Medicinal and Recreational Cannabis

MEDICINAL AND RECREATIONAL CANNABIS

Pharmacy's role in counselling patients

 

With the legalization of recreational cannabis in Canada on Oct. 17, 2018, BC Drug and Poison Information Centre pharmacist Shelina Rayani explores how pharmacists can counsel patients who are on various forms of cannabis.

 

By Shelina Rayani RPh, CSPI, BC Drug and Poison Information Centre

Reviewed by C. Laird Birmingham, MD, MHSc, FRCPC and Hanif Rayani, RPh

 

When recreational cannabis becomes legalized, pharmacists will play an active role in counselling patients on appropriate use, drug interactions, management of side effects, potential addictive behaviours and contraindications.¹ This article provides an overview of medicinal versus recreational cannabis, drug interactions and factors to consider when evaluating patients.

 

Marijuana is the common name for cannabis.^2-5 Marijuana is derived from the flowering buds of various female cannabis species.^2-5 Over one hundred unique compounds known as phytocannabinoids have been isolated from cannabis. Two of these compounds have been most studied.^1-8 These are Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD).^1-8

THC may have some beneficial effects as an analgesic, antiemetic, appetite stimulant and muscle relaxant, but it is also responsible for the euphoria as well as most of the adverse effects associated with cannabis.^1-9  CBD has antipsychotic, anxiolytic, antiepileptic and anti-inflammatory effects.^1-9 The ratio of THC to CBD in each strain of cannabis is responsible for its therapeutic and adverse effects.^1-9 Cannabis strains used recreationally for a euphoric effect contain higher levels of THC, whereas, medicinal cannabis strains have a higher CBD to THC ratio.^2,5,8

 

There are three major species of the cannabis plant, as well as hybrids of these and other species.⁵  These are Cannabis sativa (highest THC level), Cannabis indica (greater CBD than THC) and Cannabis ruderalis (least psychogenic).⁵  Table 1 compares medicinal and recreational cannabis. Non-cannabinoid compounds found within the plant (e.g. flavonoids, terpenoids) may enhance the therapeutic effects and/or reduce the adverse effects of phytocannabinoids; this is known as the entourage effect.⁸

Another variant of Cannabis sativa is Hemp. Hemp is a cultivated variety of cannabis with negligible amounts of THC (less than 0.3%) and higher levels of CBD.^3,10  It has no euphoric properties. Fibre from hemp stalks can be used in making paper, textiles, rope or twine, and construction materials.^3,10  Grain from hemp can be used in food products, cosmetics, plastics and fuel.^3,10      

 

