Feasibility and effectiveness of extended-release buprenorphine (XR-BUP) among correctional populations: a systematic review.

Background: Medications for opioid use disorder (MOUD) reduce risks for overdose among correctional populations. Among other barriers, daily dosing requirements hinder treatment continuity post-release. Extended-release buprenorphine (XR-BUP) may therefore be beneficial. However, limited evidence exists.Objectives: To conduct a systematic review examining the feasibility and effectiveness of XR-BUP among correctional populations.Methods: Searches were carried out in Pubmed, Embase, and PsychINFO in October 2023. Ten studies reporting on feasibility or effectiveness of XR-BUP were included, representing n = 819 total individuals (81.6% male). Data were extracted and narratively reported under the following main outcomes: 1) Feasibility; 2) Effectiveness; and 3) Barriers and Facilitators.Results: Studies were heterogeneous. Correctional populations were two times readier to try XR-BUP compared to non-correctional populations. XR-BUP was feasible and safe, with no diversion, overdoses, or deaths; several negative side effects were reported. Compared to other MOUD, XR-BUP significantly reduced drug use, resulted in similar or higher treatment retention rates, fewer re-incarcerations, and was cost-beneficial, with a lower overall monthly/yearly cost. Barriers to XR-BUP, such as side effects and a fear of needles, as well as facilitators, such as a lowered risk of opioid relapse, were also identified.Conclusion: XR-BUP appears to be a feasible and potentially effective alternative treatment option for correctional populations with OUD. XR-BUP may reduce community release-related risks, such as opioid use and overdose risk, as well as barriers to treatment retention. Efforts to expand access to and uptake of XR-BUP among correctional populations are warranted.

Computer-Based Training for Cognitive Behavioural Therapy for Substance Use Disorder: A Randomized Controlled Trial Including Quantitative and Qualitative Health and Economic Outcomes: Formation informatisée pour la thérapie cognitivo-comportementale pour les troubles liés à l'usage de substances : un essai randomisé contrôlé y compris les résultats quantitatifs et qualitatifs en matière de santé et d'économie.

OBJECTIVES: Heavy alcohol and drug use is reported by a substantial number of Canadians; yet, only a minority of those experiencing substance use difficulties access specialized services. Computer-Based Training for Cognitive Behavioural Therapy (CBT4CBT) offers a low-cost method to deliver accessible and high-quality CBT for substance use difficulties. To date, CBT4CBT has primarily been evaluated in terms of quantitative outcomes within substance use disorder (SUD) samples in the United States. A comparison between CBT4CBT versus standard care for SUDs in a Canadian sample is critical to evaluate its potential for health services in Canada. We conducted a randomized controlled trial of CBT4CBT versus standard care for SUD. METHODS: Adults seeking outpatient treatment for SUD (N = 50) were randomly assigned to receive either CBT4CBT or treatment-as-usual (TAU) for 8 weeks. Measures of substance use and associated harms and quality of life were completed before and after treatment and at 6-month follow-up. Qualitative interviews were administered after treatment and at follow-up, and healthcare utilization and costs were extracted for the entire study period. RESULTS: Participants exhibited improvements on the primary outcome as well as several secondary outcomes; however, there were no differences between groups. A cost-effectiveness analysis found lower healthcare costs in CBT4CBT versus TAU in a subsample analysis, but more days of substance use in CBT4CBT. Qualitative analyses highlighted the benefits and challenges of CBT4CBT. DISCUSSION: Findings supported an overall improvement in clinical outcomes. Further investigation is warranted to identify opportunities for implementation of CBT4CBT in tertiary care settings.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03767907.

Evaluating a digital intervention targeting substance use difficultiesPlain Language SummaryWhy was the study done?Heavy alcohol and drug use is frequent in the Canadian population, although very few people have access to treatment. The digital intervention, Computer-Based Training for Cognitive Behavioural Therapy (CBT4CBT), may provide a low-cost, high-quality, and easily accessible method of treatment for substance use difficulties. Limited research on this digital intervention has been conducted in Canadian populations, and few studies thus far have evaluated participants' subjective experience using the intervention, along with the cost on the Canadian healthcare system.What did the researchers do?The research team recruited participants and provided access to either CBT4CBT or to standard care at a mental health hospital for 8 weeks. Participants were asked questions about their substance use and related consequences, quality of life, and thoughts on the treatment they received. Information regarding healthcare use and the cost to the healthcare system was also gathered.What did the researchers find?Participants in both groups improved with regards to their substance use, some related consequences, and psychological quality of life. Participants provided insight on the benefits and challenges of both types of treatment. It was also found that the CBT4CBT intervention was less costly.What do these findings mean?These findings support that adults receiving CBT4CBT and standard care both improved to a similar degree in this sample. Participant feedback may inform future studies of how best to implement this intervention in clinical studies. Future studies with larger samples are needed to further examine whether CBT4CBT can increase access to supports and be beneficial in the Canadian healthcare system.

