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1.  Reaching out towards cannabis: approach-bias in heavy cannabis users predicts changes in cannabis use 
Addiction (Abingdon, England)  2011;106(9):1667-1674.
Aims
Repeated drug exposure can lead to an approach-bias, i.e. the relatively automatically triggered tendencies to approach rather that avoid drug-related stimuli. Our main aim was to study this approach-bias in heavy cannabis users with the newly developed cannabis Approach Avoidance Task (cannabis-AAT) and to investigate the predictive relationship between an approach-bias for cannabis-related materials and levels of cannabis use, craving, and the course of cannabis use.
Design, settings and participants
Cross-sectional assessment and six-month follow-up in 32 heavy cannabis users and 39 non-using controls.
Measurements
Approach and avoidance action-tendencies towards cannabis and neutral images were assessed with the cannabis AAT. During the AAT, participants pulled or pushed a joystick in response to image orientation. To generate additional sense of approach or avoidance, pulling the joystick increased picture size while pushing decreased it. Craving was measured pre- and post-test with the multi-factorial Marijuana Craving Questionnaire (MCQ). Cannabis use frequencies and levels of dependence were measured at baseline and after a six-month follow-up.
Findings
Heavy cannabis users demonstrated an approach-bias for cannabis images, as compared to controls. The approach-bias predicted changes in cannabis use at six-month follow-up. The pre-test MCQ emotionality and expectancy factor were associated negatively with the approach-bias. No effects were found on levels of cannabis dependence.
Conclusions
Heavy cannabis users with a strong approach-bias for cannabis are more likely to increase their cannabis use. This approach-bias could be used as a predictor of the course of cannabis use to identify individuals at risk from increasing cannabis use.
doi:10.1111/j.1360-0443.2011.03475.x
PMCID: PMC3178782  PMID: 21518067
Approach avoidance task; approach-bias; cannabis; cannabis use disorder; craving; dependence
2.  Implicit Associations and Explicit Expectancies toward Cannabis in Heavy Cannabis Users and Controls 
Cognitive biases, including implicit memory associations are thought to play an important role in the development of addictive behaviors. The aim of the present study was to investigate implicit affective memory associations in heavy cannabis users. Implicit positive-arousal, sedation, and negative associations toward cannabis were measured with three Single Category Implicit Association Tests (SC-IAT’s) and compared between 59 heavy cannabis users and 89 controls. Moreover, we investigated the relationship between these implicit affective associations and explicit expectancies, subjective craving, cannabis use, and cannabis related problems. Results show that heavy cannabis users had stronger implicit positive-arousal associations but weaker implicit negative associations toward cannabis compared to controls. Moreover, heavy cannabis users had stronger sedation but weaker negative explicit expectancies toward cannabis compared to controls. Within heavy cannabis users, more cannabis use was associated with stronger implicit negative associations whereas more cannabis use related problems was associated with stronger explicit negative expectancies, decreasing the overall difference on negative associations between cannabis users and controls. No other associations were observed between implicit associations, explicit expectancies, measures of cannabis use, cannabis use related problems, or subjective craving. These findings indicate that, in contrast to other substances of abuse like alcohol and tobacco, the relationship between implicit associations and cannabis use appears to be weak in heavy cannabis users.
doi:10.3389/fpsyt.2013.00059
PMCID: PMC3689035  PMID: 23801968
cannabis; implicit association test; cannabis use disorder; craving; affective associations
3.  Decreased respiratory symptoms in cannabis users who vaporize 
Cannabis smoking can create respiratory problems. Vaporizers heat cannabis to release active cannabinoids, but remain cool enough to avoid the smoke and toxins associated with combustion. Vaporized cannabis should create fewer respiratory symptoms than smoked cannabis. We examined self-reported respiratory symptoms in participants who ranged in cigarette and cannabis use. Data from a large Internet sample revealed that the use of a vaporizer predicted fewer respiratory symptoms even when age, sex, cigarette smoking, and amount of cannabis used were taken into account. Age, sex, cigarettes, and amount of cannabis also had significant effects. The number of cigarettes smoked and amount of cannabis used interacted to create worse respiratory problems. A significant interaction revealed that the impact of a vaporizer was larger as the amount of cannabis used increased. These data suggest that the safety of cannabis can increase with the use of a vaporizer. Regular users of joints, blunts, pipes, and water pipes might decrease respiratory symptoms by switching to a vaporizer
doi:10.1186/1477-7517-4-11
PMCID: PMC1853086  PMID: 17437626
4.  Cannabis and Psychopathology : Update 2004 
Indian Journal of Psychiatry  2004;46(4):299-309.