TABLE 1:  COMPARATIVE OF MEDICINAL & RECREATIONAL CANNABIS ^{1-9, 16-19, 22-26}

	MEDICINAL  CANNABIS				RECREATIONAL  CANNABIS
POSSESSION LIMITS	The lesser of a 30-day supply or 150 grams of dried marijuana or equivalent amount if in another form. Formulas are available to determine how many plants can be grown based on the daily quantity of dried marijuana authorized in the registered person's medical document.				Up to 30 grams of dried legal cannabis or equivalent in non-dried form in public Up to 4 cannabis plants per household (not per person) for personal use, from licensed seeds or seedlings Share up to 30 grams of dried cannabis or equivalent with other adults
INDICATION	Spasticity from multiple sclerosis Neuropathic pain Chronic pain (3rd line agent) Specific pediatric seizure disorders Antiemetic post chemotherapy				Recreational use 19 years and older (in B.C.)
CANNABINOID RATIO	CBD > THC (less psychoactive)				THC > CBD (more psychoactive)
TYPES	Phytocannabinoids (No Drug Identification Number (DIN) or Natural Product Number (NPN)) Synthetic cannabinoids (DIN, Requires prescription): § Nabilone (THC analogue, oral) § Sativex (THC & CBD, buccal)				Phytocannabinoids (No DIN/NPN) Illicit synthetic cannabinoids
DOSAGE FORMS	Dried cannabis, extracts in oil, tinctures, concentrates, edibles, beverages, capsules
ROUTE	Inhalation (smoking, vaporized), oral, buccal/sublingual, topical, rectal
AVAILABILITY	LEGAL Require medical document from MD or Nurse practitioner Order from Licensed Producer (LP) on Health Canada website; OR Register self or designate with Health Canada to grow own (supplies acquired from LP); OR Cannabis storefront dispensary IF licensed by Health Canada (currently majority are not)     ILLEGAL Illicit source Grow own (without registration)			LEGAL       Licensed Producers (LP) No paperwork required In B.C.: Online via BC Liquor Distribution Branch and one government-owned storefront in Kamloops open on Oct. 17, 2018 (others to follow) Limited amounts of fresh or dried cannabis, seeds and oils available Edibles, beverages, topical creams, suppositories, concentrates and vape juice are not yet legal   ILLEGAL Illicit source Grow own
PROS/CONS	Legal products are standardized for THC/CBD content, monitored, free of pesticides/mold/contaminants Legal products will probably have a higher cost Recreational cannabis easier to obtain Risk of drug diversion Risk of dependence and addiction Safety concerns
PHARMACOKINETICS*	ROUTE	BIOAVAILABILITY	ONSET			PEAK	DURATION
	Inhalation	15% to 50%	5 to 10min			10 to 20min	2 to 4h (Up to 24h)
	Oral	6% to 20%	30 to 60min (Up to 1 to 3h)			2 to 4h (Up to >6h)	Adults: 4 to 6h (Up to 24h) Children: 6 to 12h (Up to 36h)

* Inhaled bioavailability varies based on the number, depth, duration and frequency of inhalations, as well as the amount of time substance is held in the lung, and If vaporized, the temperature of the vaporizer. Oral bioavailability is reduced due to extensive first pass metabolism. Food may alter bioavailability.

 

Pharmacists evaluating patients should consider the following:

• Indication i.e. medicinal versus recreational
• Cannabis strain and THC/CBD ratio
• Route of administration and dosage form
• Dosing (start low and go slow when titrating)
• Adverse effects (depending on route, ratio and dose) ^{2-6,8,9,11-15}

ACUTE USAGE	Euphoria, hallucinations, mydriasis, conjunctivitis, sedation, increased appetite, dry mouth, cognitive and motor impairment, agitation, tachycardia, dizziness, postural hypotension, ataxia, anxiety**, nausea and vomiting**
CHRONIC/HEAVY USE	Impaired brain development in youth (possibly until mid 20s), potential decline in IQ, increased risk/worsens anxiety, depression, paranoid ideation, precipitation of psychosis in susceptible patients, increased risk of schizophrenia as an adult
OTHER	Cannabinoid Hyperemesis Syndrome (CHS), respiratory effects (chronic bronchitis, pneumonia), lung cancer and emphysema reported in heavy smokers***, cardiovascular effects (Myocardial Infarction, Stroke)

**  Paradoxical effect

*** Many smoke tobacco concurrently. The College of Family Physicians of Canada recommends vaporization or oral ingestion rather than smoking cannabis.⁸

 

• Drug interactions (See Table 2)
• Labeling e.g. label edibles (gummies, brownies, cookies) for safety. Pediatric ingestion can cause significant CNS depression, hypotonia and coma.⁴
• Storage as per manufacturer insert. Keep out of reach of children.
• Contraindications: Pregnancy, breastfeeding, known sensitivity to cannabis.⁸
• Avoid use in those under age 25, history of psychosis, cardiovascular disease, and/or respiratory disease.^2,3,8
• Tolerance with heavy or frequent use.
• Dependence i.e. withdrawal symptoms from abrupt cessation in chronic users may include anxiety, irritability, craving, dysphoria and insomnia. The dependence risk for cannabis users is 9%, and higher for those that begin use during adolescence.^5,6,13
• Addiction (Cannabis Use Disorder) is the continued use of cannabis despite harm or risky behaviour, cravings and/or impaired control over cannabis use. Especially common in those who start use as adolescents.^5,6,13

