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Healthcare Professionals

Cannabidiol (CBD) is one of the major phytocannabinoids found in the cannabis plant. Unlike THC, CBD is the non-euphoric component of the cannabis plant and does not cause a ‘high’. The pharmacokinetic and pharmacodynamic properties of CBD are summarized below. 
Pharmacokinetics1-3
Absorption: Post-inhalation the peak plasma concentration of CBD is attained rapidly (within 3–10 minutes). The bioavailability of inhaled CBD has been reported to be 31%. Following oral administration, CBD appears to have a similar plasma concentration-time profile to that of oral THC i.e. CBD may take up to 120 minutes to reach peak concentration and has low oral bioavailability (~6%). The data suggests that oral formulations may be useful for patients requiring symptomatic relief over a longer period.
Distribution: Similar to THC, CBD is also highly lipophilic in nature. CBD distributes rapidly into highly vascularized organs (e.g. lung, heart, brain, liver) followed by distribution into less vascularized tissues until equilibrium is reached. 
Metabolism: CBD is primarily metabolized in the liver via isoenzymes CYP2C19, CYP3A4, CYP1A1, CYP1A2, CYP2C9 and CYP2D6. The primary metabolite of CBD is 7 (or 11)-hydroxy-CBD.
Elimination: CBD appears to have a long terminal elimination half-life; approximately 24 hours post-inhalation and 2–5 days post oral administration. A large portion of CBD is excreted intact or as its glucuronide in the urine and feces.
Pharmacodynamics: Unlike THC, CBD does not appear to bind to either CB1 or CB2 receptors. However, evidence suggests that CBD may act as a negative allosteric modulator of CB1 receptors. A considerable body of evidence suggests that CBD may act via a significant number of other targets including ion channels, receptors, and enzymes.1-3
The complexity of pharmacology of CBD offers tremendous therapeutic potential as well as potential to interact with other medications. 
References
<ol>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a> </li>
<li>Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018;84:2477–82.</li>
<li>Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003;42(4):327–60.</li>
</ol>

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Image-PractitionerArticles-18683_PK-PD-properties-of-CBD

PK/PD properties of CBD

9-tetrahydrocannabinol (THC) is one of the major phytocannabinoids found in the cannabis plant. It is the principal constituent of the cannabis plant responsible for the euphoric effects.1 The pharmacokinetic and pharmacodynamic properties of THC are summarized below.
Pharmacokinetics1-3
<ol>
<li>Absorption: Post-inhalation, the peak plasma concentration of THC is attained rapidly within few minutes. The bioavailability of THC after inhalation ranges from 10–35%. However, post-oral ingestion, it may take up to 120 minutes to reach peak concentration and has low oral bioavailability (~6%). The oral formulations may be useful for patients requiring symptomatic relief over a longer period.</li>
<li>Distribution: Being highly lipophilic in nature, THC and its metabolites distribute rapidly to fatty tissues and the brain, causing it to accumulate and get stored in the body fat to be released slowly back into the blood for metabolism.</li>
<li>Metabolism: The metabolism of THC is predominantly hepatic via the cytochrome P450 (CYP 450) enzyme system (CYP2C9, CYP2C19, CYP3A4). It is metabolized to form 11-hydroxy-THC and 11-carboxy-THC. THC largely avoids the process of the first-pass metabolism upon inhalation (by either smoking or vaporizing) since it is absorbed from the lungs directly into the blood. Because of the differences in absorption, the THC metabolite ratios observed in the body post-administration are essentially dependent on the route of administration.</li>
<li>Elimination: THC is metabolized by the body extensively; thus, insignificant amounts of THC gets excreted in its unchanged form. Following smoking, elimination of THC and its metabolites occurs via feces (65%) and urine (20%). Following oral administration, THC and its metabolites are excreted in the feces and urine; with biliary excretion being the major route of elimination (&gt;50%). Estimates of the elimination half-life of THC appear to vary with an estimated long terminal half-life (22 hours) and even longer time in heavy users.</li>
</ol>
Pharmacodynamics: THC acts as a partial agonist at CB1 and CB2 receptors and has activity at other non-cannabinoid receptors as well. Its psychoactive effects are mediated by agonist effects at CB1 receptors. THC results in a dose-dependent impairment in performance. Tachycardia experienced by patients after using THC is probably via direct agonism of CB1 receptors. Co-administration of CBD has been reported to reduce the side effects of THC.1-3
References
<ol>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a> </li>
<li>Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018;84:2477–82.</li>
<li>Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003;42(4):327–60.</li>
</ol>

