An overview of the emerging role of medical cannabis in modern healthcare

For this article, I have split the content into two parts. In the first part, I discuss medical cannabis and the recent legislative change that allows certain named medical cannabis products to be prescribed by specialist doctors for
specific conditions.

In the second part, I discuss cannabidiol (CBD) that has been sold online and in retail stores (including pharmacies) over the past few years and recent moves to regulate the sale of CBD products.

Brief history of cannabis

Earliest evidence from archaeological work in Japan suggests that hemp/cannabis was grown and cultivated as far back as 10,000 years ago, laying weight to the theory that it was one of the earliest cultivated crop plants.

The plant has been used throughout millennia in the production of food, paper, clothes, footwear and rope, among myriad other uses. Whilst there is little evidence from that period of its use as a psychoactive substance, there is considerable mention in writings of its use as a “mind-altering” substance in ceremonial rites and traditions
going back 3,000 years.

Then primarily concentrated in the Middle East, cannabis found its way into Europe with the various colonisations/invasions going back to Napoleonic times. In fact, Napoleon, recognising the adverse effect cannabis had on soldiers ,was perhaps the first to prohibit and punish its psychoactive use. It was also around this time that the beginnings of investigations of the other efficacious properties of the effects of cannabis took shape.

Obviously, today, we are well aware of cannabis in its many guises and associations, cultural and otherwise. Similar to the majority of countries in the world, Ireland, under the Misuse of Drugs Act 1977-2017, continues to class cannabis as an illegal drug. In this regard, it remains the most commonly-used illegal drug in the country, with regular surveys on prevalence and usage rates showing figures of 25 per cent-plus among adults over 15.

Napoleon, recognising

the adverse effect

cannabis had on soldiers,

was perhaps the first

to prohibit and punish

its psychoactive use

With the negative connotations that prohibited drug use presents to society in terms of crime, healthcare cost, societal and familial breakdown, it seems slightly ambiguous to be discussing the potential health benefits of cannabis-derived products in Ireland.

With the growth in the numbers of countries globally re-examining their position on cannabis and its derivatives, allied to a seismic growth of media and information flow on the subject over recent years, public perceptions are changing.

Figures from the last 20 years show that whilst there is still not huge support for legalising cannabis altogether (around 30 per cent in favour), the numbers in support of permitting medical use in adults are now considerably higher (91 per cent) in the same survey group. 

The cannabis plant itself contains 113 compounds (phytocannabinoids) called cannabinoids, all of which can be extracted and isolated. The largest of these is cannabidiol (CBD), accounting for up to 40 per cent of the extracted materials from a single plant and was first identified in 1940. Another notable phytocannabinoid is tetrahydrocannabinol (THC); this is the compound within cannabis responsible for the associated psychoactive high that people experience when using the drug.

Products or substances that contain THC are classed as ‘controlled drugs’ subject to the Misuse of Drugs Act 1977-2017. The difference between CBD and CBD-derived products is that they do not contain THC and as such, do not fall under the remit of the Act.

We’ll look at two aspects of the use of CBD — firstly, for medical use, and then at the CBD products available to buy as a standalone or contained within an increasing number of foods, beverages, cosmetics, etc.

1.Cannibis for medical use

As a starting point, November 2016. A this time there was increasing usage and discussion-based evidence both in Ireland and throughout the developed world about the medical benefits of cannabis. Much of this information was garnered from rising medical opinion and mostly anecdotal evidence garnered from recreational users of cannabis. In light of this increased attention, the then Minister for Health, Simon Harris, wrote to the HPRA requesting them to investigate Ireland’s current policy on the medical use of cannabis.

Specifically, the HPRA was asked to advise across a number of areas, including:
Recent developments in medical cannabis use, products that had been authorised in other countries, and a wider view on emerging clinical research on new indications and efficacy.

An overview of the different regulatory frameworks in countries that permit medical use.

Draft suggested legislative changes that would allow medical use in Ireland.

The HPRA convened a working group of 10, consisting of stakeholders from both the clinical and patient representative side, to assist in developing a complete 360o response to the Minister’s request.

The final 83-page report offers an extremely detailed response covering the medical use of cannabis and the potential for use in Ireland.

In terms of conclusions, the report considered two particular disorders:

Spasticity associated with multiple sclerosis.

Nausea and vomiting in the context of chemotherapy.

The HPRA concluded there was sufficient evidence to support the use of cannabinoids in the treatment of these two conditions where other treatments have failed. In the case of spasticity, Nabiximols (Sativex), a spray which contains both THC and CBD, was already authorised in Ireland for this purpose.

