Gráinne Schafer

Cannabidiol attenuates the appetitive effects of Δ9-tetrahydrocannabinol in humans smoking their chosen cannabis.

Worldwide cannabis dependence is increasing, as is the concentration of Δ9-tetrahydrocannabinol (THC) in street cannabis. At the same time, the concentration of the second most abundant cannabinoid in street cannabis, cannabidiol (CBD), is decreasing. These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory. No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of cannabis in humans. A total of 94 cannabis users were tested 7 days apart, once while non-intoxicated and once while acutely under the influence of their own chosen smoked cannabis on dependence-related measures. Using an unprecedented methodology, a sample of cannabis (as well as saliva) was collected from each user and analyzed for levels of cannabinoids. On the basis of CBD : THC ratios in the cannabis, individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs, explicit liking, and implicit attentional bias to drug stimuli. When intoxicated, smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC. Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days. Our findings suggest that CBD has potential as a treatment for cannabis dependence. The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders.

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

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.

Associations between cigarette smoking and cannabis dependence: A longitudinal study of young cannabis users in the United Kingdom

Highlights • We studied the extent that cigarette smoking predicts level of cannabis addiction.• We tested whether cigarette smoking mediates the effect of cannabis use on dependence.• We interviewed 298 cannabis and tobacco users, of which 65 were followed up.• Cigarette smoking accounted for 29% of the variance in cannabis dependence.• Cigarette smoking mediated the relationship between cannabis use and dependence.

Investigating the interaction between schizotypy, divergent thinking and cannabis use

Highlights ► We study the acute effects of cannabis on divergent thinking and schizotypy. ► Quartile splits compared those lowest and highest in trait creativity. ► Those higher in trait creativity also had higher trait schizotypy. ► State schizotypy increased for both groups when intoxicated with cannabis. ► Acutely, cannabis increases verbal fluency in individuals low in trait creativity.

Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function

The main active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC), can acutely induce psychotic symptoms and impair episodic and working memory. Another major constituent, cannabidiol (CBD), may attenuate these effects. This study aimed to determine the effects of THC and CBD, both alone and in combination on psychotic symptoms and memory function. A randomised, double-blind crossover design compared the effects of (i) placebo, (ii) THC 8 mg, (iii) CBD 16 mg and (iv) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser. Using an experimental medicine approach to predict treatment sensitivity, we selected 48 cannabis users from the community on the basis of (1) schizotypal personality questionnaire scores (low, high) and (2) frequency of cannabis use (light, heavy). The Brief Psychiatric Rating Scale (BPRS), Psychotomimetic States Inventory (PSI), immediate and delayed prose recall (episodic memory), 1- and 2-back (working memory) were assessed on each day. Results indicated that THC increased overall scores on the PSI, negative symptoms on BPRS, and robustly impaired episodic and working memory. Co-administration of CBD did not attenuate these effects. CBD alone reduced PSI scores in light users only. At a ratio of 2:1, CBD does not attenuate the acute psychotic and memory impairing effects of vaporised THC. Frequent cannabis users may show a blunted anti- psychotic response to CBD, which is of concern due to the high rates of cannabis use disorders in patients with schizophrenia.

P.3.d.009 Individual and combined effects of delta-9-tetrahydrocannabinol and cannabidiol on model psychosis and memory function

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