The study of cannabis use and psychopathology remains an interesting area from both academic and pragmatic perspectives. This article provides an update on the progress made in this area over the past decade or so. Psychopathology and psychiatric syndromes associated with cannabis use that have received research attention in recent years include cannabis withdrawal, cannabis and psychotic disorders (especially schizophrenia), depression, anxiety, and cognitive impairment. Status of a specific cannabis withdrawal syndrome and a specific ‘cannabis psychosis’ remains controversial. Current evidence indicates that there is a clinically significant association between cannabis use disorders and psychotic syndromes, depression, anxiety and possibly mild cognitive impairment. However, the nature of this association is often not clear. Several hypothesis related to the cannabis-schizophrenia association are examined. Cannabis use might be casually related to the later development of schizophrenia in an indirect way in a few heavy users, but more commonly, its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder.
PMCID: PMC2950948  PMID: 21206788
Cannabis; psychopathology; withdrawal; psychosis; schizophrenia; depression; mania; anxiety
5.  Simultaneous alcohol and cannabis expectancies predict simultaneous use 
Background
Simultaneous use of alcohol and cannabis predicts increased negative consequences for users beyond individual or even concurrent use of the two drugs. Given the widespread use of the drugs and common simultaneous consumption, problems unique to simultaneous use may bear important implications for many substance users. Cognitive expectancies offer a template for future drug use behavior based on previous drug experiences, accurately predicting future use and problems. Studies reveal similar mechanisms underlying both alcohol and cannabis expectancies, but little research examines simultaneous expectancies for alcohol and cannabis use. Whereas research has demonstrated unique outcomes associated with simultaneous alcohol and cannabis use, this study hypothesized that unique cognitive expectancies may underlie simultaneous alcohol and cannabis use. Results: This study examined a sample of 2600 (66% male; 34% female) Internet survey respondents solicited through advertisements with online cannabis-related organizations. The study employed known measures of drug use and expectancies, as well as a new measure of simultaneous drug use expectancies. Expectancies for simultaneous use of alcohol and cannabis predicted simultaneous use over and above expectancies for each drug individually.
Discussion
Simultaneous expectancies may provide meaningful information not available with individual drug expectancies. These findings bear potential implications on the assessment and treatment of substance abuse problems, as well as researcher conceptualizations of drug expectancies. Policies directing the treatment of substance abuse and its funding ought to give unique consideration to simultaneous drug use and its cognitive underlying factors.
doi:10.1186/1747-597X-1-29
PMCID: PMC1624811  PMID: 17034634
6.  Perceptions of cannabis as a stigmatized medicine: a qualitative descriptive study 
Background
Despite its increasing prevalence and acceptance among the general public, cannabis use continues to be viewed as an aberrant activity in many contexts. However, little is known about how stigma associated with cannabis use affects individuals who use cannabis for therapeutic purposes (CTP) and what strategies these individuals employ to manage associated stigma. The aim of this Canadian study was to describe users’ perceptions of and responses to the stigma attached to using CTP.
Methods
Twenty-three individuals who were using CTP for a range of health problems took part in semi-structured interviews. Transcribed data were analyzed using an inductive approach and comparative strategies to explore participants’ perceptions of CTP and identify themes.