Neuromodulation for Cannabis Use: A Scoping Review.

This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities.

Cannabis use and mood disorders: a systematic review.

Background: Problematic cannabis use is highly prevalent among people with mood disorders. This underscores the need to understand the effects of cannabis and cannabinoids in this population, especially considering legalization of recreational cannabis use. Objectives: We aimed to (1) systematically evaluate cross-sectional and longitudinal studies investigating the interplay between cannabis use, cannabis use disorder (CUD), and the occurrence of mood disorders and symptoms, with a focus on major depressive disorder (MDD) and bipolar disorder (BD) and; (2) examine the effects of cannabis on the prognosis and treatment outcomes of MDD and BD. Methods: Following PRISMA guidelines, we conducted an extensive search for English-language studies investigating the potential impact of cannabis on the development and prognosis of mood disorders published from inception through November 2023, using EMBASE, PsycINFO, PubMed, and MEDLINE databases. Results: Our literature search identified 3,262 studies, with 78 meeting inclusion criteria. We found that cannabis use is associated with increased depressive and manic symptoms in the general population in addition to an elevated likelihood of developing MDD and BD. Furthermore, we observed that cannabis use is linked to an unfavorable prognosis in both MDD or BD. Discussion: Our findings suggest that cannabis use may negatively influence the development, course, and prognosis of MDD and BD. Future well-designed studies, considering type, amount, and frequency of cannabis use while addressing confounding factors, are imperative for a comprehensive understanding of this relationship. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023481634.

Functional and structural effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations in schizophrenia: A systematic review.

BACKGROUND: Auditory verbal hallucinations (AVH) are a disabling symptom for people with schizophrenia (SCZ), and do not always respond to antipsychotics. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for medication-refractory AVH, though the underlying neural mechanisms by which rTMS produces these effects remain unclear. This systematic review evaluated the structural and functional impact of rTMS for AVH in SCZ, and its association with clinical outcomes. METHODS: A systematic search was conducted in Medline, PsychINFO, and PubMed using terms for four key concepts: AVH, SCZ, rTMS, neuroimaging. Using PRISMA guidelines, 18 studies were identified that collected neuroimaging data of an rTMS intervention for AVH in SCZ. Risk of bias assessments was conducted. RESULTS: Low frequency (<5 Hz) rTMS targeting left hemispheric language processing regions may normalize brain abnormalities in AVH patients at structural, functional, electrophysiological, and topological levels, with concurrent symptom improvement. Amelioration of aberrant neural activity in frontotemporal networks associated with speech and auditory processing was commonly observed, as well as in cerebellar and emotion regulation regions. Neuroimaging analyses identified neural substrates with direct correlations to post-rTMS AVH severity, propounding their use as therapeutic targets. DISCUSSION: Combined rTMS-neuroimaging highlights the multidimensional alterations of rTMS on brain activity and structure in treatment-resistant AVH, which may be used to develop more efficacious therapies. Larger randomized, sham-controlled studies are needed. Future studies should explore alternate stimulation targets, investigate the neural effects of high-frequency rTMS and evaluate long-term neuroimaging outcomes.

A Systematic Review of the Clinical Effects of Cannabis and Cannabinoids in Posttraumatic Stress Disorder Symptoms and Symptom Clusters.

