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Average subjective good drug effect (rated as a percentage) experienced in each experimental condition as a function of time after cannabis administration. Symbols indicate a signi fi cant ( p o 0.01) difference between the 22 mg THC and placebo groups (*), and between the 5.5 mg THC and placebo groups (**). Error bars represent SE of the mean. 

Average subjective good drug effect (rated as a percentage) experienced in each experimental condition as a function of time after cannabis administration. Symbols indicate a signi fi cant ( p o 0.01) difference between the 22 mg THC and placebo groups (*), and between the 5.5 mg THC and placebo groups (**). Error bars represent SE of the mean. 

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Article
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Cannabis has been suggested to impair the capacity to recognize discrepancies between expected and executed actions. However, there is a lack of conclusive evidence regarding the acute impact of cannabis on the neural correlates of error monitoring. In order to contribute to the available knowledge, we used a randomized, double-blind, between-group...

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... 2.991, p =0.009); see Figure 3. For the measures of "high" and "good drug effect", no significant differences were obtained between the ratings in the 5.5 mg and 22 mg THC conditions (p40.05). ...

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... In addition, within this state, the co-use group had greater connectivity values between the postcentral and inferior frontal gyrus and the left putamen/caudate and postcentral, compared to the alcohol-only group; no differences in connectivity were found between the alcohol and cannabis co-use and cannabis-only groups. Given previous work has shown alcohol use decreases, while cannabis use increases overall brain connectivity [65,66], findings from this study suggest alcohol and cannabis may interact in ways that counterbalance changes in connectivity related to the use of alcohol alone. Although findings from these studies provide valuable insight regarding the impact of co-use on brain function and connectivity, there was no measurement of concurrent or simultaneous use patterns. ...
... Further, the majority of studies captured the quantity of alcohol used but did not measure or quantify the amount of cannabis used. Given that studies suggest a dosedependent relationship between cannabis and neurocognitive function [65], it is important to understand how specific patterns of consumption (i.e., quantity) may affect neurobiological outcomes. While cut-offs for the measurement of alcohol use are well-established in the existing literature [67], quantification of cannabis use has been inconsistent and unreliable. ...
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Purpose of Review Given increases in the rates of alcohol and cannabis co-use among adolescents and young adults, this review aims to summarize literature on the effects of alcohol and cannabis co-use on neurocognitive functioning, brain structure, and brain function. Recent Findings The limited existing studies examining concurrent, recent, and lifetime alcohol and cannabis co-use suggest effects on the brain are likely multifaceted. The majority of studies report that co-use is associated with negative outcomes such as impaired cognitive function and significant alterations in key structural and functional regions of the brain, while others report null effects of co-use compared to non-substance using control and single-substance use groups. Summary Current studies lack a general consensus on methodology, definitions of concurrent and simultaneous use, and neuroimaging approaches, which makes it challenging to draw strong conclusions about the effects of co-use. More studies are needed to explore the effects of co-use in the context of simultaneous alcohol and cannabis use.
... On the other hand, studies on the effects of cannabinoid and opioid signaling on error processing may indicate how 'liking,' in turn, may affect error processing. In general, there is growing evidence that increased cannabinoid and opioid signaling may negatively affect error processing [5,7,14,17]. More specifically, systemically-applied cannabinoid and opioid agonists have been found to decrease neural markers of error processing [5,7,14]. ...
... On the other hand, studies on the effects of cannabinoid and opioid signaling on error processing may indicate how 'liking,' in turn, may affect error processing. In general, there is growing evidence that increased cannabinoid and opioid signaling may negatively affect error processing [5,7,14,17]. More specifically, systemically-applied cannabinoid and opioid agonists have been found to decrease neural markers of error processing [5,7,14]. ...
