Psychotherapy to emphasize self-directed recovery for persons with serious mental illness: Contributions from metacognitive reflection and insight therapy (MERIT).

Recovery from serious mental illness (SMI) is a complex process that can be supported by different levels of mental health care, for example, individual psychotherapy. Current individual evidence-based psychotherapy for persons with SMI is often focused on specific objective recovery outcomes, including symptom reduction and functional improvement, and requires a minimum level of insight. Less common but also important are broader, more flexible approaches that allow clients to explore their needs and challenges, without predetermined goals or a certain level of insight. The current article aims to describe (1) the development of metacognitive reflection and insight therapy (MERIT), an evidence-based psychotherapy that is focused on self-determination, or self-directed recovery, and (2) how MERIT advances care for persons with SMI by addressing a significant gap in the field for the treatment of people with SMI with limited metacognitive capacity and insight, offering an adaptable approach emphasizing self-directed recovery. MERIT utilizes a metacognitive framework that is guided by flexible key elements and an interpersonal environment. Training MERIT therapists early in their careers may be helpful in providing a holistic view of SMI to promote self-directed recovery in ways that are personalized and meaningful for each person. MERIT training has been completed in multiple countries across different levels of training (e.g., internship and psychology practicum). Professionals such as psychologists and social workers have effectively played a role in MERIT development and dissemination, which ultimately strives to advance psychotherapy for a wide range of individuals with SMI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preliminary study of the interactive effects of THC and ethanol on self-reported ability and simulated driving, subjective effects, and cardiovascular responses.

RATIONALE: Drug- and alcohol-related motor vehicle accidents are a leading cause of morbidity and mortality worldwide. Compared to alcohol, less is known about the effects of cannabis on driving and even less about their combined effects. OBJECTIVE: To characterize the combined and separate effects of ethanol and tetrahydrocannabinol (THC) on perceived ability to drive, subjective effects, and simulated driving. METHODS: In a within-subject (crossover), randomized, placebo-controlled, double-blind, 2 × 2 design, the effects of oral THC (10 mg [dronabinol] or placebo) and low-dose intravenous ethanol (clamped at BAC 0.04% or placebo) on perceived ability to drive, simulated driving (standard deviation of lateral position [SDLP]), subjective effects (e.g., "high"), and physiological effects (e.g., heart rate) were studied in healthy humans (n = 18). RESULTS: Subjects reported reductions in perceived ability to drive (THC < ethanol < combination) which persisted for ~ 6 h (placebo = ethanol, THC < combination). Ethanol and THC produced synergistic effects on heart rate, significant differences compared to either drug alone on perceived ability to drive and feeling states of intoxication (e.g., high), as well increases in SDLP compared to placebo. CONCLUSIONS: Perceived ability to drive is reduced under the influence of THC against the backdrop of blood alcohol levels that are below the legal limit. People should be aware that the effects of oral THC on driving may persist for up to six hours from administration. Findings are relevant to the increasingly common practice of combining alcohol and cannabinoids and the effects on driving.

Delta-9-Tetrahydrocannabinol, Cannabidiol, and Acute Psychotomimetic States: A Balancing Act of the Principal Phyto-Cannabinoids on Human Brain and Behavior.

Background: THC and CBD are the principal phyto-cannabinoids in the cannabis plant. The differential and possibly antagonistic effects of these compounds on specific brain and behavioral responses, and the mechanisms underlying their effects have generated extensive interest in pre-clinical and clinical neuroscience investigations. Methods: In this double-blind randomized placebo-controlled counterbalanced Human Laboratory Study, we examined the effects of three different dose ratios of CBD:THC (1:1, 2:1, and 3:1) on "neural noise," an electrophysiological biomarker of psychosis known to be sensitive to cannabinoids as well as subjective and psychotomimetic effects. Healthy volunteers (n=28, 12 women) with at least one prior exposure to cannabis participated in the study. Outcomes: The lowest CBD (2.5 mg):THC (0.035 mg/kg) ratio (1:1) resulted in maximal attenuation of both THC-induced psychotomimetic effects (Positive and Negative Syndrome Scale [PANSS] positive: Anova Type Statistic [ATS]=7.83, pcorrected=0.015) and neural noise (ATS=8.83, pcorrected=0.009). Further addition of CBD did not reduce the subjective experience of THC-induced "high" (p>0.05 for all CBD doses). Interpretation: These novel results demonstrate that CBD attenuates specific THC-induced subjective and objective effects relevant to psychosis in a dose/ratio-dependent manner. Given the increasing global trend of cannabis liberalization and application for medical indications, these results assume considerable significance given the potential dose-related interactions of these key phyto-cannabinoids. Trial registration: The trial was registered in clinicaltrials.gov ID: NCT01180374.

