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Medical cannabis: Drug information

Medical cannabis: Drug information
For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Cannabinoid
Dosing: Adult

Note: No specific dose recommendations exist due to differences in preparations and routes of administration; for example, vaping cartridges containing cannabis products may deliver higher doses more efficiently as compared to smoking herbal cannabis products (Davenport 2021). In addition, there is wide variability between patients with regards to response to cannabinoids; treatment regimens must be patient-specific and accompanied by close monitoring (Health Canada 2018).

Inhalation, Oral, Sublingual: In general, clinicians are advised to initiate therapy at a low dose and utilize a slow titration schedule (Busse 2021; CFPC 2014). Consider repeated doses no sooner than every 10 to 20 minutes (inhalation) or ≥30 minutes (oral) to allow for impact of prior dose to be realized and to prevent overdose. Use caution when increasing daily dose; consider increase of 1 puff (inhalation) or 1 drop (sublingual) per dose per day (Health Canada 2018).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling of FDA- or Health Canada–approved cannabidiol products (has not been studied); use with caution (Dronabinol prescribing information; Sativex Canadian product monograph; Syndros Canadian product monograph).

Dosing: Hepatic Impairment: Adult

Moderate impairment: Consider avoiding use in patients with moderate impairment (Sativex Canadian product monograph).

Severe impairment: Use is not recommended in patients with severe liver disease (Health Canada 2018; Sativex Canadian product monograph).

Dosing: Older Adult

Use with caution; older adults may be more sensitive or susceptible to adverse effects (Health Canada 2018).

Dosing: Adjustment for Toxicity: Adult

Acute psychosis: Discontinue treatment and seek immediate medical attention (Health Canada 2018).

Product Availability

While cannabis is considered a Schedule I drug by the United States federal government, local state laws and regulations may differ. Refer to both federal and local laws for details.

More information on state laws within the United States can be found here: http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx#3

Controlled Substance

C-I

Note: While cannabis is considered a Schedule I drug by the federal government of the United States, local state laws and regulations may differ. Refer to both federal and local laws for details.

Prescribing and Access Restrictions

While cannabis is considered a Schedule I drug by the United States federal government, local state laws and regulations may differ. Refer to both federal and local laws for details.

More information on state laws within the United States can be found here: http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx#3

Use: Off-Label: Adult

Anxiety (alternative or adjunctive agent); Inflammatory bowel disease (alternative adjunctive agent); Pain, chronic (alternative agent); Posttraumatic stress disorder (alternative agent); Spasticity secondary to multiple sclerosis (alternative agent)

Adverse Reactions

The following adverse drug reactions are derived from limited sources (Health Canada 2018, Wang 2008).

Frequency not defined:

Cardiovascular: Acute myocardial infarction, atrial fibrillation, cerebrovascular accident, circulatory shock, deep vein thrombosis, hypertension, hypotension, orthostatic hypotension, orthostatic syncope, palpitations, supine hypertension, syncope, tachycardia, vasodilation, ventricular arrythmia, ventricular premature contractions

Dermatologic: Cellulitis, hyperhidrosis, pressure ulcer, pruritus

Endocrine & metabolic: Dehydration, hot flash, increased thirst

Gastrointestinal: Abdominal pain, constipation, decreased gastrointestinal motility, diarrhea, duodenal ulcer, dysgeusia, dysphagia, gastroenteritis, increased appetite, nausea, oral mucosa ulcer, pancreatitis, vomiting, xerostomia

Genitourinary: Bladder dysfunction, hematuria, testicular neoplasm, urinary tract infection

Hematologic & oncologic: Anemia, leukopenia, lymphadenopathy

Hepatic: Abnormal hepatic function tests, hepatic fibrosis, hepatobiliary disease (biliary cirrhosis), liver steatosis

Hypersensitivity: Hypersensitivity reaction

Infection: Infection, sepsis

Nervous system: Abnormal dreams, aggressive behavior, agitation, amnesia, anxiety, apathy, ataxia, balance impairment, bipolar mood disorder, central nervous system depression, cognitive dysfunction (and altered perception), confusion, delusion, depersonalization, depression (including a feeling of despair), disorientation, dissociative reaction, disturbance in attention, dizziness, drowsiness, drug dependence, dysarthria, dysphoria, emotional lability, euphoria, falling, fatigue, hallucination, headache, hypoesthesia, impulsivity, intoxicated feeling, irritability, lack of concentration, memory impairment (and cognitive impairment), mental deficiency, mood changes, mouth pain, myasthenia, myoclonus, nervousness, panic attack, paranoid ideation, paresthesia, psychosis, schizophrenia, sedated state, seizure, speech disturbance, suicidal ideation, suicidal tendencies, vertigo, withdrawal syndrome

