Therapeutic areas in focus
Sapphire Clinics Medical cannabis – The inhaled answer to cancer and noncancer pain?
Pharmafile speaks to
Simon Erridge from Sapphire Clinics illuminates the clinical potential of medical cannabis in treating chronic pain, and offers a reflection on how the pain management sphere has changed in the last decade
Pharmafile: How has the clinical landscape for pain management changed over the past 10 years?
I think there’s been a real emphasis to move away from many of the habits of prescribing we’ve seen in the earlier part of the last 10 years. That period saw a sharp increase in the number of patients who were prescribed opiate medications. Over the past few years, most recently with some of the NICE guidance around primary chronic pain, we’ve seen a move away from using opiates in the setting of chronic pain, and more of a focus on other medications, such as antidepressants. Even with gabapentinoids, which the medical community has been using with increasing frequency – there’s been a little bit of hesitancy around guideline makers recommending those, due to potential harms and the lack of evidence of benefit in chronic pain.
The main shift has been towards firstly working with patients to acknowledge that with the medications and other treatments that we use in chronic pain, things may get better, but there’s no certainty or guarantee that whatever we use will resolve that chronic pain. Psychological therapies such as CBT (cognitive behavioural therapy), in combination with physiotherapy, are all first line measures to try and get on top of those aspects of chronic pain.
Are there any areas of unmet need in pain management, or what changes are needed in this field?
I think the real unmet need is with respect to pharmacological management. For lots of patients that I’ve seen and have referred on to physiotherapists, often I’ll get a report back that will say ‘this patient is in too much pain to even engage in physical therapy’. Although we recognise the benefits of having a medication that enables people to engage in physiotherapy and psychological therapies, that is not a one stop fix, and takes time. Giving them options, so that they can carry on their day-to-day activities, so that they can sleep well, they can go to work, all these are really important. The real unmet need is identifying pharmacological management methods that can be used.
We have seen some work on more interventional treatments around chronic pain, and that really depends on the individual condition, and the sites, such as joint injections. We need more research into the more interventional measures.
Taking something like chronic pain, which in and of itself is a really heterogenous group of conditions, and affects a wide variety of people, what would probably benefit all patients the most is more identification of novel therapeutics for them to use.
What is the clinical potential of medical cannabis within palliative care?
We’ve seen a real increase in the amount of evidence surrounding medical cannabis and chronic non-cancer pain, but also in chronic pain related to cancer, whether that’s the cancer in and of itself, or the side effects of cancer treatment.
There was a recent, rapid recommendation based off a systematic review and metaanalysis published in the BMJ last year, which suggested that patients who have failed first line therapeutics for chronic pain could trial non-inhaled medical cannabis agents. That’s either oils, capsules, or lozenges, as they recognise that there was a small but significant benefit in respect to pain specific outcomes, but also looking at things such as sleep and general health-related quality of life.
In addition, at Sapphire Medical Clinics, we have generated evidence through the UK Medical Cannabis Registry. We published some data this year, looking at patients prescribed medical cannabis, including oils, and dried flower. In those prescribed for chronic pain, including those with cancer pain and non-cancer pain, we saw that there were statistically significant improvements in their scores for interference with the pain in dayto-day quality of life, and also with respect to anxiety symptoms, and their self-reported sleep quality.
There’s an increasing body of evidence to support the use of medical cannabis. The
makes recommendations towards utilising medical cannabis for those patients where first line therapies haven’t been effective.
In other aspects of palliative care, such as psychological components of end-of-life care, whether that’s anxiety and low mood, there’s very limited evidence directly from the palliative care population. Looking at anxiety disorders as a whole, there’s really promising preclinical evidence, and now increasing levels of clinical evidence around its utilisation in anxiety disorders. There have only been a few randomised control trials, and they’ve mainly looked at social anxiety disorder, rather than generalised anxiety disorder, or PTSD, or anxiety related to health conditions. They’ve been largely positive, and again, we’ve looked at patients prescribed medical cannabis for anxiety in the UK through the UK Medical Cannabis Registry. That select cohort of patients in the UK who were prescribed medical cannabis for that indication, we’ve seen significant improvements in their anxiety, general health related quality-of-life, and sleep.
What are the differences between the use of medical cannabis in palliative care versus for chronic pain management?
The main difference in how it’s used is largely in response to whatever symptoms you’re trying to treat. In fact, the way medical cannabis is prescribed for cancer and non-cancer pain largely is very similar. You would ideally start out with a higher dose of cannabidiol, and maybe either have no THC, or a very low dose of THC. As people start to tolerate the effects of both of those medications, you’d slowly titrate them up, until they would be receiving the maximum amount of benefits, with the lowest risk of them developing any adverse events from the medications.