Image-PractitionerArticles-18681_PK-PD-properties-of-THC

PK/PD properties of THC

While there are over 100 cannabinoids produced by cannabis only few are produced in significant quantities. The most commonly studied phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).1 THC is the primary constituent responsible for the euphoric effects of cannabis. Beside its euphoric effects, THC is a potent anti-inflammatory and analgesic. Whereas, CBD is the non-euphoric component of the cannabis plant; results from pre-clinical studies suggests CBD has anti-inflammatory, analgesic, anti-nausea, anti-emetic, anti-psychotic, anxiolytic and anti-epileptiform effects.1 Potential medical benefits of THC and CBD are summarized as below.1,2
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Information on side effects associated with the therapeutic use of cannabinoids is limited. Cannabis/cannabinoids are generally well tolerated; however, side effects are usually observed with high dose of cannabinoids.1 Some of the potential side effects associated with THC and CBD are summarized as below:
<table>
<thead>
<tr>
<th style="text-align: left;">THC1,3</th>
<th style="text-align: left;">CBD4-6</th>
</tr>
</thead>
<tbody>
<tr>
</tr>
<tr>
<td style="text-align: left;">- Tachycardia (dose-related)</td>
<td style="text-align: left;">- Elevated aminotransferase levels</td>
</tr>
<tr>
<td style="text-align: left;">- Orthostatic hypotension</td>
<td style="text-align: left;">- Diarrhea</td>
</tr>
<tr>
<td style="text-align: left;">- Dry mouth</td>
<td style="text-align: left;">- Loss of appetite</td>
</tr>
<tr>
<td style="text-align: left;">- Increased appetite</td>
<td style="text-align: left;">- Vomiting</td>
</tr>
<tr>
<td style="text-align: left;">- Paranoia</td>
<td style="text-align: left;">- Weight loss</td>
</tr>
<tr>
<td style="text-align: left;">- Psychomotor impairment</td>
<td style="text-align: left;">- Somnolence</td>
</tr>
<tr>
<td style="text-align: left;">- Somnolence</td>
<td style="text-align: left;">- Rash</td>
</tr>
<tr>
<td style="text-align: left;">- Dizziness</td>
<td style="text-align: left;">- Fatigue</td>
</tr>
<tr>
<td style="text-align: left;">- “High state” (euphoria, relaxation, distorted perception)</td>
<td style="text-align: left;">- Insomnia</td>
</tr>
<tr>
<td style="text-align: left;">- Anxiety/nervousness</td>
<td style="text-align: left;">Headache</td>
</tr>
</tbody>
</table>
In summary, both THC and CBD have potential medical benefits and are generally considered safe. However, the possibility of side effects and drug-drug interactions should be considered and caution should be exercised when initiating treatment with cannabinoids. 
References
<ol>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a> 
2.National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, The National Academies Press (2017). 
3.Canadian Pharmacists Association. Cannabis monograph, April 2018. 
4.Arzimanoglou A, Brandl U, Cross H, et al. Epilepsy and cannabidiol: A guide to treatment. Epileptic Disord 2020:22(1): 1–14. 
5.Huestis MA, Solimini R, Pichini S, et al. Cannabidiol adverse effects and toxicity. Curr Neuropharmacol. 2019;17:974–89. 
6.Santos RGD, et al. Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. Expert Opin Drug Metab Toxicol. 2020;1–10.</li>
</ol>

Intro to Cannabis

Image-PractitionerArticles-18679_CBD-or-THC

CBD or THC?

