Cannabis use is increasing worldwide and is becoming increasingly legal for both medical and recreational purposes. Delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, is known to have a variety of effects on users, ranging from euphoria and relaxation to anxiety and paranoia. However, a recent study published in the journal drug and alcohol addiction Studies suggest that D-limonene, a common terpene found in cannabis and citrus fruits, may alleviate some of the anxiety-inducing effects of THC.
Cannabis research has primarily focused 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 impact of the plant on the user. Terpenes are aromatic compounds commonly found in nature and are known for their unique aromas and biological activities, including in some cases therapeutic effects.
The concept of the “entourage effect” suggests that the therapeutic effects of cannabis are not solely due to THC alone, but may be enhanced or side effects reduced by other plant compounds. Despite this, research on how non-THC components such as terpenes interact with THC is limited and mostly anecdotal. A new study aimed to fill that gap by investigating whether D-limonene can modulate the anxiety-inducing effects of THC.
This study conducted a double-blind within-subject crossover study with 20 participants. This means that each participant received multiple treatments (different combinations of THC and D-limonene, as well as a placebo) over different sessions, and neither participants nor researchers knew which treatment was being administered at any given time. I did not know. This method helps reduce bias and increases confidence in the results by allowing comparisons of the effects of each treatment within the same individual.
Participants were selected based on specific criteria. Participants had to be healthy adults, not pregnant, not using drugs other than cannabis, alcohol, nicotine, or caffeine, and who had ever experienced anxiety when using cannabis. . These criteria ensured that the sample was representative of typical users who might benefit from anxiolytic interventions.
The study consisted of several sessions in which participants inhaled vaporized substances through a controlled setting. Each session was separated by at least 48 hours to prevent carryover of effects from the previous session. D-limonene and THC were administered alone or in combination at various doses to assess their individual interaction effects. The placebo session included inhaling distilled water vapor to establish a baseline for comparison.
The most notable result of this study was that anxiety-like and paranoid feelings were reduced when D-limonene was administered in combination with THC. This effect was especially pronounced when 30 mg of THC and 15 mg of D-limonene were combined. This finding suggests that D-limonene could be used to alleviate some of THC’s less desirable effects, making cannabis use more pleasant for people who may experience anxiety as a side effect. This is extremely important because it shows that it is possible.
“People use cannabis to reduce anxiety, depression, and post-traumatic stress disorder, but THC levels vary widely, so if a person exceeds their tolerance for THC, cannabis may not be able to alleviate anxiety, , which can induce anxiety,” explained study lead author Ryan Vandry. Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine. “Our study shows that d-limonene can modulate the effects of THC in a meaningful way and increase tolerance in people who use THC for both therapeutic and non-therapeutic purposes.”
Interestingly, D-limonene does not extensively alter all of the effects of THC. The terpene specifically reduced feelings of anxiety and paranoia without significantly affecting other subjective, cognitive, or physiological effects caused by THC. This specificity is beneficial as it increases the possibility of using D-limonene in a targeted manner.
The results also showed that while D-limonene influenced some of the psychological effects of THC, it did not affect the pharmacokinetics of THC (how THC is absorbed, distributed, metabolized, and excreted in the body). It was also shown that it had no effect.
These discoveries open new avenues for cannabis product formulation. By incorporating certain terpenes like D-limonene, it may be possible to increase the therapeutic index of THC-rich products. This could lead to the development of specialized cannabis strains and products designed to provide the benefits of THC while reducing its potential to cause anxiety and paranoia.
Despite these promising results, this study has several limitations. High doses of D-limonene are not typically found in natural cannabis products, and this study did not test for entourage effects in full-spectrum cannabis products containing multiple cannabinoids and terpenes.
“This study is a first step in identifying how the risks of THC can be reduced when used medically, and also aims to make cannabis safer for non-therapeutic consumers. ” said study lead author Associate Professor Tori Spindle. She majored in psychiatry and behavioral sciences at Johns Hopkins University School of Medicine.
Future studies could investigate the effects of different ratios and forms of THC and D-limonene, including oral administration, which is common in medical cannabis use. Additionally, this finding needs to be replicated in larger and more diverse samples to understand the 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 cannabis’s entourage effect, theorizing that THC and other components of the plant interact in meaningful ways to alter the acute effects of cannabis. “There is,” the researchers concluded.
“Given the growing interest in the use of cannabis for medical purposes and the expansion of legalization of cannabis for non-medical purposes, it is important to understand which ingredients can reduce acute adverse effects (such as anxiety and paranoia) in cannabis. It is important to further understand which ingredients have the potential to increase the safety profile and which ingredients may exacerbate the side effects that may increase the use of cannabinoids in medicine. and is paramount to protecting public health more broadly. ”
the study, “Evaporated D-limonene selectively alleviates the acute anxiolytic effects of Δ9-tetrahydrocannabinol in healthy adults who use cannabis intermittently” is written by Tory R. Spindle, C. Austin Zamarripa, Ethan Russo, Lauren Pollack, George Bigelow, Alexandra M. Ward, Bridget Thompson, Christina Sempio, Touraj Shokati, and Joost Kravitter. , Uwe Christians, and Ryan Vandrey.
