chapter
Cannabis
Pages 7

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS ANALGESICS – OPIOIDS – alfentanil, fentanyl, methadone, codeine, dextromethorphan

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS ANTIARRHYTHMICS

CANNABIS AMIODARONE Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity especially when cannabis use abruptly changes

CANNABIS PROPAFENONE Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity especially when cannabis use abruptly changes

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DRUGS OF ABUSE CANNABIS

drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity especially when cannabis use abruptly changes

CANNABIS ANTICANCER AND IMMUNOMODULATING DRUGS

CANNABIS CYTOTOXICS – CYCLOPHOSPHAMIDE, DOXORUBICIN, IFOSFAMIDE, LOMUSTINE, VINCA ALKALOIDS

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS HORMONES AND HORMONE ANTAGONISTS – TAMOXIFEN

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS IMMUNOMODULATING DRUGS – CICLOSPORIN, CORTICOSTEROIDS

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS ANTICOAGULANTS – WARFARIN

Unpredictable changes in plasma concentration

1. Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption 2. Induction of CYP1A2mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme

Be aware. Monitor INR closely, especially when cannabis use abruptly changes

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Mechanism Precautions

lithium

Mechanism uncertain Be aware and measure plasma lithium levels if indicated by clinical observations

CANNABIS FLUOXETINE Report of mania Mechanism uncertain and may not be due to an interaction

Be aware

CANNABIS FLUVOXAMINE ↓ levels, with risk of therapeutic failure

Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme

Watch for poor response to fluvoxamine; conversely, watch for toxic effects if a previously heavy cannabis user stops smoking

CANNABIS SERTRALINE, VENLAFAXINE

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS AMITRIPTYLINE, CLOMIPRAMINE, DESIPRAMINE, IMIPRAMINE, NORTRIPTYLINE

≠ risk of tachycardia. Heart rate may ≠ to 100-160 beats per minute, with some records of 300 beats per minute resistant to verapamil therapy

Additive antimuscarinic effect Ask patients about cannabis use if they present with otherwise unexplained tachycardias while taking these drugs

CANNABIS TCAs Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of TCA toxicity, especially when cannabis use abruptly changes

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Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme

Watch for poor response to mirtazapine; conversely, watch for toxic effects if a previously heavy cannabis user stops smoking

CANNABIS ANTIEMETICS – ONDANSETRON

↓ levels, with risk of therapeutic failure

Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme

Watch for poor response to ondansetron; conversely, watch for toxic effects if a previously heavy cannabis user stops smoking

CANNABIS ANTIHISTAMINES – BROMPHENIRAMINE, CHLORPHENIRAMINE

≠ risk of tachycardia. Heart rate may ≠ to 100-160 beats per minute, with some records of 300 beats per minute resistant to verapamil therapy

Additive antimuscarinic effect Ask patients about cannabis use if they present with otherwise unexplained tachycardias while taking these drugs

CANNABIS ANTIMUSCARINICS – ATROPINE, FLAVOXATE, HYOSCINE, OXYBUTYNIN, TOLTERODINE

≠ risk of tachycardia. Heart rate may ≠ to 100-160 beats per minute, with some records of 300 beats per minute resistant to verapamil therapy

Additive antimuscarinic effect Ask patients about cannabis use if they present with otherwise unexplained tachycardias while taking these drugs

CANNABIS ANTIOBESITY DRUGS – RIMONABANT

↓ most effects of cannabis that are due to its activity at central cannabinoid receptor

Rimonabant is a selective antagonist at central cannabinoid receptors, and thus the effects of either drug may be ↓

Be aware

CANNABIS ANTIPARKINSON’S DRUGS – PROCYCLIDINE, TRIHEXYPHENIDYL (BENZHEXOL)

≠ risk of tachycardia. Heart rate may ≠ to 100-160 beats per minute, with some records of 300 beats per minute resistant to verapamil therapy

Additive antimuscarinic effect Ask patients about cannabis use if they present with otherwise unexplained tachycardias while taking these drugs

DRUGS OF ABUSE CANNABIS

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Mechanism Precautions

HALOPERIDOL

clozapine may be halved), with the risk of therapeutic failure

Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme

Watch for poor response to these antipsychotics; conversely, watch for toxic effects of these antipsychotics if a previously heavy cannabis user stops smoking

CANNABIS ANTIVIRALS – PROTEASE INHIBITORS – indinavir, nelfinavir, nevirapine, ritonavir, saquinavir

Cannabis may cause ↓ plasma concentrations of protease inhibitors, particularly indinavir and nelfinavir

Cannabis may cause inhibition or induction of CYP3A4 isoenzymes, which metabolize these protease inhibitors

Be aware. Regular monitoring of viral indicators is necessary

CANNABIS ANXIOLYTICS AND HYPNOTICS – BZDs – alprazolam, diazepam, midazolam, triazolam

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS BETA-BLOCKERS – PROPRANOLOL

↓ levels, with risk of therapeutic failure

Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme

Watch for poor response to propanolol; conversely, watch for toxic effects if a previously heavy cannabis user stops smoking

CANNABIS BRONCHODILATORS – THEOPHYLLINE

↓ theophylline levels, with risk of therapeutic failure (theophylline has a narrow therapeutic range)

Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme. Although cannabis is considered to cause bronchodilatation, regular smoking leads to poorer respiratory function

Watch for poor response to theophylline; consider monitoring theophylline levels if a previously heavy cannabis user stops smoking, because of the risk of toxic effects

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DRUGS OF ABUSE CANNABIS

NISOLDIPINE

therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS VERAPAMIL Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

1. Induction of CYP1A2-mediated metabolism by any form of smoking. Foods (e.g. broccoli, cabbage, Brussels sprouts, chargrilled meat) also induce this isoenzyme 2. Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Watch for poor response to verapamil; conversely, watch for toxic effects if a previously heavy cannabis user stops smoking

CANNABIS DRUG DEPENDENCE THERAPIES

CANNABIS BUPROPION Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS DISULFIRAM Risk of hypomania Mechanism uncertain and may be due to the presence of adulterants

Be aware

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Mechanism Precautions

cocaine, leading to enhanced subjective effects of cocaine (e.g. euphoria), and ≠ heart rate and other cardiac effects such as ischaemia

Attributed to cannabis-induced vasodilatation of the nasal mucosa, which leads to ≠ absorption of cocaine

Be aware. May be the cause of ischaemic cardiac pain in young adults

CANNABIS ECHINACEA AND OTHER IMMUNOSTIMULANTS

May ↓ immunostimulant effects The cannabinoid receptor is considered to mediate immunosuppressant effects and is currently being investigated in the development of novel immunosuppressants

Be aware

CANNABIS OESTROGENS – ETHINYLESTRADIOL

Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes

CANNABIS PHOSPHODIESTERASE TYPE 5 INHIBITORS – SILDENAFIL

Report of myocardial infarction Both drugs have been independently linked to myocardial infarction. However, the exact mechanism is uncertain

Be aware

CANNABIS PROGESTOGENS Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index

Induction or inhibition of CYP3A4mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption

Be aware. Watch for signs of toxicity, especially when cannabis use abruptly changes