New research conducted by a team led by Johns Hopkins Medicine suggests that a chemical naturally occurring in cannabis could potentially reduce the anxiety-inducing effects of tetrahydrocannabinol (THC), which is the main psychoactive component of cannabis. This finding may have implications for the medical use of THC and help mitigate its negative effects.
The compound known as d-limonene, which is found in high concentrations in the cannabis plant, has shown potential in reducing anxiety behaviors in rodent studies. Terpenes, including d-limonene, play a role in the taste, aroma, and color of plants. However, there is limited research on the effects of d-limonene and other terpenes in humans.
A recent study, first published online in the Journal of Drug and Alcohol Dependence, investigated the anxiety-reducing effects of vaporized d-limonene alone and when combined with THC. The study found promising results, suggesting that d-limonene may have potential in reducing anxiety, especially when combined with THC.
in humans. They discovered that including d-limonene significantly decreased overall feelings of being “anxious/nervous” and “paranoid” compared to just using THC.
With the increasing legalization of cannabis, its usage for both medical and non-medical purposes is rapidly expanding. In recent years, the selective breeding of cannabis plants has led to strains containing 20% – 30% THC, compared to an average of 12% a decade ago. This may create challenges for users in accurately gauging the amount of THC they consume on a particular occasion.
THC affects receptors in the brain to generateFeelings of relaxation and euphoria can be experienced by cannabis users, but experts warn that higher doses of THC can also cause anxiety, fear, and panic. According to a study led by Ryan Vandrey, Ph.D., a professor at the Johns Hopkins University School of Medicine, people often use cannabis to alleviate anxiety, depression, and post-traumatic stress disorder. However, due to variations in THC levels, overshooting one’s tolerance can lead to increased anxiety rather than relief. The study also found that d-limonene has the potential to influence the effects of THC.
The researchers conducted a study to investigate the effects of d-limonene, a compound found in citrus fruits, when combined with THC. The goal was to determine if d-limonene could make THC more tolerable for both therapeutic and non-therapeutic use.
The study involved 20 healthy adults, with an average age of 26, who participated in up to 10 outpatient sessions. During these sessions, they inhaled vaporized d-limonene alone, vaporized THC alone, vaporized THC and d-limonene together, or vaporized distilled water (as a placebo).
The study was double-blinded, meaning that neither the researchers nor the participants knew which mixture was being administered. Twenty participants completed nine test sessions, while 12 participants also took part in an optional tenth session of THC com rnrn
The researchers combined a triple-dose (15 milligrams) of d-limonene with the essential oil to test its maximum effectiveness. Before this, safety data were obtained from lower doses (1 milligram and 5 milligrams).
Throughout the study, the researchers measured the participants’ subjective drug effects, mood ratings, vital signs (heart rate and blood pressure), and cognitive performance (memory, psychomotor ability, and attention) at baseline and nine additional times over the course of each six-hour test session. They also collected blood and urine samples from each participant.
Researchers tested participants’ THC and d-limonene levels before, during, and after each six-hour session to determine the effects.
The study found that combining d-limonene with THC led to a significant decrease in reported THC-induced anxiety among participants. The reduction in anxiety was greater with higher doses of d-limonene.
Furthermore, there was no evidence of d-limonene interfering with the subjective, cognitive, or physiological effects of THC when used together. D-limonene also did not produce any effects on its own that differed from the placebo.
This study marks the first step in understanding how to reduce the risks associated with THC use in individuals.dicine, and also is aimed at making cannabis safer for the general, non-therapeutic user,” says study lead author Tory Spindle, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
The researchers intend to keep testing other terpenes by themselves and together with THC to observe their interactions, as well as replicate the d-limonene study with larger and more diverse clinical populations. They also aim to explore alternative methods of administration, such as oral ingestion.
Along with Vandrey and Spindleof CReDO Science, which is a company focused on advancing cannabinoid-based medicines. Christians has received research funding from the National Institutes of Health, the Veterans Administration and the German Research Foundation. Bigelow has received research funding from the National Institute on Drug Abuse and the Food and Drug Administration. The authors declare no competing interests.The Johns Hopkins University has submitted a patent application (PCT/US2022/014296) on behalf of Vandrey, Spindle, and Russo for the use of d-limonene to reduce THC-induced anxiety, based on the data from this study. The study was conducted by CReDo Science and True Terpenes. The other authors of the study have no financial or conflict-of-interest disclosures.
Journal Reference:
- Tory R. Spindle, C. Austin Zamarripa, Ethan Russo, Lauren Pollak, George Bigelow, Alexandra M. Ward, Bridget Tompson, CristiIn a study published in Drug and Alcohol Dependence, researchers found that vaporized D-limonene can help reduce the anxiety-inducing effects of Δ9-tetrahydrocannabinol (THC) in occasional cannabis users. The study, conducted by Sempio, Shokati, Klawitter, Christians, and Vandrey, showed promising results in mitigating the acute anxiogenic effects of THC in healthy adults. The findings suggest potential benefits for individuals who intermittently use cannabis. For more information, the study can be accessed at http://dx.doi.org/10.1016/j.drugalcdep.2024.111267.