 

TABLE 2: CANNABIS DRUG INTERACTIONS

THC and CBD are metabolized by CYP1A2, 2C9, 2D6, 2C19 and 3A4 ^{3,5,8,17,18,20,21,27}

INTERACTING DRUG	EFFECT	MANAGEMENT
CYP 2C9, 2C19, 3A4 INHIBITORS a	Increase cannabinoid concentration	Monitor for increased clinical and adverse effects of cannabis
CYP 2C9, 2C19, 3A4 INDUCERS a	Reduced cannabinoid concentration	Monitor for reduced clinical effect of cannabis
CYP1A2 SUBSTRATES a	Cannabis is a CYP1A2 inhibitor SMOKING cannabis can induce CYP1A2	Monitor therapy for enhanced or reduced clinical effect of CYP1A2 substrates
Anticholinergic drugs (e.g. TCAs, sedating antihistamines)	Additive hypertension and/or tachycardia	Monitor therapy
Antipsychotics (e.g. Chlorpromazine/Thioridazine)	Marked hypotension and disorientation	Monitor therapy
Cisplatin	Case report of a fatal stroke	Avoid
CNS depressants (e.g. Alcohol, Barbiturates, Opioids, Benzodiazepines, Hypnotics)	Additive sedation and cognitive impairment	Avoid Cannabis is sometimes used with opioids for synergy
Disulfiram	May enhance adverse effect profile of cannabinoids	Monitor therapy
MAOI inhibitors	Possible serotonin syndrome	Caution/monitor therapy
Nicotine (transdermal)	Tachycardia (additive), stimulant effects	Monitor therapy
Stimulants (e.g. Amphetamines, Cocaine, MDMA)	Additive hypertension, tachycardia, cardiotoxicity Prolongation of stimulants' hyperthermia	Avoid
Highly protein bound drugs (e.g. Warfarin)	Potential to displace drugs that are protein bound	Monitor therapy

  ^a Refer to https://drug-interactions.medicine.iu.edu/Main-Table.aspx for full list of inhibitors and inducers

 

DISCLAIMER: This article is not a legal document and is not a comprehensive review of cannabis. It is recommended to access other available resources for more information. In addition, for the legal indications and limitations of cannabis use, pharmacists must refer to the most current and appropriate local, provincial and federal laws and guidelines.

 

 

REFERENCES

1.  Medical cannabis Q&A. CPJ November/December 2017; 150 (6): 353-4.

2.  Government of Canada.  About Cannabis [Internet]. 2018 [updated 2018 Aug 13; cited 2018 Sept 25].  Available from: https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis.html

3.  Kani M.  Clinical Feature: Medical marijuana.  Pharmacy Practice Plus  [Internet]. Mar 2017 [cited 2018 Sept 25].  Available from: www.canadianhealthcarenetwork.ca

4. Kent D, editor.  Poison Management Manual.  Vancouver: BC Drug and Poison Information Centre;  2015 March.  Cannabis.

5.  Continuing Education Online, Medical Marijuana. Pharmacist's Letter/Prescriber's Letter. Course No. 17-231.  2017.

6.  Gorelick DA.  Cannabis use and disorder:  Pathogenesis and pharmacology.  In: UpToDate, Post, TW (Ed). UpToDate, Waltham, MA, 2018.

7.  Leung W.  A consumer's guide to cannabis basics.  The Globe and Mail 2018 Sep 21 : Sect. Health

8.  CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c 2016 [updated 2018 Apr; cited 2018 Sep 25]. Cannabis [product monograph]. Available from: http://www.e-cps.ca or http://www.myrxtx.ca  Also available in paper copy from the publisher.

