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.     

Effects of modafinil on cognitive functions in first episode psychosis

Rationale  

Cognitive impairments are important determinants of functional outcome in psychosis, which are inadequately treated by antipsychotic medication. Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia.     

Cannabis use and psychosis

This paper reviews evidence on two hypotheses about the relationship between cannabis use and psychosis. The first hypothesis is that heavy cannabis use may cause a “cannabis psychosis”—a psychosis that would not occur in the absence of cannabis use, the symptoms of which are preceded by heavy cannabis use and remit after abstinence. The second hypothesis is that cannabis use may precipitate schizophrenia, or exacerbate its symptoms. Evaluation of these hypotheses requires evidence of an association between cannabis use and psychosis, that is unlikely to be due to chance, in which cannabis use precedes psychosis, and in which we can exclude the hypothesis that the relationship is due to other factors, such as other drug use, or a personal vulnerability to psychosis. There is some clinical support for the first hypothesis. If these disorders exist they seem to be rare, because they require very high doses of THC, the prolonged use of highly potent forms of cannabis, or a pre-existing (but as yet unspecified) vulnerability. There is more support for the second hypothesis, in that a large prospective study has shown a linear relationship between the frequency with which cannabis has been used by age 18 and the risks over the subsequent 15 years of a diagnosis of schizophrenia. It is still unclear whether this means that cannabis use precipitates schizophrenia, whether it is a form of “self-medication”, or whether the association is due to the use of other drugs, such as amphetamines, which heavy cannabis users are more likely to use. There is stronger evidence that cannabis use can exacerbate the symptoms of schizophrenia. Mental health services should identify patients with schizophrenia who use alcohol, cannabis and other drugs and advise them to abstain or to greatly reduce their drug use.     

Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis

Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent samples, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.     

Cannabis: Psychological effects of chronic heavy use

The psychological effects of chronic heavy use of Cannabis sativa were studied in a population of normal adult Jamaican males. Users had been daily consumers of the drug for a minimum of 10 years; Controls were subjects who had neither current nor past experience with the drug. Subjects were matched for age, sex, social class, alcohol use, level of general information (intelligence), education, and modernity. Three groups of objective psychological tests were administered, in addition to a questionnaire. The first group of test concerned physiological, sensory and perceptual-motor functioning; the second groups of tests measured concept formation and abstracting abilities; the third group was comprised of a number of tests of memory.An initial study failed to discover any indications of User impairment. The data was studied for possible confounding factors including drug potency, literacy, motivation, and research design. A replication of the study using an improved research design led to a strong confirmation of the original findings.It was suggested that heavy users of this drug did not show test performances indicating impairment of psychological functioning comparable to other types of organic cerebral dysfunction, nor did they show chronic changes on dimensions responsive to immediate intoxication.     

Cannabis and psychosis in acute psychiatric admissions

This study assessed the duration of admission and time to relapse in 62 acute psychiatric in-patients who had urinary drug screens performed because of suspicion of illicit drug use. Some 51% of those with psychosis (n = 45) and 29% of those with non-psychotic illness (n = 17) were THC-positive although this was not significant. In those with recurrent admissions for psychosis tetrahydrocannabinol (THC)-positive subjects were significantly younger. The duration of admission was 7 days shorter in the THC-positive group but this was not significant. Their duration since last admission (rapidity of relapse) was 10 months versus 33 months which was significant. [Grace RF, Shenfield G, Tennant C. Cannabis and Psychosis in acute psychiatric admissions. Drug Alcohol Rev 2000;19:287-290]     

齐拉西酮与氯丙嗪对首发精神分裂症患者心电图及认知功能的影响比较

目的：探讨齐拉西酮与氯丙嗪对首发精神分裂症患者心电图及认知功能的影响。方法将90例首发精神分裂症患者采用数字表法随机分为两组,每组各45例,其中对照组给予氯丙嗪,观察组口服齐拉西酮,比较两组临床疗效及治疗前后认知功能和心电图结果。结果观察组和对照组治疗后阳性和阴性症状量表（PANSS）评分分别为（57．78±4．16）分和（58．43±4．33）分,均较治疗前的（72．62±4．66）分和（72．39±4.87）分显著减少（t＝7．15、7．46,均P＜0．05）,但两组间差异无统计学意义（均P＞0．05）;观察组治疗后威斯卡星卡片分类测试（WCST）总测验次数、持续错误数和数字化消测验（CT）失误率分别为（73．32±5．08）、（40．35±4．15）和（12．72±2．00）％,均较治疗前的（86．43±5．58）、（67．72±4．26）和（21．02±2．33）％及对照组的（84．32±5．16）、（65．82±4．25）和（20．05±2．20）％显著减少（ t＝6．84、7．21、7．85、7．52、8．21、8．12,均P＜0．05）;WCST分类完成数和CT净分值分别为（5．32±0．40）和（125．83±11．65）分,均较治疗前的（3.41±0．38）和（102．82±10．72）分及对照组的（3．52±0．39）和（108．37±10．24）分显著增加（ t＝6．72、7.11、7．01、7．53,均P＜0．05）;观察组治疗后心电图异常发生率为22．22％,显著低于对照组的55．56％（χ2＝11．02,P＜0．05）。结论齐拉西酮与氯丙嗪治疗首发精神分裂症疗效相当,但齐拉西酮可明显改善患者认知功能,且对患者心电图影响小,临床安全性高。     

Asenapine effects in animal models of psychosis and cognitive function

Rationale

Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, α-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties.

