Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers

Abstract

The two main phytocannabinoids—delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)—have been extensively studied, and it has been shown that THC can induce transient psychosis. At the same time, CBD appears to have no psychotomimetic potential. On the contrary, emerging evidence for CBD's antipsychotic properties suggests that it may attenuate effects induced by THC. Thus, we investigated and compared the effects of THC and CBD administration on emotion, cognition, and attention as well as the impact of CBD pre-treatment on THC effects in healthy volunteers. We performed a placebo-controlled, double-blind, experimental trial (GEI-TCP II; ClinicalTrials.gov identifier: NCT02487381) with 60 healthy volunteers randomly allocated to four parallel intervention groups, receiving either placebo, 800 mg CBD, 20 mg THC, or both cannabinoids. Subjects underwent neuropsychological tests assessing working memory (Letter Number Sequencing test), cognitive processing speed (Digit Symbol Coding task), attention (d2 Test of Attention), and emotional state (adjective mood rating scale [EWL]). Administration of CBD alone did not influence the emotional state, cognitive performance, and attention. At the same time, THC affected two of six emotional categories—more precisely, the performance-related activity and extraversion—, reduced the cognitive processing speed and impaired the performance on the d2 Test of Attention. Interestingly, pre-treatment with CBD did not attenuate the effects induced by THC. These findings show that the acute intake of CBD itself has no effect per se in healthy volunteers and that a single dose of CBD prior to THC administration was insufficient to mitigate the detrimental impact of THC in the given setting. This is in support of a complex interaction between CBD and THC whose effects are not counterbalanced by CBD under all circumstances.

Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

“…The other main phytocannabinoid in cannabis plants is cannabidiol (CBD), which comprises up to 40% of the total compounds extract. CBD, as opposed to THC, has no psychotropic properties, as also confirmed in a recent trial where healthy volunteers did not show any effects in the emotional state, cognitive performance, or attention after receiving CBD [ 80 ]. CBD has a very low affinity to the CB1 and CB2 receptors [ 53 ], and several findings proposed that CBD operated as a negative allosteric modulator/inverse agonist in both CB1 and CB2 receptors [ 81 , 82 , 83 ].…”

Comparing older nonmedical and medical cannabis users: health-related characteristics, cannabis use patterns, and cannabis sources

“…Third, the finding that a significant proportion of medical and nonmedical users obtained cannabis via private/informal sources indicates that they are likely to use cannabis and cannabis products with unknown Δ 9 tetrahydrocannabinol (THC) potency. Given the increase in THC potency (37)(38)(39)(40)(41), healthcare professionals should educate older cannabis users, especially high-frequency users, on potential safety issues and adverse health effects of cannabis and cannabis products obtained from unregulated sources. With growing numbers of states legalizing cannabis, further examination of sources and user behaviors related to obtaining nonmedical and medical cannabis is needed to better monitor safety issues and other adverse health effects.…”

Down and High: Reflections Regarding Depression and Cannabis

“…We are unaware of any randomized controlled trial investigating nabilone (synthetic orally administered THC compound) or CBD in the treatment of MDD. Finally, while CBD has been proposed to reduce the negative psychoactive effects of THC, a recent study and meta-analysis did not find support for this proposition (130,131).…”