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D-Limonene Counteracts THC-Induced Anxiety: New Study Finds



Cannabis, a widely used psychoactive substance, contains numerous chemical compounds beyond the well-known delta-9-tetrahydrocannabinol (THC) and cannabidiol (THC). While THC is primarily associated with the psychoactive effects of cannabis, the entourage effect theory proposes that other constituents, such as terpenoids, may modulate these effects. Despite theoretical suggestions, empirical studies examining this phenomenon in humans remain limited.

A recent study conducted by researchers from different universities including Johns Hopkins University School of Medicine and University of Colorado Anschutz Medical Campus and Vashon aimed to investigate whether the terpenoid d-limonene could mitigate the acute anxiogenic (anxiety-inducing) effects of THC in healthy adults.

Twenty healthy adults participated in nine double-blind outpatient sessions. They were exposed to various combinations of vaporized THC alone (at doses of 15 mg or 30 mg), d-limonene alone (at doses of 1 mg or 5 mg), or both THC and d-limonene together. Additionally, a subset of participants underwent a tenth session with a combination of 30 mg THC and 15 mg d-limonene. The study measured subjective drug effects, cognitive/psychomotor performance, vital signs, and plasma concentrations of THC and d-limonene.


When administered alone, d-limonene did not produce significant pharmacodynamic effects compared to placebo. However, THC alone induced typical acute cannabis effects, including subjective, cognitive, and physiological changes. Interestingly, the co-administration of THC and d-limonene led to a qualitative reduction in anxiety-like subjective effects. Specifically, concurrent administration of 30 mg THC and 15 mg d-limonene significantly decreased ratings of “anxious/nervous” and “paranoid” compared to THC alone. Notably, d-limonene did not alter THC pharmacokinetics.


The findings suggest that d-limonene selectively attenuates THC-induced anxiogenic effects, potentially enhancing the therapeutic benefits of THC. Further research is warranted to explore whether these effects extend to oral cannabis formulations and to investigate interactions between d-limonene, other cannabis terpenoids, and cannabinoids. Such research could contribute to optimizing the therapeutic use of cannabis and its constituents.


Understanding the interactions between different compounds in cannabis, such as THC and terpenoids like d-limonene, holds promise for improving the therapeutic application of cannabis-based treatments. By elucidating how these compounds influence each other's effects, researchers may develop more effective and safer cannabis products for medical and recreational use. Additionally, this study underscores the importance of rigorous scientific investigation in guiding the development of cannabis therapies.