Results
Participant experiences of stigma were related to negative views of cannabis as a recreational drug, the current criminal sanctions associated with cannabis use, and using cannabis in the context of stigmatizing vulnerability (related to existing illness and disability). Strategies for managing the resulting stigma of using CTP included: keeping CTP ‘undercover’; educating those who did not approve of or understand CTP use; and using cannabis responsibly.
Conclusions
Understanding how individuals perceive and respond to stigma can inform the development of strategies aimed at reducing stigma associated with the use of CTP and thereby address barriers faced by those using this medicine.
doi:10.1186/1477-7517-10-2
PMCID: PMC3584982  PMID: 23414118
Cannabis; Medical marijuana; Stigma; Cannabis; Legal consequences; Social consequences
7.  Anxiety Sensitivity and Marijuana Use: An Analysis from Ecological Momentary Assessment 
Depression and anxiety  2011;28(5):420-426.
Background
The cognitive factor of Anxiety Sensitivity (AS; the fear of anxiety and related bodily sensations), is theorized to play a role in cannabis use and its disorders. Lower-order facets of AS (physical concerns, mental incapacitation concerns, social concerns) may be differentially related to cannabis use behavior. However, little is known about the impact of AS facets on the immediate antecedents of cannabis use.
Methods
The present study used ecological momentary assessment (EMA) to prospectively examine the relations between specific facets of AS, cannabis craving, state anxiety, and cannabis use in the natural environment using real-world data about ad-lib cannabis use episodes. Participants were 49 current cannabis users (38.8% female).
Results
AS-mental incapacitation fears were related to significantly greater severity of cannabis-related problems at baseline. During the EMA period, AS-mental incapacitation and AS-social concerns significantly interacted with cannabis craving to prospectively predict subsequent cannabis use. Specifically, individuals with higher craving and either higher AS-mental incapacitation or AS-social concerns were the most likely to subsequently use cannabis. In contrast to prediction, no AS facet significantly moderated the relationship between state anxiety and cannabis use.
Conclusions
These findings suggest facets of AS (mental incapacitation and social fears) interact with cannabis craving to predict cannabis use. Findings also suggest differential relations between facets of anxiety sensitivity and cannabis-related behaviors.
doi:10.1002/da.20816
PMCID: PMC3086947  PMID: 21449005
anxiety sensitivity; anxiety; marijuana; cannabis; ecological momentary assessment
8.  Associations between Cannabinoid Receptor-1 (CNR1) Variation and Hippocampus and Amygdala Volumes in Heavy Cannabis Users 
Neuropsychopharmacology  2012;37(11):2368-2376.
Heavy cannabis users display smaller amygdalae and hippocampi than controls, and genetic variation accounts for a large proportion of variance in liability to cannabis dependence (CD). A single nucleotide polymorphism in the cannabis receptor-1 gene (CNR1), rs2023239, has been associated with CD diagnosis and intermediate phenotypes, including abstinence-induced withdrawal, cue-elicited craving, and parahippocampal activation to cannabis cues. This study compared hippocampal and amygdalar volumes (potential CD intermediate phenotypes) between heavy cannabis users and healthy controls, and analyzed interactions between group, rs2023239 variation, and the volumes of these structures. Ninety-four heavy cannabis users participated, of whom 37 (14 men, 23 women; mean age=27.8) were matched to 37 healthy controls (14 men, 23 women; mean age=27.3) for case-control analyses. Controlling for total intracranial volume and other confounding variables, matched cannabis users had smaller bilateral hippocampi (left, p=0.002; right, p=0.001) and left amygdalae (p=0.01) than controls. When genotype was considered in the case-control analyses, there was a group by genotype interaction, such that the rs2023239 G allele predicted lower volume of bilateral hippocampi among cannabis users relative to controls (both p<0.001). This interaction persisted when all 94 cannabis users were compared to controls. There were no group by genotype interactions on amygdalar volume. These data replicate previous findings of reduced hippocampal and amygdalar volume among heavy cannabis users, and suggest that CNR1 rs2023239 variation may predispose smaller hippocampal volume after heavy cannabis use. This association should be tested in future studies of brain volume differences in CD.