Neuromuscular & skeletal: Asthenia, muscle spasm, muscle twitching, myalgia, osteomyelitis, tremor

Ophthalmic: Blurred vision, eye redness

Otic: Tinnitus

Respiratory: Acute pulmonary reaction (bronchodilation), cough, dyspnea, increased bronchial secretions, lower respiratory tract infection, nasopharyngitis, pharyngitis, pleural effusion, pleurisy, pneumonia, throat irritation, wheezing

Miscellaneous: Aggravation reaction, drug tolerance, fever

Contraindications

In general, contraindications that apply to cannabinoid-based therapies (eg, nabilone, dronabinol) also apply to the use of all cannabis products (Health Canada 2018).

Warnings/Precautions

Concerns related to adverse effects:

• Addiction and dependence: Chronic use may lead to addiction and/or dependence; risk is increased with onset of use during adolescence and prior history of substance abuse (Volkow 2014; Wang 2008). Tolerance and psychological and physical dependence may occur with prolonged use.

• Cardiovascular and cerebrovascular effects: Delta-9-tetrahydrocannabinol (THC) may cause occasional hypotension, possible hypertension, syncope, or tachycardia; patients with cardiac disorders may be at higher risk for hemodynamic instability. Monitor for changes in heart rate, BP, and for signs/symptoms of syncope after initiating treatment and with dosage increases. Avoid concomitant use with other medications associated with similar cardiovascular adverse effects (Dronabinol prescribing information; Syndros Canadian product monograph). Inhalational use of cannabis may be a rare trigger of acute myocardial infarction and/or result in an increased risk of hospitalization for acute ischemic stroke (Mittleman 2001; Rumalla 2016). Use is not recommended in patients with a prior history of severe cardiovascular or cerebrovascular disease (Franz 2016; Health Canada 2018).

• CNS depression: May cause CNS depression (including sedation and somnolence), which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). Use with caution with concomitant use of sedative-hypnotics or other psychoactive drugs; concomitant use of alcohol may increase the risk for adverse events (Health Canada 2018). Consider counseling patients who have used cannabis to avoid driving for 4 hours following inhalation, 6 hours following oral ingestion, or 8 hours following inhalation or oral ingestion if the patient is experiencing euphoria (CFPC 2014).

• E-cigarette, or vaping, product-use associated lung injury: Use of e-cigarette or vaping products has been associated with an outbreak of e-cigarette, or vaping, product-use associated lung injury (EVALI) (Ellington 2020). Epidemiologic data suggest that EVALI most often occurred in individuals who used THC-containing products obtained from informal sources. In patients who developed EVALI following use of THC-containing products during the 2019 outbreak, vitamin E acetate was often found in the vaping product; however, it is not known if other additives may also result in EVALI (Krishnasamy 2020).

• GI effects: New or worsening paradoxical nausea, vomiting, and/or abdominal pain has occurred with oral cannabinoid therapy; symptoms are similar to cannabinoid hyperemesis syndrome (CHS) (Dronabinol prescribing information; Syndros Canadian product monograph). CHS is generally associated with frequent (weekly or greater), chronic (≥1 year) use (Sorensen 2017).

• Hypersensitivity reactions: Use of cannabis may result in hypersensitivity regardless of the route of exposure. Symptoms may range from mild to life-threatening and may include respiratory symptoms following inhalation, as well as dermatologic reactions following handling. Use is not recommended in patients with a prior history of hypersensitivity to any cannabinoid or smoke (if cannabis will be smoked) (Health Canada 2018). Cross reactivity with plant-derived food allergies (cannabis-fruit/vegetable syndrome) may occur; the most commonly associated food allergies include peach, banana, apple, cherry, nuts, tomato, orange, and grapefruit (Decuyper 2015).

• Malignancy: Current, frequent (weekly or greater), or chronic (≥10 years) use of cannabis may be associated with an increased risk of nonseminoma-type testicular cancer (Gurney 2015; Huang 2015). Although data are conflicted on the risk of carcinogenesis and mutagenesis secondary to smoking cannabis, it is recommended that smoking should be avoided as a preferred route of administration and other routes should be considered (Health Canada 2018).

• Psychiatric effects: Use of cannabis, especially THC-predominant products, may be associated with an increased risk of psychosis and schizophrenia (Hindley 2020); early, chronic, and heavy use of cannabis is associated with a higher risk (Health Canada 2018; Wilkinson 2014). Use is not recommended in patients with a personal history or strong family history of schizophrenia (CFPC 2014). Use of cannabis, especially THC-predominant products, may also be associated with the onset of anxiety, depressive, and bipolar disorders as well as the exacerbation of symptoms related to posttraumatic stress, panic, depressive, and bipolar disorders (Health Canada 2018; Volkow 2014).

