Cannabidiol Does Not Dampen Responses to Emotional Stimuli in Healthy Adults

David L. Arndt and Harriet de Wit

Cannabis and Cannabinoid Research, 2017, 2, (1), 105-113

DOI: 10.1089/can.2017.0014

Abstract

Introduction : Cannabidiol (CBD) is a nonpsychoactive constituent of whole plant cannabis that has been reported to reduce anxiety-like behaviors in both pre-clinical and human laboratory studies. Yet, no controlled clinical studies have demonstrated its ability to reduce negative mood or dampen responses to negative emotional stimuli in humans. The objective of this study was to investigate the effects of CBD on responses to negative emotional stimuli, as a model for its potential anxiety-reducing effects.

Materials and Methods : The study used a double-blind, placebo (PLB)-controlled, within-subjects design in which 38 healthy, drug-free participants consumed oral CBD (300, 600, and 900mg) or PLB before completing several behavioral tasks selected to assess reactivity to negative stimuli. Dependent measures included emotional arousal to negative and positive visual stimuli, perceptual sensitivity to emotional facial expressions, attentional bias toward emotional facial expressions, and feelings of social rejection. In addition, subjective drug effects and physiological data were also gathered during each experimental session to assess drug effects.

Discussion : CBD did not dampen responses to negative emotional stimuli and did not affect feelings of social rejection. The high dose of CBD (900 mg) marginally reduced attentional bias toward happy and sad facial expressions, and produced a slight increase in late-session heart rate. CBD did not produce detectable subjective effects or alterations in mood or anxiety.

Conclusion : These findings indicate that CBD has minimal behavioral and subjective effects in healthy volunteers, even when they are presented with emotional stimuli. Further research into the behavioral and neural mechanisms of CBD and other phytocannabinoids is needed to ascertain the clinical function of this drug.

Keywords : behavior; cannabidiol; emotional stimuli; psychopharmacology

 

Introduction

Cannabidiol (CBD), a constituent of cannabis, has received enormous public and scientific attention over
the past decade. CBD citations in PubMed increased from 40 in 2000–2002 to 458 in 2014–2016. Although many of these refer to the potential of CBD to treat psychiatric or neurological disorders,1,2 there have been promising reports of its efficacy for treatment-resistant epilepsy and, combined with delta-9 tetrahydrocannabinol (THC; Sativex), for multiple sclerosis. There is also evidence that single doses of CBD alter mood or behavior, either alone or in combination with other cannabinoids.

Several studies suggest that CBD has anxiolytic effects. Zuardi et al.3 reported that CBD (about 35 mg) reduced anxiety provoked by oral THC (about 70 mg) in normal volunteers. Later, Zuardi et al.4 reported that CBD (300 mg) reduced anxiety during a stressful public speaking task in healthy adults, to a similar extent as diazepam (10 mg) and ipsaperone (5 mg). In other studies, CBD reduced anxiety during public speaking in individuals with social anxiety disorder,5 reduced amygdala responses to fearful faces in healthy men,6,7 and reduced anxiety in response to a stressful imaging procedure in men.8 CBD also produces anxiolytic-like effects in animal models.9 Together, these findings suggest that CBD may possess anxiolytic properties similar to those of known anxiolytic drugs.

The neural mechanisms by which CBD acts in the brain are poorly understood. CBD has low binding affinity for either CB1 or CB2 receptors. However, some in vivo studies indicate that the behavioral effects of CBD may be elicited indirectly through these receptors. 10,11 CB1 inverse agonists can block the behavioral effects of CBD in mouse models of fear conditioning, extinction, and marble burying behaviors.12,13 CBD administered directly into key brain regions reduces anxiety-like behavior in rodents.14–16 CBD may also reduce anxiety and alleviate other neurological disorders by enhancing anandamide through fatty acid amide hydrolase inhibition17,18 or by altering serotonergic (5-HT) neurotransmission, including actions as an indirect 5-HT1A agonist.1,18–21

In this study, we examined the effects of CBD on responses to negative emotional stimuli in healthy human volunteers.22 Single doses of anxiolytic and antidepressant drugs produce subtle changes in perception and responses to emotional stimuli in healthy individuals, effects that appear to predict their therapeutic efficacy. 23–26 In this study, we used such measures to study the effects of CBD. We tested participants’ responses to images or words with negative affective content, reactivityto threatening emotional faces, and sensitivity to social rejection after oral CBD (0, 300, 600, and 900 mg) in a double-blind design. We hypothesized that CBD would reduce reactivity to negative emotional stimuli.

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can.2017.0014