doi:10.1038/npp.2012.92
PMCID: PMC3442352  PMID: 22669173
marijuana; genetics; endocannabinoid; hippocampus; amygdala; addiction & substance abuse; amygdala; endocannabinoid; genetics; hippocampus; imaging; clinical or preclinical; marijuana; neuroanatomy; neurogenetics
9.  Motives for cannabis use in high-risk adolescent users 
The present investigation examined the relationships between motives for cannabis use and negative consequences associated with cannabis use following a brief intervention. The sample consisted of 205 adolescent cannabis users (66.3% male), who were recruited in high schools and randomly assigned to a brief two-session motivational enhancement therapy (MET) or an educational feedback control (EFC). Results supported the hypothesis that using cannabis to cope with negative affect would predict the number of problems and dependence symptoms related to cannabis use, after controlling for age, gender, years and frequency of cannabis use, and internalizing and externalizing behavior problems. Significant interactions between internalizing behavior problems and the coping motive showed that using to cope was associated with a higher number of cannabis dependence symptoms among adolescents reporting lower levels internalizing behavior problems. Findings support the potential utility of conducting further research to explore the coping motive as an important indicator of problematic cannabis use.
doi:10.1037/a0024331
PMCID: PMC3211084  PMID: 21688873
cannabis; marijuana; adolescents; cannabis use motives; internalizing behavior problems
10.  Negative consequences associated with dependence in daily cannabis users 
Background
Cannabis is the most widely consumed illicit substance in America, with increasing rates of use. Some theorists tend to link frequency of use with cannabis dependence. Nevertheless, fewer than half of daily cannabis users meet DSM-IV-TR criteria for cannabis dependence. This study seeks to determine whether the negative aspects associated with cannabis use can be explained by a proxy measure of dependence instead of by frequency of use.
Results
Over 2500 adult daily cannabis users completed an Internet survey consisting of measures of cannabis and other drug use, in addition to measures of commonly reported negative problems resulting from cannabis use. We compared those who met a proxy measure of DSM-IV-TR criteria for cannabis dependence (N = 1111) to those who did not meet the criteria (N = 1770). Cannabis dependent subjects consumed greater amounts of cannabis, alcohol, and a variety of other drugs. They also had lower levels of motivation, happiness, and satisfaction with life, with higher levels of depression and respiratory symptoms.
Conclusion
Although all of our subjects reported daily use, only those meeting proxy criteria for cannabis dependence reported significant associated problems. Our data suggest that dependence need not arise from daily use, but consuming larger amounts of cannabis and other drugs undoubtedly increases problems.
doi:10.1186/1747-597X-2-3
PMCID: PMC1783648  PMID: 17214886
11.  Impaired error awareness and anterior cingulate cortex hypoactivity in chronic cannabis users 
Drug abuse and other psychiatric conditions (e.g., schizophrenia) have been associated with a diminished neural response to errors, particularly in the anterior cingulate cortex (ACC) thought critical to error processing. A diminished capacity for detecting errors has been linked to clinical symptoms including the loss of insight, delusions and perseverative behaviour. Sixteen active chronic cannabis users and 16 control participants were administered a Go/No-go response inhibition task during event-related fMRI data collection. The task provides measures of inhibitory control and error awareness. Cannabis users’ inhibitory control performance was equivalent to that of the control group, but the former demonstrated a significant deficit in awareness of commission errors. Cannabis users demonstrated a diminished capacity for monitoring their behaviour that was associated with hypoactivity in the ACC and right insula. In addition, increased levels of hypoactivity in both the ACC and right insula regions were significantly correlated with error awareness rates in the cannabis group (but not controls). These difficulties are consistent with previous reports of hypoactivity in the neural systems underlying cognitive control and the monitoring of interoceptive awareness in chronic drug users, and highlight the potential relationship between cognitive dysfunction and behavioural deficits that have the potential to contribute to the maintenance of drug abuse.
doi:10.1038/npp.2009.67
PMCID: PMC2743772  PMID: 19553917
Performance monitoring; error-related; drug addiction; marijuana; insula; cognitive control
12.  Social Anxiety and Cannabis Use: An Analysis from Ecological Momentary Assessment 
Journal of Anxiety Disorders  2011;26(2):297-304.
