A Novel Observational Method for Assessing Acute Responses to Cannabis: Preliminary Validation Using Legal Market Strains

Abstract

Background: The development of novel cannabis research methods that are compatible with current federal regulations is imperative to conduct studies of the effects of legal market cannabis. There is very little research on higher strength, higher Δ9-tetrahydrocannabinol (THC), which has become increasingly available since legalization. Research on strains containing cannabidiol (CBD), a second primary, but nonpsychotomimetic, cannabinoid, is very limited. Materials and Methods: Using a novel observational methodology, regular cannabis users were asked to use one of two legal market cannabis strains that they purchased from a local dispensary (one strain containing 8% THC and 16% CBD (THC+CBD) and one containing a 17% THC concentration, but no CBD (THC). After using their suggested cannabis strain as they typically would for a 3-day period, participants returned to the laboratory immediately after their final use. Measures included a blood draw to measure cannabinoid blood levels and circulating cytokines, self-reported subjective drug effects, and verbal recall memory. Results: Analysis of CBD/THC concentration levels in the blood following the 3-day strain manipulation suggests that all, but one participant (n=23/24) followed instructions and used their assigned strain. Individuals in the THC group (n=11) smoked no more than their usual amount, and participants who used the THC+CBD (n=12) strain smoked more than their reported usual amount, but did not have significantly different THC+metabolite blood levels from the THC group. The THC+CBD strain was also associated with less desire to smoke, lower levels of subjective drug effects, and lower levels of circulating cytokines (TNF-α, IL-6, and IL-1β) immediately after use. Conclusions: Initial results support the feasibility of this novel observational methodology involving brief manipulation of strain use. Preliminary findings indicate that participants may self-titrate cannabis use based on cannabinoid concentration and the THC+CBD strain was associated with lower levels of cannabis craving, subjective intoxication, and circulating cytokines.

Keywords: CBD; THC; cannabis; harm reduction; subjective effects.

FIG. 1.

The THC+CBD strain was associated with lower levels of THC-related subjective intoxication and cognitive impairment. Scatter plots show the associations among THC+metabolite blood levels and cannabis intoxication measures at Time 2 (Panel 1: feeling mentally stoned, Panel 2: physically stoned, and Panel 3: verbal recall working memory errors) across the two strain groups (THC; n=11 and THC+CBD; n=12). Results suggest a positive relationship with THC+metabolite blood levels and intoxication outcomes in the THC-only strain and no significant relationship with THC+metabolite blood levels in the CBD-containing strain (THC+CBD).

FIG. 2.

The average plasma concentration of three proinflammatory cytokines (IL-1β, IL-6, and TNF-α) at Baseline and Time 2 for the two strain conditions. THC-only strain group showed a higher average plasma concentration of the three cytokines compared to THC+CBD group. Error bars indicate standard error.