Cannabis questions… so many questions!


Recently I wrote a summary of my readings around cannabis for pain. It’s a hot topic in New Zealand because we’re holding a referendum on cannabis law reform next year, and as expected, all the lobby groups are out in force! My interest is sparked because so many of the people I work with as patients also use cannabis – and the evidence from RCTs is pretty poor. And YET as a recent study colleagues and I carried out with people who have spinal cord injury and neuropathic pain, cannabis is something that holds appeal, and interestingly, seems to provide some useful effects.

The study we conducted (see it here: https://rdcu.be/bTuup) was a qualitative investigation of people with spinal cord injury who used and found cannabis helpful.

We found that people mainly trialled “conventional” pain relief such as gabapentin, pregabalin, nortriptyline, amitriptyline, and a range of opioids before they started testing cannabis and derivatives. The side effects and poor effect on pain of these pharmaceuticals have been well-documented so I wasn’t at all surprised to hear our participants describe feeling “foggy”, “unable to think”, and limited effect on their pain. This is common because neuropathic pain is such an extraordinary problem – there’s no single mechanism involved, there’s a cascade of effects, many of them in the brain and that means drugs effective on on those mechanisms are also likely to have side effects on cognitive alertness.

Our participants (and remember that cannabis is currently illegal in New Zealand but widely available in the hidden green market) researched their options carefully. They tried various forms of cannabis, often erroneously believing that CBD-heavy forms are (a) easy to identify from phenotype and (b) have an effect on pain. This isn’t the case – it’s the THC-CBD combination that appears to have greatest effect, with the THC being the heavy lifter when it comes to pain reduction.

Not only did our participants try a range of cannabis plants, they also tried various ways to use the product. Vaping, smoking, oil capsules, canna-chocolate, canna-cookies, chopped up in a salad, rubbed on in an ointment – virtually every route possible!

Importantly, every one of our participants denied wanting to feel stoned or high. In fact, they said that was the opposite of their intention – after all, if they wanted altered consciousness they all had access to prescribed medications that could do the trick! No, our participants wanted to do what we all want: take part in their own lives on their own terms. They wanted to participate in family life, do the shopping, play with their kids, just to function.

So, did it work? Well here’s where things get analytically tricky. Yes, almost all participants said cannabis acted quickly, alleviated their pain and gave them good sleep. BUT they also said their pain was altered, changed – they could more easily distance themselves from their pain. So was reduced pain intensity the critical effect, or was it more about feeling differently towards the pain? One participant described being able to “get in the zone” to meditate more easily. And from my perspective, being able to sleep better may itself provide important benefits on pain reduction (Kukushin & Poluektov, 2019).

So my question is whether pain intensity is the right metric in studies examining cannabis for pain relief? RCTs show very small effect sizes of cannabis/THC+CBD on pain intensity, and the research quality is pretty dismal (Campbell, Stockings & Neilsen, 2019).

If cannabis doesn’t reduce pain terribly much, then why are people so passionate about having it as an option? And why do they say it helps? This, my friends, is the real question I think we need to be answering.

Our study showed that participants reported doing more. And isn’t the reason for prescribing analgesia precisely so that people have less pain – and can do more? Our study also hinted at something else important: people using cannabis chose when, where and how they used this drug. To me this is something rarely discussed in pharmaceutical research. CHOICE allows people to make their own decisions. Making a decision for oneself is an important concept in New Zealand – autonomy, self efficacy, self determination. For people from whom so many freedoms have been lost (independent mobility, self cares, cooking, financial independence) being able to choose how to use a drug that alters pain even just a little is an important point.

When digging more deeply into the experiences our participants had when taking cannabis, I was struck by some intriguing points. Most acknowledged that while pain changed, it didn’t disappear. The effect was rapid when the product was vaped, or smoked. Dose didn’t escalate. There was a ritual aspect to using it – the same routine every day. There weren’t high expectations that it would help initially, but they grew quickly once participants tried it. All of which leads me to wonder at the influence of the meaning response (especially when people favoured what they thought were CBD varieties, when CBD isn’t as effective on pain as it is on anxiety).

Some additional points: many of our participants had to navigate a green, underground market. One with which they were unfamiliar and often uncomfortable with. Supply was erratic and fraught with concern about things like traveling with cannabis and cannabinoid products, the fear of discovery, the need to encounter people who are working on the wrong side of the NZ law. Supplies may, or may not, be pure or contain what the consumer wants. Many of our participants had never tried cannabis before their spinal cord injury. Information, accurate information, especially from health professionals, was scarce – and yet many medical practitioners were giving at least tacit approval (in an information vacuum). Our participants said they didn’t rely on what they were told by health professionals: they’d rather believe the grower, the naturopath, their friends, the internet.

All of these things should give health professionals, and law-makers, some food for thought. An underground market means no regulation. No regulation means cannabis is off topic for health educators. Absence of quality information means risks as well as benefits are unavailable. Lack of trust emerges when those who are usually respected for their opinions cannot, or will not, provide clear direction. And our medical practitioners may have trained in the days when popular belief was that cannabis is a ‘gateway’ drug to harder, more dangerous ones. At the very least, the attitudes towards people who use cannabis recreationally has infused our society such that to call someone a “stoner” is equivalent to calling them a “loser”.