Epilepsy. The HPRA’s view for epilepsy was that whilst there was not sufficient evidence to support use, there existed an unmet medical need regarding severe, intractable, treatment-resistant epilepsy and that the use of cannabinoids might prove beneficial.

 Chronic pain.
 Anxiety.
 An overview of 14 other conditions.

The view here was that there was not sufficient evidence to warrant the use of cannabinoids to treat these conditions. In regard to chronic pain, the feeling was that there was no unmet need and there were already large numbers of medications available to relieve this condition.

In a general sense, the report concluded that while the group had significant input from other groups, countries, regulatory bodies, etc, throughout, they felt final recommendations were hampered by a fundamental lack of clinically-proven scientific fact regarding the safe use of cannabis and its derivatives for medical purposes. Concern over long-term patient safety was also a factor, again, due to lack of evidence based experience.

Its ultimate recommendation was to accept that there was potential for medical cannabis use. To achieve more informed outcomes to form the basis of policy, the report recommended that a five-year pilot programme should be started to enable particular patients with the defined groups be prescribed cannabis and cannabinoids by their doctor. The recommendations laid out the full scope of the pilot programme and the various measures to be ascertained during its duration.

Medical cannabis legislation

Following presentation to the Minister in 2017, the go-ahead was given to source the products required to get started. Finding and agreeing supply took some time, however in July 2019, the Medical Cannabis Access Programme legislation was signed into law. In relation to the ‘controlled drugs’ aspect, a change in legislation was enacted so that products to be used came under a new legislative classification called The Misuse of Drugs (Prescription and Control of Supply of Cannabis for Medical Use) Regulations 2019.

Harris said at the time: “It is important to state that there are no plans to legalise cannabis in this country. The purpose of this programme is to facilitate compassionate access to cannabis for medical reasons, where conventional treatment has failed.” This completely reflects the position arrived at following conclusion of the
HPRA report.

Fast-forward to today, and the great news is that as of July 2021, Ireland has an operational Medical Cannabis Access Programme. Access to medical cannabis in Ireland can now be gained via three routes:

The MCAP system — for patients living with a defined number of conditions, access to a set number of products can be gained if they are registered by a specialist doctor.
Subject to approval in writing from the Minister for Health following an application from a specialist or their doctor (with specialists’ endorsement), patients can access any medical cannabis product for any condition. Patients in receipt of products following approval will have their costs directly reimbursed by the Government.

For a limited number of conditions, such as rare childhood epileptic conditions (Lennox Gastaut syndrome and Dravet syndrome) or spasticity in MS, pharmaceutical cannabis CBD meds (ie, Epidyolex or Sativex) can now be prescribed by any doctor. With a cost of around €1,200 per month, Epidyolex is potentially difficult to access, as reimbursement from the HSE is not yet sanctioned.

The system remains evidence-based for the three categories mentioned earlier, ie, have not responded to conventional treatment. The HPRA has approved four products for use with the MCAP system: Tilray Oral Solution THC10:CBD10. MGC Pharma’s CannEpil (CBD Rich). Aurora High CBD Oil Drops.Aurora Sedamen Softgels (THC Rich).Details for reimbursement and pharmacy dispensing fees have yet to be finalised. It is envisaged that the number of patients gaining access to these products will be restricted — this puts Ireland still considerably behind similarly-sized EU countries such as Denmark that currently provide access to over 1,600 patients per month. With MCAP review not due until 2026, progressing to a less restrictive regime may be some way off.

2. Non Medical CBD As discussed earlier, CBD is the largest of 113 compounds derived from the cannabis plant. CBD has no psychoactive properties, as it does not contain the ‘high’-inducing THC. The absence of THC means that, whilst it is a cannabis derivative, it does not fall under the scope of the Misuse of Drugs act when it comes to control and regulation.

Globally, non-medical CBD is classified as a food supplement, meaning that in Ireland, its regulation comes under the remit of the FSAI, our food standards authority, in conjunction with the HSE Environmental Health department for inspection and enforcement. As Ireland is part of the EU, both these organisations support top-down regulation on food standards and safety determined by the European Commission.

The phenomenal growth and proliferation of CBD-based products available for sale in the high street and the exponential growth in market size is reflected in the number of enquiries received by the FSAI regarding the legal status of hemp/cannabis-based products over the past five years. In 2016, there were only two enquiries, rising to 20 in 2017, then to over 100 in both 2018 and 2019. Whilst the market size in Ireland isn’t fully known, the European CBD market is projected to exceed €450 million in 2021, with value globally of around $30 billion.

What is it about CBD that has made it so popular ?

