Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users

Abstract

Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8 mg), CBD (16 mg), THC+CBD (8 mg+16 mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.

Cannabidiol as a Potential Treatment for Anxiety Disorders

“…CBD reduced THC-induced anxiety when administered simultaneously with this agent, but had no effect on baseline anxiety when administered alone [99,100]. Further studies using higher doses supported a lack of anxiolytic effects at baseline [101,107]. By contrast, CBD potently reduces experimentally induced anxiety or fear.…”

“…CBD produced no changes in predicted areas (relative to placebo) but reduced activation in the left insula, superior temporal gyrus, and transverse temporal gyrus. The fearful faces task activates the amygdala, and other medial temporal areas involved in [107] Varying in schizotypy and cannabis use, DBP Inhaled, 16 mg, acute Baseline VAS anxiety No significant effect of CBD HV = healthy volunteers; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; THC = Δ 9-tetrahydrocannabinol; STAI = Spielberger's state trait anxiety inventory; VAMS = visual analog mood scale; BP = blood pressure; SPST = simulated public speaking test; SCR = skin conductance response; SPECT = single-photon emission computed tomography; SSPS-N = negative self-evaluation subscale; HR = heart rate; VAS = visual analog scale, CBD = cannabidiol ↑ rCBF in the right posterior cingulate gyrus CBD = cannabidiol; HV = healthy controls; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; SPECT = single-photo emission computed tomography; rCBF = regional cerebral blood flow; fMRI = functional magnetic resonance imaging; HPC = hippocampus; HYP = hypothalamus; PHG = parahippocampal gyrus; STG = superior temporal gyrus; MTG = medial temporal gyrus; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex emotion processing, and heightened amygdala response activation has been reported in anxiety disorders, including GAD and PTSD [113,114]. CBD attenuated blood-oxygen-level dependent activation in the left amygdala, and the anterior and posterior cingulate cortex in response to intensely fearful faces, and also reduced amplitude in skin conductance fluctuation, which was highly correlated with amygdala activation [109].…”

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

“…For example, the subjective effects of nabiximols (oromucosal spray containing equal parts CBD and THC) did not differ from a comparable dose of oral THC alone (Schoedel et Oral cannabidiol and smoked cannabis M Haney et al did not alter ratings of 'stoned' following vaporized THC administration (Hindocha et al, 2015); and, cannabis smoked naturalistically (participant's own self-selected marijuana) with high CBD did not produce different ratings of 'stoned' than cannabis with low CBD concentrations (Morgan et al, 2010). Furthermore, there was no indication that cannabis bred to contain different levels of CBD (0.2, 1.0%) altered the subjective, physiological, or performance effects of smoked cannabis with varying THC concentrations (1.8, 3.6% THC; Ilan et al, 2005).…”

“…Yet most studies show that neither smoked, vaporized nor oral CBD alters THC's positive subjective effects, such as feeling 'high' or 'stoned' (Juckel et al, 2007;Roser et al, 2009;Morgan et al, 2010;see Zhornitsy and Potvin, 2012;Hindocha et al, 2015). There are several explanations for this lack of consistency.…”

Can we make cannabis safer?

“…A recent study found that CBD given orally up to 800mg did not influence the pleasurable, reinforcing or intoxicating effects of a smoked cannabis cigarette (~4.4mg THC) 23 . Two studies of inhaled cannabis vapour, with combinations including 8mg THC, 8mg THC + 10mg CBD and 8mg THC + 16mg CBD, found no differences in ratings of 'stoned' 24,25 . Lastly, a study where participants smoked their own cannabis found no difference in 'stoned' ratings when comparing low to high CBD:THC ratio strains of cannabis 26 .…”