TABLE 8.

Interaction between alkylating agents, taxanes, topoisomerase I inhibitors, xanthines, and cannabis.

Drugs	Probability	Severity	Observed effects	Patient outcomes	Recommendation	References
Alkylating agents
Temozolomide (Unknown)	Defined	N/A*	Neither temozolomide monotherapy nor temozolomide + cannabis therapy demonstrated any changes in C max, the area under the plasma concentration‐time curve to the last timepoint (AUC0−t ), and T max	Treatment‐emergent adverse events (TEAEs) were mostly related to the underlying medical condition of patients, such as glioblastoma	Condition‐based personalization of the nabiximol dose regimen should be done in patients receiving concurrent cannabis treatment and intensive temozolomide therapy	33
Taxanes
Docetaxel (CYP3A inhibition)	Defined	N/A*	Clearance and dose‐normalized AUC were not significantly affected by the concurrent use of cannabis. Plasma concentrations of docetaxel were similar in both monotherapy and combination therapy with cannabis	Hematological toxicity, which is the major adverse effect of docetaxel, was not significantly noted with the concurrent administration of cannabis Other adverse events included elevated liver transaminases and bilirubin, fatigue, mild headaches, mood disturbance, and weird dreams. In addition, most patients noticed improved sleep quality	Evaluated cannabis products can be administered together with docetaxel without any dose adjustments	34
Topoisomerase I inhibitors
Irinotecan (CYP3A inhibition)	Defined	N/A*	Irinotecan: Dose‐normalized AUC and clearance were not significantly affected by cannabis co‐administration Irinotecan metabolites (SN‐38 and SN‐38‐glucuronide): Dose‐normalized AUC and clearance were not significantly altered when cannabis was co‐administered	Similar nadir values of absolute neutrophil count (ANC) and white blood cell count (WBC) suggested that hematological toxicity (the major adverse effect) did not significantly occur with cannabis co‐administration Better sleep quality was reported by most patients, whereas some patients also reported mild headaches, mood disturbance, weird dreams, diarrhea, fatigue, nausea, and vomiting	Evaluated cannabis products can be safely administered together with irinotecan without any dose adjustments	34
Xanthines
Caffeine (Victim—CYP1A2 inhibition)	Defined	Minor (caffeine: 95%; paraxanthine: 18%)	Increments were observed in several parameters with CBD + caffeine co‐administration on Day 26, which included C max of caffeine (+15%), AUC0−t (+88%), and area under the concentration‐time curve from time zero to infinity (AUC0−∞) (+95%) Longer T max and t 1/2 were also noted when compared to a single administration of caffeine on Day 1 On Day 26, higher caffeine concentrations as well as reduced CL/F of CBD + caffeine were observed compared with Day 1	The most commonly reported adverse effect during CBD titration was diarrhea (n = 8) Laboratory results demonstrated elevated liver enzymes (ALT, AST, and gamma‐glutamyltransferase [GGT]) (n = 7) in subjects who were on either CBD maintenance dose or CBD + caffeine. Eosinophil percentage showed a significant rise during CBD maintenance dose (n = 1). Syncope was reported as well (n = 1) All reported elevations were resolved 9–49 days after onset, except for GGT elevations that were ongoing towards the end of the trial with 2.4 times ULN	No recommendation provided	35
Cannabis
THC (Victim—Complex synergistic PK, antagonistic PD interactions)	Defined	N/A*	The mean THC peak plasma concentration of 82 ng/mL was reported in a product with a lower CBD concentration (<1 mg). In products with higher CBD concentrations of about 18 mg, THC plasma concentrations were at least 50% higher than those of lower CBD content products	Not reported	No recommendation provided	36
Diuretics
Not specified	Probable	N/A*	Signs of accumulation were not evident for THC, CBD, and their metabolites. This was confirmed by data analysis of blood sampling within a 6‐month interval	Not reported	No recommendation provided	15

^*N/A implies that the severity grading is not applicable.