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Using cannabis is perceived by many as relatively harmless, but the adverse effects of problematic cannabis use are significant.

Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN) and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50) in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence) and 18 nonusers completed (1) a multifeature oddball task with duration, frequency, and intensity deviants and (2) a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating) were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation) may be related to either self-medication or an accelerated aging process.

Background: Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. Objective: We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. Method: We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. Results: The majority of the studies found altered brain function, but intact Behav task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms and family history of psychiatric disorders and substance use. Conclusion: Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal Behav performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined.

Introduction: Retaining clients in residential alcohol and other drug (AOD) treatment is difficult and cognitive impairment has been identified as a significant predictor of treatment dropout. The application of extensive screening for cognitive impairment is cost-prohibitive for most AOD treatment services. The current study aimed to explore cognitive functioning and impairment-associated factors in a typical sample of residential AOD clients using a free brief screening tool that could be utilised by front-line AOD services. Methods: Residents of an AOD therapeutic community (n = 128) and a non-substance using control group (n = 37) were administered a brief cognitive screening measure, the Montreal Cognitive Assessment (MoCA). MoCA total and domain scores were compared between these groups and within the AOD group examined in association with primary substance of misuse, severity of dependence, gender, psychological distress, and history of head injury. Results: Almost half (43.8%) of the AOD sample were identified as cognitively impaired, compared to 16.2% of the control group. Furthermore, 67.2% of the AOD sample had sustained head injuries and 50% of the sample required hospitalization for head injury. History of head injury was a significant determinant of cognitive impairment, and associated with greater levels of psychological distress. Conclusions: There are high rates of inter-related cognitive impairment, head injuries, and psychological distress among clients in residential AOD treatment. Routine screening of clients at intake for cognitive impairment by means of a brief screening measure such as the MoCA, in combination with the assessment of history of head injuries and comorbid psychological disorders, could inform treatment modifications or adjunct interventions to increase retention and improve long-term outcomes.

Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm.

The aim of this study was to assess the efficacy of cognitive training, specifically computerized cognitive training (CCT) and virtual reality cognitive training (VRCT), programs for individuals living with mild cognitive impairment (MCI) or dementia and therefore at high risk of cognitive decline. After searching a range of academic databases (CINHAL, PSYCinfo, and Web of Science), the studies evaluated (N = 16) were categorized as CCT (N = 10), VRCT (N = 3), and multimodal interventions (N = 3). Effect sizes were calculated, but a meta-analysis was not possible because of the large variability of study design and outcome measures adopted. The cognitive domains of attention, executive function, and memory (visual and verbal) showed the most consistent improvements. The positive effects on psychological outcomes (N = 6) were significant reductions on depressive symptoms (N = 3) and anxiety (N = 2) and improved perceived use of memory strategy (N = 1). Assessments of activities of daily living demonstrated no significant improvements (N = 8). Follow-up studies (N = 5) demonstrated long-term improvements in cognitive and psychological outcomes (N = 3), and the intervention groups showed a plateau effect of cognitive functioning compared with the cognitive decline experienced by control groups (N = 2). CCT and VRCT were moderately effective in long-term improvement of cognition for those at high risk of cognitive decline. Total intervention time did not mediate efficacy. Future research needs to improve study design by including larger samples, longitudinal designs, and a greater range of outcome measures, including functional and quality of life measures, to assess the wider effect of cognitive training on individuals at high risk of cognitive decline.

Background Cannabis use is associated with the development of psychotic symptoms and increased risk for schizophrenia. The mismatch negativity (MMN) is a brain event-related potential marker of change detection thought to index glutamatergic N-methyl-D-aspartate receptor-mediated neurotransmission, which is known to be deficient in schizophrenia. This study examined auditory MMN in otherwise healthy chronic cannabis users compared with nonuser control subjects. Methods Forty-two chronic cannabis users and 44 nonuser healthy control subjects completed a multi-feature MMN paradigm, which included duration, frequency, and intensity deviants (deviants 6%; standards 82%). The MMN was compared between users and control subjects as well as between long- and short-term users and age- and gender-matched control subjects. Associations between MMN, cannabis use measures, and symptoms were examined. Results The MMN amplitude was significantly reduced to frequency but not duration or intensity deviants in overall cannabis users relative to control subjects. Frequency MMN was similarly attenuated in short- and long-term users relative to control subjects. Long-term users also exhibited reduced duration MMN relative to control subjects and short-term users and this was correlated with increased duration of exposure to cannabis and increased psychotic-like experiences during intoxication. In short-term users, a younger age of onset of regular cannabis use and greater frequency of use were associated with greater psychotic-like experiences and symptomatic distress. Conclusions These results suggest impaired sensory memory that might reflect N-methyl-D-aspartate receptor dysfunction in chronic cannabis users. The pattern of MMN alterations in cannabis users differed from that typically observed in patients with schizophrenia, indicating overlapping but distinct underlying pathology.

Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls; ii) is associated with patterns of cannabis use; and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among samples that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small sample sizes, heterogeneity across studies in sample characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research.

of a poster presentation at the 27th ECNP Congress, Berlin, Germany, 18-21 October 2014.

presented at the 69th Annual Scientific Convention and Meeting, 8-10 May 2014, New York, United States

Doppler intuited that a sound’s pitch could be altered by the relative velocity between the source and an observer-70 years later Hubble used the same principle and 42 data points to prove the universe was indeed expanding. Arguably, no other data set of 0.042 Kb has done more to change our understanding of the cosmos. Although modest in volume, it took Hubble several years to acquire these precious numbers. Nowadays we conduct neuroscience in a state of instant data overload. In a matter of hours we could produce a structural image of an individual's brain comprising a matrix of 256 x 256 x 128 = 8 388 608 data points, a resting-state functional magnetic resonance imaging (MRI) time series (83MB), and from a simple blood sample, derive the person's genetic sequence by GWAS (30 K), state of gene expression by microarray (another 30 K) and metabolomic profile using any of a number of commercially available chips (1 K). We need not necessarily stop there. In principle, the number of brain-gene-omic interactions on permutation alone approaches 10 (19).

This chapter reviews structural neuroimaging studies examining the impact of regular cannabis exposure, cannabis use patterns, and psychopathology/neurocognitive measure on the human brain. Regular cannabis exposure was related to alterations in medial temporal, frontal, and cerebellar brain regions, which were most apparent in heavier using groups. A series of complex relationships between cannabis use patterns, psychopathology/neurocognitive measures, and brain volumes were apparent. Despite many methodological issues across studies to date, there is emerging evidence that regular cannabis use is related to adverse outcomes on human brain structure.

Chronic cannabis use has been associated with neurocognitive deficits, alterations in brain structure and function, and with psychosis. This study investigated the effects of chronic cannabis use on P50 sensory-gating in regular users, and explored the association between sensory gating, cannabis use history and the development of psychotic-like symptoms. Twenty controls and 21 regular cannabis users completed a P50 paired-click (S1 and S2) paradigm with an inter-pair interval of 9. s. The groups were compared on P50 amplitude to S1 and S2, P50 ratio (S2/S1) and P50 difference score (S1-S2). While cannabis users overall did not differ from controls on P50 measures, prolonged duration of regular use was associated with greater impairment in sensory gating as indexed by both P50 ratio and difference scores (including after controlling for tobacco use). Long-term cannabis users were found to have worse sensory gating ratios and difference scores compared to short-term users and controls. P50 metrics did not correlate significantly with any measure of psychotic-like symptoms in cannabis users. These results suggest that prolonged exposure to cannabis results in impaired P50 sensory-gating in long-term cannabis users. While it is possible that these deficits may have pre-dated cannabis use and reflect a vulnerability to cannabis use, their association with increasing years of cannabis use suggests that this is not the case. Impaired P50 sensory-gating ratios have also been reported in patients with schizophrenia and may indicate a similar underlying pathology.

presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australia

presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australia

presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australia

presented at the The Royal Australian and New Zealand College of Psychiatrists 2013 Congress, 26-30 May 2013, Sydney, Australia

presented at the Society of Biological Psychiatry 68th Annual Scientific Convention May 16-18 2013, San Francisco, USA

presented at the Society of Biological Psychiatry 68th Annual Scientific Convention, 16-18 May 2013, San Francisco, United States

Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment.

Published abstract from the 3rd Biennial Schizophrenia International Research Conference Florence, Italy 14-18 April 2012

The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes.

Until recently, it was possible to state with some confi - dence that there was no evidence of cannabis-related brain damage in humans. There was some support from the animal literature, but few human studies had been conducted where the findings could not be explained by methodological or other confounding factors. Recent evidence for gross morphological, connectivity and microstructural changes has now emerged that warrants further consideration. If cannabis were found to alter the structural integrity of the brain, then this may assist us to understand the mechanisms by which cannabis triggers psychotic symptoms or overt psychosis in vulnerable individuals.

from the 25th ECNP Congress, Vienna, Austria, 13-17 October 2012

presented at the 3rd Biennial Schizophrenia International Research Conference Florence, Italy 14-18 April 2012

Twenty years ago cannabis was generally perceived to be a benign drug with few significant adverse effects. As outlined elsewhere in this book, evidence has since mounted in the scientific literature for a range of harms associated with the use of cannabis, including the development of dependence and health-related harms (see also Hall and Solowij, 1998; Hall and Degenhardt, 2009). As the overall theme of this book indicates, an association between cannabis use and the development of psychotic symptoms or overt psychosis has grown to be recognized as a significant potential harm, and investigating the mechanisms by which cannabis may trigger psychosis is a priority. This includes understanding the effects of cannabis on brain structure, biology and function. We recently highlighted a similarity between the cognitive impairment that has been reported in cannabis users and the deficits observed in schizophrenia (Solowij and Michie, 2007), suggesting common underlying neuropathology. Few would argue that cognition is not impaired to some degree during acute intoxication with cannabis. That impaired cognition persists beyond the period of acute intoxication is more contentious. Despite objective appraisals of the literature in interpreting the evidence, it is inevitable that researchers will be influenced by the weight of their own data in formulating scientific opinion. Accordingly, and on the basis of the accumulating evidence, this review will come to some rather different conclusions from those made in the first edition of this book (Pope and Yurgelun-Todd, 2004). The goal of this chapter is to update our knowledge of the short- and long-term effects of cannabis on cognition based on integrating evidence from the most recent literature on this topic. We acknowledge the weight of evidence from our own studies that must inevitably guide us to the conclusions that we draw, while also aiming objectively to assess the evidence from multiple sources. We consider evidence

Verbal learning and memory in cannabis users from adolescents to adults using a range of neuropsychological and neuroimaging techniques.