Individuals with elevated social anxiety appear especially vulnerable to cannabis-related problems, yet little is known about the antecedents of cannabis-related behaviors among this high-risk population. The present study used ecological momentary assessment (EMA) to examine the relations among social anxiety, cannabis craving, state anxiety, situational variables, and cannabis use in the natural environment during ad-lib cannabis use episodes. Participants were 49 current cannabis users. During the two-week EMA period, social anxiety significantly interacted with cannabis craving to predict cannabis use both cross-sectionally and prospectively. Specifically, individuals with higher social anxiety and craving were most likely to use cannabis. There was a significant social anxiety X state anxiety X others’ use interaction such that when others were using cannabis, those with elevations in both trait social anxiety and state anxiety were the most likely to use cannabis.
doi:10.1016/j.janxdis.2011.12.006
PMCID: PMC3268873  PMID: 22246109
social anxiety; state anxiety; cannabis; marijuana; craving; ecological momentary assessment
13.  Polysubstance Use in Cannabis Users Referred for Treatment: Drug Use Profiles, Psychiatric Comorbidity and Cannabis-Related Beliefs 
Background: Population-based surveys demonstrate cannabis users are more likely to use both illicit and licit substances, compared with non-cannabis users. Few studies have examined the substance use profiles of cannabis users referred for treatment. Co-existing mental health symptoms and underlying cannabis-related beliefs associated with these profiles remains unexplored.
Methods: Comprehensive drug use and dependence severity (Severity of Dependence Scale-Cannabis) data were collected on a sample of 826 cannabis users referred for treatment. Patients completed the General Health Questionnaire, Cannabis Expectancy Questionnaire, Cannabis Refusal Self-Efficacy Questionnaire, and Positive Symptoms and Manic-Excitement subscales of the Brief Psychiatric Rating Scale. Latent class analysis was performed on last month use of drugs to identify patterns of multiple drug use. Mental health comorbidity and cannabis beliefs were examined by identified drug use pattern.
Results: A three-class solution provided the best fit to the data: (1) cannabis and tobacco users (n = 176), (2) cannabis, tobacco, and alcohol users (n = 498), and (3) wide-ranging substance users (n = 132). Wide-ranging substance users (3) reported higher levels of cannabis dependence severity, negative cannabis expectancies, lower opportunistic, and emotional relief self-efficacy, higher levels of depression and anxiety and higher manic-excitement and positive psychotic symptoms.
Conclusion: In a sample of cannabis users referred for treatment, wide-ranging substance use was associated with elevated risk on measures of cannabis dependence, co-morbid psychopathology, and dysfunctional cannabis cognitions. These findings have implications for cognitive-behavioral assessment and treatment.
doi:10.3389/fpsyt.2013.00079
PMCID: PMC3736050  PMID: 23966956
cannabis; latent class; drugs; comorbidity; expectancy; self-efficacy; treatment seeking
14.  Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis 
Schizophrenia research  2012;139(1-3):157-160.
Introduction
Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs.
Methods
Fifty seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables.
Results
After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (β=0.4, 95% CI=0.1–0.7, p=0.004) and age at first hospitalization (β=0.4, 95% CI=0.1–0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0±4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization.
Conclusion
Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time.
doi:10.1016/j.schres.2012.06.007
PMCID: PMC3415971  PMID: 22727454
cannabis; psychosis; age; sex; schizophrenia
15.  Increased Blood Pressure Following Abrupt Cessation of Daily Cannabis Use 
Journal of addiction medicine  2011;5(1):16-20.
