be clinically concerning.  Neurocognitive tests showed diminished function with cannabis – particularly in the domains of learning and memory – but, again, these effects were relatively minor.  As expected, low-dose cannabis was associated with less severe side-effects than medium-dose cannabis, yet still performed well for pain relief.

“Well,” you say, “it certainly does sound promising!”  And the title, “Low-dose vaporized cannabis significantly improves neuropathic pain”, evidently attracted substantial interest.  But within a few months, the Journal of Pain had published a letter from Brett Stacey and Jeffrey Moller that warned readers against getting too excited.[2]  Existing treatments for neuropathic pain are frustratingly inadequate, and the idea of a new one – that actually works – could tempt us to count our chickens before they’ve hatched.

The idea of treating pain with cannabis is not new, but the risks of tar exposure and psychoactive side-effects have previously tempered enthusiasm.  This study appears, on face value, to allay these concerns.  So, is vaporised low-dose cannabis the new solution to neuropathic pain?  I am not convinced.

The participants inhaled cannabis every two hours, but the apparatus used for delivering the vaporised cannabis sounds cumbersome – and possibly expensive.  This calls into question the accessibility of the treatment.  Does the patient have to be isolated every time she needs to inhale her medication?  Could it be carried around and used during a normal day’s routine?  Mini vaporisers are commercially available, but would likely contaminate public spaces.  If vaporised cannabis is, realistically, to be used as a treatment approach, someone will have to come up with a small, portable device that produces the vapour without allowing it to escape between inhalations.

The psychoactive consequences of cannabis inhalation are a longstanding concern, yet this study found minimal negative psychoactive effects of the cannabis treatment.  But hang on: the chickens haven’t yet hatched.  Don’t miss the fact that a criterion for participation in this study was previous exposure to cannabis.  This, the authors state, was “to reduce the risk of adverse psychoactive effects in naïve individuals”.  So the study tells us nothing about the psychoactive effects of cannabis treatment in people who are naïve to it – a problematic omission.  There may also be a substantial selection bias in operation: people who have previously used cannabis but had a negative experience would be less likely to volunteer, so recruitment would be biased towards those who know they respond pleasantly to the drug.  If such a bias was operating, the study is predisposed to shed a favourable light on cannabis – either through placebo mechanisms, or an individual-specific physiological responsiveness to cannabis.

An important point, also raised by Stacey and Moller, is that the authors may have jumped the gun when concluding that this study “establishes low-dose cannabis as having a favourable risk-benefit ratio”.  As far as I can see, the experiment studied the effects of cannabis for a 6-hour period.  Presumably, patients with neuropathic pain would be looking for pain relief for longer than that.  A study of long-term use would be required in order to assess the risks and benefits of long-term cannabis use for neuropathic pain.  Regular users of cannabis are known to develop tolerance to the psychoactive effects, which suggests that they may also develop tolerance to the analgesic effects.

What I’d really like to see next is a large study of long-term (or, at least, medium-term) treatment of neuropathic pain comparing low-dose vaporised cannabis to gabapentin, amitriptyline and placebo, with outcomes of pain, side-effects, function and quality of life.  And a device that makes the public, during-the-day use of vaporised cannabis a realistic option.

Wilsey et al’s study could turn out to be formative: neuropathic pain is a big problem, the treatments we currently have are not good enough, and cannabis may be less risky than we thought.  But only when the long-term use of cannabis has been studied, and the practical problems have been ironed out, will we know whether or not the chickens have actually hatched.

Tory Madden

Tory MaddenTory arrived from South Africa to start her PhD at BiM.  She is a physiotherapist who worked clinically before turning her focus toward research.  She is interested in pretty much anything related to pain and neuroscience, thanks to some particularly inspirational teaching by Romy Parker during her undergraduate training at the University of Cape Town.

Tory is rapidly developing a fondness for Australia’s amazing TimTams, but is rather worried about whether she will survive the Adelaide winter. She loves sports but has been forced to take some time out due to a knee injury. She has used this extra time to try her hand at table tennis, with which she is making moderate progress, and rowing, at which she should not yet be left unsupervised…

References

[1] Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, & Donaghe H (2013). Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain, 14 (2), 136-48 PMID: 23237736

[2] Stacey BR, & Moller JL (2013). Marijuana for pain relief: don’t jump to conclusions. J Pain, 14 (10), 1250-1 PMID: 24090991