Article
Human research has shown interactions between rewards and cognitive control. In animal models of affective neuroscience, reward administration typically involves administering orosensory sugar signals (OSS) during caloric-deprived states. We adopted this procedure to investigate neurophysiological mechanisms of reward-cognitive control interactions in humans. We predicted that OSS would affect neurophysiological and behavioral indices of error processing oppositely, depending on the relative weight of the OSS-induced ‘wanting’ and ‘liking’ components of reward. We, therefore, conducted a double-blind, non-nutritive sweetener-controlled study with a within-subject design. Fasted (16 hr) participants (N = 61) performed a modified Flanker task to assess neurophysiological (error-related negativity [Ne/ERN]) and behavioral (post-error adaptations) measures of error processing. Non-contingent to task performance, we repeatedly administered either a sugar (glucose) or non-nutritive sweetener (aspartame) solution, which had to be expulsed after short oral stimulation to prevent post-oral effects. Consistent with our hypothesis on how ‘liking’ would affect Ne/ERN amplitude, we found the latter to be decreased for sugar compared to aspartame. Unexpectedly, we found post-error accuracy, instead of post-error slowing, to be reduced by sugar relative to aspartame. Our findings suggest that OSS may interact with error processing through the ‘liking’ component of rewards. Adopting our reward-induction procedure (i.e. administering OSS in a state of high reward sensitivity [i.e. fasting], non-contingent to task performance) might help future research investigating the neural underpinnings of reward-cognitive control interactions in humans.
... Dose-dependent cannabis effects have also been identified using human laboratory procedures (40,90). These studies consistently find that cardiovascular outcomes and (to a lesser extent) self-rated subjective responses are sensitive to variation in THC content (40). ...
... Dose-response relationships for subjective responses have been more difficult to establish, possibly due to stronger influence of expectancy effects on self-report outcomes. Performance on error-monitoring tasks (e.g., the Flanker task) and other neurocognitive measures has also been shown to vary with THC dose (90). ...
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Cannabis is increasingly used by individuals with mental health diagnoses and often purported to treat anxiety and various other psychiatric symptoms. Yet support for using cannabis as a psychiatric treatment is currently limited by a lack of evidence from rigorous placebo-controlled studies. While regulatory hurdles and other barriers make clinical trials of cannabis challenging to conduct, addiction researchers have decades of experience studying cannabis use in human laboratory models. These include methods to control cannabis administration, to delineate clinical and mechanistic aspects of cannabis use, and to evaluate potential treatment applications for cannabis and its constituents. In this paper, we review these human laboratory procedures and describe how each can be applied to study cannabis use in patients with psychiatric disorders. Because anxiety disorders are among the most common psychiatric illnesses affecting American adults, and anxiety relief is also the most commonly-reported reason for medicinal cannabis use, we focus particularly on applying human laboratory models to study cannabis effects in individuals with anxiety and related disorders. Finally, we discuss how these methods can be integrated to study cannabis effects in other psychiatric conditions and guide future research in this area.
... Of these, 88 studies were excluded due to irrelevant cognitive data (n = 48), subject population (n = 4), overlapping findings (n = 13), the lack of placebo (n = 10), or incomplete or unusable data (n = 13). Finally, 52 studies were included in the meta-analysis, comprising a total of 1580 healthy volunteers (Anderson et al., 2010;Ballard and de Wit, 2011;Bedi et al., 2013;Block et al., 1992;Böcker et al., 2010;Chait and Perry, 1994;Curran et al., 2002;D'Souza et al., 2008a;D'Souza et al., 2008b;Dumont et al., 2011;Freeman et al., 2015;Hart et al., 2001;Hart et al., 2002;Hartley et al., 2019;Heishman et al., 1989;Hindocha et al., 2017;Hunault et al., 2009;Kollins et al., 2015;Lane et al., 2005;Liem-Moolenaar et al., 2010;Makela et al., 2006;McDonald et al., 2003;Metrik et al., 2012;Mokrysz et al., 2016;Morgan et al., 2018;Morrison et al., 2009;Ramaekers et al., 2009;Ramaekers et al., 2006;Ramaekers et al., 2016a;Ramaekers et al., 2016b;Ramesh et al., 2013;Ranganathan et al., 2012;Ranganathan et al., 2017;Rogers et al., 2007;Roser et al., 2009;Spindle et al., 2018;Theunissen et al., 2015;Tunbridge et al., 2015;Wesnes et al., 2010;Wilson et al., 1994;Bossong et al., 2012;Bossong et al., 2013;Colizzi et al., 2018;Ilan et al., 2004;Ilan et al., 2005;Hart et al., 2010;Kowal et al., 2015;Mason et al., 2019;Morrison et al., 2011;Nicholson et al., 2004;O'Leary et al., 2007;Weinstein et al., 2008). Twenty five studies examined THC administration; 27 examined THC-rich cannabis, and 2 examined nabilone (THC analogue, partial CB 1 receptor agonist) administration. ...
