@article{pmid42485844,

title = {Cannabis and tobacco co-use and its association with striatal brain morphometry: Leveraging data from the ENIGMA addiction working group},

author = {Zac J S Yeap and Anthony Juliano and Devarshi Pancholi and Hugh Garavan and Albert Batalla and Janna Cousijn and Francesca Filbey and Edythe D London and Valentina Lorenzetti and Rocio Martin-Santos and Angelica Morales and Nadia Solowij and Murat Yucel and Rachel A Rabin},

doi = {10.1016/j.drugalcdep.2026.113270},

issn = {1879-0046},

year  = {2026},

date = {2026-07-01},

journal = {Drug Alcohol Depend},

volume = {286},

pages = {113270},

abstract = {BACKGROUND: The striatum plays a central role in the pathophysiology of addiction. Studies report that cannabis use is associated with greater striatal gray matter volume (GMV), while tobacco use is associated with both greater and lower striatal GMV. However, their combined effects on striatal GMV remain unclear.nnMETHODS: Using two MRI processing methods, we investigated associations between these substances and striatal GMV. Men and women from eight ENIGMA Addiction sites (N = 302) were parsed into 4 groups; individuals with: co-use (CT, n = 38); cannabis-only use (CO, n = 34); tobacco-only use (TO, n = 61), and controls (CTL, n = 169). Striatal GMV was assessed using (1) Freesurfer-extracted region-specific estimates and (2) voxel-based morphometry using FSL within a striatal mask. Analyses employed 2 × 2 ANCOVAs.nnRESULTS: With Freesurfer, a main effect of cannabis use (CT and CO) emerged in the right nucleus accumbens, and was replicated using FSL (ps ≤ 0.05). With FSL, main effects of cannabis use were found in the putamen and caudate (ps ≤ 0.01), and were modulated by tobacco use (cannabis-tobacco interaction ps ≤ 0.02). Post-hoc comparisons revealed: CT =  CTL >  TO in the putamen and caudate (ps ≤ 0.04); and CTL >  CO (ps ≤ 0.06) and CT >  CO (p = 0.03) in the caudate.nnCONCLUSIONS: Results demonstrate that in the putamen and caudate, individuals who co-use have greater GMV compared to those who use either substance alone, whereas individuals using either substance alone have lower GMV compared to controls. Future research should replicate our novel findings and investigate the clinical correlates of this unique pattern to clarify the functional significance of these findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41265541,

title = {Cannabis and nicotine/tobacco co-use and its association with cognitive and neural outcomes: A systematic review},

author = {Zac J S Yeap and Mathilde Argote and Emma Nadler and Pinning He and Muhammad A Parvaz and Rachel A Rabin},

doi = {10.1016/j.neubiorev.2025.106480},

issn = {1873-7528},

year  = {2026},

date = {2026-01-01},

journal = {Neurosci Biobehav Rev},

volume = {180},

pages = {106480},

abstract = {BACKGROUND: Cannabis and nicotine/tobacco products (NTP) are among the most widely used substances worldwide and are commonly used together. The rising rates of co-use have resulted in a growing number of studies examining the association between cannabis and NTP co-use and cognitive and brain outcomes. Therefore, we synthesized findings from studies investigating the associations between co-use and cognition, brain structure, brain function, and molecular outcomes.nnMETHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched four databases for human and animal studies examining the relationship between co-use and cognition, brain structure, brain function, and molecular outcomes.nnRESULTS: Thirty-nine studies were reviewed. Patterns emerged across cognitive and functional studies, such that people who co-use showed similar working memory performance, resting-state connectivity, and task-based activation compared to people without substance use. Structural and molecular findings were heterogeneous and inconsistent. Animal research was sparse, with no studies examining brain structure or function. While molecular outcomes were mixed and often contradicted human findings, results on memory were more consistent and aligned with human data.nnCONCLUSIONS: Although findings were heterogenous, converging evidence suggests that cannabis and NTP use may offset each other in cognitive and brain functional outcomes, mitigating impairments linked to single-substance use. These results offer novel insight into the cognitive and neurobiological factors that may underlie co-use and may help inform treatment. Rather than extrapolating cannabis and NTP co-use treatment from single-substance treatment approaches, interventions targeting the unique mechanisms of co-use may prove most effective.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40988858,