With respect to some other symptoms around palliative care, for instance – if they’re having difficulty sleeping, or with anxiety and they need something that’s more shortacting, in order to manage symptoms quickly, rather than slowly titrating up with an oil, they might be better off taking their medication in the form of dried flower.
That dried flower is vaporised to a lower temperature than it would be for people who would smoke it, and we specifically counsel patients not to smoke medical cannabis because of the associated carcinogenic risk.
However, when it’s taken at lower temperatures through inhalation, the onset of action is much quicker, and then drops off much quicker as well. Normally, these would contain a slightly higher dose of THC compared to if they were titrated up solely through oil, so these patients get a quick relief of their symptoms, and then the effects of the medication quickly taper off.
What impact do you anticipate medical cannabis having in five years’ time?
At the moment, there are quite a few barriers to medical cannabis in the UK. One is knowledge – the general public really are quite unaware as to some of the legislation changes, even though we’re two and a half years down the line from when some legislation changes came into effect.
A lot of patients say to us, they wouldn’t be willing to even disclose that they’re taking medical cannabis even though whatever they’re doing is completely legal
We did a YouGov survey last year which showed that only approximately 50% of people that were surveyed were aware of the legislation changes. That’s obviously a big barrier for those people who it may otherwise be appropriate treatment for, with these people not understanding that medical cannabis is even a possibility for them. To some degree, that problem exists amongst clinicians as well. It’s to a lesser extent; lots of clinicians are aware of its legal status – but for many, when they were coming through medical school and their training, medical cannabis wasn’t on the curriculum. Because of this, they have less of an understanding of what it is, what it does, how to prescribe it effectively and safely. Therefore, they’re more reticent to either recommend or prescribe it themselves.
Knowledge and education is a big barrier. Another major barrier is stigma. A lot of patients say to us, they wouldn’t be willing to even disclose that they’re taking medical cannabis, even though whatever they’re doing is completely legal. They find it really difficult to share that, whether that be with members of the criminal justice system, police courts, the other health care providers, or family and friends. Some people really find that quite difficult, because of the stigma that’s still associated between recreational cannabis use and those being prescribed it for medicinal reasons.
Finally, cost is a barrier: it’s not available on the NHS. Apart from a very small number of patients – I believe only three to date – have managed to get medical cannabis prescription through the NHS. But how do I think it’s going to change from that point? Things will slowly change in terms of education, and this will help address stigma. The key to unlocking all of this is more research, as we do more research, and more specifically, do randomised control trials that compare medical cannabis against first line therapies for some of the conditions in which it’s being prescribed. We can more clearly find out where this sits in our treatment arsenal for any specific condition, because at the moment, you need to have tried first-line licenced therapies before you can even be considered to start medical cannabis treatments. Once we have that extra data, we can perhaps say that actually for chronic pain, it might be a first line treatment, or that for some of the other conditions that it’s been prescribed for currently, there are better things out there, and we probably shouldn’t be using it. I think that’s how things are going to change: we’ll see medical cannabis being more widely used in individual conditions, hopefully within the NHS if they can demonstrate cost effectiveness as well as through health economic analyses. But alongside this, in some conditions, we may in fact see medical cannabis’s use being far less.
What makes cannabis useful for pain management?
When you look at the cannabis plant, and how it gets distilled down to what causes its effects, you have what’s thought to be over 400 potential active pharmaceutical ingredients in the plants. The two main ones that we understand are THC and CBD. This is what the prescription is made up of. But there are over 100 potential cannabinoids, and then many more terpenes and flavonoids, which are all purported to have individual effects on many receptors across the body. We understand that those three compounds are actually quite low potency, in that they don’t elicit really strong effects in receptors across the body.
With respect to chronic pain, we have evidence that the major compounds in cannabis-based products dampen down the response at peripheral pain receptors. Chronic pain is really complex, and a lot of the experience and severity of pain can also be modulated by your own central nervous system. For instance, we all understand that if you’re laughing, you’re really enjoying yourself, and you don’t feel the effects of chronic pain as much as you would do if you’re stuck inside on a grey rainy day. We understand that the cannabinoid receptors in the brain have lots of particular roles in terms of modulating anxiety, and other emotions, and this has a really clear role in heightening or dampening down the effects of your interpretation of chronic pain. If we look at those people who have high levels of anxiety with their chronic pain, those people can have an even greater response than those where anxiety doesn’t do much of a role in their experience of chronic pain. That’s one of the main points: you have so many compounds, and so many different receptors that can potentially be acted upon.
