Table 6. Drug interactions of cannabinoids-containing herbal drugs (Cannabis flos, Cannabis herba, Cannabis resina).

ATC therapeutic subgroup	ATC pharmacological/chemical subgroup	Drugs	Pharmacokinetic basis of interaction	Pharmacodynamic basis of interaction	Manifestation of interaction
Stomatological preparation, in dentistry (A01)	Salicylic acid and derivatives	Acetylsalicylic acid	CYP1A2 CYP2C9 CYP3A4		↓ analgetic effect	Petersen, Bergien & Staerk (2021)
Antithrombotic agents (B01)
Analgetics (N02)
Antihypertensives (C02)	Imidazoline receptor agonists	Clonidine	CYP1A2	Cannabis has β-agonistic effect.	↑ adverse reaction (tachycardia) ! exclude marijuana	Cone, Welch & Lange (1988)
Analgesics (N02)	Other antimigraine preparations
Ophtalmologicals (S01)	Sympathomimetics in glaucoma therapy
Antivirals for systemic use (J05)	Protease inhibitors	Indinavir Nelfinavir	CYP3A4 P-gp		↓ plasma level ↓ AUC (10%, and 14%)	Kosel et al. (2002)
Antineoplastic agents (L01)	Cytotoxic antibiotics and related substances	Bleomycin	CYP2B1	Cannabis and Δ9-THC are used as analgesics and antiemetics in oncology.	↑ adverse reactions (cephalea, paresis, aphasia, stroke, exitus) ! exclude marijuana	Merkle & Tavernier (2018)
	Platinum compounds	Cisplatin	CYP3A4	Cannabis and Δ9-THC are used as analgesics and antiemetics in oncology.	↑ adverse reactions (cephalea, paresis, aphasia, stroke, exitus) ! exclude marijuana ! medicinal Cannabis herbal tea does not affect the level of cytostatics but inhalation (joint smoking) is risky	Marzęda et al. (2022)
	Topoisomerase 1 inhibitors	Irinotecan	CYP3A4	Cannabis and Δ9-THC are used as analgesics and antiemetics in oncology.	↑ adverse reactions (cephalea, paresis, aphasia, stroke, exitus) ! exclude marijuana ! medicinal Cannabis herbal tea does not affect the level of cytostatics but inhalation (joint smoking) is risky	Engels et al. (2007)
Immunosuppressants drugs (L04)	Calcineurin inhibitors	Cyclosporine Tacrolimus	CYP3A4 P-gp		↑ cyclosporine plasma level (73%–83%) ↓ metabolism	Czigle & Tóth (2011), Leino et al. (2019)
Anti-inflammatory and antirheumatic drugs (M01)	Anti-inflammatory and antirheumatic products, non-steroids	Celecoxib Diclofenac Ibuprofen Indometacin Naproxen Piroxicam	CYP2C9 CYP3A4	Cannabis affects prostaglandins levels.	antagonistic effect ↓ NSAIDs effect	Czigle & Tóth (2011), Emiga et al. (2020)
Analgesics (N02)	Opioids, natural opium alkaloids	Morphine Codeine Hydromorphone Oxymorphone	CYP2D6	Phytocannabinoids are CB1, CB2 receptor agonists.	↑ Improvement in analgesic effects (without adverse reactions increase). ! dosage adjustment (reduce the dose of anodyne by 60–100%)	Czigle & Tóth (2011), Fattore et al. (2004)
	Opioids, benzomorphan derivatives	Methadone	CYP3A4 CYP2C19	Phytocannabinoids are CB1, CB2 receptor agonists.	↑ Improvement in analgesic effects (without adverse reactions increase). ! dosage adjustment (reduce the dose of anodyne by 60–100%)	Madden, Tanco & Bruera (2020)
	Other analgesics and antipyretics, anilides	Paracetamol	CYP1A2 CYP3A4 CYP2E1	Cannabis affects prostaglandins levels.	↓ analgetic effect	van Amerongen et al. (2018)
