CLASStime: Cannabis-based medicines

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You can choose how many elements you wish to undertake, depending on your professional development plan, but it is recommended that you complete both CLASStime and CLASSact before CLASSmates.

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This CLASStime article supports professional development with respect to:

• Understanding administration and action of cannabis-based medicines
• Identifying at-risk patients, medicine interactions and adverse effects associated with cannabis-based medicines
• Providing education and advice to patients about cannabis-based medicines

As you read, highlight new knowledge or areas where you need to know more. You can also use the Capture button online to keep notes of your thoughts and reflections on this article. This may be useful if you choose to proceed to CLASSact and CLASSmates for this topic.

Completing this CLASStime activity may allow you to fulfil some or all of the following elements of your Pharmacy Council annual recertification requirements:

• Keeping up to date – go to MyRecert (myrecert.pharmacycouncil.org.nz), select the “Keeping up to date” page of your portfolio, then enter a description of this article
• Reflection on practice

This activity has been endorsed by the Pharmaceutical Society of New Zealand as suitable for inclusion in a pharmacist's continuing education records for continuing professional development purposes.

A variety of standardised cannabis-based medicines and modes of administration are available globally. It is likely New Zealand will have access to these, and similar medicines produced domestically, as more products are assessed by the Medicinal Cannabis Agency and Medsafe. Pharmacists and prescribers need to work collaboratively as cannabis-based medicines continue to be introduced into New Zealand.

Cannabis comprises a single species of dioecious plant, Cannabis sativa L., one of the oldest known medicinal plants. Cannabis-based medicines are derived from cannabis, with defined and standardised cannabinoid content (eg, tetrahydrocannabinol [THC] and cannabidiol [CBD], which act on the cannabinoid receptors) in standard dosages.

As of 1 October, cannabis-based medicines distributed in New Zealand must meet the Medicinal Cannabis Agency minimum quality standards or be approved or provisionally approved by Medsafe. The minimum quality standard aims to standardise medicines to assure dosage composition, repeatability of dose, and the ability to adjust dose by titration. To ensure patient safety, these products should be free of contaminants such as microbes, pesticides, impurities and heavy metals.¹

A list of verified and approved products is available on the Ministry of Health website (tinyurl.com/MedCannabisProducts). All medical practitioners are able to prescribe these products. Unverified products can be prescribed/imported for a named patient with ministry or chief medical officer approval.¹

In New Zealand, all CBD products are prescription medicines. A CBD product may contain only trace amounts of THC (the cannabinoid with psychoactive effects). Any product made from a cannabis extract which is not a CBD product (ie, THC products) is a Class B1 controlled drug, on prescription. The cannabis flower (fruit) and any part of any plant (eg, leaves) containing cannabis resin (ie, glandular trichomes containing THC) are Class C1 controlled drugs, on prescription.

Only a few cannabis-based medicines are officially approved (eg, in New Zealand, Sativex oromucosal spray) for specific conditions.

The prescription of unapproved medicines, or prescribing off label, requires a good clinical argument. It then becomes the dispensing pharmacist’s role to ensure the medicines prescribed are suitable, to advise patients about the medicine (how to take them, what reactions may occur) and to answer patient questions (which could be few or many).

Like opioid receptors reacting to opioid agonists (morphine, codeine, oxycodone), humans have a distinct receptor system for cannabinoids. Phytocannabinoids produced by C. sativa L. (THC and CBD) elicit their effects by binding to specific cannabinoid receptors, which belong to the superfamily of G-protein-coupled receptors. Two types of cannabinoid receptors – CB1 and CB2 – have been identified with certainty.

Phytocannabinoids work in a similar way to our naturally produced endocannabinoids, which are neurotransmitters with biological activities within the human endocannabinoid system. The ECS is involved in a host of homeostatic and physiologic functions. It plays a critical role in our nervous system and regulates multiple physiological processes, including the adjustment of our response to pain, appetite, digestion, sleep, mood and memory.

