Duran, M., Perez, E., Abanades, S., Vidal, X., Saura, C., Majem, M., … Capella, D. (2010). Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology, 70, 656–663.

To evaluate the effect, toleration, and pharmacokinetics of dose titration of cannabis oral spray added to standard therapy to control chemotherapy-induced nausea and vomiting (CINV) in patients receiving a moderately emetogenic regimen

• Patients were eligible if they had experienced more than 24 hours of CINV despite standard antiemetic treatment after receiving one day of moderately emetogenic chemotherapy (MEC).
• Standard antiemetics included corticosteroids, 5-HT₃ antagonists, or metoclopramide.
• The Cannabis-based medicine (CBM) used was a mixture of tetrahydrocannabinol (THC) and cannabidiol 1:1 (Sativex®), with other cannabinoid derivatives, delivered in an oral spray.
• Patients were randomly assigned to the Cannabis spray (CBM) or a placebo, which was designed to match the appearance, smell, and taste of the active formula.
• On the first day of treatment, subjects received up to 3 sprays within a two-hour period following chemotherapy administration. If no signs of intoxication were seen after the first spray, a second and third were given after 30 minutes and 120 minutes.
• Patients were advised to increase home dose until day four, with up to 8 sprays within any four-hour period, every 24 hours.
• Blood samples were collected at several time points for the pharmacokinetic analysis.

• The study consisted of 16 participants.
• Median age was 50 with a range of range 34–76 years.
• The majority of participants were female (94%).
• Most patients had breast cancer.
• All patients had received one cycle of chemotherapy and were enrolled in the following cycle that included MEC agents. All had good performance status.
• Exclusion criteria were current use of illicit drugs or alcohol abuse, radiation therapy to abdomen or pelvis within one week, or cannabinoid use within 30 days prior to enrollment.

They study was conducted at multiple outpatient settings in Barcelona, Spain.

All patients were in active treatment.

This was a randomized, double-blind, placebo-controlled, parallel, phase-II trial.

Complete response was defined as no vomiting and a mean nausea score of ≤ 10 mm.

Partial response was defined as vomiting 1-4 times daily and a mean nausea score of ≤ 25 mm on a 100-mm visual analogue scale (VAS).

The following additional measurement instruments were used.

• Morrow Assessment of Nausea and Vomiting (MANE) questionnaire for frequency and duration of nausea and vomiting
• Functional Living Index-Emesis (FOIE) patient daily diary for recording of adverse events
• Daily structured telephone interview

• The mean number of daily sprays during the four days after chemotherapy was 4.81 in the CBM group, equivalent to 12.9 mg of THC.
• In the CBM group, 6 out of 7 patients tolerated dose titration. One patient discontinued treatment because of anxiety, somnolence, visual hallucinations, and confusion. These symptoms disappeared after three hours.
• Somnolence, dry mouth, and fatigue were the most common adverse events in both groups.
• In the delayed period, complete response was higher in the CBM group (71.4%) than in the placebo group (22.2%).
• In the acute period, no difference was found between the groups.
• A larger percentage of patients in the CBM group had no delayed emesis (71.4%) or nausea (57.1%) than in the placebo group (22.2%).
• Plasma concentrations showed a wide variability across subjects and suggested that patients following a repeat-administration schedule accumulate CBM active compound over time, despite the relatively short half-life of the active compounds.

The addition of this formulation of Cannabis to standard antiemetic treatment appears to improve control of delayed nausea and vomiting with MEC.

• The sample size was extremely small.
• The standard antiemetic regimen was less than what is currently recommended; however, it did follow recommendations at the time of the study.
• No discussion of the use of or need for rescue medications was provided.

• Other research has shown effectiveness of Cannabis compounds for CINV.
• The addition of Cannabis compounds to other antiemetic regimens may be specifically helpful in patients with refractory CINV, and it may be most helpful with delayed nausea and vomiting.
• The delivery system of an oral spray provides an alternative that may be helpful. Further research in the use of this formulation is warranted.