The Relationship Between Cannabinoids and Neural Oscillations: How Cannabis Disrupts Sensation, Perception, and Cognition.

Disruptions in neural oscillations are believed to be one critical mechanism by which cannabinoids, such as delta-9-tetrahyrdrocannabinol (THC; the primary psychoactive constituent of cannabis), perturbs brain function. Here we briefly review the role of synchronized neural activity, particularly in the gamma (30-80 Hz) and theta (4-7 Hz) frequency range, in sensation, perception, and cognition. This is followed by a review of clinical studies utilizing electroencephalography (EEG) which have demonstrated that both chronic and acute cannabinoid exposure disrupts neural oscillations in humans. We also offer a hypothetical framework through which endocannabinoids modulate neural synchrony at the network level. This also includes speculation on how both chronic and acute cannabinoids disrupt functionally relevant neural oscillations by altering the fine tuning of oscillations and the inhibitory/excitatory balance of neural circuits. Finally, we highlight important clinical implications of such oscillatory disruptions, such as the potential relationship between cannabis use, altered neural synchrony, and disruptions in sensation, perception, and cognition, which are perturbed in disorders such as schizophrenia.

Translating an integrative metacognitive model of psychotherapy for serious mental illness into a group format: A pilot investigation on feasibility.

Metacognitive reflection and insight therapy (MERIT) is an one-on-one intervention that targets insight with the aim to help people with serious mental illness develop more integrated ideas about themselves and others in order to respond to their psychological and social challenges more adaptively. There is a growing body of evidence on MERIT's effectiveness. Considering the clinical demand for more cost-effective group psychotherapies, we modified the original individual MERIT format to a group-based intervention (MERITg) for application in inpatient and outpatient psychiatric settings. Thirty-one participants (inpatient = 10; outpatient = 21) with serious mental illness were surveyed on their experience of MERITg, which was offered adjunctively to their routine clinical care. Program evaluation measures were used to assess the feasibility and acceptance of the group. Across locations, more than half of all participants attended more than one group. Participants reported attending the group initially because they thought writing would be helpful, and further reported that they liked the group because they enjoyed writing and the discussion, and that they found it interesting to hear the perspectives and writings of others. Findings further support the need for future research on the efficacy and effectiveness of the group and its relationship to changes in metacognitive capacity and recovery. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The relationship between cannabis use and taurine: A MRS and metabolomics study.

Taurine is an essential amino acid. It has been shown to be neuroprotective including protecting against the neurotoxic effects of glutamate. The goal of the current study was to examine the relationship between CB use and taurine measured in brain using magnetic resonance spectroscopy (MRS), and peripherally from a urine sample. Two experiments are presented. The first is a reanalysis of published data that examined taurine and glutamate in the dorsal anterior cingulate of a CB user group and non-user group using MRS. The second experiment, in a separate CB user group, used metabolomics analysis to measure taurine levels in urine. Because body composition has been associated with the pharmacokinetics of cannabis and taurine levels, a moderation model was examined with body composition included as the covariate. The MRS study found taurine levels were correlated with glutamate in both groups and taurine was correlated with frequency of CB use in the CB user group. The moderation model demonstrated significant effects of CB use and BMI; the interaction was marginally significant with lower BMI individuals showing a positive relationship between CB use and taurine. A similar finding was observed for the urine analysis. Both CB use and weight, as well as the interaction were significant. In this case, individuals with higher weight showed an association between CB use and taurine levels. This study shows the feasibility and potential importance of examining the relationship between taurine and CB use as it may shed light on a mechanism that underlies the neuroprotective effects of CB.

Differential Cognitive Performance in Females and Males with Regular Cannabis Use.

OBJECTIVES: Preclinical and clinical studies suggest that males and females may be differentially affected by cannabis use. This study evaluated the interaction of cannabis use and biological sex on cognition, and the association between observed cognitive deficits and features of cannabis use. METHODS: Cognitive measures were assessed in those with regular, ongoing, cannabis use (N = 40; 22 female) and non-using peers (N = 40; 23 female). Intelligence, psychomotor speed, and verbal working memory were measured with the Wechsler Abbreviated Scale of Intelligence, Digit Symbol Test, and Digit Span and Hopkins Verbal Learning Test, respectively. Associations between cognitive measures and cannabis use features (e.g., lifetime cannabis use, age of initiation, time since last use of cannabis, recent high-concentration tetrahydrocannabinoid exposure) were also evaluated. RESULTS: No main effects of group were observed across measures. Significant interactions between group and biological sex were observed on measures of intelligence, psychomotor speed, and verbal learning, with greatest group differences observed between males with and without regular cannabis use. Psychomotor performance was negatively correlated with lifetime cannabis exposure. Female and male cannabis use groups did not differ in features of cannabis use. CONCLUSIONS: Findings suggest that biological sex influences the relationship between cannabis and cognition, with males potentially being more vulnerable to the neurocognitive deficits related to cannabis use.