The typical model for drug prescribing does not work with cannabis-based therapeutics due to the presence of variables which does not support this model.1 The complex pharmacology of cannabinoids, prior exposure to cannabis/cannabinoids, genetic factors, cannabinoid receptor distribution/density or function changes due to a medical condition, varying ratio of cannabinoids, etc. contribute to the challenge in reporting/establishing precise and uniform dosing schedules for cannabis (and/or cannabinoids).1-3
To date, there are no established dosing guidelines for cannabis. Individualization of dosing is the preferred option and depends mostly on titration.3 Patients with no prior experience with cannabis and initiating therapy with cannabis-based therapeutics for the first time are advised to commence at a very low dose and gradually increase the dose to achieve the optimal therapeutic outcome and reduce possible adverse effects (“Start low, go slow”). Patients should discontinue the treatment upon undesirable side effects.3 For patients with cannabis/cannabinoid usage history, consider current consumption quantity and method of administration (inhalation, oral, or combination).
The general recommended dose for dried cannabis is 1–3 g/day. Mean daily dose of 10–30 mg THC has been used in different studies.4-7 Chronic use and high dose up to 1,500 mg/day CBD is reportedly well tolerated in humans.8 Smoked/inhaled or oral cannabis should be consumed gradually, waiting for at least 10–20 minutes between puffs and for 30–90 minutes between the ingestion of cannabis-based oral products (drops and capsules) to gauge for strength of effects and avoid possible overdosing. Following oral administration, the effects are observed 30–60 min post-ingestion and peak at 3–4 hrs.3 Subsequent dose escalation should be slow once the subjective effects are experienced and examined carefully.
For therapeutic purposes, clinical studies of cannabis-based products are limited and are restricted to those carried out with cannabinoid isolates that have received market authorization.9,10
References
<ol>
<li>Carter GT, Weydt P, Kyashna-Tocha M, et al. Medicinal cannabis: Rational guidelines for dosing. IDrugs. 2004;7:464–70.</li>
<li>Huestis MA. Human Cannabinoid Pharmacokinetics. Chem Biodivers. 2007;4(8):1770–1804.</li>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a> </li>
<li>Carroll CB , Bain PG, Teare L, et al. Cannabis for dyskinesia in Parkinson disease: A randomized double-blind crossover study. Neurology. 2004;63:1245–50.</li>
<li>Holdcroft A, Maze M, Doré C, et al. A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiology. 2006;104:1040–46.</li>
<li>Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: A randomized, double-blind,placebo-controlled, crossover study. Mult Scler. 2004;10:417–24.</li>
<li>Zajicek J, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial. Lancet. 2003;362:1517–26.</li>
<li>Bergamaschi MM, Queiroz RHC, Zuardi AW, et al. Safety and side effects of cannabidiol, a Cannabis Sativa constituent. Curr Drug Saf. 2011;6:237–49.</li>
<li>Epidiolex®, FDA Prescribing information. Available at <a href="https://www.epidiolex.com/sites/default/files/pdfs/0820/EPX-03645-0820_EPIDIOLEX_%28cannabidiol%29_USPI.pdf">https://www.epidiolex.com/sites/default/files/pdfs/0820/EPX-03645-0820_EPIDIOLEX_%28cannabidiol%29_USPI.pdf</a></li>
<li>Sativex Oromucosal spray. Summary of Product characteristics. Available at <a href="https://www.medicines.org.uk/emc/product/602">https://www.medicines.org.uk/emc/product/602</a> </li>
</ol>

Dosage of medical cannabis

In light of the rapid shift in the usage pattern of cannabis for medical and recreational purposes, patients are more likely to ask/consult their healthcare practitioners about its side effects. It is important to ensure that patients understand that potential side effects of cannabis as some of the side effects such as sedation or cognitive impairment, can impact their safety. Some of the side effects of cannabis are summarized as below:1,2
Initial use:
<ul>
<li>Patients may experience amnesia, agitation, anxiety, paranoia, delusions, or hallucinations</li>
<li>Facial flushing or red eyes may occur</li>
<li>Dizziness or light-headedness are common when raising from lying or sitting position </li>
<li>Tachycardia could be more problematic in patients with cardiovascular disease</li>
</ul>
Most common: Sedation, dizziness, drowsiness, increased appetite, and dry mouth
Common:
<ul>
<li>Euphoria, red eyes, blurred vision, headache, and postural hypotension</li>
<li>Impaired memory and disturbances in attention, concentration and ability to think and make</li>
<li>decisions</li>
<li>Disorientation, confusion, feeling drunk, feeling &quot;too high&quot;</li>
<li>Episodes of anxiety resembling a panic attack, paranoia, hallucinations</li>
<li>Impairment in motor skills, altered bodily perceptions, loss of full control of bodily movements, falls</li>
</ul>
Long-term use:
<ul>
<li>Wheezing or chronic cough (if cannabis is smoked)</li>
<li>May impair short-term attention and concentration</li>
<li>Increase the risk of triggering or aggravating psychiatric and/or mood disorders</li>
<li>Negatively affect cognitive functions (ability to think and make decisions)</li>
<li>Lead to a decrease in one or more of the effects of cannabis (tolerance)</li>
<li>Withdrawal-type symptoms when use of cannabis is abruptly discontinued.</li>
<li>Reduced sperm count and motility and abnormal sperm morphology</li>
<li>Increased risk of cannabis hyperemesis syndrome with heavy (THC-predominant) cannabis use</li>
</ul>
Side effects are usually observed with high dose of cannabis or cannabinoids.1 Though there is no scientifically defined dose of cannabis, generally, a low dose is well-tolerated with infrequent side effects. A higher-dose or an overdose is often associated with short- or long-term side effects.1
If your patients experience any side effects or any unexpected effects while using cannabis, it is recommended that they stop using cannabis immediately and seek medical attention.
References
<ol>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a> </li>
<li>Health Canada, “Consumer Information – Cannabis (Marihuana, marijuana). Available at <a href="https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/marihuana/info/cons-eng.pdf">https://www.canada.ca/content/dam/hc-sc/migration/hc-sc/dhp-mps/alt_formats/pdf/marihuana/info/cons-eng.pdf</a> </li>
</ol>