If you can find the right formulation for the right patient, then there’s a multitude of possibilities, but obviously it goes without saying that medical cannabis may not be the right thing for them at all.
See the report ‘Cannabis-based products for medicinal use (CBPMs) in humans’, published November 2020
is a medical doctor who graduated from Imperial College London in 2018, also completing an intercalated BSc in Surgery and Anaesthesia. He is the Head of Research and Access at Sapphire Medical Clinics, an award-winning medical cannabis clinic in the UK. Simon leads on the development and analysis of the UK Medical Cannabis Registry, the largest bespoke clinical registry for patients treated with medical cannabis in Europe. Since 2019, he and colleagues have published outcomes in chronic pain, anxiety, and palliative care in several prestigious journals.
Pain management and pharmaceutical compounding
Treatment of pain is often at the forefront of both healthcare professional and patient’s minds. How might compunding medication aid in treatment?
Pain is an unpleasant bodily sensation that causes mild-to-severe physical and emotional distress, usually deriving from an injury or illness. Pain can be classed as one of the most common reasons patients seek healthcare worldwide, and is a significant contributor to healthcare costs. It is difficult to define the epidemiology of pain, because of the subjective nature of the symptoms, and the lack of consensus for specific diagnosis and conditions. It is, therefore, hard to talk about evidence for the true incidence of most pain conditions.
Pain can vary from acute, intermittent, or chronic, depending on its duration and severity. Acute pain is generally a shorter duration, lasting up to six months, and is resolved when the bodily distress is healed by itself. Examples of acute pain can range from a broken arm, cosmetic procedures, or healing from a surgery. Pain that comes and goes is called intermittent pain, and an example of this is toothache. On the other hand, chronic pain lasts longer than six months and can vary from patient to patient. Some chronic pains can be a result of nerve damage pain, lower back pain, or even from cancer treatment. Due to the long-lasting duration, chronic pain produces anxiety and emotional distress, interferes with functional capacity, and hinders the ability to participate in family and social events. It is hard to diagnose chronic pain due to its complexity and, in some cases, it is misdiagnosed.
Therefore, the optimal management of pain, either acute, intermittent, or chronic, is imperative for a patient’s wellbeing.
A good pain management treatment plan will provide the patient with the pain relief they need, while also offering them the ability to regain their range of motion and mobility as quickly as possible without injury.
Current pain management treatments
Current pain management treatments primarily aim to reduce or eliminate pain with minimal side effects through pharmacological and non-pharmacological therapy.
Pharmacological therapy is done by administering a range of analgesic drugs, and can be divided into:
Non-opioid analgesics include paracetamol and non-steroidal anti-inflammatory drugs. Opioid analgesics can be divided into those used for mild-to-moderate pain (such as codeine phosphate), and those used for moderate-to-severe pain (such as morphine or oxycodone hydrochloride). Adjuvant analgesics include drugs such as antidepressants, antiepileptics, benzodiazepines and other muscle relaxants, bone-modulating drugs, corticosteroids, topical capsaicin, lidocaine, and rubefacients.
Non-pharmacological therapy is the management of pain without medications. This method utilises ways to alter thoughts and focus concentration to better manage and reduce pain. Methods of nonpharmacological pain therapy include neurostimulation, hypnosis, comfort therapy, education and psychological interventions, and physical therapies.
Pharmaceutical compounding can offer better results
Throughout the years of pain management research, we can see that the art of compounding medication and personalising dosage forms for an individual patient can potentially become an optimal solution for patients. Pharmaceutical compounding is the creation and dispensing of tailormade medications, and can be used as a pharmacological approach to benefit patients suffering with pain. Compounding allows the pharmacist to work with the patient and the prescriber, to customise pain medication to meet the patient’s specific needs.
Pharmaceutical compounding offers a much wider choice of pain-relieving ingredients than mass produced, single-dose medicines, and the ability to target pain in a multitude of ways. A prescriber working closely with a pharmacist can prescribe a range of active ingredients, each of which may target a specific mechanism in the body. As a result, compounding usually results in smaller concentrations of each medication, and more overall targeted pain management.
While single-ingredient analgesics are preferred to allow for independent titration of each drug, fixed-dose compounded analgesics may be considered for those with stable chronic pain. Sometimes analgesic preparations that contain multiple analgesics, such as aspirin or paracetamol with an opioid component, reduce the scope for effective titration of the individual components in the management of pain of varying intensity.