For what it’s worth, I do not currently support medical prescribing of cannabis the plant. I think doctors need to know the effects, side effects, interactions, indication, doses, and contraindications of a drug before they put their signature on the line. After all, their responsibility is “first do no harm”. Yes I know cannabis is thought to be a safe drug – but there are adverse effects, the active components do interact with other drugs, and when it’s unknown how much to take, or the best route for administration, then I think it’s unfair to place that burden on a medical practitioner. Does this mean I think cannabis should remain illegal? Not at all! The current legal situation is absolutely doing harm. Regulation, information and maybe allowing people to make their own informed decisions about cannabis might be a better option. After all, alcohol is an analgesic – but we don’t march down to our doctors asking for a prescription for gin and tonic, now do we? We don’t need to because alcohol with all its harms is legal.

Where do we go from here? I think there’s merit in at least two questions being explored. (1) What is the effect of cannabis on pain – not on intensity, but on the experience of pain? Does cannabis help people achieve a meditation state? Does cannabis help via reduced anxiety? Does cannabis help via improved sleep? and (2) How does cannabis use influence participation? Is it through being able to choose when, where, and how cannabis is used? Is it indirectly through reduced anxiety?

And of course, if much of the effect is via a meaning response, what does this tell us about how we can harness our own endogenous opioid and cannabinoid systems? Can we do it without needing to use agents like cannabis?

Campbell, G., Stockings, E., & Nielsen, S. (2019). Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. European archives of psychiatry and clinical neuroscience, 269(1), 135-144.

Kukushkin, M. L., & Poluektov, M. G. (2019). Current Views on Chronic Pain and Its Relationship to the State of Sleep. Neuroscience and Behavioral Physiology, 49(1), 13-19. doi: 10.1007/s11055-018-0684-3

8 comments

  1. “Indian hemp produces a peculiar kind of intoxication, attended with exhilaration of the spirits and hallucinations, said to be generally of a pleasing kind. They are followed by narcotic effects, sleep and stupor.”

    “In its anodyne and soporific actions it resembles opium, but its aftereffects are considered less unpleasant; it does not produce constipation or loss of appetite.”

    Reference: Bentley’s Series on Medicinal Plants, 1880.

    1. And then in 1925 the second Opium Conference in Geneva Mohammed El Guindy, the delegate from Egypt secured the inclusion of Indian Hemp with his unsubstantiated claim that “Hashish was at least as harmful as opium, if not more so.”
      In the UN Convention on Drugs cannabis was placed in same category as morphine, heroin, and cocaine
      Schedule IV – “particularly liable to abuse and to produce ill effects, and such liability is not offset by substantial therapeutic advantages”
      – The same category as some synthetic opioids and more restrictive than coca and opium…
      Meanwhile alcohol is readily available, but regulated.

      1. Bronnie, what are the likely implications for formal pain management services if and when cannabinoids become readily available and legally acceptable? Has this issue been discussed in New Zealand?

  2. Lots of open discussion, with a position statement from the Australasian Faculty of Pain Medicine indicating that currently cannabinoid medications are not frontline because of limited evidence, and prescribing “the plant” is not supported. Prescribing commercial preparations (eg Sativex) is limited by cost – it’s not funded by Medsafe and ACC will fund only if it’s the last resort AND is effective.

    Patients already acknowledge using cannabis, and there is some cannabis testing at some tertiary pain management facilities, but to my knowledge this doesn’t mean patients will be prescribed any differently than if they were not positive for cannabis.

    I’ve participated in a public forum of University of Otago researchers discussing cannabis law reform – we have some highly respected researchers who are informing the public debate.
    My questions are more around whether the current situation is protecting public safety (I don’t believe prohibition works for anything much), and whether public funding should be used to pay for prescribed treatments of dubious quality/effect (but then again, people are being funded for platelet rich plasma, extracorporeal shockwave treatment, MBBs and RFs, so why am I worried about cannabis-based medications?!).

    I’m also curious about the effects our participants reported – can this be a meaning response? Or are we failing to measure important aspects of pain experience when we use VAS pain intensity as a measure? What would happen if we looked at pain interference instead, or participation, or quality of life?
    And finally, I’m intrigued at the popular notion of pain relief from CBD oil when this has little effect on pain but does have other effects, including anti-inflammatory and anti-anxiety.

  3. Tough situation on legalization. We have it here, in Canada. I’ve treated patients with severe burns from cannabis hyperemesis. (https://globalnews.ca/news/5689712/cannabinoid-hyperemesis-legal-weed/). They get burnt in the hot showers when they seek for relief of the pain and hyperemesis.
    Many also state legalization did not work out as planned in Canada (https://www.google.ca/amp/s/globalnews.ca/news/5770642/marijuana-legalization-illegal-purchasing/amp/)
    No easy answers, except we do not yet have enough robust and high quality research, which we would demand if this was a ‘regular’ drug. If we don’t know the real risks, how can we make an informed choice about taking it?

  4. Excellent post. I’m grateful for the analysis of the qualitative study. And especially for the questions you identified: what is the effect of cannabis on the experience of pain? On daily life functioning? On anxiety? And how does meaning affect the experience? And how can clinicians advise their patients, when the substances are underground and inadequately tested, and they have no training?

    Because of the urgency of the pain crisis, and the potential imminence of regulatory changes, let’s hope more studies can address these BPS questions, not just usual comparisons to pain rating scales.

    Thank you for encouraging deeper thinking.

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