Treatment outcomes in individuals diagnosed with comorbid opioid use disorder and Posttraumatic stress disorder: A review.

OBJECTIVES: Opioid use disorder (OUD) is a public health emergency. Evidence suggests that posttraumatic stress disorder (PTSD) is common among individuals with OUD; however, few studies evaluate whether concurrent diagnoses affect treatment outcomes. This review examines the impact of concurrent diagnoses of OUD and PTSD on treatment outcomes. METHODS: A search was performed using articles identified through June 30, 2020 in PubMed, PsycINFO, and EMBASE. Included peer-reviewed articles evaluated individuals with OUD and a PTSD diagnosis via standardized assessment and/or medical record diagnoses, and reported relationships between diagnosis and treatment outcomes and/or other psychiatric conditions. RESULTS: Out of 412 articles, 17 studies met inclusion criteria for this review (from 13 databases). Articles included had a total of n = 2190 with OUD, with n = 79 non-OUD comparison participants. Studies examining individuals with OUD revealed comorbid PTSD was associated with more severe addiction, higher rates of depression, attempted suicide, and psychosocial problems. CONCLUSIONS: Among individuals with OUD, presence of PTSD is associated with multiple mental health problems. The impact of PTSD on drug use is inconclusive. Although only 5 studies examined psychosocial PTSD treatment, all found PTSD-focused treatment to be effective for those with comorbid OUD. Overall, results suggest the need to better identify PTSD among those with OUD, and to develop and evaluate interventions that are brief, integrative, and easy to implement in clinical settings.

Altered cerebellar-cortical resting-state functional connectivity in cannabis users.

BACKGROUND: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. AIMS: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. METHODS: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). RESULTS: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. CONCLUSIONS: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.

Meaning, integration, and the self in serious mental illness: Implications of research in metacognition for psychiatric rehabilitation.

OBJECTIVE: It has been established that recovery is a common outcome for adults diagnosed with serious mental illness which involves objective and subjective phenomenon. While considerable work has examined objective aspects of recovery, it remains difficult to know how to quantify the processes which support more subjective aspects of recovery related to sense of self. This article explores the potential of recent research on metacognition to offer new avenues to measure the processes which make a sense of self available within the flow of life. METHOD: Emerging definitions of metacognition using an integrative model of metacognition are reviewed. Research is presented suggesting adults diagnosed with serious mental illness are often confronted by metacognitive deficits which interfere with their ability to make sense of their psychiatric challenges and effectively direct their own recovery. FINDINGS: Metacognitive capacity may be a quantifiable phenomenon which contributes to certain aspects of recovery related to meaning making, agency and self-direction. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Promoting metacognitive capacity may be a previously unrecognized active element of existing rehabilitative interventions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

In an exploratory randomized, double-blind, placebo-controlled, cross-over study, psychoactive doses of intravenous delta-9-tetrahydrocannabinol fail to produce antinociceptive effects in healthy human volunteers.

RATIONALE: Animal studies and anecdotal human reports suggest that cannabinoids have antinociceptive effects. Controlled human studies have produced mixed results. OBJECTIVES: We sought to reduce existing variability by investigating the effects of intravenous delta-9-tetrahydrocannabinol (THC) in several pain paradigms within the same human subjects, addressing some of the limitations to the published literature. METHODS: In this exploratory randomized, double-blind, placebo-controlled, cross-over study, healthy human subjects received 0.01 mg/kg or 0.03 mg/kg intravenous THC or placebo (ethanol vehicle) infused over 10 min on three test days, each separated by at least 72 h. Capsaicin (250 µg) was injected intradermally to induce chemical pain and hyperalgesia. Four other forms of acute pain were induced: mechanical (von Frey filament), hot and cold (thermode), and electrical (pulse generator). Pain ratings were obtained before drug administration, at peak drug effects, and 2 h after drug administration and included both objective and subjective measures. THC drug effects and vital signs were also collected during experimental sessions. Nonparametric analysis with repeated measures was performed. RESULTS: THC induced euphoria, perceptual and cognitive alterations, and tachycardia in a dose-related manner, but failed to have significant effects in experimentally induced acute chemical, mechanical, thermal, or electrical pain and capsaicin-induced hyperalgesia. CONCLUSIONS: In this exploratory controlled study, intravenous THC lacked significant antinociceptive properties in experimental models of acute pain and capsaicin-induced hyperalgesia in healthy human subjects. Continued study of THC and other cannabinoids through high-quality, controlled studies in both healthy volunteers and patients with pain conditions is warranted to inform the growing demand for the clinical application of cannabinoids in pain management.