title = {A systematic review investigating prenatal cannabis and tobacco co-exposure: Impacts on neonatal, behavioral, cognitive and physiological outcomes},

author = {Mathilde Argote and Leah Hilson and Maryam Sorkhou and Rachel A Rabin},

doi = {10.1016/j.dadr.2025.100376},

issn = {2772-7246},

year  = {2025},

date = {2025-12-01},

journal = {Drug Alcohol Depend Rep},

volume = {17},

pages = {100376},

abstract = {BACKGROUND: Despite the high and increasing rates of cannabis and nicotine/tobacco product (NTP) use during pregnancy, the impact of their combined use on health outcomes in offspring remains poorly understood. Given the growing body of research on prenatal cannabis and NTP co-exposure and its effects on neonatal, behavioral, cognitive, and physiological outcomes in offspring, we conducted a systematic review to synthesize the existing literature and evaluate whether prenatal co-exposure results in additive and/or synergistic adverse effects compared to prenatal cannabis-only exposure and prenatal NTP-only exposure.nnMETHODS: We searched Medline, Embase, and PsycINFO databases via OVID for human and animal studies examining the association between prenatal co-exposure and single-substance exposure on neonatal, behavioral, cognitive, and physiological outcomes in offspring.nnRESULTS: Of 3217 records identified, 46 articles were included in the review (human, n = 43; preclinical n = 3). For select neonatal outcomes, co-exposed infants exhibited a higher risk of compromised physical development and birth defects relative to infants with single-substance exposure. Behavioral outcomes, particularly emotion regulation/reactivity, and physiological outcomes demonstrated a similar pattern. In contrast, other neonatal outcomes (e.g., preterm birth and respiratory distress), and cognition were similar between the prenatal co-exposure and single-substance exposure groups.nnCONCLUSIONS: This review suggests additive and/or synergistic adverse consequences associated with co-exposure on several outcomes in offspring relative to single substance exposure. These findings highlight the urgent need for prevention and treatment strategies addressing cannabis and NTP use in pregnant women. We discuss the limitations of the included studies and highlight key areas for future research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41001470,

title = {Cannabis and Tobacco Co-Use Predicts Psychosis in Clinical High Risk Cohorts},

author = {Daniel Bello and Sophia H Blyth and Rachel A Rabin and Jean Addington and Carrie E Bearden and Kristin Cadenhead and Tyrone D Cannon and Ricardo E Carrión and Barbara Cornblatt and Matcheri Keshavan and Daniel H Mathalon and Diana O Perkins and Larry Seidman and William S Stone and Ming T Tsuang and Elaine F Walker and Scott Woods and Roscoe O Brady and Heather Burrell Ward},

doi = {10.1101/2025.09.19.25336202},

year  = {2025},

date = {2025-09-01},

journal = {medRxiv},

abstract = {Cannabis and tobacco use are highly prevalent among people with psychosis and are associated with medical comorbidities and poor prognosis. Concurrent use of cannabis and tobacco ("co-use") is rising in the general population but has not been studied in psychosis. Given the devastating consequences of cannabis and tobacco use, it is critical to understand how their co-use affects psychiatric symptoms and the development of psychosis. We used the North American Prodrome Longitudinal Study 2, a multi-site prospective study of individuals at clinical high risk for psychosis (CHR) and healthy controls, to examine baseline differences in psychiatric symptoms and conversion to psychosis across substance groups: 1) CHR tobacco use, 2) CHR cannabis use, 3) CHR co-use, 4) CHR non-tobacco or cannabis substance use, 5) CHR without substance use, and 6) healthy controls. Among 1,014 participants (734 CHR, 280 controls), more frequent cannabis and tobacco use was linked to greater psychiatric symptom severity, including psychosis, anxiety, and depression. In survival analyses, co-use (HR  2.53, 95% CI [1.44-4.45],  = .001), especially heavy co-use (HR = 3.63, 95% CI: 1.53-8.63,  = 0.003), was associated with increased risk of conversion to psychosis. Co-use of tobacco and cannabis was not associated with psychiatric symptom severity but did predict higher risk of conversion to psychosis. The combination of cannabis and tobacco use may exert a synergistic effect, amplifying conversion risk more than either substance alone, or may be a marker of an elevated underlying psychosis risk. These results highlight the need for early intervention strategies that address co-use in CHR populations to mitigate potential long-term psychiatric consequences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40202728,