• Respiratory effects: Use of inhaled cannabis, especially chronic use, is associated with inflammation of the large airways, increased airway resistance, lung hyperinflation, and chronic bronchitis (Tashkin 2013). Use of inhaled cannabis is not recommended in patients with a history of respiratory disease (eg, asthma, chronic obstructive pulmonary disease) (Health Canada 2018).

Disease-related concerns:

• Hepatic impairment: Use is not recommended in patients with severe liver disease (Health Canada 2018). Daily use of cannabis may be associated with moderate to severe fibrosis in patients with hepatitis C virus infection (Ishida 2008).

• Renal impairment: Use is not recommended in patients with severe kidney disease (Health Canada 2018).

Special populations:

• Adolescents and young adults: Regular use of cannabis products during adolescence and young adulthood may impair brain development and result in cognitive impairment (Volkow 2014). In addition, young patients who smoke cannabis are at a higher risk for adverse psychosocial effects (eg, suicidal ideation, illicit drug use, cannabis use disorder) (CFPC 2014; Gobbi 2019). Use in people <25 years of age is not recommended (Health Canada 2018).

• CYP2C9 polymorphism: THC is metabolized via CYP2C9 to 11-hydroxy-delta-9-THC, the major active metabolite (Dean 2020; Hryhorowicz 2018; Sachse-Seeboth 2009; Watanabe 2007; Syndros Canadian product monograph). According to dronabinol labeling, individuals with decreased CYP2C9 function have 2- to 3-fold times higher exposure than individuals with normal CYP2C9 function (Dronabinol prescribing information; Syndros Canadian product monograph).

• Older adults: Older adults may be more sensitive to the neurological, psychoactive, and postural hypotensive effects of THC; use with caution (Dronabinol prescribing information; Syndros Canadian product monograph). Consider use of smaller initial doses.

Metabolism/Transport Effects

Substrate of CYP2C9 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): Cannabis may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Anticholinergic Agents: May enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Beta-Blockers: May enhance the adverse/toxic effect of Cannabis. Specifically, the risk of hypoglycemia may be increased. Risk C: Monitor therapy

CarBAMazepine: Cannabis may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cocaine (Topical): May enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CYP1A2 Substrates (High risk with Inducers): Cannabis may decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Propofol: Cannabis may diminish the therapeutic effect of Propofol. Risk C: Monitor therapy

Sympathomimetics: Cannabinoid-Containing Products may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Tacrolimus (Systemic): Cannabis may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the tachycardic effect of Cannabinoid-Containing Products. Blood pressure raising effects and drowsiness may also be enhanced. Risk C: Monitor therapy

Warfarin: Cannabinoid-Containing Products may increase the serum concentration of Warfarin. Risk C: Monitor therapy

Food Interactions

Oral: The AUC increases about 4-fold when oral cannabidiol is administered with a high-fat meal (Perucca 2020).

Reproductive Considerations

Delta-9-tetrahydrocannabinol (THC), a main component of marijuana, may interfere with endogenous regulation of the male and female reproductive systems. THC activates cannabinoid receptors, which can be found in the uterus, ovaries, oviduct, follicles, sperm, and testis (Ezechukwu 2020). Marijuana exposure may lead to changes in semen parameters (including changes in sperm count, motility, morphology, and DNA fragmentation) and prolong the menstrual cycle, which could influence reproduction. However, available human studies evaluating the actual impact of cannabis on male and female fertility are inconclusive (Corsi 2021; Dubovis 2020; Harlow 2021; Mumford 2021).

Until sufficient data become available, patients planning to become pregnant are encouraged to discontinue use of medical cannabis and use therapies with pregnancy-specific safety information (ACOG 2017).

Pregnancy Considerations

Delta-9-tetrahydrocannabinol (THC) crosses the placenta (NASEM 2017). The active metabolite, 11-hydroxy-tetrahydrocannabinol (11-OH-THC), can be detected in the umbilical cord (Metz 2019). In addition, cannabidiol, 11-OH-THC, and other metabolites can be detected in the meconium (Kim 2018).

