US research has shown the d-limonene terpene found in cannabis can – in the right amounts – reduce the anxiety-inducing effects of THC.
D-limonene is one of the most abundant terpenes in the cannabis plant, and has shown promise in rodent studies in reducing anxiety behaviours – although there has been little research in humans until now.
In a recent study published in the Journal of Drug and Alcohol Dependence, investigators from Johns Hopkins Medicine tested the effects of vaporised d-limonene alone and mixed with THC to examine the anxiety-reducing effects in humans.
They found the addition of d-limonene significantly reduced overall ratings of feeling “anxious/nervous” and “paranoid” compared with THC alone.
Senior author Professor Ryan Vandrey said: “People use cannabis to help reduce anxiety, depression and post-traumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it.
“Our study demonstrates that d-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes.”
In the double-blinded study, 20 healthy adults with a median age of 26 participated in up to 10 outpatient sessions during which they inhaled vaporised doses of d-limonene alone, THC alone, THC and d-limonene together, or distilled water as a placebo.
The 20 participants completed nine test sessions and 12 also took part in an optional 10th session of THC combined with a triple-dose (15mg) of d-limonene to test the extreme extent of the dose-response curve. This was conducted after appropriate safety data was obtained from the lower doses (1mg and 5mg).
In all participants, the researchers measured subjective drug effects and ratings of mood, vital signs (heart rate and blood pressure) and cognitive performance (measures of memory, psychomotor ability and attention) at baseline, and then an additional nine times after initial exposure over the course of each of the six-hour test sessions.
They also collected blood and urine samples from each subject before, during and after each session to test for THC and d-limonene levels.
The team concluded that combining d-limonene with THC significantly reduced subjective indicators/reports of THC-induced anxiety in participants. These reductions were greater as the dose of d-limonene was increased.
Additionally, they saw no interference with THC’s subjective, cognitive or physiological effects when co-administered with d-limonene, and no effects from d-limonene alone that differed from the placebo test.
Lead author Associate Professor Tory Spindle said: “This study is a first step in uncovering how we can mitigate risks of THC when used in medicine, and also is targeted at making cannabis safer for the general, non-therapeutic consumer.”
The researchers plan to continue experimenting with other terpenes alone and in combination with THC to see how they interact with each other, as well as replicating the d-limonene study in larger and more diverse clinical populations. They also plan to test alternative methods of administration, such as oral ingestion.
A patent application has been submitted by Johns Hopkins University on behalf of some members of the research team for the use of d-limonene to reduce THC-induced anxiety, based on the data presented in this study.
