Chandni Hindocha

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.

No smoke without tobacco: a global overview of cannabis and tobacco routes of administration and their association with intention to quit.

Cannabis and tobacco are common drugs of abuse worldwide and are often used in combination through various routes of administration (ROAs). Here, we aimed to provide an overview of how cannabis and tobacco routes varied across countries and assess the impact of tobacco-based ROAs on motivation to use less cannabis, and less tobacco, in different models. A cross-sectional online survey (Global Drugs Survey 2014) was completed by 33,687 respondents (mean age = 27.9; % female = 25.9) who smoked cannabis at least once in the last 12 months. Most common ROA, frequency of cannabis/tobacco use, and questions about motivation to use less cannabis/tobacco were recorded. Tobacco-based ROA were used by 65.6% of respondents. These were most common in Europe (77.2–90.9%) and Australasia (20.7–51.6%) and uncommon in the Americas (4.4–16.0%). Vaporizer use was most common in Canada (13.2%) and the United States (11.2%). Using a non-tobacco ROA was associated with a 10.7% increase in odds for “desire to use less” tobacco (OR: 1.107, 95% CI: 1.003, 1.221), 80.6% increase in odds for “like help to use less tobacco” (OR: 1.806, 95% CI: 1.556, 2.095), and a 103.9% increase in the odds for “planning to seek help to use less tobacco” (OR: 2.039, 95% CI: 1.638, 2.539), in comparison to using a tobacco-based ROA. Associations between ROA and intentions to use less cannabis were inconsistent. Results support considerable global variation in cannabis and tobacco ROA. Tobacco routes are common, especially “joints with tobacco,” especially in Europe, but not in the Americas. Non-tobacco-based routes are associated with increased motivation to change tobacco use. Interventions addressing tobacco and cannabis need to accommodate this finding and encourage non-tobacco routes.

Emotional processing deficits in chronic cannabis use: A replication and extension

Heavy cannabis use is associated with interpersonal problems that may arise in part from the inaccurate perception of emotional faces. Only one study reports impairments in emotional facial affect processing in heavy cannabis users; however, it is not clear whether these findings were attributable to differences between cannabis users and controls in schizotypy or gender, rather than from cannabis use itself. A total of 25 frequent cannabis users and 34 non-using controls completed an emotional processing task in an independent groups design. We asked participants to identify the emotions on faces morphed from neutral to 100% intensity, for six basic emotions. We measured percentage hit rate, sensitivity and response bias. Schizotypy was indexed using the Schizotypal Personality Questionnaire. Cannabis users showed lower accuracy and sensitivity on the emotional recognition task. Gender and schizotypy did not differ between the two groups. Men showed lower accuracy on the emotional processing task, but impairments in cannabis users remained when covarying for gender. Schizotypy negatively correlated with sensitivity scores, but this was unreliable when accounting for the groups. Chronic cannabis users showed generalised impairment in emotional processing. These results appeared as independent of the emotional processing deficits amongst men, and were not related to schizotypy.

Acute memory and psychotomimetic effects of cannabis and tobacco both ‘joint’ and individually: a placebo-controlled trial

Background Cannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research. Method The individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions. Results Cannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of ‘stoned’ and ‘dizzy’ induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure. Conclusions Relative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.

Legal regulated markets have the potential to reduce population levels of harm associated with cannabis use

Caulkins & Kilmer [1] provide a framework for assessing the potential impact of legalizing cannabis. Their insightful analysis is timely: despite a rapidly evolving legislative landscape, relatively little attention has been paid to the range and variation of legislative approaches being considered and the potential of these reforms to either increase or limit the population level harms associated with cannabis use. Illustrating the complexity of this issue, Caulkins & Kilmer propose 12 alternative approaches to cannabis control, ranging from complete prohibition, with enhanced penalties, to an unregulated, open market not subject to any control or criminal sanctions. Each alternative is assessed along multiple dimensions, including product quality and ability to raise taxes (their Fig. 1). We would like to the highlight potential health benefits of legal but regulated cannabis availability in addition to the benefits of reduced costs of policing (although Caulkins & Kilmer note that these benefits would be minimal in jurisdictions that have decriminalized personal use) and adverse effects of the criminalization of users. First, the potential respiratory effects of smoked cannabis may be among the greatest possible harms associated with the use of this drug. There is some evidence that US States that have legalized either medicinal or recreational use of cannabis have led a move away from smoked routes of administration, with both ingestion and vaporization increasing in popularity [2,3]. The potential health benefits of using vaporizers include reduced respiratory symptoms [4]. Additionally, cannabis use is associated with higher rates of tobacco use [5]. It may increase risks both for initiation of tobacco use [6] and for escalation to daily tobacco use and nicotine dependence [7]. Mechanisms underlying this associationmay include co-use, particularly in Europe, where the combined smoking of cannabis and tobacco is common [2]. Given that few people report combined cannabis and nicotine use when vaping [8], regulations which encourage non-smoked routes of administration may reduce tobacco use and nicotine dependence among those who use cannabis. A second area where regulation could reduce more risky patterns of cannabis use is by eliminating uncertainty about the purity and potency of products. There is emerging evidence that the potential harms associated with the use of natural cannabis may vary according to the ratio of Δ-tetrahydrocannabinol (THC) to cannabidiol (CBD). Specifically, varieties with high THC/CBD ratios appear to increase the risks for developing both psychosis [9] and dependence [10]. Cannabis users in unregulated markets rarely know THC and CBD content of the products that they use, which may increase the risks of these adverse effects due to excessive dosing [11]. In recent years there has been an increase in the potency of natural cannabis products: ElShouly et al. [12] reported that the potency of natural cannabis in the United States increased from 4% in 1995 to 12% in 2014. A corresponding decline in cannabidiol resulted in a change in the THC/CBD ratio from 14 times in 1995 to 80 times in 2014. Additionally, the use of alternative product formulations, including edible products and cannabis concentrates (e.g. butane hash oil or dabbing, which may be as potent as 70% THC [13,14]), has increased in jurisdictions in which cannabis has been legalized. Specific concerns about these products include their high potency and the ways in which edibles are marketed that may be attractive to adolescents and children [15]. Tight regulation, including limits on potency, labelling and standardization of dose and packaging that does not appeal to young people and cannot be mistaken for non-cannabis products, could reduce the potential for increased harm. Finally, in many jurisdictions in which natural cannabis remains illegal the use of synthetic cannabinoids (e.g. ‘Spice’, ‘K2’ or ‘Kronic’) has increased, particularly among adolescents [16]. One motive for the use of these drugs is their legal status. However, these products also have a less desirable effect profile and are associated with markedly higher rates of accident and emergency (A&E) attendance [17]. The majority of synthetic users prefer natural cannabis [18]. Access to natural cannabis through legal, regulated markets would probably reduce (although not necessarily eliminate) the use of these more harmful synthetic substances, producing a net positive for population health. As Caulkins & Kilmer discuss, legalization of cannabis may takemany different forms, and there is already considerable variation in aspects of thesemarkets. If accompanied by appropriate regulation, however, legalization can potentially reduce population levels of cannabis-related harm.

