The effects of cannabis use are often considered complex and extremely variable from patient to patient. Nonetheless, it is generally accepted (with the support of extensive literature) that acute cannabis use is often associated with positive mood and reward. On the other hand, it is also accepted that cannabis use – due to tetrahydrocannabinol (THC), the main psychoactive compound found in the plant – can also be linked to several unpleasant and negative effects.
For example, while THC has been seen to reduce anxiety levels at low doses, it has also been seen to increase anxiety at higher doses. Furthermore, several studies have demonstrated that higher doses of THC can produce psychotomimetic effects, including reports of paranoia, dissociation, and depersonalisation – the acute effects of which may be worse in those at risk for psychosis. Growing evidence, however, suggests that the risks of these negative effects may be somewhat alleviated by the coadministration of cannabidiol (CBD). These studies are supported by mechanistic studies which provide a pharmacological hypothesis for how CBD may do this.
There remains uncertainty around how CBD may impact or change the effects of THC. Some studies suggest that CBD may diminish the effects of THC on positive mood and cognition, however, more recent data does not support this hypothesis. While the results of one study suggest that CBD may even enhance the positive mood effects of THC, there is a consensus within the literature that CBD may mitigate the adverse effects. The mechanisms through which it achieves this, however, remains a topic of contention.
While there is growing literature on this topic, the researchers of a recent study note that many of these studies do not reflect the strengths and concentrations of cannabis products that are widely available through both illicit and legal sources. Furthermore, the drug administration approaches do not reflect real-world cannabis consumption methods. As such, a recent study used a naturalistic at-home administration procedure in concert with a mobile pharmacology laboratory to examine the effects of three different forms of cannabis flower with different ratios of CBD and THC.
Design and Methods of the Study
Participants were recruited using social media postings and mailed flyers. Those who wanted to participate were then screened over the phone by research staff: participants must be aged between 21 and 70; used cannabis flower at least four times in the last month; endorsed prior use of the highest potency of flower that could be assigned in the study (24% THC, 1% CBD); no recreational drug use (other than cannabis) in the past 7 days (confirmed with urine toxicology screening); no daily tobacco use; and not receiving treatment for/no reported diagnosis of psychotic disorder, bipolar disorder, or schizophrenia – among other inclusion requirements. The sample consisted of 159 participants.
Following a baseline appointment with researchers – at which data on demographics, lifestyle, medical history, and measures of subjective drug effects, substance use, and other measures of mood, were collected – participants were randomly assigned to one of three chemovars of flower, each with a different ratio of THC to CBD: THC dominant (24% THC; 1% CBD); THC + CBD (9% THC; 10% CBD); or CBD dominant (1% THC; 23% CBD).
Participants were asked to purchase their assigned chemovar from a legal study-partnered dispensary and to purchase enough cannabis flower for five days of use. During this five-day period, participants were instructed to use the product as they chose to familiarise themselves with their allocated product in the lead up to their second study appointment. Participants were asked to refrain from cannabis use on the day of the first mobile pharmacology lab appointment to complete the outcome measures (pre-use).
Following this appointment, participants again returned home and used their allocated product – each participant weighed the product before and after use using a study-approved scale to report how much of the product they had used. For the second mobile pharmacology lab appointment, participants completed the outcome measures while acutely intoxicated (acute post-use). Participants remained in the lab for 1 hour and completed the measure again for a final time (1-h post-use).
Primary Outcome Measures
Plasma Cannabinoid Concentrations
The first primary outcome measure was blood cannabinoid concentration. This was determined by collecting blood from each participant. This plasma sample was then separated from red blood cells for 10 minutes, transferred to a fresh microcentrifuge tube for phytocannabinoid analysis and a separate microcentrifuge tube for endocannabinoid analysis. Researchers quantified the concentration of THC and CBD, in addition to tetrahydrocannabivarin (THCV), cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC).
Subjective high and mood effects
Several measures were used to determine the subjective high and mood effects of cannabis. Three items assessed cannabis high: “feel high” (10-point Likert-type scale); “mentally stoned” (5-point Likert-type scale); and “physically stoned” (5-point Likert-type scale). These items were averaged to create a composite subjective high score.
The researchers also employed a modified version of the Profile of Mood States (POMS) questionnaire: elation and anxiety/tension subscales of the POMS were retained as the two primary outcomes for this study. Paranoia was also measured using the “paranoia” item on the POMS. A single item from the Drug Effects Questionnaire (DEQ) was also used to assess ‘drug liking’ (“Do you like any of the effects you’re feeling?”) on a 5-point Likert-type scale with responses ranging from 1 (not at all) to 5 (extremely).
Results of the Study
As expected, plasma levels of THC were significantly higher among individuals who were using the THC dominant chemovar, significantly lower among those using the THC+CBD chemovar, and lowest among those using the CBD dominant chemovar. The plasma CBD concentration also reflected these findings.
High and Elation
The analyses indicated that the THC dominant and THC + CBD chemovars were associated with almost identical increases in high and elation, despite plasma level analyses that those in the THC + CBD condition had significantly less (approx. 50% less) THC in their plasma. The data also indicated that participants reported ‘liking’ the THC+ CBD chemovar as much as the THC chemovar.
Therefore, as these results suggest that the combination of THC + CBD was no different than THC with respect to positive subjective effects, it is reasonable to assume that individuals using a THC + CBD chemovar would not have a reason to increase their cannabis use to achieve higher levels of THC. These findings are consistent with the results of previous studies which have suggested that CBD does not diminish the effects of THC on positive mood – or may enhance these positive effects.
Paranoia and Anxiety
In contrast to the analyses of positive effects, analyses of negative effects indicated that use of the THC dominant chemovar was associated with increased levels of anxiety and paranoia than that of the THC + CBD and CBD dominant chemovars. Thus, the present analyses suggest that chemovars with greater CBD and less THC are associated with differential effects on paranoia and anxiety among experienced users during ‘ad libitum’ use, which is associated with laboratory studies.
While it is possible that CBD has a direct effect on anxiety and paranoia, it may also be interpreted that differences in anxiety and paranoia might be related to the positive mood and self-titration.
Researcher Conclusions
The researchers note that the data collected in this study suggested that CBD may be associated with an overall reduction of THC exposure and may mitigate the negative psychomimetic effects of THC without diminishing the effects of THC that individuals report as beneficial. As policy regarding cannabis legalisation continues to evolve around the world, the risks associated with the use of cannabis have become an increasingly important topic. This study is an important step in identifying cannabinoid ratios that may alter risk for the user, thus highlighting a critical avenue in harm reduction.