title = {Convergence of Cannabis and Psychosis on the Dopamine System},

author = {Jessica Ahrens and Sabrina D Ford and Betsy Schaefer and David Reese and Ali R Khan and Philip Tibbo and Rachel Rabin and Clifford M Cassidy and Lena Palaniyappan},

doi = {10.1001/jamapsychiatry.2025.0432},

issn = {2168-6238},

year  = {2025},

date = {2025-06-01},

journal = {JAMA Psychiatry},

volume = {82},

number = {6},

pages = {609--617},

abstract = {IMPORTANCE: Despite evidence that individuals with a cannabis use disorder (CUD) are at elevated risk of psychosis and that the neurotransmitter dopamine has a role in psychosis, the mechanism linking cannabis use and psychosis remains unclear.nnOBJECTIVE: To use neuromelanin-sensitive magnetic resonance imaging (MRI), referred to as the neuromelanin-MRI signal, a practical, proxy measure of dopamine function, to assess whether a common alteration in the dopamine system may be implicated in CUD and psychosis and whether this alteration can be observed in those with a CUD whether or not they have a diagnosis of first-episode schizophrenia (FES).nnDESIGN, SETTING, AND PARTICIPANTS: This longitudinal observational cohort study recruited individuals from 2019 to 2023 from an early psychosis service and the surrounding communities in London, Ontario. The sample included individuals with and without CUD, with some in each group also diagnosed with FES.nnEXPOSURES: FES and CUD diagnoses from the Structured Clinical Interview for DSM-5.nnMAIN OUTCOMES AND MEASURES: Neuromelanin-MRI signals within the midbrain (substantia nigra [SN]/ventral tegmental area [VTA]) including a subregion previously linked to the severity of untreated psychosis (a priori region of interest). Linear mixed-effects analyses were performed relating neuromelanin-MRI signals to clinical measures.nnRESULTS: A total of 36 individuals without CUD (mean [SD] age, 22.3 [3.2] years; 29 male [81%]; 12 with FES) and 25 individuals with CUD (mean [SD] age, 24.3 [4.7] years; 22 male [88%]; 16 with FES) participated in the study. One-year follow-up was completed for 12 individuals with CUD and 25 without CUD. CUD was associated with elevated neuromelanin-MRI signal in a set of ventral SN/VTA voxels (387 of 2060 SN/VTA voxels, corrected P = .03, permutation test). CUD was also associated with elevated neuromelanin-MRI signal in the psychosis-related region of interest (t92 = 2.12, P = .04) with a significant dose-dependent association (higher burden of CUD symptoms associated with higher neuromelanin-MRI signal, F1, 96 = 4.89; P = .03). In contrast, participants with FES did not exhibit a significant elevation in neuromelanin-MRI signal (241 SN/VTA voxels had elevated signal, corrected P = .09). There was no association between time and neuromelanin-MRI signal.nnCONCLUSIONS AND RELEVANCE: Elevated dopamine function in a critical SN/VTA subregion may be associated with psychosis risk in people with CUD. Cannabis was associated with the hypothesized final common pathway for the clinical expression of psychotic symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40480970,

title = {The electroencephalography protocol for the Accelerating Medicines Partnership® Schizophrenia Program: Reliability and stability of measures},