The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards

RationaleDrug addiction may be characterised by a hypersensitivity to drug rewards and a hyposensitivity to non-drug rewards. This imbalance may become further polarised during acute abstinence.Objectives(i) Examine the differences between dependent and occasional smokers in choices for, motivation for and self-reported wanting and liking of cigarette and non-drug rewards. (ii) Examine the effects of 12-h nicotine abstinence on these metrics.MethodsDependent (n = 20) and occasional, non-dependent smokers (n = 20) were tested after ad libitum smoking and ≥12-h of nicotine abstinence. A novel task was developed (Drug, Reward and Motivation–Choice (DReaM-Choice)) in which different rewards (cigarettes, music and chocolate) could be won. In each trial, participants chose between two rewards and then could earn the chosen reward via repeated button-pressing. Participants subsequently ‘consumed’ and rated subjective liking of the rewards they had won.ResultsCompared with occasional smokers, dependent smokers made more choices for (p < 0.001), pressed more for (p = 0.046) and reported more wanting (p = 0.007) and liking (p < 0.001) of cigarettes, and also made fewer choices for chocolate (p = 0.005). There were no differences between the groups on button-pressing for chocolate or music. However, the balance between drug and non-drug reward processing was different between the groups across all metrics. Twelve-hour nicotine abstinence led to more cigarette choices (p < 0.001) and fewer music choices (p = 0.042) in both groups.ConclusionsNicotine dependence was associated with a hypersensitivity to cigarette rewards, but we found little evidence indicating a hyposensitivity to non-drug rewards. Our findings question the moderating influence of dependence on how acute nicotine abstinence affects reward processing.

The idiosyncratic nature of confidence

Confidence is the ‘feeling of knowing’ that accompanies decision-making. Bayesian theory proposes that confidence is a function solely of the perceived probability of being correct. Empirical research has suggested, however, that different individuals may perform different computations to estimate confidence from uncertain evidence. To test this hypothesis, we collected confidence reports in a task in which subjects made categorical decisions about the mean of a sequence. We found that for most individuals, confidence did indeed reflect the perceived probability of being correct. However, in approximately half of them, confidence also reflected a different probabilistic quantity: the perceived uncertainty in the estimated variable. We found that the contribution of both quantities was stable over weeks. We also observed that the influence of the perceived probability of being correct was stable across two tasks, one perceptual and one cognitive. Overall, our findings provide a computational interpretation of individual differences in human confidence.Using behavioural experiments and computational modelling, Navajas and colleagues provide a systematic characterization of individual differences in human confidence.

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion

Abstract Background Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms. Methods Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05). Results Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001). Conclusions Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal

Abstract Background and Aims Cannabidiol (CBD), a non‐intoxicating cannabinoid found in cannabis, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side effects and research showing that it may modify drug cue salience. We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette‐related stimuli and increased craving and withdrawal; and (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette‐related stimuli, craving and withdrawal and not produce any side effects. Design Randomized, double‐blind cross‐over study with a fixed satiated session followed by two overnight abstinent sessions. Setting UK laboratory. Participants Thirty non‐treatment‐seeking, dependent cigarette smokers recruited from the community. Intervention and comparator 800 mg oral CBD, or matched placebo (PBO) in a counterbalanced order Measurements AB to pictorial tobacco cues was recorded using a visual probe task and an explicit rating task. Withdrawal, craving, side effects, heart rate and blood pressure were assessed repeatedly. Findings When participants received PBO, tobacco abstinence increased AB (P = 0.001, d = 0.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (P = 0.007, d = 0.704) and no longer differed from satiety (P = 0.82). Compared with PBO, CBD also reduced explicit pleasantness of cigarette images (P = 0.011; d = 0.514). Craving (Bayes factor = 7.08) and withdrawal (Bayes factor = 6.95) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence. Conclusions A single 800‐mg oral dose of cannabidiol reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. Cannabidiol did not influence tobacco craving or withdrawal or any subjectively rated side effects.