Verbal learning and memory in adolescent cannabis users,alcohol users and non-users

Rationale  

Long-term heavy cannabis use can result in memory impairment. Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis.     

Neurophysiological functioning of occasional and heavy cannabis users during THC intoxication

Rationale  

Experienced cannabis users demonstrate tolerance to some of the impairing acute effects of cannabis.     

Alterations to pre-pulse inhibition (PPI) in chronic cannabis users are secondary to sustained attention deficits

Rationale  

Given the hypothesised association between cannabis use and schizophrenia, and the well documented alterations in pre-pulse inhibition (PPI) that are observed in schizophrenia, it is of interest to examine the effects of cannabis use on PPI.     

Examining the effects of former cannabis use on cerebellum-dependent eyeblink conditioning in humans

Rationale  

Previous work in humans has shown that chronic cannabis users exhibit disruptions in classical eyeblink conditioning (EBC), a form of associative learning that is known to be dependent on the cerebellum. Based upon previous work in animals, it was hypothesized that these learning deficits were related to cannabinoid receptor (CB1R) downregulation. However, it remains unclear whether there is a recovery of cerebellum-dependent learning after the cessation of cannabis use.     

Quantifying cannabis use with the Timeline Followback approach: A psychometric evaluation

Background

In the absence of a standardized cannabis unit, self-report instruments are inadequate for accurate quantification of cannabis use. The study extends the feasibility of using a cannabis substitute to reliably and validly measure quantity of cannabis use.

Method

Ninety-eight adult Australian cannabis users (M age = 27.98, SD = 11.10; 65.31% male) completed a 90-day Timeline Followback interview regarding their cannabis use, utilizing the cannabis substitute Marijuanilla to report on quantity of use. Ninety-two of these individuals completed the interview at two time-points, and 56 of these participants had collaterals corroborate their cannabis use reports.

Results

Inter-rater reliability was excellent, while test–retest reliability was good to excellent. Intra-class correlation coefficients between participant and collateral reports, while similar to previous research, were unacceptable. Quantity of cannabis use statistically significantly added to frequency of use in predicting cannabis problems and dependence severity. Concurrent and discriminant validity were established with single-item and positive impression management measures, respectively. In addition, Marijuanilla appeared similar to one specimen of street seized cannabis, but not to two others. Importantly, participants’ cravings to use cannabis did not increase as a result of using the cannabis substitute to report on their cannabis use.

Conclusions

These data suggest that utilizing Marijuanilla to facilitate the reporting of grams of cannabis use may be reliable and valid; however, such comprehensive assessment may only be necessary for clinical trials and epidemiological studies, which rely on precise estimates of cannabis use.     

Development and validation of the Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) in adult cannabis users in treatment

Background

There are few valid clinical assessment instruments for cannabis. Self-efficacy, or the ability of users to resist temptation, is a central feature of social cognitive theory. This study outlines the development and validation of the Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ), which measures the situational confidence to refuse cannabis.

Method

One thousand two hundred and forty-six patients referred for cannabis assessment completed the CRSEQ including measures of cannabis consumption and dependence severity (Severity of Dependence Scale-Cannabis, SDS-C). The CRSEQ was subject to independent exploratory (n = 621, mean age 26.88, 78.6% male) and confirmatory (n = 625, mean age 27.51, 76.8% male) factor analysis.

Results

Three factors: Emotional Relief, Opportunistic and Social Facilitation were identified. They provided a good statistical and conceptual fit for the data. Emotional Relief cannabis refusal self-efficacy was identified as most predictive of cannabis dependence, after controlling for cannabis consumption.

Conclusions

The CRSEQ is recommended as a psychometrically sound and clinically useful measure for cannabis misuse treatment planning and assessment.     

Altered parahippocampal functioning in cannabis users is related to the frequency of use

Rationale  

Converging lines of evidence suggest an association between cannabis use and impaired episodic memory as well as related associative learning. These deficits have been associated with the duration, frequency, and age of onset of cannabis use. However, it remains unclear whether these parameters of use differently impact memory-related hippocampal functioning.     