Objectives

The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone.

Materials and methods

Amphetamine-stimulated locomotor activity (Amp-LMA; 1.0 or 3.0 mg/kg s.c.) and apomorphine-disrupted prepulse inhibition (Apo-PPI; 0.5 mg/kg s.c.) were used as tests for antipsychotic activity. Delayed non-match to place (DNMTP) and five-choice serial reaction (5-CSR) tasks were used to assess short-term spatial memory and attention, respectively. Asenapine doses varied across tasks: Amp-LMA (0.01–0.3 mg/kg s.c.), Apo-PPI (0.001–0.3 mg/kg s.c.), DNMTP (0.01–0.1 mg/kg s.c.), and 5-CSR (0.003–0.3 mg/kg s.c.).

Results

Asenapine was highly potent (active at 0.03 mg/kg) in the Amp-LMA and Apo-PPI assays. DNMTP or 5-CSR performance was not improved by asenapine, olanzapine, or risperidone. All agents (P?<?0.01) reduced DNMTP accuracy at short delays; post hoc analyses revealed that only 0.1 mg/kg asenapine and 0.3 mg/kg risperidone differed from vehicle. All active agents (asenapine, 0.3 mg/kg; olanzapine, 0.03–0.3 mg/kg; and risperidone, 0.01–0.1 mg/kg) significantly impaired 5-CSR accuracy (P?<?0.05).

Conclusions

Asenapine has potent antidopaminergic properties that are predictive of antipsychotic efficacy. Asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Rather, at doses greater than those required for antipsychotic activity, asenapine impaired cognitive performance due to disturbance of motor function, an effect also observed with olanzapine and risperidone.     

Gray and white matter changes and their relation to illness trajectory in first episode psychosis

Previous works have studied structural brain characteristics in first-episode psychosis (FEP), but few have focused on the relation between brain differences and illness trajectories. The aim of this study is to analyze gray and white matter changes in FEP patients and their relation with one-year clinical outcomes. A sample of 41 FEP patients and 41 healthy controls (HC), matched by age and educational level was scanned with a 3 T MRI during the first month of illness onset. One year later, patients were assigned to two illness trajectories (schizophrenia and non-schizophrenia). Voxel-based morphometry (VBM) was used for gray matter and Tract-based spatial statistics (TBSS) was used for white matter data analysis. VBM revealed significant and widespread bilateral gray matter density differences between FEP and HC groups in areas that included the right insular Cortex, the inferior frontal gyrus and orbito-frontal cortices, and segments of the occipital cortex. TBSS showed a significant lower fractional anisotropy (FA) in 8 clusters that included segments of the anterior thalamic radiation, the left body and forceps minor of corpus callosum, the right anterior segment of the inferior fronto-occipital fasciculus and the anterior segments of the cingulum. The sub-groups comparison revealed significant lower FA in the schizophrenia sub-group in two clusters: the anterior thalamic radiation and the anterior segment of left cingulum. These findings are coherent with previous morphology studies. The results suggest that gray and white matter abnormalities are present at early stages of the disease, and white matter differences may distinguish different illness prognosis.     

Cannabis use, cognitive performance and mood in a sample of workers

There are well documented acute and chronic effects of cannabis use on mental functioning. However, less is known about any effects on cognition within the context of work and everyday life.The aim of the study was to examine any association between cannabis use and cognitive performance, mood and human error at work.Cannabis users and controls completed a battery of laboratory based computer tasks measuring mood and cognitive function pre- and post-work at the start and end of a working week. They also completed daily diaries reporting their work performance.Cannabis use was associated with impairment in both cognitive function and mood, though cannabis users reported no more workplace errors than controls. Cannabis use was associated with lower alertness and slower response organization. In addition, users experienced working memory problems at the start, and psychomotor slowing and poorer episodic recall at the end of the working week.This pattern of results suggests two possible effects. First a 'hangover'-type effect which may increase with frequency of use. Second a subtle effect on cognitive function, perhaps more apparent under cognitive load and/or fatigue, which may increase with more prolonged use. The results also highlight the importance of the timing of testing within the context and routine of everyday life.     

Effects of acute antipsychotic treatment on brain activation in first episode psychosis: an fMRI study.

This study aimed to assess the neurophysiological effects of acute atypical antipsychotic treatment on cognitive functioning in subjects presenting with a first episode of psychosis. We used functional MRI to examine the modulatory effects of acute psychopharmacological intervention on brain activation during four different cognitive tasks: overt verbal fluency, random movement generation, n-back and a spatial object memory task. Treatment with atypical antipsychotics was associated with alterations in regional activation during each task and also when task demands were manipulated within paradigms. The initial treatment of psychosis with atypical antipsychotics thus appears to be associated with modifications of the neurofunctional correlates of executive and mnemonic functions. These effects need to be considered when interpreting group differences in activation between medicated patients and controls.     

Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study.

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.