Pharmac’s Pharmacology and Therapeutics Advisory Committee (PTAC) recently considered “medicinal cannabis”, which they defined as a prescription-only plant component, extract or processed product derived from C. sativa, for therapeutic use, with a defined content of CBD and THC. In the report, PTAC raise two very important points:²

• The full cost of medicinal cannabis is currently privately funded (out-of-pocket payments).
• There may be an unmet need for effective, accessible therapy and, therefore, there may be an interest in the use of medicinal cannabis in a range of often complex conditions.

These conditions include, but are not necessarily limited to: degenerative conditions; epilepsy, including paediatric epilepsy; chronic mental health conditions, such as PTSD or severe anxiety; chronic pain, including neuropathic pain; spasticity associated with multiple sclerosis; and autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease and chronic fatigue syndrome.²

The two points made by PTAC have implications for prescribing and dispensing cannabis-based medicines. First, patients self-fund the medication for the duration of that prescribed treatment. Second, patients are likely to present with complex health conditions, on multiple medications, at various stages of disease progression. For pharmacists, this raises issues around:

• dealing with potential medicine–medicine interactions
• managing cannabis-based medicine initiation and titration to an optimal dosage
• potentially, cessation of the medicine.

Patients may want to stop taking a cannabis-based medicine due to the ongoing costs or if the medicine is found not to be efficacious or to cause intolerable side effects. Remember that the rational use of medicines requires that “patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community”.

The form in which a cannabis-based medicine is administered determines the onset, intensity and duration of effects (how it moves and works in our body – see table).

Like other medicines, cannabis-based medicines are available in different dose forms. This is because the dose form can influence patient behaviour in different ways, including:

• whether people actually take their medicine and adhere to their daily regimen
• when the medicine is taken (time of day)
• how often it is taken (frequency of use)
• how much is taken (total daily dosage)
• side effects and how these are tolerated

There are two major administration routes – inhalation and oral.

Inhalation

The immediate onset of action means inhalation is the preferred choice for many patients.

Given the risks from smoking, patients now seek reliable, affordable and portable vaporisers or inhalation devices. Research dedicated to advancing vaporiser and inhalation technology has seen major developments in device quality.

Using a vaporiser medical device, cannabinoids are inhaled (from dried cannabis inflorescence/flos/flower) as a vapour, and then enter the bloodstream from the lungs.

These medicines are not yet available in New Zealand (tinyurl.com/MedCannabisProducts).

Oral and oromucosal

Oral preparations are familiar dose forms (eg, tablet, capsule, oral liquid). They are similar to other medicines that patients already take, and they are easy to administer. As a result, concentrated cannabis extracts are becoming increasingly popular.

Cannabinoids (whole plant extracts or individual cannabinoids) are taken by mouth and either swallowed (oral) or applied to the oromucosal surface (sublingual/buccal). When swallowed, the medicine enters the bloodstream via the stomach, intestines and liver. When absorbed from the oral mucosa, the medicine bypasses the liver and enters into the bloodstream directly. Consequently, absorption and onset of action are faster via the sublingual/buccal route.

Pharmacists can assist patients with managing their medicine-use behaviours and ensuring their safety. When introducing cannabinoids into a patient’s therapeutic regimen, pharmacists should consider the following.

At-risk patients

Consider potential risks in older people (eg, postural hypotension), young people (given the potential risk to the developing brain), and in those with cardiac risk factors (cardiopulmonary disease) or a history of psychosis or depression.

The use of cannabis-based medicines is not advised in pregnancy or during breast feeding. A reliable contraception is advised for the duration of, and several months after, treatment.

Absolute contraindications include acute psychosis and other unstable psychiatric conditions. Relative contraindications include severe cardiovascular disease (may exacerbate arrhythmia or a history of arrhythmias), immunological, liver or kidney disease, especially in acute illness.

Potential medicine interactions

Medicines can interact with each other. The risk increases if a patient is taking many medicines at once. Patients prescribed cannabis-based medicines may have complex conditions and take multiple medicines.