author = {Daniel H Mathalon and Spero Nicholas and Brian J Roach and Tashrif Billah and Suzie Lavoie and Thomas Whitford and Holly K Hamilton and Lauren Addamo and Andrey Anohkin and Tristan Bekinschtein and Aysenil Belger and Kate Buccilli and John Cahill and Ricardo E Carrión and Stefano Damiani and Ilvana Dzafic and Bjørn H Ebdrup and Igor Izyurov and Johanna Jarcho and Raoul Jenni and Anna Jo and Sarah Kerins and Clarice Lee and Elizabeth A Martin and Rocio Mayol-Troncoso and Margaret A Niznikiewicz and Muhammad Parvaz and Oliver Pogarell and Julio Prieto-Montalvo and Rachel Rabin and David R Roalf and Jack Rogers and Dean F Salisbury and Riaz Shaik and Stewart Shankman and Michael C Stevens and Yi Nam Suen and Nicole C Swann and Xiaochen Tang and Judy L Thompson and Ivy Tso and Julian Wenzel and Juan Helen Zhou and Jean Addington and Luis Alameda and Celso Arango and Nicholas J K Breitborde and Matthew R Broome and Kristin S Cadenhead and Monica E Calkins and Rolando I Castillo-Passi and Eric Yu Hai Chen and Jimmy Choi and Philippe Conus and Cheryl M Corcoran and Barbara A Cornblatt and Covadonga M Diaz-Caneja and Lauren M Ellman and Paolo Fusar-Poli and Pablo A Gaspar and Carla Gerber and Louise Birkedal Glenthøj and Leslie E Horton and Christy Lai Ming Hui and Joseph Kambeitz and Lana Kambeitz-Ilankovic and Matcheri S Keshavan and Minah Kim and Sung-Wan Kim and Nikolaos Koutsouleris and Jun Soo Kwon and Kerstin Langbein and Daniel Mamah and Vijay A Mittal and Merete Nordentoft and Godfrey D Pearlson and Jesus Perez and Diana O Perkins and Albert R Powers and Fred W Sabb and Jason Schiffman and Jai L Shah and Steven M Silverstein and Stefan Smesny and William S Stone and Gregory P Strauss and Rachel Upthegrove and Swapna K Verma and Jijun Wang and Daniel H Wolf and Tianhong Zhang and Sylvain Bouix and Ofer Pasternak and Kang-Ik K Cho and Michael J Coleman and Dominic Dwyer and Angela Nunez and Zailyn Tamayo and Stephen J Wood and Rene S Kahn and John M Kane and Patrick D McGorry and Carrie E Bearden and Barnaby Nelson and Scott W Woods and Martha E Shenton and  and Gregory A Light},

doi = {10.1038/s41537-025-00622-0},

issn = {2754-6993},

year  = {2025},

date = {2025-06-01},

journal = {Schizophrenia (Heidelb)},

volume = {11},

number = {1},

pages = {85},

abstract = {Individuals at clinical high risk for psychosis (CHR) have variable clinical outcomes and low conversion rates, limiting development of novel and personalized treatments. Moreover, given risks of antipsychotic drugs, safer effective medications for CHR individuals are needed. The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) Program was launched to address this need. Based on past CHR and schizophrenia studies, AMP SCZ assessed electroencephalography (EEG)-based event-related potential (ERP), event-related oscillation (ERO), and resting EEG power spectral density (PSD) measures, including mismatch negativity (MMN), auditory and visual P300 to target (P3b) and novel (P3a) stimuli, 40-Hz auditory steady state response, and resting EEG PSD for traditional frequency bands (eyes open/closed). Here, in an interim analysis of AMP SCZ EEG measures, we assess test-retest reliability and stability over sessions (baseline, month-2 follow-up) in CHR (n = 654) and community control (CON; n = 87) participants. Reliability was calculated as Generalizability (G)-coefficients, and changes over session were assessed with paired t-tests. G-coefficients were generally good to excellent in both groups (CHR: mean = 0.72, range = 0.49-0.85; CON: mean = 0.71, range = 0.44-0.89). Measure magnitudes significantly (p < 0.001) decreased over session (MMN, auditory and visual target P3b, visual novel P3a, 40-Hz ASSR) and/or over runs within sessions (MMN, auditory/visual novel P3a and target P3b), consistent with habituation effects. Despite these small systematic habituation effects, test-retest reliabilities of the AMP SCZ EEG-based measures are sufficiently strong to support their use in CHR studies as potential predictors of clinical outcomes, markers of illness progression, and/or target engagement or secondary outcome measures in controlled clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39140868,

title = {Prenatal Cannabis and Tobacco Co-Exposure and Its Association with Behavioural Outcomes in Middle Childhood: Co-exposition prénatale au cannabis et au tabac et son association avec les résultats comportementaux au cours de l'enfance intermédiaire},

