Substance Interactions and Safety

Introduction to Risks

The combination of cannabis and benzodiazepines significantly increases the risk of respiratory depression, sedation, cognitive impairment, and potentially fatal adverse events, and should be avoided due to these serious safety concerns 1
Combined use of cannabis and benzodiazepines increases the risk of respiratory depression through pharmacodynamic interactions, where both substances have CNS depressant effects that synergistically enhance sedation 1
Benzodiazepines enhance GABA activity while cannabis affects cannabinoid receptors, creating compounded sedative effects 2

CBD (cannabidiol) inhibits enzymes that metabolize many benzodiazepines, which can lead to increased blood levels and prolonged effects of benzodiazepines 3
This inhibition can result in increased risk of adverse events due to elevated benzodiazepine levels 3

The following medications have potential interactions with CBD:

Medication	Interaction
Warfarin	Increased bleeding risk through CYP2C9 inhibition
Tacrolimus	Increased risk of toxicity
Buprenorphine	Increased risk of side effects
Carbamazepine	Increased levels through CYP inhibition
Benzodiazepines	Increased sedation
Antiepileptics	Potential for increased levels and side effects
Antidepressants and antipsychotics	Potential for increased levels and side effects
Chemotherapeutic agents	Potential for altered metabolism

When benzodiazepines and other CNS depressants are used together, respiratory depression risk increases dramatically, with hypoxemia occurring in up to 92% of subjects and apnea in 50% 1
The American College of Emergency Physicians strongly cautions against co-prescribing benzodiazepines with other CNS depressants due to significantly increased mortality rates 5
Mortality rates are 3-10 times higher when benzodiazepines are combined with other CNS depressants compared to benzodiazepines alone 5
The American College of Clinical Pharmacology recommends avoiding concurrent use of marijuana with psychiatric medications like Abilify and Effexor due to significant risk of adverse effects, including increased sedation, confusion, and potential psychiatric complications 3

In the emergency department setting, guidelines strongly caution against co-prescribing benzodiazepines with other CNS depressants 5
During procedural sedation, the risk of respiratory events increases significantly when benzodiazepines like midazolam are used with other substances 6
Careful monitoring is essential if these combinations cannot be avoided, particularly in settings like procedural sedation 1
Patients with cardiovascular conditions may experience additional risks, including tachycardia and potential myocardial ischemia 7

If a patient is using both substances despite recommendations against it, monitor for signs of excessive sedation, confusion, and respiratory depression 1
Consider lower benzodiazepine doses and alternative therapies to minimize risks 5
Patient education should emphasize the risks of driving or operating machinery and the dangers of additive sedative effects 1
Healthcare providers should screen for cannabis use in patients taking psychiatric medications, monitor for signs of increased medication effects, and consider dose adjustments of medications if cannabis use cannot be discontinued, as suggested by the American Academy of Family Physicians and the Substance Abuse and Mental Health Services Administration 3
Baseline assessment should include checking liver function before starting CBD, and regular monitoring should include monitoring drug levels for medications with narrow therapeutic windows and checking liver enzymes periodically, as recommended by the American College of Clinical Oncology 3