Individuals with psychosis and a lifetime history of cannabis use show greater deficits in emotional experience compared to non-using peers.

Background: While previous research suggests that active cannabis use is a barrier to the emotional experiences of anticipating pleasure and expressing emotion in early psychosis, the relationship between lifetime cannabis use, emotional experience and social function over time has been understudied.Aims: This study sought to characterize the influence of lifetime cannabis use on emotional experience in prolonged psychosis and the influence of the interaction of cannabis use and emotional expression on social function.Methods: Emotional expression, experience of pleasure in the moment, anticipatory anhedonia and social functioning were measured concurrently using the Emotional Expressivity Scale (EES), Temporal Experience of Pleasure Scale (TEPS) and Social Functioning Scale (SFS), respectively. Participants were adults with schizophrenia either with (n = 35) or without (n = 36) a lifetime history of cannabis use.Results: Compared to non-using participants, individuals with a history of cannabis use expressed lesser abilities to express emotion, were less likely to expect pleasure and had poorer social function. Cannabis use moderated the relationship between anticipatory pleasure and prosocial activities.Conclusions: Lifetime cannabis use in schizophrenia may be associated with greater deficits in emotional expressivity, anticipation of pleasure and social function. Cannabis use may disrupt the relationship between anticipatory pleasure and social functioning.

An investigation of the relationship between glutamate and resting state connectivity in chronic cannabis users.

Human and animal studies have shown that heavy cannabis (CB) use interacts with glutamatergic signaling. Additionally, recent studies have suggested that glutamate (Glu) may drive resting state functional connectivity (RSfc). The aims of the current preliminary study were to: 1) determine whether dorsal anterior cingulate cortex (dACC) Glu is related to RSfc between the dACC and two nodes of the reward network, the nucleus accumbens (NAc) and hippocampus (Hp); and 2) determine whether CB use interacts with the relationship between dACC Glu and RSfc. A group of 23 chronic CB users and 23 healthy controls participated in this multimodal MRI study. Glu levels were assessed in the dACC using magnetic resonance spectroscopy (MRS). Linear regression models were used to determine whether dACC Glu and CB use predicts RSfc between the dACC and the NAc and Hp. While the effect size is small, the results showed that the connectivity between the dACC and right NAc was predicted by the interaction between dACC Glu levels and monthly CB use. Additionally, while there is some suggestion that dACC Glu is correlated with dACC-hippocampal connectivity, unlike for dACC/NAc connectivity the relationship between them does not appear to be affected by CB use. These preliminary findings are significant in that they demonstrate the need for future studies with larger sample sizes to better characterize the relationship between resting state connectivity and neurochemistry as well as to characterize how CB use interacts with that relationship.

An Investigation of Neurochemical Changes in Chronic Cannabis Users.

With the legalization of recreational cannabis (CB) the characterization of how it may impact brain chemistry is essential. Magnetic resonance spectroscopy (MRS) was used to examine neurometabolite concentrations in the dorsal anterior cingulate (dACC) in chronic CB users (N = 26; 10 females) and controls (N = 24; 10 females). The concentrations of glutamate (Glu), total creatine (tCr), choline (Cho), total N-acetylaspartate (tNAA), and myo-inositol (mI) were estimated using LCModel. The ANCOVAs failed to show significant differences between controls and CB users. Regression analyses were then performed on the CB group to model each neurometabolite to determine its relationship to monthly CB use, sex, the interaction between CB use and sex. tCr was found to be predicted by both monthly CB use and sex. While the regression model was not significant the relationship between monthly CB use and Glu appears to be modulated by sex with the effect of monthly use (dose) being stronger in males. tNAA failed to show an effect of CB use but did reveal an effect of sex with females showing larger tNAA levels. Although the results presented are preliminary due to the small sample size they do guide future research. The results presented provide direction for further studies as they suggest that dose may significantly influence the observance of CB effects and that those effects may be modulated by sex. Studies with significantly larger sample sizes designed specifically to examine individuals with varying usage as well as sex effects are necessary.