Article
Background Impairment in cognition is frequently associated with acute cannabis consumption. However, some questions remain unanswered as to which deficits are most prominent and which demographic groups are most vulnerable. Methods A literature search yielded 40 experimental studies of acute administration of partial CB1 receptor agonists (i.e. cannabis, THC, and nabilone) that assessed cognitive dysfunction in 1403 healthy volunteers. Effect size estimates were calculated using the Comprehensive Meta-Analysis for the following six cognitive domains: attention, executive functions, impulsivity, speed of processing, verbal learning/memory, and working memory. Results There were small-to-moderate impairments across all cognitive domains. Deficits in verbal learning/memory and working memory were more prominent, whereas attention and impulsivity were the least affected. Meta-regression analysis revealed that the greater the male ratio is in a sample, the greater the negative effect of cannabinoids on speed of processing and impulsivity. Analysis of route of administration showed that the deficits in speed of processing were smaller in the oral, relative to smoking, vaping, and intravenous administration studies. A publication bias was observed. Discussion Verbal learning/memory and working memory are most prominently affected by acute administration of partial CB1 receptor agonists. The results are consistent with the residual cognitive effects that have been documented among chronic cannabis users.
... In Experiment 2, we tested whether poor metacognition (i.e., performance monitoring) likewise co-occurs with behavioral decrements and the acute administration of THC. Prior work has found acute administration of THC decreased performance monitoring in a simple visual attention task [42,43]. Here we tested whether acute administration of THC likewise disrupts performance monitoring during a working memory task using metacognitive accuracy of task performance [44] as an index of performance monitoring. ...
... To our knowledge, our work provides the first demonstration of THC's effects on mind wandering during a concurrent cognitive task. These finding are consistent with prior work on THC, including task-independent reports of mind wandering in structured interviews [86,87], failure to de-activate the default mode network during task performance [88] (but see [89]), and decreased error monitoring [42,43,90]. Similar to the effects of nicotine cravings [40] and alcohol [41], THC appears to increase mind wandering and other off-task mental states (e.g., "zoning out" or "mind blanking" [55]), and decrease awareness of task performance. ...
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With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ9-tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly little empirical support for an effect of THC or cannabis on working memory. We thus conducted a study with three main goals: (1) quantify the effect of THC on visual working memory in a well-powered sample, (2) test the potential role of cognitive effects (mind wandering and metacognition) in disrupting working memory, and (3) demonstrate how insufficient sample size and task duration reduce the likelihood of detecting a drug effect. We conducted two double-blind, randomized crossover experiments in which healthy adults (N = 23, 23) performed a reliable and validated visual working memory task (the “Discrete Whole Report task”, 90 trials) after administration of THC (7.5 and/or 15 mg oral) or placebo. We also assessed self-reported “mind wandering” (Exp 1) and metacognitive accuracy about ongoing task performance (Exp 2). THC impaired working memory performance (d = 0.65), increased mind wandering (Exp 1), and decreased metacognitive accuracy about task performance (Exp 2). Thus, our findings indicate that THC does impair visual working memory, and that this impairment may be related to both increased mind wandering and decreased monitoring of task performance. Finally, we used a down-sampling procedure to illustrate the effects of task length and sample size on power to detect the acute effect of THC on working memory.
... The literature on error processing relevant to the substance use factor is more mixed (Euser et al., 2012). Specifically, whereas drug dependence relates to blunted ERN/ Pe amplitude (Franken, van Strien, Franzek, & van de Wetering, 2007;Kowal et al., 2015;Spronk et al., 2016b), alcohol dependence has shown mixed findings (Easdon, Izenberg, Armilio, Yu, & Alain, 2005;Schellekens et al., 2010;Spronk, Dumont, Verkes, & de Bruijn, 2014)-reflecting potentially different processes involved in drug versus alcohol problems. The discrepancies in the literature can potentially be clarified by focusing less on individual disorders and more on latent sources of variance that are common and unique across externalizing disorder symptoms. ...
