Subjective and physiological effects after controlled Sativex and oral THC administration

Abstract

Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

Figure 1

Mean ± SE (n = 9) changes in (a) systolic blood pressure, (b) diastolic blood pressure, (c) pulse rate, and (d) respiration rate relative to baseline and placebo after 5 and 15 mg oral Δ-tetrahydrocannabinol (THC) and low-dose (5.4 mg THC + 5 mg cannabidiol (CBD)) and high-dose (16.2 mg THC + 15 mg CBD) oromucosal Sativex.

Figure 2

Mean ± SE (n = 9) changes in (a) “good drug effect,” (b) “high,” (c) marijuana (M)-scale, (d) state anxiety, and (e) “anxious” relative to baseline and placebo after 5 and 15 mg oral Δ-tetrahydrocannabinol (THC) and low-dose (5.4 mg THC + 5 mg cannabidiol (CBD)) and high-dose (16.2 mg THC + 15 mg CBD) oromucosal Sativex. “Good drug effect,” “high,” and “anxious” scores were based on a maximum score of 100, M-scale on a maximum of 12, and state anxiety on a maximum of 80 points.