Aberrant structural-functional coupling in adult cannabis users.

Cellular studies indicate that endocannabinoid type-1 retrograde signaling plays a major role in synaptic plasticity. Disruption of these processes by delta-9-tetrahydrocannabinol (THC) could produce alterations either in structural and functional brain connectivity or in their association in cannabis (CB) users. Graph theoretic structural and functional networks were generated with diffusion tensor imaging and resting-state functional imaging in 37 current CB users and 31 healthy non-users. The primary outcome measures were coupling between structural and functional connectivity, global network characteristics, association between the coupling and network properties, and measures of rich-club organization. Structural-functional (SC-FC) coupling was globally preserved showing a positive association in current CB users. However, the users had disrupted associations between SC-FC coupling and network topological characteristics, most perturbed for shorter connections implying region-specific disruption by CB use. Rich-club analysis revealed impaired SC-FC coupling in the hippocampus and caudate of users. This study provides evidence of the abnormal SC-FC association in CB users. The effect was predominant in shorter connections of the brain network, suggesting that the impact of CB use or predispositional factors may be most apparent in local interconnections. Notably, the hippocampus and caudate specifically showed aberrant structural and functional coupling. These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.

The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.

RATIONALE: Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). OBJECTIVE: This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. METHODS: This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. RESULTS: There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. CONCLUSIONS: At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00588731.

Auditory feature perception and auditory hallucinatory experiences in schizophrenia spectrum disorder.

Schizophrenia spectrum disorder (SZ) is associated with deficits in auditory perception as well as auditory verbal hallucinations (AVH). However, the relationship between auditory feature perception and auditory verbal hallucinations (AVH), one of the most commonly occurring symptoms in psychosis, has not been well characterized. This study evaluated perception of a broad range of auditory features in SZ and determined whether current AVHs relate to auditory feature perception. Auditory perception, including frequency, intensity, duration, pulse-train and temporal order discrimination, as well as an embedded tone task, was assessed in both AVH (n = 20) and non-AVH (n = 24) SZ individuals and in healthy controls (n = 29) with the Test of Basic Auditory Capabilities (TBAC). The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) was used to assess the experience of auditory hallucinations in patients with SZ. Findings suggest that compared to controls, the SZ group had greater deficits on an array of auditory features, with non-AVH SZ individuals showing the most severe degree of abnormality. IQ and measures of cognitive processing were positively associated with performance on the TBAC for all SZ individuals, but not with the HPSVQ scores. These findings indicate that persons with SZ demonstrate impaired auditory perception for a broad range of features. It does not appear that impaired auditory perception is associated with recent auditory verbal hallucinations, but instead associated with the degree of intellectual impairment in SZ.

Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats.

BACKGROUND/AIMS: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.

Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information.

INTRODUCTION: Cannabis and agonists of the brain cannabinoid receptor (CB1R) produce acute memory impairments in humans. However, the extent to which cannabinoids impair the component processes of encoding and retrieval has not been established in humans. The objective of this analysis was to determine whether the administration of Δ9-Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, impairs encoding and/or retrieval of verbal information. MATERIALS AND METHODS: Healthy subjects were recruited from the community. Subjects were administered the Rey-Auditory Verbal Learning Test (RAVLT) either before administration of THC (experiment #1) (n=38) or while under the influence of THC (experiment #2) (n=57). Immediate and delayed recall on the RAVLT was compared. Subjects received intravenous THC, in a placebo-controlled, double-blind, randomized manner at doses known to produce behavioral and subjective effects consistent with cannabis intoxication. RESULTS: Total immediate recall, short delayed recall, and long delayed recall were reduced in a statistically significant manner only when the RAVLT was administered to subjects while they were under the influence of THC (experiment #2) and not when the RAVLT was administered prior. CONCLUSIONS: THC acutely interferes with encoding of verbal memory without interfering with retrieval. These data suggest that learning information prior to the use of cannabis or cannabinoids is not likely to disrupt recall of that information. Future studies will be necessary to determine whether THC impairs encoding of non-verbal information, to what extent THC impairs memory consolidation, and the role of other cannabinoids in the memory-impairing effects of cannabis. CLINICAL TRIAL INFORMATION: Cannabinoids, Neural Synchrony, and Information Processing (THC-Gamma) http://clinicaltrials.gov/ct2/show/study/NCT00708994 NCT00708994 Pharmacogenetics of Cannabinoid Response http://clinicaltrials.gov/ct2/show/NCT00678730 NCT00678730.