Vyleesi Cannabis Interaction Profile: What You Need to Know Before Combining Bremelanotide and Cannabis

What the Vyleesi label says about interactions

The label's drug interactions section covers two routes. Vyleesi may slow gastric emptying and reduce absorption of oral medicines; the label says to avoid it with oral drugs that depend on threshold concentrations, such as antibiotics, and to consider discontinuing Vyleesi if a quick effect of an oral medicine such as indomethacin is needed [1]. Vyleesi may also significantly decrease exposure to oral naltrexone, and the label says to avoid that combination when naltrexone is used for alcohol or opioid addiction [1]. In clinical pharmacology studies, only naltrexone and indomethacin were meaningfully affected [1].

Where the two overlap: nausea

Nausea is the most common adverse reaction on Vyleesi: 40.0% versus 1.3% on placebo in the pooled phase 3 trials, with median onset within one hour and duration about two hours; 13% received an antiemetic and 8% discontinued because of it [1]. It was highest after the first dose (21%) and fell to about 3% with later doses [1]. A phase 4 study of 228 healthy women found that 8 mg of oral ondansetron taken 30 minutes before the injection did not reduce nausea; the label says pretreatment is not recommended [1].

Animal research suggests that cannabinoids can suppress nausea and vomiting; cannabidiol (CBD) did so within a limited dose range [5]. On the other hand, cannabinoid hyperemesis syndrome is cyclic vomiting associated with regular cannabis use. A systematic review of 183 articles found symptom resolution after stopping cannabis in 96.8% of the cases assessed for that characteristic [4].

Where the two overlap: blood pressure

Each Vyleesi dose transiently raises blood pressure and lowers heart rate. The label reports maximal increases of 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, with a heart rate reduction of up to 5 beats per minute and a return to baseline usually within 12 hours [1]. These are maximal figures; in an ambulatory study of 127 women dosed daily for 8 days, the mean increases were 1.9 mmHg systolic and 1.7 mmHg diastolic [1]. Vyleesi is contraindicated in uncontrolled hypertension or known cardiovascular disease [1].

A review reports that acute cannabis use has been shown to increase systolic blood pressure and cause orthostatic hypotension, and that cannabis has been linked to arrhythmia and a higher risk of myocardial infarction, especially in the first hours after use [2]. In a cross-sectional analysis of pooled 2016 to 2017 survey data on adults aged 18 to 44, recent marijuana use was associated with higher odds of stroke (adjusted odds ratio 1.82, 95% CI 1.08 to 3.10) [6].