A number of medicines potentially interact with cannabis-based medicines. Pharmacists should be aware of potential medicine–medicine interactions and how these will be identified and treated.

Care should be taken when cannabis-based medicines are co-prescribed with medicines that:

• interact with the cytochrome P450 (CYP450) metabolic enzymes, as these also metabolise cannabinoids (THC and CBD are metabolised by CYP3A4 and CYP2C9; CYP3A4 inhibitors slightly increase THC levels; CYP3A4 inducers slightly decrease THC and CBD levels; CBD, but not THC, is metabolised by CYP2C19)
• have sedating effects (also co-administration with alcohol), as the combination can affect response time, coordination and concentration
• influence heart and circulation (eg, beta-blockers, diuretics, adrenaline), as THC influences blood pressure
• have action at the opioid receptors, as THC appears to enhance the action of opioids (eg, codeine, morphine).

This list is not exhaustive. A full review should be undertaken before co-prescribing, in particular, those medicines that interact with the CYP450 metabolic enzymes.

Potential side effects

In general, patients seem to tolerate cannabis-based medicines well. However, some patients taking cannabinoids have worsened symptom control and new side effects, such as sleepiness and diarrhoea, or have affected normal liver function. In particular, large doses of THC have been shown to pose a risk of harm (eg, postural hypotension resulting in a fall).

There are also many unknowns with large doses of CBD – indeed, the US Food and Drug Administration continue to monitor their use, given “there are many unanswered questions about the science, safety, and quality of products containing CBD”.³

Side effects mainly occur after taking high doses or when used in combination with other substances. These tend to occur quickly after use. For THC-dominant medicines, these include:

• dry mouth
• redness of the eyes
• heightened appetite (which may be desirable)
• mild euphoria
• reduction of alertness of the user, especially in the few hours directly after consumption
• increased heart rate
• lowering of blood pressure and dizziness.

In general, all side effects will slowly decrease and then disappear within a few hours. This depends on the dose taken and mode of administration.

Forget the hype – cannabis-based medicines are not a panacea or a cure for disease. Focus on providing good advice to patients – they need a supportive but critical view of the risks and benefits of cannabis-based medicines.

For pharmacists, dispensing cannabis-based medicines is similar to other medicines. However, many patients will have an opinion about cannabis. Some patients will be armed with information, whereas others will be naive to the topic.

A solid understanding of these medicines and clear communication are really important. In particular, pharmacists must be able to:

• answer tricky medicine queries
• promote patient medicine compliance and share patient-friendly medicine information
• assist in identifying side effects and adverse reactions – report them and encourage patients and carers to inform their doctors
• support prescribers in decision-making and with medicine regimen review.

When talking with patients, first, ask the patient what they already know about cannabis-based medicines. Inform them about the mechanism of action, how to use it, the dosage regimen, possible side effects and how to safely store it.

Make sure the patient takes notice of contraindications – certain conditions where cannabis-based medicines should not be used – and possible interactions with other medicines.

In a follow-up discussion, ask the patient about their experience with the medicine, with extra attention to side effects and the medicine’s effectiveness.

Martin Woodbridge is a research, technical advisory and policy consultant who has undertaken projects with primary healthcare, ministries of health, universities, the pharmaceutical industry and front-line health services here and abroad

Please CAPTURE this article before leaving this page. To move on to CLASSact, where you can download an interactive PDF that provides you with both knowledge and reflective questions for independent learning, click the button below.

Completing this CLASSact worksheet may allow you to fulfil some or all of the following elements of your annual recertification requirements:

• Keeping up to date
• Reflection on practice

Please CAPTURE this article before leaving this page. To move on to CLASSmates, where you can access a peer group meeting guide and activity tool based on CLASStime and CLASSact, click the button below. It includes a facilitator guide, user guide, notes template and Jamboard tool (for online meetings).

Completing this CLASSmates activity may allow you to fulfil some or all of the following elements of your annual recertification requirements:

• Keeping up to date
• Reflection on practice
• Meeting with professional peers