Objective
Cannabis is the most widely used illicit drug. Acute cannabis administration increases blood pressure and heart rate and tolerance develops to these effects with heavy use. A valid and reliable withdrawal syndrome occurs in most daily users, but few studies have assessed the cardiovascular effects of withdrawal. The objective of this report is to describe unexpected changes in cardiovascular function during brief periods of supervised cannabis use and abstinence in daily cannabis users.
Methods
A within-subjects ABAC crossover study in which inpatient volunteers smoked cannabis ad-libitum (A), and abstained from cannabis (B/C). Vital signs were obtained three times daily during eleven inpatient days for thirteen daily cannabis users (11 Male, 8 African American).
Results
Blood pressure increased significantly during periods of cannabis abstinence compared with periods of cannabis use. The magnitude of increase was substantial in a subset (N=6) of participants, with mean increases of up to 22.8mmHg systolic and 12.3mmHg diastolic blood pressure observed. Heart rate also increased during abstinence when measures collected during periods of acute intoxication were excluded, but the magnitude of effect was not clinically significant.
Conclusions
Abrupt cessation of heavy cannabis use may cause clinically significant increases in blood pressure in a subset of users. Blood pressure should be monitored among those attempting to reduce or quit frequent cannabis use, particularly those with preexisting hypertension. The time course of this effect is currently unknown and requires further study.
doi:10.1097/ADM.0b013e3181d2b309
PMCID: PMC3045206  PMID: 21359104
Cannabis; Marijuana; Blood Pressure; Hypertension; Withdrawal
16.  Psychological adverse effects of cannabis smoking: a tentative classification 
This paper stresses the need for an early definition and description of the “deviant” cannabis smoker in North America. Attention is called to the fact that on this continent heavy smokers have not yet been separated as “problem” users from other smokers.
A comprehensive review of possible psychological adverse effects of the drug is made. The following classification is suggested: a) Severe intoxications, b) Pathological intoxications, c) Acute cannabis psychoses, d) Subacute and chronic cannabis psychoses and e) Residual conditions.
PMCID: PMC1941148  PMID: 4569453
17.  Cannabis users differ from non-users on measures of personality and schizotypy 
Psychiatry research  2011;186(1):46-52.
Accumulating evidence indicates that cannabis use may be a risk factor for schizophrenia (SZ), and chronic cannabis users score higher than non-users on measures of schizotypal personality traits. The purpose of the present study was to investigate the relations between normal personality, schizotypy, and cannabis use. Sixty-two chronic cannabis users and 45 cannabis-naïve controls completed a measure of normal personality, the NEO-Five Factor Inventory (NEO-FFI), and two measures of schizotypy, the Schizotypal Personality Questionnaire (SPQ) and Perceptual Aberration Scale (PAS). Substance use was assessed using the SCID I alcohol/drug module and a locally developed drug use questionnaire. On the NEO-FFI, users scored higher than controls on Openness, but lower on Agreeableness and Conscientiousness, and endorsed greater schizotypy on the SPQ and PAS. Higher Neuroticism predicted greater schizotypy in both groups, and, higher Extraversion predicted lower negative-syndrome schizotypy among users. Finally, duration of cannabis use was positively correlated with scores on the SPQ and PAS among users, suggesting a relation between overall cannabis use chronicity and schizotypy. These data show that cannabis users differ from non-users on dimensions of normal personality and schizotypy, and provide further evidence that cannabis use is associated with increased levels of psychosis-related personality traits.
doi:10.1016/j.psychres.2010.07.035
PMCID: PMC3036782  PMID: 20813412
Five-factor model; marijuana; Schizotypal Personality Questionnaire; Perceptual Aberration Scale; schizophrenia
18.  Sensory Gating Impairments in Heavy Cannabis Users are Associated with Altered Neural Oscillations 
Behavioral neuroscience  2009;123(4):894-904.