Side effects of medical cannabis

Cannabis-based therapeutics are implemented in several physiological processes such as appetite stimulation, pain modulation, control of chemotherapy induced nausea and vomiting etc.1 When used in combination with other drugs, pharmacokinetic and pharmacodynamic interaction(s) could be expected. The potential drug interaction outcomes can be either synergistic (1+1&gt; 2), additive (1+1= 2), or antagonistic (1+1&lt; 2).2 Thus, an improved response of the drug or unexpected adverse effects could be expected due to drug-drug interaction, e.g., potential risk of bleeding observed with patients receiving concomitant warfarin with cannabis or use of cannabis at the same time as other tranquilizing substances such as alcohol, benzodiazepines and opiates can cause cumulative effects.1
Given that cannabis undergoes first pass metabolism in the liver, the inhibition or induction of CYP-450 enzymes by cannabinoids (THC as CYP1A2 inducer and CBD as CYP3A4 and CYP2D6 inhibitor) may potentially affect the metabolism of many drugs.1,2 THC is oxidized by CYP mixed-function oxidases 2C9, 2C19, and 3A4 into over 80 metabolites.1,3 Thus, some antidepressants, proton pump inhibitors, macrolides, antimycotics, calcium antagonists, HIV protease inhibitors, grapefruit juice, and others that inhibit the CYP isoenzymes can potentially increase the bioavailability of THC (and 11-hydroxy-THC, a metabolite of THC) alongside the risk of drug interaction-related side effects.1,4
Like THC, CBD is also metabolized by CYP2C19 and CYP3A4 but could also act as a potential substrate for CYP 1A1, 1A2, 2C9, 2D6, 2E1, and 3A5.1 Hence, using CBD along with medications that are metabolized by CYP isoenzymes might increase the effects and side effects of some medications. As CYP3A4 metabolizes about a quarter of all drugs, CBD may increase serum concentrations of macrolides, calcium channel blockers, benzodiazepines, cyclosporine, sildenafil (and other PDE5 inhibitors), antihistamines, haloperidol, antiretrovirals, and some statins (atorvastatin and simvastatin, but not pravastatin or rosuvastatin). CYP2D6 metabolizes many antidepressants; CBD may increase serum concentrations of SSRIs, tricyclic antidepressants, antipsychotics, beta blockers and opioids (including codeine and oxycodone).1,4
Drug interactions involving cannabis and cannabinoids can vary considerably in their clinical significance given the wide variability in potencies, ratios of THC and CBD, route of administration, etc. It is advised to monitor patients who are initiating treatment with cannabis-based therapeutics concomitantly with other medications, for safety purposes, especially elderly, those with chronic diseases or kidney and liver problems.
References
<ol>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a>. </li>
<li>Alsherbiny MA and Li CG. Medicinal cannabis—Potential drug interactions. Medicines. 2019;6:3.Huestis MA. Human cannabinoid pharmacokinetics. Chem.Biodivers. 2007;4:1770–804.</li>
<li>Canadian Pharmacists Association. Cannabis monograph, April 2018.</li>
<li>Medical cannabis: Adverse effects and drug interactions. Government of the District of Columbia, Department of Health. Available at <a href="https://doh.dc.gov/sites/default/files/dc/sites/doh/publication/attachments/Medical%20Cannabis%20Adverse%20Effects%20and%20Drug%20Interactions_0.pdf">https://doh.dc.gov/sites/default/files/dc/sites/doh/publication/attachments/Medical%20Cannabis%20Adverse%20Effects%20and%20Drug%20Interactions_0.pdf</a> </li>
</ol>