Millions of people worldwide regularly consume CBD, as there is a perception that it is an effective treatment for chronic pain, arthritis relief, stress and anxiety reduction, cancer relief (even claims it cures cancer!) and insomnia, among many others. This misinformation that it is very effective medically is part of a healthy living or general wellbeing narrative promoted by those with a vested interest, generally suppliers and manufacturers, along with anecdotal evidence from users.

In addition, people are perhaps guided by the name of many of the products that suggest healing or a stronger relationship to cannabis (the illegal form), which is actually not present at all. When CBD first appeared for public sale, it was largely only available online in liquid form, either as oral drops as CBD oil or e-liquids that could be vaped. It wasn’t long before it appeared on retail shelves, available mostly in health food stores and pharmacies. Today, there is a proliferation of presentations of CBD; for example, it can be infused in food, coffee, tea, water, cosmetics, etc. With this level of market penetration, it easy to see why it represents such a potentially huge source of revenue, which may explain why some of its benefits tend to be over-exaggerated at times.

This growth is then reflected in what we see today. CBD is everywhere; we see it classed as a ‘superfood’ or ‘the next big thing’. We see endorsement from celebrities, famous sports people, etc .

On the surface then, the continued global growth of this healthy wellbeing product should not be a concern. However, as the profile and use of CBD has increased, so too has the level of concern regarding the validity of claims made both regarding the benefits of using the product, and also the integrity of the quality and content of what people actually get for their money. Whilst there is no doubt that there are many reputable manufacturers and suppliers of CBD, the lucrative nature of the large profits to be made has attracted players into the CBD space interested only in what they can make, with no thought or care as to the product and the wellbeing of the end user.

In simple terms, the explosion of interest in the product and proliferation of products has left regulators and legislation struggling to keep up. The problem has been that up to now, literally anyone, in any country, could produce a CBD product, make some ‘healthy’ claims about it, give it a suggestive name, stick a label on it listing contents that bear no relation to what’s actually contained therein, and sell it to the Irish public either directly online or via retail channels — all because there was absolutely no regulation or standard regarding CBD, meaning the less-legitimate suppliers could effectively ‘get away with it’.

The novel food status of any approved CBD

product can now be checked via the Novel

Food Catalogue on the EU Commission website

Regulation of CBD products by regulators is not an easy task. As we saw earlier, the amount of scrutiny, clinical trials, and evidence-based reporting it took via oversight and control from the HPRA to make just four medical cannabis products available to a very limited number of people following a five-year pilot was huge.

In addition, any pharmacy or pharmacist that ever produced and sold ‘own label’ products such as iron-based tonics or the like in pharmacy will know the extent of the detail, oversight, and compliance in terms of ingredients, labelling, testing, risk analysis, etc, needed to produce to satisfy the HSE Environmental Health Inspectors.

Enhanced regulation for cbd products
The position of CBD products available for sale in Ireland has now changed. The FSAI, in line with EC regulation, has put in place a range of measures, enforceable through Environmental Health inspection, designed to ensure the integrity of CBD products both in terms of any claims made, and the accurate description of contents through approved labelling. This oversight will benefit the consumer by ensuring at least a minimum standard for each and every CBD-based product for sale on the Irish market.

Novel food status
CBD products now have a classification within the EU/Ireland as a ‘novel food’. The definition of a novel food is a food or food ingredient that was not available in the EU market to any significant degree prior to 15 May 1997. Before a novel food can be available for sale within the EU, it must be authorised through an approved application process. Within the application process, a supplier has to provide significant detail regarding ingredients, demonstrate defined good manufacturing practice, and also details of contents, labelling and testing.

CBD industry bodies, on two separate occasions, presented to the EU Commission evidence to suggest availability pre-1997 and avoid novel food classification and on both occasions their claims were rejected.
The novel food status of any approved CBD product can now be checked via the Novel Food Catalogue on the EU Commission website.

A deadline of 31 March 2021 was established for receipt of novel food applications for CBD products already on the market. Any new products coming to market cannot avoid this process. Be aware also of suppliers or manufacturers who state that they have made an application and it’s pending, claiming it is fine to take their product. This is false — there is no ‘grace period’ now.

Reasons legislation was needed

This shift was also prompted by growing evidence that there were many shortcomings within the CBD marketplace. This had previously been highlighted by surveys carried out in 2019 on a wide selection of CBD products available for sale in the UK. One particularly notable and very public survey carried out by the BBC’s Trust me, I’m a Doctor programme sampled and tested 12 CBD products obtained from various high-street retailers. The tests, carried out at an accredited independent laboratory, focused on measuring the amount of CBD contained in each product against the amount described on the packaging.