Central cannabinoid receptors are thought to mediate neural oscillations and are localized to brain regions implicated in auditory P50 sensory gating, including the hippocampus and neocortex. The current study therefore examined if neural oscillations evoked by the paired clicks (S1, S2) are associated with impaired P50 gating reported in cannabis users. Seventeen heavy cannabis users and 16 cannabis naïve controls participated. Analyses included P50 amplitudes, and time x frequency analyses examining event-related spectral perturbations (ERSP) and inter-trial coherence (ITC). In agreement with prior studies, cannabis users exhibited reduced P50 gating. The ERSP analysis yielded attenuated high frequency activity in the beta range (13-29 Hz) post-S1 and in the gamma range (30-50 Hz) post-S2 in the cannabis group, compared to the control group. Attenuated ITC was also observed in the cannabis group in the post-S2 theta band (4-7 Hz). Greater levels of cannabis use were positively associated with high P50 ratios and negatively with post-S2 ERSP gamma power. These findings suggest that heavy cannabis use is associated with aberrant beta and gamma activity in the dual-click procedure, which corroborates recent work demonstrating disruption of beta/gamma by cannabinoid receptor (CB1) agonists in a rat analogue of this procedure and highlights the translational potential of the dual-click procedure.
doi:10.1037/a0016328
PMCID: PMC3536882  PMID: 19634950
P50; Marijuana; auditory gating; beta; gamma; time-frequency
19.  Preliminary Evidence for a Sex-Specific Relationship between Amount of Cannabis Use and Neurocognitive Performance in Young Adult Cannabis Users 
Accumulating evidence suggests neuropsychological deficits from cannabis use, with a burgeoning area of preclinical research indicating possible sex-differences. However, few studies have examined how cannabis use may differentially impact neurocognition in male and female cannabis users. As such, we examined potential sex-differences in associations between amount of cannabis use (across several time-frames) and neurocognitive performance among young adult regular cannabis users. Consistent with previous studies, more cannabis use was generally associated with poorer episodic memory and decision-making, but not other measures of inhibitory control. However, patterns of results suggested sex-specific dissociations. In particular, more cannabis use was more consistently associated with poorer episodic memory performance in females than males. Conversely, more cannabis use was associated with poorer decision-making performance for males, but not females. These results provide further evidence for residual cannabis-associated neurocognitive deficits and suggest the importance of examining the impact of cannabis on neurocognition separately for males and females.
doi:10.1017/S135561771300088X
PMCID: PMC3895398  PMID: 23962414
cannabis; cognition; marijuana; neuropsychology; sex differences; THC
20.  Effects of Chronic Active Cannabis Use on Visuomotor Integration, in Relation to Brain Activation and Cortisol Levels 
The Journal of Neuroscience  2011;31(49):17923-17931.
Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. 30 cannabis users (16 men and 14 women, 18 to 45 years old) and 30 non-drug user controls (16 men and 14 women, 19 to 44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and functional MRI (fMRI), using a 3 Tesla scanner, during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in the male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. These brain activities may be attenuated by the higher cortisol levels in the cannabis users which in turn may lead to less efficient visual-motor function.
doi:10.1523/JNEUROSCI.4148-11.2011
PMCID: PMC3273845  PMID: 22159107
21.  Gene-Environment Interplay Between Cannabis and Psychosis 
Schizophrenia Bulletin  2008;34(6):1111-1121.
Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Studies using genetic, epidemiological, experimental, and observational techniques will be discussed to investigate gene-environment correlation gene-environment interaction, and higher order interactions within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. In this respect, multiple variations within multiple genes—rather than single genetic polymorphisms—together with other environmental factors (eg, stress) may interact with cannabis to increase the risk of psychosis. Further research on these higher order interactions is needed to better understand the biological pathway by which cannabis use, in some individuals, may cause psychosis in the short- and long term.
doi:10.1093/schbul/sbn108
PMCID: PMC2632498  PMID: 18723841
psychotic disorders; genetics; environment; cannabis; tetrahydrocannabinol; schizophrenia
22.  Quantifying the Clinical Significance of Cannabis Withdrawal 
PLoS ONE  2012;7(9):e44864.
