Chronic cannabis use and error awareness: The effect on learning from errors

Opposing Effects of Cannabis Use on Late Auditory Repetition Suppression in Schizophrenia Patients and Healthy Control Subjects

Altered attentional control strategies but spared executive functioning in chronic cannabis users

Early onset of substance use has demonstrated a robust relationship with later severity of use, yet this relationship has been less examined in criminal justice contexts or examined differentially by gender. The present study utilized secondary data from a sample of offenders in one small Midwestern state entering corrections-based substance abuse treatment in prison, jail, or community settings to address these gaps in the literature. Findings indicated that age of regular cigarette use did not uniquely affect severity of illicit drug use in adulthood, defined as the frequency of use or endorsement of substance use disorder criteria. In comparison, ages of onset for alcohol and illicit drug use were significantly associated with multiple severity variables examined. Gender was not found to moderate these relationships. These findings emphasize that age of use onset for alcohol and illicit drugs can be valuable in identifying offenders at risk of severe substance use in adulthood.

Introduction: Chronic cannabis use is associated with neuroanatomical alterations in the hippocampus. While adverse impacts of cannabis use are generally attributed to Δ9-tetrahydrocannabinol, emerging naturalistic evidence suggests cannabidiol (CBD) is neuroprotective and may ameliorate brain harms associated with cannabis use, including protection from hippocampal volume loss. This study examined whether prolonged administration of CBD to regular cannabis users within the community could reverse or reduce the characteristic hippocampal harms associated with chronic cannabis use.Materials and Methods: Eighteen regular cannabis users participated in an ∼10-week open-label pragmatic trial involving daily oral administration of 200 mg CBD, with no change to their ongoing cannabis use requested. Participants were assessed at baseline and post-CBD treatment using structural magnetic resonance imaging. Automated longitudinal hippocampal segmentation was performed to assess volumetric change over the whole hippocampus and within 12 subfields.Results: No change was observed in left or right hippocampus as a whole. However, left subicular complex (parasubiculum, presubiculum, and subiculum) volume significantly increased from baseline to post-treatment (p=0.017 uncorrected) by 1.58% (Cohen's d=0.63; 2.83% in parasubiculum). Heavy cannabis users demonstrated marked growth in the left subicular complex, predominantly within the presubiculum, and right cornu ammonis (CA)1 compared to lighter users. Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.Conclusions: Our findings suggest a restorative effect of CBD on the subicular and CA1 subfields in current cannabis users, especially those with greater lifetime exposure to cannabis. While replication is required in a larger, placebo-controlled trial, these findings support a protective role of CBD against brain structural harms conferred by chronic cannabis use. Furthermore, these outcomes suggest that CBD may be a useful adjunct in treatments for cannabis dependence and may be therapeutic for a range of clinical disorders characterized by hippocampal pathology (e.g., schizophrenia, Alzheimer's disease, and major depressive disorder).

Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration

Patterns of Cannabis Use in Patients With Cyclic Vomiting Syndrome

BackgroundPreclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults.MethodsAs part of the ‘CannTeen’ project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16–17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26–29-year-olds) and adult controls (n = 64). Users used cannabis 1–7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively.ResultsUsers had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition.ConclusionsConsistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.

