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Introduction Varying public views on cannabis use across countries may explain the variation in the prevalence of use, policies, and research in individual countries, and global regulation of cannabis. This paper aims to describe the current state of cannabis use, policies, and research across sixteen countries. Methods PubMed and Google Scholar were searched for studies published from 2010 to 2020. Searches were conducted using the relevant country of interest as a search term (e.g., “Iran”), as well as relevant predefined keywords such as “cannabis,” “marijuana,” “hashish,” “bhang “dual diagnosis,” “use,” “addiction,” “prevalence,” “co-morbidity,” “substance use disorder,” “legalization” or “policy” (in English and non-English languages). These keywords were used in multiple combinations to create the search string for studies’ titles and abstracts. Official websites of respective governments and international organizations were also searched in English and non-English languages (using countries national languages) to identify the current state of cannabis use, policies, and research in each of those countries. Results The main findings were inconsistent and heterogeneous reporting of cannabis use, variation in policies (e.g., legalization), and variation in intervention strategies across the countries reviewed. European countries dominate the cannabis research output indexed on PubMed, in contrast to Asian countries (Thailand, Malaysia, India, Iran, and Nepal). Conclusions Although global cannabis regulation is ongoing, the existing heterogeneities across countries in terms of policies and epidemiology can increase the burden of cannabis use disorders disproportionately and unpredictably. There is an urgent need to develop global strategies to address these cross-country barriers to improve early detection, prevention, and interventions for cannabis use and related disorders.

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Globally, there are concerns about access to healthcare and harm reduction services for people who use drugs (PWUD) during the coronavirus disease 2019 (COVID-19) pandemic. Members from the Network of Early Career Professionals working in Addiction Medicine shared their experiences of providing treatment to PWUD during the COVID-19 pandemic. Drawing on these qualitative reports, we highlight the similarities and discrepancies in access to services for PWUD in 16 countries under COVID-10 restrictions. In most countries reported here, efforts have been made to ensure continued access to services, such as mobilising opioid agonist maintenance treatment and other essential medicines to patients. However, due to travel restrictions and limited telemedicine services, several Network of Early Career Professionals working in Addiction Medicine members from lower-resourced countries experienced challenges with providing care to their patients during periods of COVID-19 lock-down. The insights provided in this commentary illustrate how the COVID-19 lock-down restrictions have impacted access to services for PWUD.

Substance use disorders (SUDs) are associated with impairments of cognitive functions, and cognitive training programs are thus rapidly developing in SUD treatment. However, neuropsychological impairments observed early after withdrawal (i.e., early impairments), that is, approximately in the first six months, may be widespread. Consequently, it might not be possible to train all the identified early impairments. In these situations, we propose that the priority of cognitive training should be given to the early impairments found to be associated with early dropout or relapse (i.e., relapse-related impairments). However, substance-specific relapse-related impairments have not been singled out among all early impairments so far. Using a systematic literature search, we identified the types of established early impairments for all SUDs, and we assessed the extent to which these early impairments were found to be associated with relapse-related impairments. All cognitive functions were investigated according to a classification based on current neuropsychological models, distinguishing classical cognitive, substance-bias, and social cognition systems. According to the current evidence, demonstrated relapse-related impairments in alcohol use disorder comprised impulsivity, long-term memory, and higher-order executive functions. For cannabis use disorder, the identified relapse-related impairments were impulsivity and working memory. For stimulant use disorder, the identified relapse-related impairments were attentional abilities and higher-order executive functions. For opioid use disorder, the only identified relapse-related impairments were higher executive functions. However, many early impairments were not explored with respect to dropout/relapse, particularly for stimulant and opioid use disorders. The current literature reveals substance-specific relapse-related impairments, which supports a pragmatic patient-tailored approach for defining which early impairments should be prioritized in terms of training among patients with SUDs.

Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress dramatically enhanced the skin delayed-type hypersensitivity reaction to haptens, which is mediated by CD8+ CTLs. This effect was due to increased migration of skin DCs, resulting in augmented CD8+ T cell priming in draining lymph nodes and enhanced recruitment of CD8+ T cell effectors in the skin upon challenge. This adjuvant effect of stress was mediated by norepinephrine (NE), but not corticosteroids, as demonstrated by normalization of the skin delayed-type hypersensitivity reaction and DC migratory properties following selective depletion of NE. These results suggest that release of NE by sympathetic nerve termini during a psychological stress exerts an adjuvant effect on DC by promoting enhanced migration to lymph nodes, resulting in increased Ag-specific T cell responses. Our findings may open new ways in the treatment of inflammatory diseases, e.g., psoriasis, allergic contact dermatitis, and atopic dermatitis.