Background and Aims
Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.
Methods and Results
A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001).
Conclusions
Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.
doi:10.1371/journal.pone.0044864
PMCID: PMC3458862  PMID: 23049760
23.  Altering endocannabinoid neurotransmission at critical developmental ages: impact on rodent emotionality and cognitive performance 
The endocannabinoid system shows functional activity from early stages of brain development: it plays an important role in fundamental developmental processes such as cell proliferation, migration, and differentiation, thus shaping brain organization during pre- and postnatal life. Cannabis sativa preparations are among the illicit drugs most commonly used by young people, including pregnant women. The developing brain can be therefore exposed to cannabis preparations during two critical periods: first, in offspring of cannabis-using mothers through perinatal and/or prenatal exposure; second, in adolescent cannabis users during neural maturation. In the last decade, it has become clear that the endocannabinoid system critically modulates memory processing and emotional responses. Therefore, it is well possible that developmental exposure to cannabinoid compounds induces enduring changes in behaviors and neural processes belonging to the cognitive and emotional domains. We address this issue by focusing on rodent studies, in order to provide a framework for understanding the impact of cannabinoid exposure on the developing brain.
doi:10.3389/fnbeh.2012.00002
PMCID: PMC3265033  PMID: 22291624
endocannabinoid system; behavior; development; emotion; cognition; pregnancy; adolescence
24.  The Role of Study and Work in Cannabis Use and Dependence Trajectories among Young Adult Frequent Cannabis Users 
Life course theory considers events in study and work as potential turning points in deviance, including illicit drug use. This qualitative study explores the role of occupational life in cannabis use and dependence in young adults. Two and three years after the initial structured interview, 47 at baseline frequent cannabis users were interviewed in-depth about the dynamics underlying changes in their cannabis use and dependence. Overall, cannabis use and dependence declined, including interviewees who quit using cannabis completely, in particular with students, both during their study and after they got employed. Life course theory appeared to be a useful framework to explore how and why occupational life is related to cannabis use and dependence over time. Our study showed that life events in this realm are rather common in young adults and can have a strong impact on cannabis use. While sometimes changes in use are temporary, turning points can evolve from changes in educational and employment situations; an effect that seems to be related to the consequences of these changes in terms of amount of leisure time and agency (i.e., feelings of being in control).
doi:10.3389/fpsyt.2013.00085
PMCID: PMC3739012  PMID: 23950748
frequent cannabis use; cannabis dependence; young adults; qualitative research; life course approach; longitudinal study; education; employment
25.  Does Change in Cannabis Use in Established Psychosis Affect Clinical Outcome? 
Schizophrenia Bulletin  2011;39(2):339-348.
Background: Cannabis use has been identified as a potent predictor of the earlier onset of psychosis, but meta-analysis has not indicated that it has a clear effect in established psychosis. Aim: To assess the association between cannabis and outcomes, including whether change in cannabis use affects symptoms and functioning, in a large sample of people with established nonaffective psychosis and comorbid substance misuse. Methods: One hundred and sixty participants whose substance use included cannabis were compared with other substance users (n = 167) on baseline demographic, clinical, and substance use variables. The cannabis using subgroup was examined prospectively with repeated measures of substance use and psychopathology at baseline, 12 months, and 24 months. We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes. Results: Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms. Second, cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity, even when patients became abstinent. However, greater cannabis exposure was associated with worse functioning, albeit with a small effect size. Conclusions: We did not find evidence of an association between cannabis dose and psychotic symptoms, although greater cannabis dose was associated with worse psychosocial functioning, albeit with small effect size. It would seem that within this population, not everyone will demonstrate durable symptomatic improvements from reducing cannabis.
doi:10.1093/schbul/sbr152
PMCID: PMC3576157  PMID: 22037770
psychosis; schizophrenia; cannabis; substance use; dual diagnosis; positive symptoms

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