Animal and cellular work has shown that central cannabinoid-1 receptors modulate neural oscillations in the gamma range (40 Hz), which may be important for normal perceptual and cognitive processes. In order to assess the effect of cannabinoids on broadband-frequency neural oscillations in humans, the current study examined the effect of chronic cannabis use on auditory steady-state responses (ASSRs) utilizing electroencephalography (EEG). Passive ASSRs were assessed using varying rates of binaural stimulation (auditory click-trains; 10-50 Hz in increments of 5 Hz; 80 dB SPL) in carefully screened cannabis users and controls. Chronic cannabis users (n=22; 12 h abstinence before study; positive 11-nor-9-carboxy-delta-9-tetrahydrocannabinol urine levels) and cannabis naïve controls (n=24) were evaluated. Time X frequency analyses on EEG data were performed using Fourier-based mean trial power (MTP) and phase-locking (inter-trial coherence; ITC). Transient ERPs to stimulus onset (auditory N100 components) were also evaluated. As predicted, a decrease in spectral power (MTP) at 40 Hz was observed in the cannabis group (p<0.018). No effects on phase-locking (ITC) or the N100 were observed. Further, within the cannabis group, lower 40 Hz power correlated with an earlier age of onset of cannabis use (p<0.04). These data suggest that chronic exposure to exogenous cannabinoids can alter the ability to generate neural oscillations, particularly in the gamma range. This is consistent with preclinical animal and cellular data, which may have implications for understanding the short- and long-term psychopharmacological effects of cannabis.

Cannabis is the most widely used psychoactive drug in the United States. While multiple studies have associated acute cannabis consumption with alterations in cognitive function (e.g., visual and spatial attention), far less is known regarding the effects of chronic consumption on the neural dynamics supporting these cognitive functions. We used magnetoencephalography (MEG) and an established visuospatial processing task to elicit multi-spectral neuronal responses in 44 regular cannabis users and 53 demographically matched non-user controls. To examine the effects of chronic cannabis use on the oscillatory dynamics underlying visuospatial processing, neural responses were imaged using a time-frequency resolved beamformer and compared across groups. Neuronal oscillations serving visuospatial processing were identified in the theta (4-8 Hz), alpha (8-14 Hz), and gamma range (56-76 Hz), and these were imaged and examined for group differences. Our key results indicated that users exhibited weaker theta oscillations in occipital and cerebellar regions and weaker gamma responses in the left temporal cortices compared to non-users. Lastly, alpha oscillations did not differ, but alpha connectivity among higher-order attention areas was weaker in cannabis users relative to non-users and correlated with performance. Overall, these results suggest that chronic cannabis users have alterations in the oscillatory dynamics and neural connectivity serving visuospatial attention. Such alterations were observed across multiple cortical areas critical for higher-order processing and may reflect compensatory activity and/or the initial emergence of aberrant dynamics. Future work is needed to fully understand the implications of altered multispectral oscillations and neural connectivity in cannabis users.

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition.Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial.Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users.Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.

Rationale: Cannabis use is increasing worldwide, especially among older individuals at risk for chronic ischemic heart disease (IHD). However, little is known about the arrhythmic effects of cannabis use in IHD. Accordingly, we prospectively assessed the relationship between cannabis use, heart rate (HR), and arrhythmias in healthy age-matched controls and subjects with IHD. Methods: Healthy controls (n=37, 57% men) and subjects with IHD (myocardial infarction ≥3 months ago; n=24, 58% men) who used cannabis wore a Zio® (iRhythm Technologies) monitor for 14 days. Noncannabis using ischemic subjects (n=35, 51% males) wore Zio monitors for standard clinical indications. Baseline HR was compared with average HR measured for 4 h following consumption and changes in HR and frequency of arrhythmias were correlated with cannabis use. Results: In controls, HR increased 20 min (4.99±6.7 bpm, p=0.08) after use, then declined 4 h following use (-7.4±7.7, p<0.001). Conversely, subjects with IHD showed minimal HR increase (1.6±3.9 bpm) and blunted HR decline (-3.4±5.6 bpm, p<0.001). Supraventricular tachycardia (SVT) (29.7% vs. 58.3%; p=0.04) and nonsustained ventricular tachycardia (NSVT) (5.6% vs. 47.8%, p=0.01) were the most frequently occurring arrhythmias in controls and IHD subjects, respectively. Incidence of SVT decreased as cannabis use increased in both groups. Conversely, NSVT tended to increase with increased use in controls, and was significantly more prevalent in IHD. However, overall arrhythmia burden did not differ between cannabis users and nonusers with IHD. Conclusion: Our findings demonstrate that chronic cannabis use is associated with only mild HR changes, which are blunted in IHD. In addition, our data suggest that among cannabis users, arrhythmias are more frequent in IHD subjects that in healthy subjects.