author = {Emma Nadler and Joanna Jacobus and Rachel A Rabin},

doi = {10.1177/07067437241271696},

issn = {1497-0015},

year  = {2025},

date = {2025-01-01},

journal = {Can J Psychiatry},

volume = {70},

number = {1},

pages = {41--53},

abstract = {OBJECTIVES: Cannabis legalization has triggered an increase in prenatal cannabis use. Given that tobacco is commonly co-used with cannabis, determining outcomes associated with prenatal cannabis and tobacco co-exposure is crucial. While literature exists regarding the individual effects of prenatal cannabis and tobacco exposure on childhood behaviour, there is a gap regarding their combined use, which may have interactive effects. Therefore, we investigated whether prenatal cannabis and tobacco co-exposure was associated with greater externalizing and internalizing problems in middle childhood compared to prenatal exposure to either substance alone or no exposure.nnMETHODS: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study (collected in children ages 9-11) were used to explore differences in externalizing and internalizing scores derived from the Childhood Behavior Checklist across four groups: children with prenatal cannabis and tobacco co-exposure (CT,  = 290), children with prenatal cannabis-only exposure (CAN,  = 225), children with prenatal tobacco-only exposure (TOB,  = 966), and unexposed children (CTL,  = 8,311). We also examined if the daily quantity of tobacco exposure modulated the effect of cannabis exposure on outcomes.nnRESULTS: Adjusting for covariates, a 2 × 2 ANCOVA revealed significant main effects for prenatal cannabis ( = 0.03) and tobacco exposure ( < 0.001), and a significant interaction effect on externalizing scores ( = 0.032); no significant main effects or interactions were found for internalizing scores. However, interactions between daily quantity of cannabis and tobacco exposure significantly predicted both externalizing and internalizing scores ( < 0.01).nnCONCLUSIONS: These findings indicate that co-exposure is associated with greater externalizing problems than exposure to either substance alone, which did not differ from each other. Further, greater tobacco exposure may amplify the negative effect of cannabis exposure on both externalizing and internalizing behaviours in children. These findings underscore the need for interventions that target cannabis and tobacco co-use in pregnant women to circumvent their adverse impact on middle childhood behaviour.nnPLAIN LANGUAGE SUMMARY TITLE: Prenatal Cannabis and Tobacco Co-exposure and its Association with Middle Childhood Behaviours.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38678736,

title = {Neuromelanin levels in individuals with substance use disorders: A systematic review and meta-analysis},

author = {Jessica Ahrens and Farida Zaher and Rachel A Rabin and Clifford M Cassidy and Lena Palaniyappan},

doi = {10.1016/j.neubiorev.2024.105690},

issn = {1873-7528},

year  = {2024},

date = {2024-06-01},

journal = {Neurosci Biobehav Rev},

volume = {161},

pages = {105690},

abstract = {Dopamine's role in addiction has been extensively studied, revealing disruptions in its functioning throughout all addiction stages. Neuromelanin in the substantia nigra (SN) may reflect dopamine auto-oxidation, and can be quantified using neuromelaninsensitive magnetic resonance imaging (neuromelanin-MRI) in a non-invasive manner.In this pre-registered systematic review, we assess the current body of evidence related to neuromelanin levels in substance use disorders, using both post-mortem and MRI examinations. The systematic search identified 10 relevant articles, primarily focusing on the substantia nigra. An early-stage meta-analysis (n = 6) revealed varied observations ranging from standardized mean differences of -3.55 to +0.62, with a pooled estimate of -0.44 (95 % CI = -1.52, 0.65), but there was insufficient power to detect differences in neuromelanin content among individuals with substance use disorders. Our gap analysis highlights the lack of sufficient replication studies, with existing studies lacking the power to detect a true difference, and a complete lack of neuromelanin studies on certain substances of clinical interest. We provide recommendations for future studies of dopaminergic neurobiology in addictions and related psychiatric comorbidities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38214479,

title = {Cannabis cravings predict cigarette use in schizophrenia: a secondary analysis from two cannabis abstinence studies},

author = {Samantha Johnstone and Maryam Sorkhou and Molly Zhang and Sarah S Dermody and Rachel A Rabin and Tony P George},

