Time to acknowledge the mixed effects of cannabis on health: a summary and critical review of the NASEM 2017 report on the health effects of cannabis and cannabinoids

This is a summary and critical review of the National Academies of Sciences, Engineering and Medicine (NASEM) report of the health effects of cannabis. The report stated that effects of cannabis are understudied, and research findings are mixed. It concluded that the under‐developed evidence base poses a public health risk and rightly addressed complexities of cannabis research that need to be resolved collaboratively. We support NASEM's urgent call for research, but add that the mixed evidence base cannot be attributed solely to research limitations. Rather, we propose a need to acknowledge the heterogeneity in the effects of cannabis to advance the field

Unique Aspects of Impulsive Traits in Substance Use and Overeating: Specific Contributions of Common Assessments of Impulsivity

Part of this work was supported by grants from NIDA for marijuana studies (K01 DA021632-01A1 to FMF) and The Mind Research Network for control, nicotine, and obesity studies (Institutional Grant to FMF). FMF and DB are currently supported by NIDA (R01 DA030344-01 and F31 DA035039-01A1, respectively). DB and HA createdRunning Head: UNIQUE IMPULSE IN SUBSTANCE USE AND OVEREATING 2 some of the open source software used for analysis in this manuscript (TExPosition and TInPosition). The authors have no other declarations of interest. The American Journal of Drug and Alcohol Abus

Determining Risks for Cannabis Use Disorder in the Face of Changing Legal Policies

Purpose of Review: This review aims to summarize and critically evaluate the current literature on the associations between individual and socio-cultural factors that increase risk for cannabis use disorder (CUD), and policy change. Recent findings: Epidemiological studies show that areas with permissive legal cannabis climates are associated with greater individual risk factors for CUD. This includes (1) higher rates of edible consumption and vaping, (2) higher delta-9-tetrahydrocannabinol (THC) potency and lower cannabidiol (CBD) levels, and (3) younger age of initiation of use. Summary: A change in the socio-cultural level, such as shifts in the legalization of cannabis, could interact with individual-level factors in their associations with CUD. There is currently a lack of empirical studies that evaluate this interaction. We propose that future research consider a bioecological framework for CUD to allow for a comprehensive understanding of the effects of legal climate that could inform policy and clinical practice

Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

Mediators and modulators of immunity to helminths

Parasitic helminths infect millions of people and animals worldwide. A key feature of their lifecycle is the longevity of survival within a single host, which is often attributed to the ability of the parasite to divert or modulate the immune response against it. The excretory-secretory (ES) products released by helminths are of interest as the mediators of such immunomodulation. Heligmosomoides polygyrus is an excellent model of gastrointestinal (GI) helminth infection in rodents, and has been used here to investigate several aspects of the immune response, and the manipulation of these, in mice. Firstly, the roles of B cells and antibodies in infection with H. polygyrus and towards the adult ES (HES) were investigated. Using several B cell-deficient mouse strains, a minimal effect on immunity to primary infection with H. polygyrus was demonstrated. However, primary infection serum binds to a select set of highly immunodominant components of the complex protein mixture of HES, which were identified as venom allergen-like proteins (VALs). Utilising four strains of mice that vary in their resistance phenotype to H. polygyrus, several aspects of immunity towards the worm were investigated. Increased levels of markers of alternatively activated macrophages, which are a key component of the granulomatous inflammatory response around invading H. polygyrus larvae, were found in the most resistant strains, SJL and BALB/c. Depletion of macrophages, by administration of clodronate, severely disrupted the granuloma and parasite clearance. Numbers of innate lymphoid cells and the subsequent Th2 response, specificity range and titre of antibody, and activation of regulatory T cells all correlate with a resistant phenotype. A deficiency in the cytokine macrophage migration inhibitory factor (MIF) renders a resistant BALB/c mouse completely susceptible to infections with H. polygyrus, and Nippostronygylus brasiliensis, an acute model of GI helminth infection. This is accompanied by a failure to induce both ILCs and an early myeloid-derived cell population upon infection. The influx of alternatively activated macrophages around larvae in the mucosa of the small intestine is delayed in MIF-/- mice, although all immunological parameters are comparable to wild-type by day 14 post-infection. The susceptible phenotype of MIF-/- mice can be replicated using a chemical inhibitor of MIF in BALB/c mice. Finally, the previously documented transforming growth factor-β (TGF-β) activity of HES was dissected out further using two methods of fractionation. Distinct fractions with TGF-β activity were subjected to mass spectrometry to identify protein components that could be potential candidates for this activity

