Since our beloved Justin Trudeau has promised to legalize marijuana in Canada during the last election in 2015, I have been thinking how this will affect pharmacists. It’s happening very quickly. Health Canada has currently issued 30 licensed producers of marijuana for medical use. Of the 30 producers, 17 are based in Ontario.[1] However, LCBO may soon take over the entire responsibility of distributing and selling marijuana.  The Canadian Pharmacist Association has put out a statement in Feb 2016 that a review of their policies is in process related to the use of medical marijuana[2].  RxFiles (an academic detailing program based on Saskatoon) has also developed a quick Q&A document to describe and summarize the various options of marijuana and the clinical considerations[3].

Marijuana refers to the crude product such as the dried leaves and flower of the plant[4]. The natural plant sources include Cannabis sativa and Cannabis indica.

Cannibis contains about 100s of compounds including about 70 cannabinoids and the most common two are delta-9-tetrahydrocannabinol (known as THC or dronabinol) and cannabidiol (known as CBD). The psychoactive properties of marijuana comes from the THC, whereas the calming effect is from the CBD component. It is also thought that the CBD has analgesic and anti-inflammatory properties via the Cox-II inhibition.

Currently there are two available prescription drugs containing either synthetically made or naturally extracted marijuana:

  • Nabilone (Cesamet) is a synthetic cannabis that only contains THC without any CBD. It is indicated for nausea and vomiting from chemo induced therapy. It is available as capsule or oral liquid, currently covered by ODB.
  • Tetranbinex/nabidiolex (Sativex) is a buccal spray solution containing naturally extracted THC (2.9mg) and CBD (2.5mg) per spray. It is indicated for adjunctive relief of advanced cancer pain and MS neuropathic pain or spasticity. It is expensive and costs about $252 per vial. However, it can be covered by ODB via the exceptional access program for neuropathic pain related to multiple sclerosis and refractory pain in palliative cancer patients according to specific criteria.

Because Nabilone does not contain any CBD which is thought to have analgesic and anti-inflammatory properties, one may argue that the claimed benefits of Marijauana may not be extrapolated to this synthetic compound.

Cannibis is most commonly known to be smoked in a joint or inhaled via a vapourizer; but it can also be applied topically on skin as cannabis oil.   Cannibis can also be ingested orally – actually it can also be added to teas or used in baking!

The smoking and inhalation methods are most common as they allow the marijuana to reach a high concentration in the brain quickly to produce the various psychoactive effects.  Taking marijuana by mouth may be less messy but has a slower onset and does not produce the same euphoria. Cannibis is extensively metabolized by the liver, hence renal impairment does not affect dosing, or at least it has not been formally evaluated.

There are other considerations too. Marijuana is known to be psychoactive, so taking it with other opioids, barbiturates, CNS depressants and other psychotropic medications can potentiate various CNS side effects such as drowsiness and ataxia. It can also exert sympathomimetic activity and may throw the hemodynamic parameters off balance (tachycardia and hypertension), especially in people with pre-existing cardiac conditions and on cardiac medications. It has anti-cholinergic properties and may add to the anti-cholinergic burden for an individual.

When taken via inhalation, marijuana bypasses our digestive and hepatic systems (first pass effect), thereby minimizing the effects on the cytochrome P450 system – a collection of enzymes that can either increase or decrease the metabolism and clearance of the drugs.  But now that oral ingestion may become more popular and may be used in people with more complex comorbidities, the impact of the drug interaction may become more prominent.

Horn and Hansten has summarized some of the potential drug interactions based on theoretical assumptions[5].  THC is metabolized by CYP2C9 and CYP3A4; the THC level may be increased by CYP2CP inhibitors such as amiodarone, cotrimoxazole, fluoxetine, fluoncazole and voriconazole. Likewise, inhibitors of CYP3A4 such as ketoconazole, clarithromycin may increase THC level.  On the other hand, inducer of CYP3A4 such as rifampin may decrease THC level.

Marijuana has been reported to potentially offer benefits in a number of medical conditions including pain (neuropathic pain), spasticity, seizure control, chemotherapy induced nausea and vomiting and weight loss in AIDS/HIV population and many others.  But there is generally a lack of high quality research to support these claims.  However, this may soon change as we move forward with the legalization of marijuana.

One of my concerns is how do we quantify intake – what is the average dose to produce clinical significant effects?  With legalization, I hope the manufacturing of marijuana must meet some standard quality assurance prior to distribution and sales.  On average, it is proposed the daily intake amount via smoking or inhalation should not exceed 5 gram per day. If used for pain and neuropathy, the maximum daily amount is around 3 gram per day.  When ingested orally (added to tea / baking), the maximum daily amount is 2.5 gram per day when used for pain.  Clearly, this area is still a bit gray. But if we gain more experience with use for wider indications, I suspect the dosing guideline will be revised and updated. It is important to note that the ratio or percentage of THC to CBD is important when reviewing the dose. If the plant or product has a higher percentage of THC, it may cause more psychoactive side effects to the individual.

I am not sure the legalization of marijuana truly solves the problem we have in Canada.  Just because everyone is smoking marijuana doesn’t mean we have to validate it by means of legalization.  The rationale is that this will minimize the impact of drug trafficking when we have a legal means of accessing the drug. However, are we legalizing it for medical use or recreational use? The way by which we should implement policies will depend greatly how we answer this question.  I would imagine with increased use of marijuana for medical use, we also need a monitoring system or a registry in place to understand its true impact on a wider population with complex co-morbidities.   How do we minimize the impact of smoking weed and driving? If I can purchase a bottle of wine and some weed from LCBO knowing that mixing the two is not wise, how do we ensure the public will consume marijuana safely?

Can you imagine going to Starbucks in the future and ask for a splash of weed on your Chia Latte? How do you feel about leglization of marijuana?

Thank you for reading my post.

[1] http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/list-eng.php

[2] http://www.pharmacists.ca/advocacy/advocacy-activities/cpha-statement-on-medical-marijuana/

[3] http://www.rxfiles.ca/rxfiles/uploads/documents/Pain-QandA-cannabinoids.pdf

[4] Seamon MJ et al. Medical marijuana and the developing role of the pharmacist. Am J Health-Syst Pharm Vol 64 May 15 2007: 1037-44

[5] Horn JR and Hansten PD. Drug Interactsion with Marijuana. Pharmacy Times Dec 2014 (http://www.pharmacytimes.com/publications/issue/2014/December2014/Drug-Interactions-with-Marijuana)

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