April 10, 2024

Researchers from Johns Hopkins University and the University of Colorado conducted a double-blinded, placebo controlled crossover study which found that limonene, a commonly occurring terpene in cannabis, when combined with THC can significantly reduce anxiety that can be exacerbated by THC alone.

The study was comprised of 38 participants randomized into groups while 20 (10 males and 10 females) participants completed the study and were included in the analyses. The study only utilized vaporized compounds that were consumed via inhalation, which included “d-limonene alone (1 mg; 5 mg), THC alone (15 mg; 30 mg), THC and d-limonene together (15 and 30 mg THC + 1 mg d-limonene; 15 and 30 mg THC + 5 mg d-limonene), or placebo (distilled water).” After the study began, an optional test studied a dose of 30mg THC combined with 15mg d-limonene and yielded the most promising results in reducing anxiety, nervousness, and paranoia. The authors noted that this is one of “the first clinical studies that demonstrate the validity of the entourage effect” theory that promotes the idea that the effects of cannabinoids such as THC and CBD can have enhanced medical benefits or mitigated side-effects when combined with terpenes and other cannabinoids naturally occurring within the cannabis plant.

An interesting aspect of this study was that it utilized the Foltin paced puffing procedure. This procedure originated in 1987 in an effort to standardize dosing as it relates to inhalation. The procedure dictates that study participants take 5 second hits, followed by a 10 second hold of the hit before exhaling, a 45 second break between hits, and repeated 15 times over 15 minutes or continued until there is no more vapor left upon exhale. This protocol led to the first three participants withdrawing from the study due to adverse effects. The researchers then relaxed the administration guidance to avoid these adverse effects.