Objective: Given the high rate of comorbid posttraumatic stress disorder (PTSD) and cannabis use, it is critical that further research be conducted to address the associated benefits and risks of cannabis use in this population. This systematic review evaluated evidence on the effects of cannabis and cannabinoids on PTSD symptoms and PTSD clusters.Data Sources: A systematic search of PubMed, PsycINFO, and EMBASE databases was performed using terms related to cannabis, cannabinoids, and PTSD. Peer-reviewed studies available online in English and published from January 1990 through February 2023 were considered.Study Selection: Included studies were experimental or observational in design, were conducted in cannabis-using patients with PTSD, used validated measures of PTSD, and were published in English.Data Extraction: Extracted information included study aims, study design, sample size and sex, comparator group, cannabis-related characteristics, psychometric instruments, and relevant clinical findings regarding overall PTSD symptoms and cluster symptoms.Results: Fourteen studies were included, 3 in a comorbid PTSD and cannabis use disorder (CUD) sample and 11 in a non-CUD sample. Of the 10 studies examining overall PTSD symptoms in a non-CUD sample, 5 suggested benefits associated with cannabis use and 5 suggested no effect or worsening of symptoms. Four studies reported benefits of cannabis for cluster B- and E-related symptoms in a non-CUD sample. All 3 studies in cannabis-using patients with a comorbid PTSD and CUD diagnosis reported risks for worsening of overall symptoms.Conclusions: This review did not find major benefits of cannabinoids in improving overall PTSD symptoms. Some benefits with regard to cluster B and E symptoms were observed. Some risks with regard to worsening suicidal ideation and violent behavior were also reported. Individuals with a comorbid CUD diagnosis may be at greater risk for negative cannabis-related PTSD outcomes. More experimental studies are needed to determine the causal effects of cannabis and cannabinoids in PTSD.

Cannabis use in adolescents and anxiety symptoms and disorders: a systematic review and meta-analysis.

Background: The use of cannabis is highly prevalent during adolescence compared to the general adult population. In addition to the high comorbidity between cannabis use and anxiety disorders, early evidence suggests that cannabis may precede the development of anxiety. Moreover, adolescence represents a major developmental period for both neurobiological and psychological processes, placing these individuals at a heightened vulnerability to the influence of cannabis.Objectives: This systematic review and meta-analysis examined the prospective associations between adolescent cannabis use and subsequent anxiety outcomes (i.e. anxiety disorders and/or symptoms).Methods: Following PRISMA guidelines, a systematic review and meta-analysis were conducted encompassing data from articles published between database inception and September 2022.Results: Six longitudinal studies were identified for quantitative analysis, while twelve non-overlapping longitudinal studies were identified for qualitative review (total N = 18; 33380 subjects). Meta-analytical findings supported an association between adolescent cannabis use and the development of a subsequent anxiety disorder (Odds Ratio = 2.14, 95% CI: 1.37-3.36, p < .01). These findings were consistent with our qualitative synthesis where nine of the twelve longitudinal studies observed a significant relationship between adolescent cannabis use and exacerbation of anxiety symptoms later in life, irrespective of an anxiety disorder diagnosis.Discussion: In summary, the current evidence suggests a prospective association between adolescent cannabis use and later anxiety symptoms and disorders. These findings underscore the importance of refining research methodologies, considering sex-based differences and controlling for confounding factors, as well as implementing educational initiatives and developing clinical interventions to address the mental health risks associated with cannabis use among adolescents.

Effects of open access publishing on article metrics in Neuropsychopharmacology.

Neuropsychopharmacology (NPP) offers the option to publish articles in different tiers of an open access (OA) publishing system: Green, Bronze, or Hybrid. Green articles follow a standard access (SA) subscription model, in which readers must pay a subscription fee to access article content on the publisher's website. Bronze articles are selected at the publisher's discretion and offer free availability to readers at the same article processing charge (APC) as Green articles. Hybrid articles are fully OA, but authors pay an increased APC to ensure public access. Here, we aimed to determine whether publishing tier affect the impact and reach of scientific articles in NPP. A sample of 6000 articles published between 2001-2021 were chosen for the analysis. Articles were separated by article type and publication year. Citation counts and Altmetric scores were compared between the three tiers. Bronze articles received significantly more citations than Green and Hybrid articles overall. However, when analyzed by year, Bronze and Hybrid articles received comparable citation counts within the past decade. Altmetric scores were comparable between all tiers, although this effect varied by year. Our findings indicate that free availability of article content on the publisher's website is associated with an increase in citations of NPP articles but may only provide a moderate boost in Altmetric score. Overall, our results suggest that easily accessible article content is most often cited by readers, but that the higher APCs of Hybrid tier publishing may not guarantee increased scholarly or social impact.

Cannabis cravings predict cigarette use in schizophrenia: a secondary analysis from two cannabis abstinence studies.

CLINICAL TRIAL NAME: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in SchizophreniaURL: www.clinicaltrials.gov; Registration Number: NCT03189810.