9. Clinical Resource, Comparison of Cannabinoids.  Pharmacist's Letter/Prescriber's Letter.  September 2018 - Resource #340904.

10.  About Hemp and Canada's Hemp Industry, Government of Canada.  Industrial Hemp [Internet] 2011https://www.canada.ca/en/health-canada/services/health-concerns/controlled-substances-precursor-chemicals/industrial-hemp/about-hemp-canada-hemp-industry.html

11.  Bridgeman MB, Abazia DT.  Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. Pharmacy and Therapeutics 2017 Mar;42(3):180-188.

12. Memedovich KA, Dowsett LE, Spackman E et al. The adverse health effects and harms related to marijuana use: an overview review.  CMAJ OPEN 2018; 6(3): E339-346.

13. Keehbauch J, Rensberry M.  Editorials Effectiveness, Adverse Effects, and Safety of Medical Marijuana.  Am Fam Physician 2015 Nov 15: 92(10): 856-863.

14. Li R. DPIC: Cannabinoid Hyperemesis Syndrome. The Tablet 2017 Oct 16

15. BCCDC Health Canada Cannabis Report : 2018 June. 140 p.

16. Want to buy legal pot on Oct. 17? Here's what you need to know. CBC News [Internet]. 2018 Sep 17 [cited 2018 Sep 18]:  Available from: www.cbc.ca/news/canada/british-columbia/want-to-buy-legal-pot-on-oct-17-here-s-what-you-need-to-know-1.4827323

17. Cesamet Drug Product Monograph. Health Canada Drug Product Database [Internet] [Cited 2018 Sep 25] Available from: https://health-products.canada.ca/dpd-bdpp/index-eng.jsp

18. Sativex Drug Product Monograph.  Health Canada Drug Product Database [Internet] [Cited 2018 Sep 25] Available from: https://health-products.canada.ca/dpd-bdpp/index-eng.jsp

19. Densmore C.  The confusion surrounding marijuana dispensaries-legal or illegal? Ottawa Life [Internet]. 2018 January 09 [Cited 2018 Sep 18]: Available from: http://www.ottawalife.com/article/the-confusion-surrounding-marijuana-dispensaries-legal-or-illegal?c=1

20. Preston C, editor. Stockley's Drug Interactions, 11th edition.  London: Pharmaceutical Press; 2016.

21. Procyshyn RM, Bezchlibnyk-Butler K, Jeffries J, editors.  Clinical HandBook of Psychotropic Drugs , 22nd edition.  Boston, MA: Hogrefe Publishing Corp; 2017.

22. Department of Justice, Government of Canada.  Cannabis Legalization and Regulation [Internet]. 2018 [updated 2018 Aug 09; cited 2018 Sept 27].  Available from: https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/laws-regulations.html

23. Accessing cannabis for medical purposes, Government of Canada.  Cannabis for medical purposes [Internet] 2016 [updated 2016 Aug 24; cited 2018 Sept 27].  Available from: https://www.canada.ca/en/health-canada/topics/accessing-cannabis-for-medical-purposes.html

24. Accessing cannabis for medical purposes from a licenced producer, Government of Canada. Cannabis for medical purposes [Internet] 2016 [updated 2017 Jan 05; cited 2018 Sept 27].  Available from: https://www.canada.ca/en/health-canada/services/getting-cannabis-from-licensed-producer.html

25. Information for Health Care Practitioners - Medical Use of Cannabis, Government of Canada [Internet]. 2016 [updated 2016 Aug 19; cited 2018 Sept 27].  Available from:  https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners.html

26. Public Safety & Emergency Services, Province of British Columbia.  Cannabis  [Internet] 2018 [cited 2018 Sept 27].  Available from: https://www2.gov.bc.ca/gov/content/safety/public-safety

27. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). https://drug-interactions.medicine.iu.edu  Accessed Sept 25, 2018.