Chronic cannabis users show altered neurophysiological functioning on Stroop task conflict resolution

Rationale  

Chronic cannabis use has been related to deficits in cognition (particularly memory) and the normal functioning of brain structures sensitive to cannabinoids. There is increasing evidence that conflict monitoring and resolution processes (i.e. the ability to detect and respond to change) may be affected.     

Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users

Introduction

Previous research has shown that heavy cannabis users develop tolerance to the impairing effects of ??9-tetrahydrocannabinol (THC) on neurocognitive functions. Animal studies suggest that chronic cannabis consumption may also produce cross-tolerance for the impairing effects of alcohol, but supportive data in humans is scarce.

Purpose

The present study was designed to assess tolerance and cross-tolerance to the neurocognitive effects of THC and alcohol in heavy cannabis users.

Methods

Twenty-one heavy cannabis users participated in a double-blind, placebo-controlled, three-way study. Subjects underwent three alcohol-dosing conditions that were designed to achieve a steady blood alcohol concentration of about 0, 0.5, and 0.7?mg/ml during a 5-h time window. In addition, subjects smoked a THC cigarette (400???g/kg) at 3?h post-onset of alcohol dosing during every alcohol condition. Performance tests were conducted repeatedly between 0 and 7?h after onset of drinking and included measures of perceptual motor control (critical tracking task), dual task processing (divided-attention task), motor inhibition (stop-signal task), and cognition (Tower of London).

Results

Alcohol significantly impaired critical tracking, divided attention, and stop-signal performance. THC generally did not affect task performance. However, combined effects of THC and alcohol on divided attention were bigger than those by alcohol alone.

Conclusion

In conclusion, the present study generally confirms that heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive task performance. Yet, heavy cannabis users did not develop cross-tolerance to the impairing effects of alcohol, and the presence of the latter even selectively potentiated THC effects on measures of divided attention.     

A follow-up study: acute behavioural effects of Δ9-THC in female heterozygous Neuregulin 1 transmembrane domain mutant mice

Rationale  

Heavy cannabis use is linked with an increased risk for schizophrenia. We showed previously that male heterozygous neuregulin 1 transmembrane domain (Nrg1 HET) mice are more sensitive to some effects of the psychotropic cannabis constituent Δ⁹-tetrahydrocannabinol (THC). We report data from a follow-up study in female Nrg1 HET mice, investigating THC effects on behaviours with some relevance to schizophrenia.     

Cannabis,Cigarettes, and Their Co-Occurring Use: Disentangling Differences in Gray Matter Volume

Background:

Structural magnetic resonance imaging techniques are powerful tools for examining the effects of drug use on the brain. The nicotine and cannabis literature has demonstrated differences between nicotine cigarette smokers and cannabis users compared to controls in brain structure; however, less is known about the effects of co-occurring cannabis and tobacco use.

Methods:

We used voxel-based morphometry to examine gray matter volume differences between four groups: (1) cannabis-dependent individuals who do not smoke tobacco (Cs); (2) cannabis-dependent individuals who smoke tobacco (CTs); (3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (Ts); and (4) healthy controls (HCs). We also explored associations between gray matter volume and measures of cannabis and tobacco use.

Results:

A significant group effect was observed in the left putamen, thalamus, right precentral gyrus, and left cerebellum. Compared to HCs, the Cs, CTs, and Ts exhibited larger gray matter volumes in the left putamen. Cs also had larger gray matter volume than HCs in the right precentral gyrus. Cs and CTs exhibited smaller gray matter volume than HCs in the thalamus, and CTs and Ts had smaller left cerebellar gray matter volume than HCs.

Conclusions:

This study extends previous research that independently examined the effects of cannabis or tobacco use on brain structure by including an examination of co-occurring cannabis and tobacco use, and provides evidence that cannabis and tobacco exposure are associated with alterations in brain regions associated with addiction.     

Acute effects of MDMA (3,4-methylenedioxymethamphetamine) on EEG oscillations: alone and in combination with ethanol or THC (delta-9-tetrahydrocannabinol)

Rationale  

Typical users of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)].     

Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal

Background

Sleep difficulty is a common symptom of cannabis withdrawal, but little research has objectively measured sleep or explored the effects of hypnotic medication on sleep during cannabis withdrawal.

Methods

Twenty daily cannabis users completed a within-subject crossover study. Participants alternated between periods of ad libitum cannabis use and short-term cannabis abstinence (3 days). Placebo was administered at bedtime during one abstinence period (withdrawal test) and extended-release zolpidem, a non-benzodiazepine GABA_A receptor agonist, was administered during the other. Polysomnographic (PSG) sleep architecture measures, subjective ratings, and cognitive performance effects were assessed each day.

Results

During the placebo-abstinence period, participants had decreased sleep efficiency, total sleep time, percent time spent in Stage 1 and Stage 2 sleep, REM latency and subjective sleep quality, as well as increased sleep latency and time spent in REM sleep compared with when they were using cannabis. Zolpidem attenuated the effects of abstinence on sleep architecture and normalized sleep efficiency scores, but had no effect on sleep latency. Zolpidem was not associated with any significant side effects or next-day cognitive performance impairments.

Conclusions

These data extend prior research that indicates abrupt abstinence from cannabis can lead to clinically significant sleep disruption in daily users. The findings also indicate that sleep disruption associated with cannabis withdrawal can be attenuated by zolpidem, suggesting that hypnotic medications might be useful adjunct pharmacotherapies in the treatment of cannabis use disorders.     

Dopaminergic augmentation of delta-9-tetrahydrocannabinol (THC) discrimination: possible involvement of D2-induced formation of anandamide

Rational  

Although delta-9-tetreahydrocannabinol (THC)-induced elevations in accumbal dopamine levels are believed to play an important role in the abuse-related effects of cannabis, little direct evidence has been provided that the dopaminergic system is involved in the psychotropic effects of THC.     

Cannabis use and cognitive functions in at-risk mental state and first episode psychosis

Background

Meta-analyses suggest that schizophrenia patients with a history of cannabis use have less impaired cognitive functioning compared to patients without cannabis use.

Aims

The objective of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in at-risk mental state for psychosis (ARMS) and first episode psychosis (FEP) individuals.

Methods

One hundred thirty-six participants completed a cognitive test battery and were assessed for current and past cannabis use. Analyses of covariance models were applied to evaluate the main effects of cannabis use and patient group (ARMS vs. FEP) as well as their interactions on cognitive functioning.

Results

No differences were observed in cognitive performance between current, former, and never users, and there were no significant interactions between cannabis use and patient group. Furthermore, within the group of current cannabis users, the frequency of cannabis use was not significantly associated with cognitive functioning.

Conclusion

The results of the present study do not support the notion that FEP patients and ARMS individuals with a history of cannabis use have less impaired cognitive functioning compared to those without cannabis use.     

Intellectual,neurocognitive, and academic achievement in abstinent adolescents with cannabis use disorder

Rationale

The active component of cannabis, delta-9 tetrahydrocannabinol (THC), has a long half-life and widespread neurocognitive effects. There are inconsistent reports of neurocognitive deficits in adults and adolescents with cannabis use disorders (CUD), particularly after a period of abstinence.

Objectives

This study aims to examine neurocognitive measures (IQ, academic achievement, attention, memory, executive functions) in abstinent adolescents with CUD, while controlling for demographic, psychopathology, and poly-substance confounders.

Methods

We investigated neurocognitive performance in three groups: adolescents with CUD after successful first treatment and in full remission (n?=?33); controls with psychiatric disorders without substance use disorder history (n?=?37); and healthy adolescents (n?=?43).

Results

Adolescents with psychiatric disorders, regardless of CUD status, performed significantly worse than the healthy adolescents in academic achievement. No group differences were seen in IQ, attention, memory, or executive functions. Lower academic achievement was positively associated with younger age of CUD onset, regular cannabis use, and maximum daily use. In the CUD group, lifetime nicotine use episodes were negatively associated with IQ. Lower overall neurocognitive function was associated with younger age of onset of regular cannabis use and relapse within the 1 year follow-up.