Drug-drug interactions

As per recommendations from Health Canada, the risk/benefit ratio of using cannabis-based therapeutics should be carefully examined in individuals with the following medical conditions.
<ul>
<li>Cannabis containing primarily THC should not be used in individuals &lt;25 years old, unless the benefit/risk ratio is considered favourable by the physician.</li>
<li>History of hypersensitivity to any cannabinoid or to smoke (if cannabis will be smoked).</li>
<li>Patients with severe cerebrovascular or cardiovascular disease because of occasional hypotension, possible hypertension, tachycardia, syncope, myocardial infarction, and stroke.</li>
<li>Smoked cannabis is not recommended in patients with respiratory disease (e.g., asthma or chronic obstructive pulmonary disease).</li>
<li>Patients with severe renal or hepatic disease. In patients with chronic hepatitis C, daily use of cannabis acts as a predictor of steatosis severity. </li>
<li>Cannabis containing primarily THC and especially higher levels of THC should not be used in patients with a personal history of psychiatric disorders such as schizophrenia, anxiety, mood disorders, and psychosis, or familial history of schizophrenia.</li>
<li>History of alcohol or drug abuse or substance dependence; increased cognitive impairment may be observed when cannabis is consumed along with alcohol or other psychoactive drugs.</li>
<li>Patients receiving concomitant therapy with sedative-hypnotics or other psychoactive drugs because of the potential for additive or synergistic CNS depressant or psychoactive effects.</li>
<li>Women of childbearing age not on a reliable contraceptive, as well as those planning pregnancy, and those who are pregnant, or breastfeeding.</li>
<li>Men who wish to start a family.1,2</li>
</ul>
Patients using cannabis/cannabinoids (THC-predominant) should be warned not to drive or operate heavy machinery; the use of cannabis or cannabinoids may impair the mental alertness and physical coordination of the person thereby significantly decreasing their ability to perform such tasks. The impairment can last for over 24 hours after last use, depending on the dose, the route of administration and the frequency of use. The highest risk is at onset of treatment, during the titration phase and when the dose is changed. Furthermore, impairment can be exacerbated with co-consumption of other CNS depressants (e.g., benzodiazepines, barbiturates, opioids, anti-histamines, muscle relaxants, or ethanol).1,2
It is advised that patients should not drive for a minimum of 3–6 hours after inhalation and 8 hours after oral ingestion, or longer if they experience euphoria.1
There may be other conditions wherein cannabis should not be used but which may be unknown due to limited scientific information. It is advised that patients should be supervised when administration of cannabis is initiated and should be monitored on a regular basis.
References
<ol>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a>.</li>
<li>Canadian Pharmacists Association. Cannabis monograph, April 2018.</li>
</ol>

