With increasing legal acceptance for medical and recreational purposes, the use of cannabis is increasing worldwide. Delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, is known for its varied effects on users, from euphoria and relaxation to anxiety and paranoia. However, recent studies have been published in the journal Drug and alcohol addiction D-limonene, a common terpene found in cannabis and citrus fruits, suggests that it may reduce some of the anxiety-inducing effects of THC.
The focus of cannabis research has been primarily on cannabinoids such as THC and CBD. However, the cannabis plant contains many other compounds, including terpenes such as d-limonene, which can affect the overall effect of the plant on users. Terpenes are aromatic compounds widely found in nature and known for their unique aromas and biological activities, which in some cases include therapeutic properties.
The concept of the “entourage effect” suggests that the therapeutic effects of cannabis may be enhanced or reduced by other plant compounds, not just THC. Despite this, research on how non-THC compounds such as terpenes interact with THC is limited and largely anecdotal. The new study aims to fill that gap by examining whether d-limonene can moderate the anxiety-inducing effects of THC.
The study was a double-blind, within-subjects crossover study with 20 participants. This meant that each participant received multiple treatments (THC and D-limonene in different combinations and placebo) in different sessions, and neither the participants nor the researchers knew which treatment was being administered at any given time. This method allows to reduce bias and to compare the results of each treatment in the same individuals, which increases the reliability of the results.
Participants are selected according to certain criteria. Adults had to be in good health, not pregnant, not using drugs other than cannabis, alcohol, nicotine, or caffeine, and with no history of depression while using cannabis. These criteria ensured that the sample was representative of typical users likely to benefit from stress interventions.
The study consisted of several sessions in which participants inhaled vaporized substances through a controlled device. Each session was spaced at least 48 hours apart to prevent carryover effects from previous sessions. D-limonene and THC were administered separately and in combination at different doses to evaluate their individual and interactive effects. The placebo session consisted of inhalation of distilled water vapor to create a baseline for comparison.
The most notable result of the study was the reduction of anxiety-like and paranoid feelings when D-limonene was administered with THC. The results were particularly pronounced when 30 mg of THC was combined with 15 mg of D-limonene. This finding is important because it suggests that D-limonene may be used to reduce some of the less desirable effects of THC, making cannabis more palatable to people who may experience anxiety as a side effect.
“People use cannabis to reduce anxiety, depression, and post-traumatic stress disorder, but because THC levels vary so much, if a person exceeds their tolerance for THC, cannabis can cause anxiety rather than relief,” said Ryan Vandre, senior author of the study. Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine. “Our research shows that d-limonene can meaningfully moderate the effects of THC and make THC more tolerable for people who use it for medical and non-medical purposes.”
Interestingly, D-limonene did not significantly alter the effects of THC. The terpene reduced anxiety and paranoia without significantly affecting other subjective, cognitive, and physiological effects induced by THC. This difference is important because D-limonene can be used in the intended way
The results showed that although d-limonene affected some of the psychoactive effects of THC, the pharmacokinetics of THC (how THC is absorbed, distributed, assimilated and excreted by the body) was not changed.
These findings open up new ways to develop cannabis products. By including certain terpenes, such as D-limonene, it may be possible to increase the therapeutic index of THC-rich products. This could lead to the development of specific cannabis strains or products designed to deliver the benefits of THC while reducing its ability to induce anxiety and paranoia.
Despite these promising results, the study has several limitations. High levels of D-limonene are not used in natural cannabis products, and the study did not examine its effects in full-spectrum cannabis products containing multiple cannabinoids and terpenes.
“This study is the first step in how we can reduce the risks of THC when we use it medically, and is aimed at making cannabis safer for general and non-medical consumers,” said study leader Tory Spindle. in Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine.
Future research could examine the effects of different ratios and forms of THC and D-limonene, including oral administration and the use of medical cannabis. The findings require replication in larger and more diverse samples to understand variability in response based on individual differences such as genetics, prior cannabis use, and gender.
“This is one of the first clinical studies to demonstrate the validity of the synergistic effects of cannabis, suggesting that THC and other components of the plant interact in a meaningful way that alters the acute effects of cannabis,” the researchers said.
“Given the growing interest in the use of cannabis for medicinal purposes and the expansion of the legalization of cannabis for non-medicinal purposes, a better understanding of which components can increase the safety of cannabis by reducing its significant negative effects (such as anxiety and paranoia). It is very important to maintain health.
The study “Vaporized d-limonene attenuates the acute anxiolytic effects of Δ9-tetrahydrocannabinol in healthy adults who regularly use cannabis.” by Tori R. Spidle, C. Austin Zamaripa, Ethan Russo, Lauren Pollack, George Bigelow, Alexandra M. Written by Ward, Bridget Thompson, Christina Cempio, Turaj Shocati, Jost Klawiter, Uwe Christians, and Ryan Vandre.