THC activates cannabinoid receptors, which can be found in the placenta and uterus; exposure during pregnancy may lead to embryotoxic and fetotoxic effects (Ezechukwu 2020). THC is highly lipophilic, which leads to slow clearance from fetal tissues. Due to delayed clearance, fetal exposure may be prolonged after maternal discontinuation (Corsi 2021). Most pregnancy outcome data are from nonmedicinal exposure and may be confounded by concomitant use of tobacco, alcohol, and/or illicit substances. Quantification of maternal marijuana exposure is often self-reported (which may not reflect actual use), exposure is variable (route of administration, frequency of use), and the potency of marijuana has increased over time, limiting comparisons from earlier studies to current data (Bailey 2020; Coleman-Cowger 2018; Conner 2016; Corsi 2020; Grzeskowiak 2020; Gunn 2016; Howard 2019; Luke 2019; Metz 2017; Metz 2019; Metz 2022; Nawa 2020; Paul 2021; Peterson 2020; Sharapova 2018; Stroud 2018). In general, there may be an association with in-utero cannabis exposure and a risk for small gestational age, prematurity, low birthweight, and adverse neurobehavioral development (Dubovis 2020; Grant 2020; Nashed 2021). However, available information following maternal use of marijuana is unclear and insufficient to evaluate cannabis exposure on pregnancy outcomes (ACOG 2017; NASEM 2017).

Use of medical cannabis has been evaluated for nausea and vomiting associated with chemotherapy, and some pregnant patients have reported use of marijuana for pregnancy-associated nausea and vomiting. However, use for this purpose cannot be recommended based on available information (Dickson 2018; Koren 2020; Westfall 2006).

There are no FDA-approved uses of medical cannabis for pregnant patients. Until sufficient safety data become available, pregnant patients are encouraged to discontinue use of medical cannabis and use therapies with pregnancy-specific safety information (ACOG 2017).

States with medical marijuana laws allowing medical cannabis or recreational use have seen an increased use by patients who are pregnant. Reviews highlight that increased availability does not imply safety for pregnancy. In addition, health care providers and patients should be aware of state specific laws related to reporting marijuana exposure in pregnant patients (Krening 2018; Meinhofer 2019; Miller 2019).

Breastfeeding Considerations

Delta-9-tetrahydrocannabinol (THC) and the active metabolites 11-hydroxy-tetrahydrocannabinol (11-OH-THC) and 9-hydroxy-tetrahydrocannabinol (9-OH-THC) can be detected in breast milk following maternal inhalation of marijuana (Perez-Reyes 1982). THC and 11-OH-THC can also be detected in breast milk following maternal use of edible products (Moss 2021).

Reported breast milk concentrations of THC are highly variable and influenced by the frequency of maternal use and sampling time since last exposure (Bertrand 2018; Moss 2021). Cannabinoids are highly lipophilic and have a relatively low molecular weight, allowing for easy transfer into breast milk. The fat composition in breast milk is variable, which can also impact cannabinoid content (Corsi 2021).

A study evaluated the pharmacokinetics of medical cannabis in the breast milk of 8 women 3 to 5 months postpartum who were exclusively breastfeeding full-term infants. Breast milk was sampled prior to and between 20 minutes and 4 hours after inhalation of a specified product obtained from a single dispensary. Maximum concentrations of THC in breast milk occurred 1 hour after inhalation. Metabolites were not detected; however, a longer study period may be required to evaluate breast milk concentrations of 11-OH-THC and 9-OH-THC (Baker 2018). THC was measurable in breast milk 6 days following maternal use in 1 mother (Bertrand 2018). A second study suggests the half-life of THC in breast milk could be 17 days (Wymore 2021).

A case report notes the presence of 11-OH-THC and 9-OH-THC in a fecal sample of a breastfed infant following maternal use of inhaled marijuana, used daily for 8 months (Perez-Reyes 1982).

Neurodevelopment may be impaired; however, studies evaluating infant development following exposure to cannabis via breast milk have conflicting outcomes. Outcome data are from nonmedicinal exposure and may be confounded by concomitant use of tobacco, alcohol, and/or illicit substances. Quantification of maternal marijuana exposure is self-reported (which may not reflect actual use), exposure is variable (route of administration, frequency of use), and the potency of marijuana has increased over time, limiting comparisons from earlier studies to current data. Maternal marijuana use may also be associated with a shorter duration of breastfeeding (Ordean 2020).

Limited guidance is available specific to the use of marijuana in breastfeeding patients due to variations in marijuana potency, differences in legal availability, and the wide range of maternal exposure in available studies. The Academy of Breastfeeding Medicine recommends use of marijuana be eliminated or reduced in patients who are breastfeeding. Patients using marijuana should be counseled that long-term neurobehavioral effects to a breastfed infant are possible. In addition, secondhand marijuana smoke may be associated with sudden infant death syndrome (ABM [Reece-Stremtan 2015]). Mothers should avoid coexposures of substances such as alcohol and tobacco and avoid breastfeeding within 1 hour of inhaled cannabis use (Ordean 2020). Until sufficient safety data become available, breastfeeding patients are encouraged to discontinue use of medical cannabis and use therapies with breastfeeding-specific safety information (ACOG 2017).