doi = {10.1080/00952990.2023.2292010},

issn = {1097-9891},

year  = {2024},

date = {2024-01-01},

journal = {Am J Drug Alcohol Abuse},

volume = {50},

number = {1},

pages = {95--105},

abstract = {Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in SchizophreniaURL: www.clinicaltrials.gov; Registration Number: NCT03189810.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37667020,

title = {Brain health in ethnically minority youth at risk for psychosis},

author = {Rachel A Rabin and Lena Palaniyappan},

doi = {10.1038/s41386-023-01719-9},

issn = {1740-634X},

year  = {2023},

date = {2023-09-01},

journal = {Neuropsychopharmacology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37689129,

title = {How do modifiable risk factors affect Alzheimer's disease pathology or mitigate its effect on clinical symptom expression?},

author = {Valentin Ourry and Alexa Pichet Binette and Frédéric St-Onge and Cherie Strikwerda-Brown and Audrey Chagnot and Judes Poirier and John Breitner and Eider M Arenaza-Urquijo and Jennifer S Rabin and Rachel Buckley and Julie Gonneaud and Natalie L Marchant and Sylvia Villeneuve},

doi = {10.1016/j.biopsych.2023.09.003},

issn = {1873-2402},

year  = {2023},

date = {2023-09-01},

journal = {Biol Psychiatry},

abstract = {Epidemiological studies show that modifiable risk factors account for about 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (sAD). Recent findings suggest that these factors might also modify disease trajectories of people with autosomal dominant Alzheimer's disease (ADAD). With positron emission tomography (PET) imaging it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former "resistance pathway" suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment. Alternatively, the "resilience pathway" suggests that modifiable risk factors might mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and might appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sAD and ADAD. We then propose mechanisms for their protective effect. Among possible mechanisms, we examine neural and vascular mechanisms for the resistance pathway. We also describe brain maintenance and functional compensation as bases for the resilience pathway. Improved mechanistic understanding of both pathways may suggest new interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36815595,

title = {Does tobacco dependence worsen cannabis withdrawal in people with and without schizophrenia-spectrum disorders?},

author = {Zac J S Yeap and Justine Marsault and Tony P George and Romina Mizrahi and Rachel A Rabin},

doi = {10.1111/ajad.13394},

issn = {1521-0391},

year  = {2023},

date = {2023-07-01},

journal = {Am J Addict},

volume = {32},

number = {4},

pages = {367--375},

abstract = {BACKGROUND AND OBJECTIVES: Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co-use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well-established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD.nnMETHOD: Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT-, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT-, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12-h of cannabis abstinence.nnRESULTS: There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002).nnCONCLUSION AND SCIENTIFIC SIGNIFICANCE: Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co-use when treating CUD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36994910,

title = {Sex differences in associations between APOE ε2 and longitudinal cognitive decline},

author = {Madeline E Wood and Lisa Y Xiong and Yuen Yan Wong and Rachel F Buckley and Walter Swardfager and Mario Masellis and Andrew S P Lim and Emma Nichols and Renaud La Joie and Kaitlin B Casaletto and Raj G Kumar and Kristen Dams-O'Connor and Priya Palta and Kristen M George and Claudia L Satizabal and Lisa L Barnes and Julie A Schneider and Alexa Pichette Binet and Sylvia Villeneuve and Judy Pa and Adam M Brickman and Sandra E Black and Jennifer S Rabin and },

doi = {10.1002/alz.13036},

issn = {1552-5279},

year  = {2023},

date = {2023-03-01},

journal = {Alzheimers Dement},

abstract = {INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples.nnMETHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.nnRESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010).nnDISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline.nnHIGHLIGHTS: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35690891,

title = {Effects of 28 days of cannabis abstinence on cognition in major depressive disorder: A pilot study},

author = {Maryam Sorkhou and Rachel A Rabin and Jennifer S Rabin and Stefan Kloiber and Roger S McIntyre and Tony P George},