In some instances, chronic pain sufferers are likely to be placed on a variety of medications to help address the symptoms associated with their condition. With compounding, multiple medications can be combined into a single dose of a specially prepared compound either as a capsule or topical treatment, providing greater convenience for the patient, and therefore improving overall compliance.
Many patients experience stomach irritation or other unpleasant side effects from taking pain medication. Some patients have difficulty taking the medication in its commercially available form, and this is where compounding provides patients access to personalised medication, which can lead to less displeasing side effects and a more palatable formulation.
Compounding also allows patients to choose how the medicine is delivered and absorbed into their body. This is particularly useful if you have difficulty taking or swallowing capsules and need an alternative solution, such as topical preparations, customflavoured troches that dissolve buccally or sublingually, sublingual drops, rapid dissolve sublingual tablets, nasal spray, or a suppository. Such dosage forms may bypass the gastrointestinal tract, providing optimal results with less gastrointestinal irritation, reducing pain, and overall removing another source of aggravation.
Patients, particularly those who suffer from allergies, can also benefit from compounded pain medications. As well as active ingredients, medications can also contain inactive ingredients such as binders, fillers, and dyes. Some people are allergic to these ingredients, which can make a medical treatment potentially fatal. Commonly used allergens include peanut oil derivatives, gelatine, corn, dairy, wheat, coconut, and potatoes. If there are allergens in a prescription medication, a compounding pharmacist can reformulate the drug, removing the non-essential ingredients to which a patient is allergic.
Lastly, a considerable number of patients with long-term pain management treatment may have the issue of their drug becoming discontinued. This often occurs not because the drug is unsafe or ineffective, but simply because it is no longer cost-effective for large pharma companies to manufacture. Compounding pharmacies can recreate the exact formulation of the original drug, and deliver it in the precise dose required by the prescriber for a truly personalised pain management option.
Compounded pain medication
Compounded analgesics can be created by compounding pharmacies and customised to patients’ specifications, to help develop an effective pain management treatment plan. The compounded formulations can include ingredients such as amantadine, amitriptyline, benzocaine, baclofen, clonidine, diclofenac, lidocaine, ketoprofen, and tetracaine, to name a few. These can be formulated to deliver a concentrated analgesic at the site of application. Low-dose and/or multi-drug formulations can be prescribed to reach multiple pain pathways optimising and targeting pain relief for patients.
Either combined or alone, active pain medications can be compounded into a topical cream, gel, or ointment, which can offer tailored, effective pain management, whilst also providing the opportunity to reduce adverse side effects, increase efficacy, reduce opioid use, and improve patient compliance.
Furthermore, expert compounding pharmacists can compound low-dose naltrexone primarily used to help reduce pain and inflammation, in any strength ranging from 0.5mg to 6mg in different formulations. Capsules tend to be the preferred formulation; however, other formulations can be compounded such as buccal lozenges, topical creams, and sublingual drops (depending on patient preference with swallowing difficulties or allergies/intolerances).
Regardless of advanced research and scientific development, many patients are still taking pain medication, which may not provide optimal results. Compounding pain medication can help reduce these cases and create a unique medication specific for the individual. Each compounded analgesic medication is patient specific, and the ingredients can also be altered for dietary requirements such as lactose or glucose intolerance, or allergies to dyes found in the commercial drugs. Compounding opens a new avenue for prescribers who in the past were not able to prescribe medication due to the various reasons discussed above. Since traditional compounding practice might be the only viable option to meet individualised patient needs, more healthcare professionals should be encouraged to publish case reports and participate in small or large investigational studies to further the data we can gather on compounded pain medications. Having all experiences gathered and shared may benefit the growing, yet important, practice of compounding personalising the treatment of pain.
Henschke N et al, The epidemiology and economic consequences of pain, Mayo Clinic Proceedings, 90(1): pp39–47, 2015.
Katz N, Proceedings from the Roundtable on “The Role of Coxibs in Successful Pain Management”, The Impact of Pain Management on Quality of Life, Journal of Pain and Symptom Management, 24, 2002.
Pak SC et al, Nonpharmacological interventions for pain management in paramedicine and the emergency setting: A review of the literature, Evidence-based Complementary and Alternative Medicine, 2015.
www.researchgate.net/ publication/322862247_Pain_Systematic_Review_of_Pharmacy_Compounding_of_ Pain_Medication
is Operations and Quality Assurance Pharmacist at Specialist Pharmacy, a compounding pharmacy, producing custommade medications across a wide range of treatment areas such as bioidentical hormones, pain management, dermatology, and haircare.