HOW: PRESCRIBING MEDICINAL CANNABIS
Although a physician may want to prescribe medicinal cannabis to a certain patient, a physician might still have a lot of questions about what to expect from medicinal cannabis. Learn more about how medicinal cannabis is used by patients and how that could impact the prescription process.
How much or what dosage of medicinal cannabis should physicians prescribe?
The ideal dosage of medicinal cannabis should be always determined for each patient based on many factors, including the THC content of the medicinal cannabis product, the selected route of administration, and the specific medical condition of the patient. As a general rule, the optimal dose is the lowest dose that can control a patient’s symptoms without side effects. To accomplish this objective, a physician may ask the patient to start with a low dose and to up-titrate according to a proposed titration scheme. This may allow for better tolerability. Different patients may require or tolerate different doses.
Is there a recommended starting dose for medicinal cannabis?
For patients who are taking oral forms of medicinal cannabis, the recommendation is to start with a total daily dose of 2.5mg THC (or 1.25mg for frail patients), typically taken in the evening.1 For patients in need of inhaled medicinal cannabis, there is a greater variability based on the deepness or type of inhalation, so the dosage needs to be highly individualized. However, a general starting point can be between 25mg and 100mg of inhaled dried flower per day.2
Is there a recommended scheme for increasing dosage for medicinal cannabis?
For patients who are taking oral forms of medicinal cannabis (e.g., capsules), the recommendation is to increase the total daily dose in 2.5mg THC increments every two days.1 If a patient starts with 2.5mg THC on Day 1, that means going to 5mg THC on Day 3. If a patient follows this scheme, they should make sure not to exceed 40mg THC daily, or a lower dose that meets the right balance of positive vs negative effects for their situation. The average daily dose for oral administration is about 15mg THC based on available data. If the oral formulation does not contain THC (CBD-dominant), then patients could start with about 50mg CBD on Day 1, going up in 50mg increments daily, up to a maximum of about 1,400mg per day.
For patients who are inhaling medicinal cannabis, there is much greater variability, especially based on inhalation morphology, so the dosage needs to be highly individualized. However, the recommendation is to increase the total daily dried flower dose in 100mg increments every day.2 If a patient starts with 100mg on Day 1, that means going to 200mg on Day 2 (100mg twice a day), and so on. The average daily dose for inhaled administration is about 500mg to 1500mg dried flower based on available data, with a maximum recommended dose being about 3000mg of dried flower daily.
What are the pharmacokinetic profiles of cannabinoids?
The pharmacokinetics (PK) for cannabinoids differs depending on the route of administration.1 The inhaled bioavailability of THC ranges between 20% and 30% and varies according to depth and duration of inhalation. The bioavailability of inhaled CBD is similar to THC, with an estimated bioavailability ranging from 11% to 45%.3 THC from inhaled medicinal cannabis reaches a peak blood concentration at about 5 to 10 minutes, with about 10% of the peak concentration remaining 1 hour after inhalation.3 Inhalation results in about 33% exposure of the 11-OH-THC metabolite, compared to the oral administration. This is crucial as this metabolite is a more potent agonist at the CB1 receptor and produces a more pronounced psychoactive effect than THC.
The oral bioavailability of THC ranges normally between 10% and 20% and varies according to the food intake.3 High-fat meals are associated with a higher absorption rate. There is low oral bioavailability due to the high lipid solubility and first-pass hepatic metabolism. The PK parameters of oral CBD are similar to THC, with an estimated oral bioavailability of 6%. THC from oral medicinal cannabis reaches a peak blood concentration at about 3 to 4 hours, with about 30% of the peak concentration remaining 12 hours after ingestion.3
How are cannabinoids metabolized and excreted?
Both THC and CBD are metabolized by the cytochrome P450 (CYP) system. CYP2C9, CYP2C19, and CYP3A4 are the primary enzymes in the metabolism of THC, while CYP2C19 and CYP3A4 are the primary enzymes in the metabolism of CBD. Both cannabinoids are primarily excreted via feces, with some elimination in urine. Like THC, the elimination half-life of CBD is estimated at about 2 to 5 days after oral administration.3-5
Is there a food effect for medicinal cannabis?
There is a food effect for THC and CBD pharmacokinetics.5 In studies, a high-fat, high-calorie meal results in an appreciable delay in the Tmax, an increase in Cmax, and an increase in the total exposure (AUC; area under the curve), compared with the fasted state. It’s therefore recommended that patients take their oral medicinal cannabis product under the same conditions to help maintain a stable pharmacokinetic profile.
Does a patient have to smoke medicinal cannabis?
No. In fact, smoking is not recommended.1,2 There are many ways to inhale or ingest medicinal cannabis. For example, as an alternate to smoking, medicinal cannabis can be inhaled through a vaporizer. A vaporizer is not only safer, since a patient will not inhale a product resulting from the combustion of the dried flower, but also more accurate from a dosing standpoint.
Is there a recommendation on how to inhale medicinal cannabis?
The Foltin Puff Procedure is a good starting point.5 It has four key points:
- Recommend vaporization temperature of 190ºC or higher5
- When the vaporizer is ready, inhale on the mouthpiece for 5 seconds6
- Hold the vapor in the lungs for 10 seconds6
- Exhale and wait for 10 to 20 minutes between inhalations
A standardized procedure will guarantee safer administration and will reduce the inter- and intra-variability between patients and administrations.
What is a vaporizer?