doi = {10.1111/ajad.13305},

issn = {1521-0391},

year  = {2022},

date = {2022-09-01},

journal = {Am J Addict},

volume = {31},

number = {5},

pages = {454--462},

abstract = {BACKGROUND AND OBJECTIVES: Cannabis is a widely used substance that may impair select cognitive domains, including attention and memory. Problematic cannabis use is a common clinical problem among patients with major depressive disorder (MDD). Few studies have investigated the effects of cannabis abstinence on cognition in MDD. Thus, our study aimed to determine whether a 28-day period of cannabis abstinence is associated with improvements in cognition in patients with MDD and comorbid cannabis use disorder (CUD).nnMETHODS: We evaluated the effects of 28 days of cannabis abstinence on cognition in MDD patients with comorbid CUD facilitated by contingency management, motivational interviewing, psychoeducation, and coping-skills training (N = 11). Primary outcomes included Baseline to Day 28 changes in verbal memory and learning, while secondary outcomes included Baseline to Day 28 changes in working memory, visuospatial working memory (VSWM), visual search speed, mental flexibility, response inhibition, attention, manual dexterity, and fine motor movement.nnRESULTS: Eight participants (72.7%) met the pre-specified criteria for cannabis abstinence and three participants significantly reduced their cannabis use (≥90%). Visual search speed, selective attention, and VSWM improved over the study period. These improvements were not associated with changes in cannabis metabolite levels from baseline to endpoint.nnDISCUSSION AND CONCLUSIONS: Our findings suggest that 28 days of cannabis abstinence may improve select cognitive domains in patients with MDD and comorbid CUD.nnSCIENTIFIC SIGNIFICANCE: This is the first study to longitudinally examine the effects of cannabis on cognition in MDD.nnCLINICAL TRIAL: Effects of Cannabis Abstinence on Symptoms and Cognition in Depression (NCT03624933; https://www.nnCLINICALTRIALS: gov).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35395548,

title = {Dose-dependent effects of Varenicline on tobacco craving and withdrawal in tobacco smokers with and without schizophrenia},

author = {Samantha Johnstone and Maryam Sorkhou and Rachel A Rabin and Tony P George},

doi = {10.1016/j.drugalcdep.2022.109412},

issn = {1879-0046},

year  = {2022},

date = {2022-05-01},

journal = {Drug Alcohol Depend},

volume = {234},

pages = {109412},

abstract = {BACKGROUND: People with schizophrenia (SCZ) have significantly higher tobacco smoking rates and lower quit rates than the general population. Varenicline, a partial agonist at α4β2 nicotinic acetylcholine receptors (nAChRs) is an effective smoking cessation pharmacotherapy, however, investigation into its effects in SCZ are less well-studied and mechanisms may differ from non-psychiatric controls due to dysregulation in nAChR neurotransmission associated with SCZ. Here, we investigate whether Varenicline attenuates acute abstinence-induced increases in craving and withdrawal in participants with and without SCZ.nnMETHODS: Following biochemically-verified overnight abstinence and subsequent smoking reinstatement, individuals with nicotine-dependence (n = 13 SCZ or schizoaffective; n = 12 controls) were assessed on the Minnesota Nicotine Withdrawal Scale (MNWS) and Tiffany Questionnaire for Smoking Urges (TQSU). Participants were pretreated in a double-blind, counterbalanced manner with Varenicline (0, 1 or 2 mg/day x 3 days) over three separate weeks. Data were analyzed using linear mixed-effects modelling and estimated marginal means.nnRESULTS: Robust effects of smoking abstinence were observed on TQSU and MNWS scores in SCZ and control participants. Relative to 1 mg, 2 mg/day of Varenicline attenuated abstinence-induced increases in craving (TQSU Factor 1 d=-0.47, p = .006; TQSU Factor 2 d=-0.42, p = .008) and withdrawal (MNWS d=-0.35, p = .03) in both groups.nnCONCLUSION: Our preliminary findings suggest that subacute Varenicline treatment reduces abstinence-induced craving and withdrawal in participants with and without SCZ. The efficacy of Varenicline on tobacco withdrawal and craving requires further study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35077955,

title = {Structural and functional brain recovery in individuals with substance use disorders during abstinence: A review of longitudinal neuroimaging studies},

author = {Muhammad A Parvaz and Rachel A Rabin and Faith Adams and Rita Z Goldstein},