A recent meta-analysis showed that the mean age of onset of psychosis among cannabis users was almost three years earlier than that of non-cannabis users. However, because cannabis users usually smoke tobacco, the use of tobacco might independently contribute to the earlier onset of psychosis. We aimed to use meta-analysis to compare the extent to which cannabis and tobacco use are each associated with an earlier age at onset of schizophrenia and other psychoses. We also examined other factors that might have contributed to the finding of an earlier age of onset among cannabis users, including the proportion of males in the samples, the diagnostic inclusion criteria and aspects of study quality. The electronic databases MEDLINE, EMBASE, PsycINFO and ISI Web of Science, were searched for English-language peer-reviewed publications that reported age at onset of schizophrenia and other psychoses separately for cannabis users and non-users, or for tobaccosmokers and non-smokers. Meta-analysis showed that the age at onset of psychosis for cannabis users was 32 months earlier than for cannabis non-users (SMD=- 0.399, 95%CI -0.493 - -0.306, z=-8.34, p < 0.001), and was two weeks later in tobacco smokers compared with non-smokers (SMD=0.002, 95%CI -0.094 - 0.097, z=0.03, p=0.974). The main results were not affected by subgroup analyses examining studies of a single sex, the methods for making psychiatric diagnoses and measures of study quality. The results suggest that the association between cannabis use and earlier onset of psychosis is robust and is not the result either of tobacco smoking by cannabis using patients or the other potentially confounding factors we examined. This supports the hypothesis that, in some patients, cannabis use plays a causal role in the development of schizophrenia and raises the possibility of treating schizophrenia with new pharmacological treatments that have an affinity for endo-cannabinoid receptors.

Background: Although the relation between impulsivity and substance use outcomes is well-documented (Jones et al., 2014; Stautz et al., 2017), less is known about individual facets of impulsivity among individuals who use cannabis. There is some research suggesting that positive urgency, sensation seeking, and lack of premeditation are associated with greater cannabis use problems, but much of this research has been conducted in normative adolescent or young adult samples (VanderVeen et al., 2016). Given that more than 11% of legal cannabis users currently use daily/near daily (Goodman et al., 2020), this study examined relations between individual facets of impulsivity and cannabis use, alcohol use, simultaneous cannabis and alcohol use, and problem use within a sample of frequent, adult cannabis users. Methods: Individuals (n=167) with a mean age of 34.89 (SD=11.19) who reported using cannabis on average once per day completed measures of individual facets of impulsivity (positive urgency, negative urgency, lack of premeditation, lack of perseverance, and sensation seeking; UPPS-P), cannabis use frequency, alcohol use frequency, simultaneous cannabis and alcohol use frequency, cannabis use problems, cannabis use disorder, and alcohol use disorder. Path models were used to predict frequency of use (cannabis, alcohol, and simultaneous cannabis/alcohol) and problem use (cannabis consequences, cannabis use disorder, and alcohol use disorder) from each facet of impulsivity. Models were first run using sex, age, and race as covariates, and subsequently run after adding depressive and anxiety symptoms as covariates. Results: After controlling for sex, age, and race, positive urgency was associated with less frequent cannabis use (b=-0.28, S.E.=0.13, p=0.03), more frequent simultaneous cannabis and alcohol use (b= 0.24, S.E.=0.11, p=.04), and greater cannabis consequences (b=0.30, S.E.=0.10, p=0.002). Negative urgency was associated with greater cannabis consequences (b=0.31, S.E.=0.09, p&lt;0.001), cannabis use disorder (b=0.27, S.E.=0.09, p=0.002), and alcohol use disorder (b=0.27, S.E.=0.10, p=0.01). After including depressive and anxiety symptoms as covariates, relations with positive urgency, but not negative urgency, remained significant. Conclusions: The findings of the current study suggest that positive urgency may be uniquely linked to riskier behavior in frequent cannabis users given that no other facet of impulsivity was significantly associated with cannabis use outcomes after all covariates were included in the model. Although not directly assessed in the current study, the findings suggest that relations between negative urgency and cannabis use frequency and cannabis and alcohol use disorder may be mediated by depressive and anxiety symptoms. This possibility should be explicitly examined in future studies. The lack of relations between other facets of impulsivity and alcohol and cannabis use outcomes in the current study suggest that effects of impulsivity among daily users may be restricted to urgency, in contrast to studies in normative adolescent and young adult samples (VanderVeen et al., 2016).