Article
A prominent characteristic of externalizing psychopathology is the inability to suppress or modulate behavioral responses and impulses. These tendencies have been associated with cognitive indicators of inhibitory control (P3) and error processing (error-related negativity [ERN] and positivity [Pe]). However, the extent to which these trait-like components are characteristic of specific manifestations, or externalizing proneness more generally, remains unclear. Our study aimed to further contextualize externalizing behaviors by examining associations between distinct facets of externalizing symptoms and relevant behavioral phenotypes (substance use, aggression, pathological personality and internalizing symptoms) as well as electrophysiological and behavioral indices of inhibitory control (congruence and no-go P3, flanker interference, commission errors) and error processing (ERN and Pe, post-error slowing). Using a sample of community and jail dwelling offenders (N = 497), we used Confirmatory Factor Analyses to estimate a general externalizing factor (EXT), representing shared variance, and latent factors representing symptoms related to callous-aggression (CAL; conduct disorder and antisocial personality disorder) and alcohol and drug dependence (AD and DD). Additionally, a subset of participants (N = 89) had their brain activity recorded during a flanker task. Factor analyses supported general EXT and CAL factors; however, unique AD/DD overlapped highly with shared EXT, suggesting that DSM substance use symptoms in our study reflect more general problems with disconstraint/impulsivity rather than variance specific to substances. The general EXT was marked by behavioral correlates of impulsivity and negative affect, and laboratory task deficits in error monitoring, but with greater differential processing of inhibitory cues. The CAL specific factor was associated with affective shallowness phenotype, and, interestingly, laboratory measures of enhanced processing of inhibitory cues and error adjustment. This research has implications for understanding neurocognitive processes associated with distinct manifestations of disordered behavioral inhibition.
... Those with CUD report greater disability [11,28], report engaging in violent, suicidal and non-suicidal self-injurious behavior [29], and are more likely to report inpatient and emergency room visits than those without CUD [30]. Because those with CUD use cannabis more frequently than cannabis users without CUD [11], it warrants mention that increasing evidence has linked frequency of cannabis use, amount used, age of first use, and CUD severity with a wide array of cognitive impairments [31][32][33][34]. Further, some consequences that have been associated with CUD stem from the pharmacological effects of cannabis intoxication and chronic use (e.g., driving accidents, risky sexual behavior). ...
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Confusion and controversy related to the potential for cannabis use to cause harm, or alternatively to provide benefit, continues globally. This issue has grown in intensity and importance with the increased recognition of the public health implications related to the escalation of the legalization of cannabis and cannabinoid products. This selective overview and commentary attempt to succinctly convey what is known about one potential consequence of cannabis use, the development of cannabis use disorder (CUD). Such knowledge may help guide a reasonable and objective public health perspective on the potential impact of cannabis use and CUD. Current scientific data and clinical observation strongly support the contention that cannabis use, like the use of other substances such as alcohol, opioids, stimulants, and tobacco, can develop into a use disorder (addiction) with important clinical consequences. Epidemiological data indicate that the majority of those who use cannabis do not have problems related to their use, but a substantial subset (10–30%) do report experiencing symptoms and consequences consistent with a CUD. Treatment seeking for CUD comprises a substantial proportion of all substance use treatment admissions, yet treatment response rates show much room for improvement. Changing cannabis policies related to its therapeutic and recreational use are likely to impact the development of CUD and its course; however, definitive data on such effects are not yet available. Clearly, the development of more effective prevention and treatment strategies is needed for those vulnerable to developing a CUD and for those with a CUD.
... The most commonly described acute positive effect is euphoria, or feeling high or "stoned," as well as several others including feeling "calm and relaxed," "tired" and conversely, especially at higher doses, feeling anxious and experiencing perceptual alterations [17-23, 24•]. Data remain mixed regarding the dose-dependent nature and development of tolerance to subjective effects [18,22,25,26] induced by cannabis or THC. Dose and route of administration of cannabis/THC, as well as wide inter-individual variability in response, may contribute to the mixed data. ...
Article
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Purpose of Review To summarize the current literature on the effects of cannabinoids in humans and to discuss the existing literature on the sex- and gender-related differences in the effects of cannabinoids. Recent Findings Cannabis and its constituent cannabinoids are associated with risk of addiction, cognitive deficits, and mood/psychotic disorders. Preclinical and emerging clinical data suggest greater sensitivity to the effects of cannabinoids in women. Summary Cannabis is one of the most commonly used drugs with increasing rates of use. Women in particular may be at a greater risk of adverse outcomes given the previously described “telescoping effect” of substance use in women. Human data examining the sex- and gender-related differences in the effects of cannabinoids and factors underlying these differences are very limited. This represents a critical gap in the literature and needs to be systematically examined in future studies.
... Diminished PES was observed after acute administration of disinhibiting substances, such as alcohol (Bombeke et al., 2013) or amphetamine (Wardle et al., 2012). In contrast, there were no effects after acute use of cannabis (Spronk et al., 2011(Spronk et al., , 2016Kowal et al., 2015) or benzodiazepines (Riba et al., 2005). PES was heightened (i.e. ...