Single doses of CBD (300, 600, and 900 mg oral) did not dampen responses to negative emotional stimuli in healthy volunteers. The highest dose of CBD (900 mg) produced a slight, delayed increase in heart rate 240 min after administration (Fig. 6), and decreased attentional bias toward emotional facial expressions. But, CBD produced no detectable subjective effects (e.g., “feeling” a drug effect or ratings of momentary mood states) and had little effect on reactions to negative emotional stimuli on standardized tasks. The drug was well tolerated in these healthy young adults, and no participants experienced any adverse effects.

Previous findings on the effects of CBD on mood or subjective state have been mixed. Several previous studies have suggested that CBD has stress-dampening effects, either alone or when it is administered in combination with other constituents of the cannabis plant.³⁸ Our finding that CBD had little or no effect on behavioral measures of negative emotionality is apparently inconsistent with the prior reports of anxiolytic effects. However, our findings are consistent with other recent reports that CBD has minimal psychological or behavioral effects. In particular, Babalonis et al.⁵² reported that oral CBD (200, 400, and 800 mg) produced no detectable subjective or behavioral effects in regular cannabis users on measures of psychomotor performance and selective attention. In a related report, Haney et al.⁵³ reported that CBD also did not change responses to cannabis.

An important shortcoming of this study was the absence of pharmacokinetic data to confirm that the drug was absorbed and that the participants were exposed to the intended plasma concentrations of drug. Because the drug, unexpectedly, had little effect on any outcome measure, we cannot be assured that the appropriate dose was delivered. Furthermore, Haney et al.⁵³ reported a great deal of inter-individual variability in the peak plasma levels of CBD: among the eight participants in their study who received 800 mg CBD, peak plasma levels ranged from 1.6 to 271.9 ng/ml for the 6-h session, and the time to peak ranged from 120 to 360 min. This level of variability makes it difficult to measure the effects of the drug, and, if present in our study, could have contributed to our negative findings. Unpublished data from the supplier of the CBD formulation used here indicated that peak plasma CBD concentrations after a single dose occurred 4.5 h after oral administration (standard deviation [SD] 1.62 in 20 healthy volunteers), suggesting that absorption here was adequate and plasma levels were rising when we implemented our behavioral tasks. On a separate issue, it also would be of interest to study the effects of chronic doses of CBD to determine whether steady-state concentrations of CBD produce detectable behavioral effects.

Little is known about effects of CBD on attentional bias. One study⁵⁴ compared attentional bias to drug and food stimuli in individuals who reported smoking high CBD:THC strains compared with low CBD:THC ratios, and found that high CBD:THC smokers showed lower attentional bias to drug and food stimuli. However, it is difficult to relate those findings to the present results because of differences in drugs, participants, and study stimuli. It remains to be determined whether CBD truly alters attentional bias to emotional stimuli.

One question to be addressed in any study, especially one with “negative” findings, is whether the measures used were sensitive to the purported drug effect. In this case, we used four tasks assessing reactivity to emotional stimuli, and each task was previously shown to be sensitive to the effects of psychoactive drugs. Moreover, our tasks provided orderly and expected effects, independently of CBD administration. On the DEIT, subjects were quicker to identify angry facial expressions than other emotions, as previously reported,⁴⁴ and other drugs are known to alter DEIT performance.^44,55 Yet, we found no effect with CBD. On the IAPS task, participants rated positive pictures positively and negative pictures negatively, and previous studies have shown that stimulant drugs alter ratings of images.^44,55 Again, CBD did not affect responses to images of any valence. In the Cyberball task, participants reported greater feelings of social rejection after the exclusion game in this study, and we have previously reported that certain psychoactive drugs reduce feelings of rejection.⁵¹ Yet, CBD did not blunt feelings of rejection in this study. Finally, on the ABT, the mean reaction times in this study were comparable to those in previous studies,⁴⁷ and on the Stroop task, we detected the usual slowing on the color control condition, but CBD did not alter performance in either of these measures. Thus, CBD had little or no effect on tasks with known sensitivity.

This study had limitations. We assessed attentional bias using reaction time to detect a stimulus, whereas previous studies used eye gaze, measured with electrooculography⁴⁴ (EOG). It is possible that the EOG measure provides a more sensitive index of attention. It is possible that the emotional stimuli used here were not salient enough to induce negative mood states or anxiety, or that the mood effects of CBD are only evident in individuals with high levels of anxiety, because of an underlying trait, or because of a contextual stressor (an anxiogenic drug or a stressful task^4,5), as in prior reports of anxiolysis with CBD. Thus, it is possible that we did not detect a mood effect because participants were not experiencing anxiety at the time of CBD administration.