A vaporizer is a device that heats medicinal cannabis in the form of dried flowers. It uses a lower temperature than an open flame, so a vaporizer allows patients to inhale cannabis in vapor form, rather than smoke. Inhalation allows cannabinoids within the plant to be volatilized with heat, enter the bloodstream, and reach the brain more quickly via inhalation, thereby providing fast-acting relief of symptoms. In addition, vaporization avoids combustion and reduces the presence of potentially harmful irritants that may be contained in cannabis smoke.
Which form of medicinal cannabis should physicians prescribe?
Generally, medicinal cannabis that is intended for inhalation acts more quickly and lasts a shorter period, so it is more appropriate for episodic acute symptoms. In contrast, medicinal cannabis intended for oral use usually takes a longer time to act, but then lasts for a longer period, so it is more appropriate for chronic conditions.
Are there drug-drug interactions with cannabinoids?
There is a potential for some drug-drug interactions with cannabinoids.4 A pharmacodynamic interaction may occur with the co-administration of anti-spasticity drugs, as a reduction in muscle tone may occur, leading to a greater risk of falls and injury.
Pharmacodynamic interactions, leading to CNS effects (e.g., dizziness, confusion, sedation, somnolence) may occur when medicinal cannabis is taken concomitantly with drugs that have similar effects on the central nervous system such as CNS depressants.3
Both THC and CBD are metabolized by the cytochrome P450 (CYP) system. CYP2C9 and CYP3A4 are the primary enzymes in the metabolism of THC, while CYP2C19 and CYP3A4 are the primary enzymes in the metabolism of CBD.3-5 Inhibitors of these enzymes may increase, while inducers may decrease, the systemic exposure of cannabinoids and/or their active metabolite resulting in an increase in adverse reactions or loss of efficacy of the medicinal cannabis.
Physicians should monitor for potentially increased cannabinoid-related adverse reactions when medicinal cannabis is co-administered with inhibitors of CYP2C9 (e.g., amiodarone, fluconazole), CYP2C19 (e.g., ketoconazole, isoniazid), and CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin).2,5 Likewise, physicians should monitor for potentially decreased efficacy when medicinal cannabis is co-administered with inducers of CYP2C9, CYP2C19, or CYP3A4 (e.g., rifampicin, rifabutin).2,5 Finally, physicians should monitor for potentially increased adverse reactions associated with substrates of CYP2C9, CYP2C19, or CYP3A4 (e.g., clarithromycin, erythromycin) when medicinal cannabis is co-administered with them.5
There are also potential interactions with highly protein-bound active substances and THC.3
Can medicinal cannabis replace opioids?
The decision to start or stop a medication is up to the prescribing physician, in dialogue with the patient. That said, there are multiple studies showing that patients who start medicinal cannabis for various pain conditions end up primarily substituting or reducing the dose for opioids
Pre-clinical data show a fair amount of evidence to suggest a functional interaction between the cannabinoid and the opioid systems, although additional research is needed to understand precisely how the two systems communicate with one another. A recent systematic review and meta-analysis of pre-clinical studies examining the strength of the existing evidence for the “opioid-sparing” effect of cannabinoids in the context of analgesia concluded that there was a significant opioid-sparing effect between morphine and THC when co-administered, although there was significant heterogeneity in the data.7
Clinical case series and epidemiological data, like surveys of authorized medical cannabis patients, showed that opioids accounted for more than 40% of substituted medications in patients using medicinal cannabis for pain.8,9 In another study, more than 70% of chronic pain patients who self-reported substituting one or more medications with medicinal cannabis reported substituting opioids.10
Should a patient drive when taking medicinal cannabis?
Medicinal cannabis can influence a patient’s ability to stay alert, drive, or operate heavy machinery.2,5 Patients should understand how their medicinal cannabis product and dosage affects their ability to function and stay alert prior to driving, operating machinery, or engaging in other dangerous activities. Patients should avoid driving until they reach a stable dosage.2
Patients should be familiar with the legal amount of THC and comply with local rules and regulations before driving. A patient should wait at least 3 hours after inhalation of medicinal cannabis, or up to 8 hours if psychotropic effects are experienced. Conversely, a patient should wait at least 6 hours after oral ingestion of medicinal cannabis, or up to 8 hours if psychotropic effects are experienced.2
- MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing. Eur J Intern Med. 2018 Mar;49: 12-9.
- Häuser W, Finn DP, Kalso E, et al. European Pain Federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. Eur J Pain. 2018 Oct;22(9): 1547-64.
- Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4): 327-60.
- Bouquié R, Deslandes G, Mazaré H, et al. Cannabis and anticancer drugs: societal usage and expected pharmacological interactions - a review. Fundam Clin Pharmacol. 2018 Oct;32(5): 462-84.
- Health Canada. Information for Health Care Professionals: Cannabis and the cannabinoids. October 2018. ISBN: 978-0-660-27828-5
- Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013 Feb;14(2): 136-48.
- Nielsen S, Sabioni P, Trigo JM, et al. Opioid-sparing effect of cannabinoids: a systematic review and meta-analysis. Neuropsychopharmacology. 2017 Aug;42(9): 1752-65.
- Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017 Apr;42: 30-5.
- Lucas P, Baron EP, Jikomes N. Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients. Harm Reduct J. 2019 Jan;16(1): 9.
- Baron EP, Lucas P, Eades J, Hogue O. Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort. J Headache Pain. 2018 May 24;19(1): 37.