Law changes, such as the 2018 rescheduling of cannabis in the UK, have permitted the legal supply of cannabis products containing both cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) when initiated by a doctor listed on the GMC’s Specialist Register. These compounds represent the most numerous cannabinoids found in the cannabis plant and each has been extensively researched to better understand its potential for use in medical settings.
THC is most widely known for its psychoactive and intoxicating effects. On the other hand, whilst THC can now be prescribed for medicinal reasons in the UK, there is also evidence – from both medical and recreational populations – that THC may induce unwanted feelings of anxiety at certain doses. These effects are typically induced through THC’s effects on the cannabinoid type 1 (CB1) receptor. In contrast, one of the mechanisms of action of CBD is to reduce the activation of CB1 receptors which is subsequently thought to negate some of the effects of THC.
It has been theoried that both state and trait anxiety prior to cannabis intake may impact the effects of CBD and THC on anxiety. A recent study aimed to further assess the potential of cannabis products with a 1:1 CBD/THC ratio by analysing the anxiety data collected in a randomised controlled trial that investigated THC and CBD effects on cognition and driving performance.
Design and Methods of the Study
The study involved a double-blind, placebo-controlled, within-subjects design with four treatment conditions. Each condition was separated by a minimum washout period of 7 days to ensure accurate results. Preparations included a THC-dominant cannabis product (13.74 mg THC), a CBD-dominant cannabis product (13.75 mg CBD), a THC/CBD-equivalent cannabis product (13.75 mg THC/13.75 mg CBD), and a cannabis placebo. The order of treatment was randomised across the study sample and each was self-administered by vaporisation at 200˚C.
A total of 26 participants (all occasional cannabis users) were recruited for the study. Applicants who had a history of drug abuse or addiction, current or history of psychiatric disorder, including anxiety-related disorders, or with cardiovascular abnormalities, hypertension, liver dysfunction, or any serious prior adverse response to cannabis were excluded from the study.
Participants completed the trait section of the State-Trait Anxiety Inventory questionnaire (STAI-trait). They were instructed to refrain from illicit substance use and alcohol for 7 days and 1 day, respectively, prior to each study session. Baseline state anxiety was measured by a visual analogue scale (VAS). Once treatment was administered, patients completed an emotional Stroop task (EST) and rated their anxiety on the state section of the STAI-state) and VAS. The VAS was assessed repeatedly up to 5.5 hours after cannabis inhalation. Blood samples were also taken at similar intervals.
Measuring Anxiety Levels
The State-Trait Anxiety Inventory consists of both a trait and a state section, each designed to assess respectively relatively stable aspects of anxiety proneness and current anxiety levels. Each section consists of 20 four-point Likert statements with answer options ranging from “almost never” to “almost always” (trait section) and “not at all” to “very much so” (state section). Each section has a min-max score range of 20-80 with a higher score indicating higher anxiety. Participants also indicated their level of anxiety on a VAS scale where zero meant “not anxious” and 10 meant “very anxious. The Emotional Stroop Task (EST) was also used to assess implicit anxiety.
Results of the Study
Overall, participants had a mean score of 33.13 on trait anxiety, as measured by the STAI-trait questionnaire. Trait anxiety scores for healthy adults and college students range, respectively, between 36–38 and 38–40. State anxiety was seen to increase with the administration of both THC-dominant and THC/CBD cannabis compared to placebo; however, self-rated state anxiety after THC/CBD was lower compared to THC.
CBD was seen to counteract THC-induced anxiety completely when baseline anxiety was low, partly counteracted THC-induced anxiety when baseline anxiety was medium but did not counteract THC-induced anxiety when baseline anxiety was high. Furthermore, CBD, by itself, did not significantly change anxiety ratings as indicated by any of the anxiety measures.
These findings show that CBD may partially reduce THC-induced anxiety when both cannabinoids are delivered in equal combination. This finding is in line with previous studies. These findings, which are in line with a number of previous studies, should be of interest to medical cannabis clinicians when making prescribing decisions.
The researchers acknowledge some limitations of this study. Firstly, this study focused only on the acute effects of CBD on THC-induced anxiety in occasional cannabis users. These results may, therefore, differ in chronic cannabis users who may be at risk of higher levels of anxiety or the development of anxiety disorder. Furthermore, this study was part of a larger trial which measured cognition and driving ability following cannabis administration. This trial measured anxiety before and after a potentially anxiety-inducing task (driving simulation), but not during.
To gain a better understanding of the anxiety-reducing potential of CBD in association with THC administration, the researchers note that “future studies need to examine whether CBD is able to counteract THC-induced anxiety completely when an explicit stressor is present.” They also suggest that future research in this area should also include patients or participants with either a diagnosis of an anxiety disorder or with high trait anxiety.