Antiepileptics (N03)	Antiepileptics, barbiturates and derivatives	Phenobarbital Pentobarbital Secobarbital	CYP2C9	Cannabinol is a CB1, CB2 receptor agonist, used as antiepileptic (Dravet-, and Lennox-Gastaut syndrome).	↑ metabolism ↓ anticonvulsive effect	Czigle & Tóth (2011), Hollister (1986)
	Antiepileptics, hydantoin derivatives	Phenytoin	CYP2C9 CYP2C19	Cannabinol is a CB1, CB2 receptor agonist, used as antiepileptic (Dravet-, and Lennox-Gastaut syndrome).	↑ metabolism ↓ anticonvulsive effect ! exclude marijuana	Jessen (2004)
Psycholeptics (N05)	Antipsychotics	Chlorpromazine Clozapine Lithium	CYP1A2 CYP2D6	Phytocannabinoids are CB1, CB2 receptor agonists.	↓ chlorpromazine plasma level ↑ chlorpromazine clearance (tobacco smoking: by 38%, joint smoking: by 50%, smoking both: by 107%) ! exclude marijuana	Babatope et al. (2016), Brunette et al. (2011), Singh et al. (2020)
	Anxiolytics, benzodiazepine derivatives	Alprazolam Diazepam	CYP2C19 CYP3A4	Phytocannabinoids are CB1, CB2 receptor agonists.	↓ anxiolytic effect	Lile, Kelly & Hays (2014)
	Hypnotics and sedatives, benzodiazepine derivatives	Midazolam	CYP2C19 CYP3A4	Phytocannabinoids are CB1, CB2 receptor agonists.	↓ hypnotic effect	Twardowski, Link & Twardowski (2019)
Psychoanaleptics (N06)	Antidepressants, non-selective monoamine reuptake inhibitors	Amitriptyline Nortriptyline Desipramine Imipramine	CYP3A4 CYP2C9 CYP2D6 Pgp	Cannabis has β-agonistic effect.	additive β-agonistic effect ↑ adverse reactions (tachycardia, delirium) ! exclude marijuana	Vázquez et al. (2020)
	Antidepressants, selective serotonin reuptake inhibitors	Fluoxetine Sertraline	CYP2D6 CYP3A4	Phytocannabinoids are CB1, CB2 receptor agonists.	synergistic (serotonergic) effect ↑ adverse reactions (serotonin syndrome, hypomanic periode risk) ! exclude marijuana	Vaughn et al. (2021)
Other nervous system drugs (N07)	Drugs used in nicotine dependence	Nicotine (transdermally)	CYP2C9	Phytocannabinoids are CB1, CB2 receptor agonists.	additive effect ↑ adverse reactions (tachycardia, vigilantia) ! exclude marijuana	Mohamed et al. (2011), Tucker et al. (2019)
	Drugs used in alcohol dependence	Disulfiram	CYP1A2 CYP3A4	Phytocannabinoids are CB1, CB2 receptor agonists.	↑ adverse reactions (hypomanic syndrome) ! exclude marijuana	Lacoursiere & Swatek (1983)
Drugs for obstructive airway diseases (R03)	Other systemic drugs for obstructive airway diseases, xanthines	Aminophylline Theophylline	CYP1A2	Cannabinoids have bronchodilatory effects.	↑ metabolism ↓ plasma level ! exclude marijuana	Antoniou, Bodkin & Ho (2020), Jusko et al. (1978)
All other therapeutic products (V03)	Nerve depressants	Ethanol	CYP2D6	Phytocannabinoids are CB1, CB2 receptor agonists.	additive effect ↑ adverse reaction (delirium) ↓ psychomotoric test results ! exclude marijuana (↑ fatal accident risk)	Mohamed et al. (2011)

Note:

ATC, Anatomical Therapeutic Chemical Classification System (WHO, 2023); ↑, increase (of); ↓, decrease (of); !, warning; CB₁, cannabinoid receptor type 1; CB₂, cannabinoid receptor type 2; ∆⁹-THC, ∆⁹-tetrahydrocannabinol; P-gp, P-glycoprotein.