Discriminability of personality profiles in isolated and Co-morbid marijuana and nicotine users

AbstractSpecific personality traits have been linked with substance use disorders (SUDs), genetic mechanisms, and brain systems. Thus, determining the specificity of personality traits to types of SUD can advance the field towards defining SUD endophenotypes as well as understanding the brain systems involved for the development of novel treatments. Disentangling these factors is particularly important in highly co morbid SUDs, such as marijuana and nicotine use, so treatment can occur effectively for both. This study evaluated personality traits that distinguish isolated and co-morbid use of marijuana and nicotine. To that end, we collected the NEO Five Factor Inventory in participants who used marijuana-only (n=59), nicotine-only (n=27), both marijuana and nicotine (n=28), and in non-using controls (n=28). We used factor analyses to identify personality profiles, which are linear combinations of the five NEO Factors. We then conducted Receiver Operating Characteristics (ROC) curve analysis to test accuracy of the personality factors in discriminating isolated and co-morbid marijuana and nicotine users from each other. ROC curve analysis distinguished the four groups based on their NEO personality patterns. Results showed that NEO Factor 2 (openness, extraversion, agreeableness) discriminated marijuana and marijuana+nicotine users from controls and nicotine-only users with high predictability. Additional ANOVA results showed that the openness dimension discriminated marijuana users from nicotine users. These findings suggest that personality dimensions distinguish marijuana users from nicotine users and should be considered in prevention strategies

Gender differences in cannabis use disorder symptoms:A network analysis

BACKGROUND: While cannabis use in women is increasing worldwide, research into gender differences in cannabis use disorder (CUD) symptomology is lacking. In response to limited effectiveness of addiction treatment, research focus has been shifting from clinical diagnoses towards interactions between symptoms, as patterns of symptoms and their interactions could be crucial in understanding etiological mechanisms in addiction. The aim of this study was to evaluate the CUD symptom network and assess whether there are gender differences therein. METHODS: A total of 1257 Dutch individuals reporting weekly cannabis use, including 745 men and 512 women, completed online questionnaires assessing DSM-5 CUD symptoms and additional items on plans to quit or reduce use, cigarette use, and the presence of psychological diagnoses. Gender differences were assessed for all variables and an Ising model estimation method was used to estimate CUD symptom networks in men and women using network comparison tests to assess differences. RESULTS: There were gender differences in the prevalence of 6 of the 11 symptoms, but symptom networks did not differ between men and women. Cigarette use appeared to only be connected to the network through withdrawal, indicating a potential role of cigarette smoking in enhancing cannabis withdrawal symptoms. Furthermore, there were gender differences in the network associations of mood and anxiety disorders with CUD symptoms. CONCLUSION: The association between smoking and withdrawal as well as gender differences in the role of comorbidities in the CUD network highlight the value of using network models to understand CUD and how symptom interactions might affect treatment

Editorial: Recent advances in the immunology of helminth infection – protection, pathogenesis and panaceas

[Extract] Helminths (parasitic worms) are a diverse group of organisms that utilize a wide range of species as their intermediate and definitive hosts. The nematodes consist of the whipworms, roundworms, hookworms and filarial worms, and these sit alongside the platyhelminth flatworms (or blood flukes) and tapeworms - all of which have species that cause serious disease in humans. Some species have free living stages, others rely on insect vectors for transmission, while some can reproduce to release live larval stages within their mammalian host. The diversity of infection route, larval migration within the host and the location of the adult parasite have major implications for the pathology and immune responses elicited by each species. Here, we briefly outline the contributions to the Research Topic Recent Advances in the Immunology of Helminth Infection – Protection, Pathogenesis and Panaceas