Conclusions

Verifiably, abstinent adolescents with CUD history did not differ from the two comparison groups, suggesting that previously reported neurocognitive deficits may be related to other factors, including residual drug effects, preexisting cognitive deficits, concurrent use of other substances (e.g., nicotine), or psychopathology. Adolescents with CUD may not be vulnerable to THC neuropsychological deficits once they achieve remission from all drugs for at least 30 days.     

Chronic use of cannabis and poor neural efficiency in verbal memory ability

Introduction  

The endogenous cannabinoid system is sensitive to the introduction of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, which are known to impact upon memory functioning. We sought to examine the impact of chronic cannabis use upon memory-related brain function via examination of the subsequent memory effect (SME) of the event-related potential (ERP).     

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Rationale  

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues.     

Neural responses to subliminally presented cannabis and other emotionally evocative cues in cannabis-dependent individuals

Rationale

Addiction theories posit that drug-related cues maintain and contribute to drug use and relapse. Indeed, our recent study in cocaine-dependent patients demonstrated that subliminally presented cocaine-related stimuli activate reward neurocircuitry without being consciously perceived. Activation of reward neurocircuitry may provoke craving and perhaps prime an individual for subsequent drug-seeking behaviors.

Objectives

Using an equivalent paradigm, we tested whether cannabis cues activate reward neurocircuitry in treatment-seeking, cannabis-dependent individuals and whether activation was associated with relevant behavioral anchors: baseline cannabis craving (drug-seeking behavior) and duration of use (degree of conditioning).

Methods

Twenty treatment-seeking, cannabis-dependent individuals (12 males) underwent event-related blood oxygen level-dependent functional magnetic resonance imaging during exposure to 33-ms cannabis, sexual, and aversive cues presented in a backward-masking paradigm. Drug use history and cannabis craving were assessed prior to imaging.

Results

Participants showed increased activity to backward-masked cannabis cues in regions supporting reward detection and interoception, including the left anterior insula, left ventral striatum/amygdala, and right ventral striatum. Cannabis cue-related activity in the bilateral insula and perigenual anterior cingulate cortex was positively associated with baseline cannabis craving, and cannabis cue-related activity in the medial orbitofrontal cortex was positively correlated with years of cannabis use. Neural responses to backward-masked sexual cues were similar to those observed during cannabis cue exposure, while activation to aversive cues was observed only in the left anterior insula and perigenual anterior cingulate cortex.

Conclusions

These data highlight the sensitivity of the brain to subliminal reward signals and support hypotheses promoting a common pathway of appetitive motivation.     

Do early experiences with cannabis vary in cigarette smokers?

Introduction

We examine whether regular cigarette smokers were more likely to be exposed to and use cannabis at an earlier age, and further, upon initiation, whether their initial experiences with cannabis varied from those reported by never/non-regular cigarette smokers.

Method

A sample of 3797 Australian twins and siblings aged 21–46 years was used. Survival analyses examined whether cigarette smokers were at increased likelihood of early opportunity to use cannabis and early onset of cannabis use. Logistic regression examined whether cigarette smokers reported greater enjoyment of their cannabis experience, inhaling on the first try, differing positive and negative initial subjective reactions, smoked cigarettes with cannabis the first time and were more likely to try cannabis again within a week.

Results

Regular cigarette smokers were more likely to report an earlier opportunity to use cannabis and early onset of cannabis use. Regular cigarette smokers were also considerably more likely to have enjoyed their first experience with cannabis and reported higher rates of positive initial reactions. They were more likely to report inhaling on the first try and smoking cigarettes with cannabis. Potentially negative subjective reactions were also elevated in regular cigarette smokers. Importantly, cigarette smokers were at 1.87 increased odds of smoking cannabis within a week of their initial use.

Conclusion

These findings indicate that the well-known overlap in cannabis and cigarette smoking behaviors may evolve as early as opportunity to use and extend through the course of the substance use trajectory.