States with medical marijuana laws allowing medical cannabis or recreational use have seen an increased use by patients who are breastfeeding. Reviews highlight that increased availability does not imply safety for breastfeeding patients. In addition, health care providers and patients should be aware of state specific laws related to reporting marijuana exposure in breastfeeding patients (Krening 2018; Meinhofer 2019; Miller 2019)

Monitoring Parameters

Monitor for adverse effects and cannabis use disorder (Busse 2021; CFPC 2014).

Mechanism of Action

Cannabis encompasses drugs and products produced from the plant Cannabis sativa. Although cannabis contains over 100 phytocannabinoids, the main active components include delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD); the specific concentration of each component will vary depending upon the specific product or strain, cultivation environment, and techniques used (Ebbert 2018). THC and CBD interact with the endocannabinoid system, including direct or indirect activation of type 1 (CB1) and type 2 (CB2) cannabinoid receptors. CB1 receptors are found primarily in the CNS (especially in the prefrontal cortex, basal ganglia, hippocampus, amygdala, hypothalamus, and cerebellum), smooth muscle, myocardium, adipocytes, and preganglionic sympathetic neurons (Ebbert 2018). THC is a partial agonist at CB1 receptors which results in the therapeutic and psychoactive effects of cannabis; CBD has week affinity for CB1 receptors but may have indirect effects at these sites (Health Canada 2018; NASEM 2017). CB2 receptors are found in peripheral blood mononuclear cells, natural killer cells, myocardium, vascular endothelium, smooth muscle mesenchymal-derived CNS microglia (Ebbert 2018); THC is an agonist at CB2 receptors while CBD does not directly interact at these sites (NASEM 2017). In addition, CBD may exhibit activity at other targets (eg, ion channels, receptors, enzymes), which may be associated with therapeutic effects (Health Canada 2018).

Pharmacokinetics

Onset of action (Health Canada 2018):

Inhalation (smoking or vaporization): Rapid (Huestis 2007); within ~5 minutes (Health Canada 2018).

Oral: 30 to 90 minutes.

Sublingual: 5 to 30 minutes.

Peak effect (Health Canada 2018):

Inhalation (smoking or vaporization): 20 to 30 minutes.

Oral: 2 to 3 hours.

Sublingual: 1.5 to 4 hours.

Duration of action (Health Canada 2018):

Inhalation (smoking or vaporization): 2 to 3 hours.

Oral: 4 to 12 hours.

Sublingual: 12 to 24 hours.

Absorption:

Inhalation (smoking): Up to 25% to 27% with practical use (Health Canada 2018).

Oral: Varied based on vehicle used to deliver the dose; following ingestion of delta-9-tetrahydrocannabinol (THC) added to a chocolate cookie, absorption was 4% to 12% (Ohlsson 1980).

Distribution: THC: 10 L/kg (Huestis 2007).

Protein binding: 95% to 99% primarily to lipoproteins (Huestis 2007).

Metabolism: Hepatic via CYP isoenzymes (2C9, 2C19, 2D6, and 3A4) (Sativex Canadian product monograph).

THC: Primarily via CYP2C9 to an active metabolite (11-hydroxy-delta-9-THC) and CYP3A4 (Dean 2020; Watanabe 2007); undergoes significant first pass metabolism following oral administration (Perucca 2020).

Cannabidiol (CBD): Hepatic via CYP isoenzymes to 7-hydroxy-cannabidiol (Sativex Canadian product monograph); undergoes significant first pass metabolism following oral administration (Huestis 2007).

Bioavailability:

Inhalation (smoking): 2% to 56%. Note: Variability may be due to efficiency and method of smoking (Huestis 2007).

Oral: Fasting: ~6%; Administration with a high fat meal: ~25% (Perucca 2020).

Half-life elimination:

Initial (plasma; prolonged with higher doses): CBD: ~5 to 9 hours; THC: ~2 to 5 hours (Sativex Canadian product monograph).

Terminal: 24 to 36 hours (or longer) secondary to redistribution from fatty tissue (Sativex Canadian product monograph).

Time to peak, serum:

Inhalation (smoking): 9 minutes (Huestis 2007).

Oral: 1 to 5 hours (Ohlsson 1980).

Excretion: Urine and feces, primarily as metabolites (Huestis 2007).

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