doi = {10.1016/j.drugalcdep.2022.109319},

issn = {1879-0046},

year  = {2022},

date = {2022-03-01},

journal = {Drug Alcohol Depend},

volume = {232},

pages = {109319},

abstract = {BACKGROUND: Neuroimaging studies reveal structural and functional including neurochemical brain abnormalities in individuals with substance use disorders compared to healthy controls. However, whether and to what extent such dysfunction is reversible with abstinence remains unclear, and a review of studies with longitudinal within-subject designs is lacking. We performed a systematic review of longitudinal neuroimaging studies to explore putative brain changes associated with abstinence in treatment-seeking individuals with substance use disorders.nnMETHODS: Following PRISMA guidelines, we examined articles published up to May 2021 that employed a neuroimaging technique and assessed neurobiological recovery in treatment-seeking participants at a minimum of two time-points separated by a period of abstinence (longer than 24 h apart) or significant reduction in drug use.nnRESULTS: Forty-five studies met inclusion criteria. Encouragingly, in this limited but growing literature, the majority of studies demonstrated at least partial neurobiological recovery with abstinence. Structural recovery appeared to occur predominantly in frontal cortical regions, the insula, hippocampus, and cerebellum. Functional and neurochemical recovery was similarly observed in prefrontal cortical regions but also in subcortical structures. The onset of structural recovery appears to precede neurochemical recovery, which begins soon after cessation (particularly for alcohol); functional recovery may require longer periods of abstinence.nnCONCLUSIONS: The literature is still growing and more studies are warranted to better understand abstinence-mediated neural recovery in individuals with substance use disorders. Elucidating the temporal dynamics between neuronal recovery and abstinence will enable evidence-based planning for more effective and targeted treatment of substance use disorders, potentially pre-empting relapse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35210458,

title = {Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia},

author = {Karolina Kozak Bidzinski and Darby J E Lowe and Marcos Sanches and Maryam Sorkhou and Isabelle Boileau and Michael Kiang and Daniel M Blumberger and Gary Remington and Clement Ma and David J Castle and Rachel A Rabin and Tony P George},

doi = {10.1038/s41537-022-00210-6},

issn = {2754-6993},

year  = {2022},

date = {2022-02-01},

journal = {Schizophrenia (Heidelb)},

volume = {8},

number = {1},

pages = {2},

abstract = {Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen's d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34280058,

title = {A systematic review and meta-analysis of sex differences in cannabis use disorder amongst people with comorbid mental illness},

author = {Karolina Kozak and Philip H Smith and Darby J E Lowe and Andrea H Weinberger and Ziva D Cooper and Rachel A Rabin and Tony P George},

doi = {10.1080/00952990.2021.1946071},

issn = {1097-9891},

year  = {2021},

date = {2021-09-01},

journal = {Am J Drug Alcohol Abuse},

volume = {47},

number = {5},

pages = {535--547},

abstract = {BACKGROUND: While males are more likely diagnosed with cannabis use disorder (CUD), females are more susceptible to developing and maintaining CUD. Yet, for both sexes, CUD is associated with high rates of comorbid mental illness (MI).nnOBJECTIVES: To identify and compare sex differences in the prevalence of comorbid CUD amongst individuals with/without MIs.nnMETHODS: This systematic review generated pooled odds ratios (OR) and 95% confidence intervals (CI) from 37 studies (including clinical trials, cohort, and case-control studies) among individuals with and without MIs, quantifying sex differences in rates of comorbid CUD. A meta-analysis was also completed.nnRESULTS: In the CUD-only group, males were twice as likely to have CUD than females (OR = 2.0, CI = 1.9-2.1). Among MIs, males were more likely than females to have CUD comorbid with schizophrenia (OR ~2.6, CI = 2.5-2.7) and other psychotic, mood, and substance use disorders (1> OR <2.2, CI = 0.7-2.6). The reverse association (females > males) was observed for anxiety disorders and antisocial personality disorder (OR = 0.8, CI = 0.7-1.0). Among females, MIs increased the likelihood of having CUD, except for psychotic disorders and depression. A meta-analysis was inconclusive due to high heterogeneity across studies. Thus, comparisons across MI groups were not possible.nnCONCLUSION: While males are more likely to be diagnosed with CUD, there are important sex differences in the prevalence of CUD across MI diagnoses that should be taken into account when approaching CUD prevention and determining treatment efficacy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}