Precautions and warnings when using medical cannabis

The International Centre for Science in Drug Policy (ICSDP) has contributed significantly to the conversation regarding the use of cannabis and commonly heard claims on the use of cannabis by utilizing the scientific evidence available.1 “Common claims on cannabis use” was published as a part of the report “Using evidence to talk about cannabis” by ICSDP and highlights scientific evidence on frequently heard claims about cannabis use, including the addictive potential of cannabis, cannabis as a &quot;gateway&quot; drug, its impact on cognitive function, etc. The table below summarizes the findings from the report.1
<table>
<thead>
<tr>
<th style="text-align: left;">Claims</th>
<th style="text-align: left;">Strength of supporting evidence</th>
<th style="text-align: left;">Bottom line</th>
</tr>
</thead>
<tbody>
<tr>
<td style="text-align: left;">&quot;Cannabis [is] as addictive as heroin.&quot;</td>
<td style="text-align: left;">Weak</td>
<td style="text-align: left;">“A lifetime of cannabis use carries a low risk of dependence (9%), while the risk of cannabis dependence is very low among those who report using it for one year (2%) or even 10 years (5.9%). This is much lower than the estimated lifetime risk of dependence to heroin (23.1%).”</td>
</tr>
<tr>
<td style="text-align: left;">&quot;I'm opposed to legalizing marijuana because it acts as a gateway drug.&quot;</td>
<td style="text-align: left;">Weak</td>
<td style="text-align: left;">“Evidence to date does not support the claim that cannabis use causes subsequent use of “harder” drugs”.</td>
</tr>
<tr>
</tr>
<tr>
<td style="text-align: left;">Cannabis use &quot;can cause potentially lethal damage to the heart and arteries.&quot;</td>
<td style="text-align: left;">Weak</td>
<td style="text-align: left;">“There is little evidence to suggest that cannabis use can cause lethal damage to the heart, nor is there clear evidence of an association between cannabis use and cancer.”</td>
</tr>
<tr>
<td style="text-align: left;">Cannabis use lowers IQ by up to 8 points.</td>
<td style="text-align: left;">Weak</td>
<td style="text-align: left;">“There is little scientific evidence suggesting that cannabis use is associated with declines in IQ.”</td>
</tr>
<tr>
<td style="text-align: left;">Cannabis use impairs cognitive function.</td>
<td style="text-align: left;">Moderate</td>
<td style="text-align: left;">“While the evidence suggests that cannabis use (particularly among youth) likely impacts cognitive function, the evidence to date remains inconsistent regarding the severity, persistence, and reversibility of these cognitive effects.”</td>
</tr>
<tr>
<td style="text-align: left;">&quot;[Cannabis] is a drug that can result [in] serious, long-term consequences, like schizophrenia.&quot;</td>
<td style="text-align: left;">Weak</td>
<td style="text-align: left;">“While scientific evidence supports an association between cannabis use and schizophrenia, a causal relationship has not been established.”</td>
</tr>
</tbody>
</table>
Thus, most claims on the use of cannabis outlined in the reports tend to either misinterpret or overstate the existing scientific evidence. The review of often-repeated claims about cannabis use was not found to be strongly supported by scientific evidence. 
References
<ol>
<li>International Centre for Science in Drug Policy (ICSDP). Using evidence to talk about cannabis. International Centre for Science in Drug Policy (ICSDP), Toronto, 2017. Available at <a href="https://cdpe.org/wp-content/uploads/2018/04/Using_Evidence_to_Talk_About_Cannabis_ENG.pdf">https://cdpe.org/wp-content/uploads/2018/04/Using_Evidence_to_Talk_About_Cannabis_ENG.pdf</a> </li>
</ol>