Many previous studies have reported that alcohol and cannabis produce additive psychomotor effects in acute combination, but few have explicitly tested whether chronic exposure to cannabis, in the absence of acute administration, alters the effects of alcohol on psychomotor performance. To test whether long-term cannabis use modulates the effects of alcohol on psychomotor skills and self-reported mood and sensation. Regular cannabis users (minimum: daily use for at least 3 years) and infrequent users (maximum: once-monthly use for at most 3 years) were matched for sex, age, alcohol intake and other drug use (14 participants in each group). Participants received alcohol (females 0.35 g/kg; males 0.45 g/kg) and placebo drinks. By urinalysis, only regular users tested positive for metabolites of Delta(9)-tetrahydrocannabinol; breath alcohol levels were similar between groups. Participants were tested on a computerised tracking task that has been used to screen drugs for adverse effects on driving. The task involved tracking a moving target on a computer screen while simultaneously responding to occasional presentations of stimuli in the periphery of the screen. Tracking accuracy was similar for both groups after placebo, but alcohol caused a significant deterioration in performance among infrequent cannabis users relative to regular users. These changes were mirrored by significant changes in self-reported scores for dizziness, measured by visual analogue scales. Alcohol slowed reaction times, but not differentially between groups. For psychomotor skills relevant to driving, chronic cannabis use (in the absence of acute administration) does not potentiate the effects of alcohol. In fact, the superior tracking accuracy of regular users relative to infrequent users after alcohol, and their lower scores for dizziness, suggest that chronic cannabis use may instead confer cross-tolerance to specific effects of alcohol on behaviour.

Cannabis, as the most widely used illicit substance in the world, also remains among the most frequently used psychoactive substances by patients with schizophrenia. It is well known that cannabis use in schizophrenia patients favors relapse, resistance to antipsychotic treatments and therefore more frequent hospitalizations. However, many studies report considerable improvement in cognitive performance in substance users, while others show the opposite. Hence, the aim of our study is to examine the relationship between schizophrenia and cannabis use in clinical and socio-de- mographic aspects. This is a cross-sectional study of patients with schizophrenia hospitalized for relapse at the Ar-Razi psychiatric hospital in Salé, Morocco. A questionnaire was established in order to search for socio- demographic data, evolutionary and prognostic criteria of the disease. Cannabis use was assessed using the Cannabis Abuse Screening Test (CAST), for the severity of schizophrenia symptoms we used the Positive And Negative Syndrome Scale (PANSS) and for perceptual and memory abilities we used the numerical version of the Rey's Complex Figure-A (RCF-A). It was found that in a sample of 115 schizophrenic patients, 47.82% (n=55) were cannabis users. The mean PANSS (negative) and (general psychopathology) scores of non-cannabis users were significantly higher than those of cannabis users with P values of (P&lt;0.001) and (P&lt;0.005) respectively. For the numerical assessment scores of the RCF-A, cannabis users had a significantly higher mean score than non-cannabis users (copy phase (P&lt;0.016) and memory (P&lt;0.001) As one of the leading risk factors for the emergence of schizophre- nia, chronic cannabis use also has a negative influence on the prognosis of patients already suffering from schizophrenia. Nevertheless, the results of our study show that cannabis-using schizophrenic patients had fewer negative symptoms according to the PANSS and an improved cognitive performance compared to non- cannabis-using patients.