Birth, cognitive and behavioral effects of intrauterine cannabis exposure in infants and children: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Δ9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, has been implicated in affecting fetal neurodevelopment by readily crossing the placenta. However, little is known regarding the long-term effects of intrauterine cannabis exposure. This systematic review and meta-analysis synthesized prospective and cross-sectional human studies to measure the effects of intrauterine cannabis exposure on birth, behavioral, psychological and cognitive outcomes in infancy until early childhood. METHODS: Reporting according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, cross-sectional and prospective studies published from database inception until June 2023, investigating developmental outcomes of infants, toddlers and young children with intrauterine cannabis exposure were considered. All articles were obtained from PubMed or PsycINFO databases. RESULTS: The literature search resulted in 932 studies, in which 57 articles met eligibility criteria. The meta-analysis revealed that intrauterine cannabis exposure increases the risk of preterm delivery [odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.05-2.71, P = 0.03], low birth weight (OR = 2.60, CI = 1.71-3.94, P < 0.001) and requirement for neonatal intensive care unit (NICU) admission (OR = 2.51, CI = 1.46-4.31; P < 0.001). Our qualitative synthesis suggests that intrauterine cannabis exposure may be associated with poorer attention and externalizing problems in infancy and early childhood. We found no evidence for impairments in other cognitive domains or internalizing behaviors. CONCLUSIONS: Prenatal cannabis use appears to be associated with lower birth weight, preterm birth and neonatal intensive care unit admission in newborns, but there is little evidence that prenatal cannabis exposure adversely impacts behavioral or cognitive outcomes in early childhood, with the exception of attention and externalizing problems.

A systematic review and meta-analysis of neuromodulation therapies for substance use disorders.

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

Circulating Endocannabinoids and N-Acylethanolamines in Individuals with Cannabis Use Disorder-Preliminary Findings.

BACKGROUND: Endocannabinoids and related N-acylethanolamines (NAEs) are bioactive lipids with important physiological functions and putative roles in mental health and addictions. Although chronic cannabis use is associated with endocannabinoid system changes, the status of circulating endocannabinoids and related NAEs in people with cannabis use disorder (CUD) is uncertain. METHODS: Eleven individuals with CUD and 54 healthy non-cannabis using control participants (HC) provided plasma for measurement by high-performance liquid chromatography-mass spectrometry of endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and related NAE fatty acids (N-docosahexaenoylethanolamine (DHEA) and N-oleoylethanolamine (OEA)). Participants were genotyped for the functional gene variant of FAAH (rs324420, C385A) which may affect concentrations of AEA as well as other NAEs (OEA, DHEA). RESULTS: In overnight abstinent CUD, AEA, OEA and DHEA concentrations were significantly higher (31-40%; p < 0.05) and concentrations of the endocannabinoid 2-AG were marginally elevated (55%, p = 0.13) relative to HC. There were no significant correlations between endocannabinoids/NAE concentrations and cannabis analytes, self-reported cannabis use frequency or withdrawal symptoms. DHEA concentration was inversely related with marijuana craving (r = -0.86; p = 0.001). Genotype had no significant effect on plasma endocannabinoids/NAE concentrations. CONCLUSIONS: Our preliminary findings, requiring replication, might suggest that activity of the endocannabinoid system is elevated in chronic cannabis users. It is unclear whether this elevation is a compensatory response or a predating state. Studies examining endocannabinoids and NAEs during prolonged abstinence as well as the potential role of DHEA in craving are warranted.

Cannabis self-administration in the human laboratory: a scoping review of ad libitum studies.

Cannabis self-administration studies may be helpful for identifying factors that influence cannabis consumption and subjective response to cannabis. Additionally, these paradigms could be useful for testing novel pharmacotherapies for cannabis use disorder. This scoping review aims to summarize the findings from existing ad libitum cannabis self-administration studies to determine what has been learned from these studies as well as their limitations. We examined studies that specifically examined cannabis smoking, focusing on subjective response and self-administration behavior (e.g., smoking topography). A systematic search was conducted using PubMed and Embase from inception to October 22, 2022. Our search strategy identified 26 studies (total N = 662, 79% male) that met our eligibility criteria. We found that tetrahydrocannabinol (THC) concentration significantly affected subjective response to cannabis in some but not all studies. In general, cannabis self-administration tended to be most intense at the beginning of the laboratory session and decreased in later parts of the session. There was limited data on cannabis self-administration in adults older than 55. Data on external validity and test-retest reliability were also limited. Addressing these limitations in future ad libitum cannabis self-administration studies could lead to more valid and generalizable paradigms, which in turn could be used to improve our understanding of cannabis use patterns and to help guide medication development for cannabis use disorder.