Scientific evidence on common claims about cannabis

Over the past couple of decades, there have been significant changes in the policy landscape surrounding cannabis legalization and these changes in policies have markedly changed cannabis use patterns. In Canada, the use of cannabis for medical purposes has been approved since 2001.1 While a myriad of studies2,3 has examined the use of cannabis in its various forms, there still is a need for randomized controlled trials to generate robust evidence on the efficacy of cannabinoids. Over the past couple of decades, there have been significant changes in the policy landscape surrounding cannabis legalization and these changes in policies have markedly changed cannabis use patterns. In Canada, the use of cannabis for medical purposes has been approved since 2001.1 While a myriad of studies2,3 has examined the use of cannabis in its various forms, there still is a need for randomized controlled trials to generate robust evidence on the efficacy of cannabinoids.
A broad review of scientific evidence related to the potential therapeutic benefits of cannabis is provided by the National Academies of Sciences, Engineering, Medicine in the book titled ‘Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research’.4 Findings from their research is summarized as below.
Conclusive or substantial evidence
<ul>
<li>Chronic pain</li>
<li>Chemotherapy-induced nausea and vomiting</li>
<li>Spasticity associated with multiple sclerosis</li>
<li>Epilepsy</li>
</ul>
Moderate evidence
<ul>
<li>Sleep disorders</li>
<li>Fibromyalgia</li>
<li>Post-traumatic stress disorder (PTSD)</li>
</ul>
Limited evidence
<ul>
<li>Anorexia</li>
<li>Tourette syndrome</li>
<li>Anxiety</li>
<li>Alzheimer’s disease and dementia</li>
<li>Glaucoma</li>
<li>Depression</li>
<li>Arthritis and musculoskeletal disorders</li>
</ul>
Insufficient evidence to support or refute
<ul>
<li>Cancer</li>
<li>Irritable bowel syndrome</li>
<li>Irritable bowel disease</li>
<li>Spinal cord injury</li>
<li>Amyotrophic lateral sclerosis</li>
<li>Huntingtons disease</li>
<li>Parkinsons disease</li>
<li>Schizophrenia</li>
<li>Wasting syndrome</li>
<li>Anorexia nervosa</li>
</ul>
In June 2018, CBD was approved by the US Food and Drug Administration for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients aged 2 years or above. Later the approval was expanded to include seizures associated with tuberous sclerosis complex and in patients 1 year of age or older for all the aforementioned conditions.5
References
<ol>
<li>Understanding the New Access to Cannabis for Medical Purposes Regulations. Government of Canada. Available at <a href="https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/understanding-new-access-to-cannabis-for-medical-purposes-regulations.html">https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/understanding-new-access-to-cannabis-for-medical-purposes-regulations.html</a> </li>
<li>Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015;313(24):2456–73.</li>
<li>Montero-Oleas N, Arevalo-Rodriguez I, Nunez-Gonzalez S, et al. Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews. BMC Complement Med Ther. 2020;20:12.</li>
<li>National Academies of Sciences, Engineering, and Medicine. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research, The National Academies Press (2017). </li>
<li>Epidiolex®, FDA Prescribing information. Available at <a href="https://www.epidiolex.com/sites/default/files/pdfs/0820/EPX-03645-0820_EPIDIOLEX_%28cannabidiol%29_USPI.pdf">https://www.epidiolex.com/sites/default/files/pdfs/0820/EPX-03645-0820_EPIDIOLEX_%28cannabidiol%29_USPI.pdf</a> </li>
</ol>

Image-PractitionerArticles-18668_Who-may-benefit-from-medical-cannabis

Who may benefit from medical cannabis?

Cannabis (also known as marijuana, marihuana) is a herbaceous flowering plant which belongs to the family Cannabacceae.1 It is commonly found in the temperate and tropical climates.2 Taxonomists have classified the cannabis plant variously. The most common species of cannabis plant are Cannabis sativa, Cannabis indica and Cannabis ruderalis. However, there is still much debate surrounding the taxonomy of cannabis due to the wide variation in its gene pool.1 Cannabis has been used for medicinal purposes for centuries. In Canada, the production, distribution, sale, and possession of cannabis is controlled per the framework defined in the Cannabis Act,3 which came into force in October 2018. The Cannabis Act replaced the Access to Cannabis for Medical Purposes Regulations (ACMPR).
Active constituents of cannabis
In the cannabis plant, there are 500 distinct compounds distributed among 18 different chemical classes present. Cannabis plants produce a unique family of terpeno-phenolic compounds called cannabinoids. While there are over 100 different phytocannabinoids produced by cannabis plant, only few are present in high concentration.2 The quantity of the phytocannabinoids might vary based on the cannabis strain, the soil and climate conditions, and the cultivation techniques.2 Delta-9-tetrahydrocannabinol (Δ9-THC or THC) and cannabidiol (CBD) are the principal phytocannabinoids. While THC is the primary constituent responsible for the euphoric effects of cannabis, CBD is the non-euphoric component. Other phytocannabinoids include cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG), tetrahydrocannabivarin (THCV), and others.2
Cannabis-based medications can be either plant-derived or synthetic, contains different ratio of cannabinoids, and can be delivered via inhalation, oromucosal, ingestion, and topical routes. The administration route affects the rate of THC and CBD absorption, and thus influences the onset, intensity, and duration of the clinical effect(s) of cannabis-based therapeutics.2
References
<ol>
<li>Gloss D. An overview of products and bias in research. Neurotherapeutics. 2015;12:731–34.</li>
<li>Health Canada, &quot;Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids, 2018&quot;. Available at: <a href="https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html">https://www.canada.ca/en/health-canada/services/drugsmedication/cannabis/information-medical-practitioners/information-health-care-professionalscannabis-cannabinoids.html</a> </li>
<li>Cannabis Act. Government of Canada, Justice Laws Website. Available at <a href="https://laws-lois.justice.gc.ca/eng/acts/C-24.5/">https://laws-lois.justice.gc.ca/eng/acts/C-24.5/</a> </li>
</ol>

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