Tests were also made to assess the content of THC present.The results made for interesting reading, with 25 per cent of products containing less than 50 per cent CBD than that stated on the label — in fact, one popular Irish brand showed virtually no CBD present against a stated amount of 500mg. More worryingly, two of the products contained significantly higher amounts of THC than the prescribed EU standard for CBD of 1mcg/kg of body weight based on a daily adult dosage of 70mcg.

Another independent UK survey of 30 CBD products gave more mixed results. It became apparent that due to a lack of regulation, product claims varied considerably, and the public was simply not getting what they believed they were buying.

FSAI Survey of CBD products on the Irish market
In February 2020, the FSAI published results of their own extensive survey carried out in the last quarter of 2019 of 38 CBD products for sale throughout Ireland. This survey was enabled by a newly-accredited laboratory in Ireland to test products effectively. Most of the products available for sale in Ireland originate outside of the country, which in itself is a major area of concern in terms of quality control, standards, etc.
The summary of the main findings of this FSAI survey were:

37 per cent (14/38) of the products tested had levels of THC that if consumed at the maximum stated dosage, could significantly exceed the safe limit set by EFSA of 1µg/kg/body weight/per day. These are unsafe products.

34 per cent (13/38) of the samples are classified as novel foods and thus require authorisation before being placed on the EU market. These products should not be on the market.

36 per cent (13/36) of samples classed as food supplements had not been notified to the FSAI before being placed on the market, as required by the law. Many of those that had been notified also had issues to be addressed, such as notifying changes of labels.

41 per cent (15/37) of the products tested contained CBD levels which differed by 50% compared to the declared level (one product did not declare CBD levels). This rose to >92% of products where the analytical and declared CBD content differed by at least 10 per cent. Some products had barely detectable levels of CBD.

50 per cent (19/38) made misleading claims, including lactose-free, gluten-free, non-GMO, along with unauthorised health claims and some which may be considered medical claims.

As you can see, the results here alarming — of particular note are the figures for THC content. Fourteen products basically contained illegal drugs at levels where a person’s ability to drive and operate machinery would be seriously impaired; the person could also likely fail a roadside drug test. People who drive for a living or fly aircraft could be particularly at risk. If a person had one of these unsafe products in their bag or luggage on arrival in some countries in the world, they could perhaps be subject to arrest, all because they unwittingly bought a product that they believed would do them some good.

Implications also exist for sports people, as they risk failing drug tests. Interestingly, in 2018, WADA, the global sport anti-doping organisation, removed CBD from its banned list. This prompted Sport Ireland to issue an advisory note in 2019, basically advising athletes that they use CBD at their own risk. This was somewhat ironic, as many high-profile sport stars promote its use in aiding recovery, boosting energy, etc. Following on from the FSAI survey, the FSAI has acted in removing products from shelves. In July 2021, eight products from five brands were removed from sales due to unsafe levels of THC discovered following FSAI testing. These included products from The Herb Stone, Cannapol, The Healing Stone, Phyto+ and Cannibigold.

The regulation is working, although it is playing catch-up. It has been reported anecdotally, but reliably, that due to nonessential retail being closed while Covid-19 restrictions had been in place and due to the fact many quality control officials had been seconded to contact-tracing duties, the ability of the FSAI and HSE to act quickly following the survey results by inspecting premises and products was limited. Now that ‘normality’ was returning, CBD products are now top of the list for action.

Where are we now?
The answer is, we don’t know enough. There is not sufficient long-term evidence to indicate any benefit to taking CBD at all. Particular areas of concern are the lack of evidence concerning interaction with medication that people take for many of the conditions CBD allegedly can relieve. The evidence is so limited, it has led the FSA in the UK to advise that those on any medication or who are pregnant or breastfeeding should avoid using CBD products altogether.

In the absence of concrete information, this seems like sound advice. It would at least suggest that we ask the question: ‘Have you spoken to your doctor about this?’ when people purchase the product at the counter. If a drug manufacturer made claims that were unsupported by evidence, that drug, for all sorts of reasons, would not get through the door of your pharmacy. There isn’t any reason why CBD suppliers shouldn’t be able to produce similar evidence now that the legislative requirements are there, to ensure at the very least that you know your customer are getting what it states on the label.

Hopefully, if you are selling or are thinking of stocking CBD products in your pharmacy, this article has given you sufficient information to enable you to make a more informed choice.


Disclaimer: Brands mentioned in this article are meant as examples only and not meant as preference to other brands.
References upon request


CONTRIBUTOR INFORMATION


Written and researched by
Eamonn Brady (MPSI), owner
of Whelehans Pharmacies in
Mullingar Tel 04493 34591
(Pearse St) or 04493 10266
(Clonmore). http://www.whelehans.
inet. Eamonn specialises in
the supply of medicines and
training needs of nursing homes throughout Ireland.
Email ebrady@whelehans.ie