Contact sensitivity (CS) is a form of delayed-type hypersensitivity to haptens applied epicutaneously and is thought to be mediated, like classical delayed-type hypersensitivity responses, by CD4+ T helper-1 cells. The aim of this study was to identify the effector T cells involved in CS. We studied CS to the strongly sensitizing hapten dinitrofluorobenzene (DNFB) in mice rendered deficient by homologous recombination in either major histocompatibility complex (MHC) class I, MHC class II, or both, and which exhibited deficiencies in, respectively, CD8+, CD4+, or both, T cells. MHC class I single-deficient and MHC class I/class II double-deficient mice, both of which have a drastic reduction in the number of CD8+ T cells, were unable to mount a CS response to DNFB. In contrast, both MHC class II-deficient mice and normal mice treated with an anti-CD4 monoclonal antibody (mAb) developed exaggerated and persistent responses relative to heterozygous control littermates. Furthermore, anti-CD8 mAb depletion of class II-deficient mice totally abolished their ability to mount an inflammatory response to DNFB. Removal of residual CD4+ T cells in class II-deficient mice by anti-CD4 mAb treatment did not diminish the intensity of CS. These data clearly demonstrate that class I-restricted CD8+ T cells are sufficient for the induction of CS to DNFB, and further support the idea that MHC class II-restricted CD4+ T cells down-regulate this inflammatory response.

The mechanisms underlying the induction of immunological tolerance after feeding soluble exogenous antigens, including proteins and haptens, are still unclear. Using a model of oral tolerance to the contact-sensitizing hapten 2,4-dinitrochlorobenzene (DNCB), we have compared the ability-of intestinal epithelial cells and of Peyer's patch APC to present DNCB in vitro or ex vivo after oral feeding, to specific peripheral lymph node T cells from DNCB-sensitized mice. In contrast to Peyer's patch APC, which induce efficient hapten-specific T cell activation upon exposure to the hapten either in vitro or in vivo, mature MHC class-II-positive intestinal epithelial cells were unable to induce T cell activation in either case. Interestingly, enterocytes from DNCB-fed mice exerted a dramatic inhibitory effect on the proliferative response of hapten-primed T cells in response to dinitrobenzene sulfonate presented by syngeneic spleen cells. This inhibitory effect, which was also observed with supernatant of intestinal epithelial cells from DNCB-fed mice, could be reversed by neutralizing anti-transforming growth factor (TGF)-beta antibodies. In addition, pre-incubation of hapten-sensitized T cells with enterocytes from DNCB-fed mice induced T cell anergy, which could be reversed by exogenous interleukin-2 or interleukin-4. These data demonstrate that intestinal epithelial cells activated in vivo by oral administration of DNCB are able to block proliferation of activated T cells through secretion of immunosuppressive cytokines such as TGF-beta. It is proposed that intestinal epithelial cells may play a significant role in oral tolerance by limiting T cell-mediated hypersensitivity responses.

Les pemphigus sont des maladies auto-immunes des desmosomes (jonctions entre les keratinocytes de l'epiderme). La perte de l'adherence entre keratinocytes entraine la formation de bulles cutanees intra-epidermiques. La connaissance des auto-antigenes du desmosome a permis une meilleure classification nosologique des pemphigus. Les bulles cutanees sont profondes dans le pemphigus vulgaire ou l'antigene desmosomial est la desmogleine 3, superficielles dans le pemphigus superficiel ou l'auto-antigene est la desmogleine 1. Deux nouvelles entites ont ete recemment decrites : les pemphigus, ou pustuloses intra-epidermiques, a IgA, ou les auto-antigenes sont les desmocollines, et les pemphigus paraneoplasiques dans lesquels les auto-antigenes sont multiples (desmoplakines, antigene de la pemphigoide bulleuse...). Une association forte avec certains haplotypes (HLA-DR4 et HLA-DR6) suggere que chez des sujets predisposes exposes a certains antigenes de l'environnement, il y aurait production d'anticorps capables de reactions croisees avec des proteines desmosomiales.

We read the article by Pang et al 1 concerning the use of frog skin for the differentiation of bullous pemphigoid (BP) from epidermolysis bullosa acquisita (EBA). Based on sporadic observations of a floor-pattern indirect immunofluorescence on 1 mol/L of sodium chloride—split skin (SSS) obtained from BP sera, these authors used skin from a toad to establish a differential diagnosis between BP and EBA. Their rationale was the fact that, as suggested by earlier studies, the BP antigen is present in the skin of some animals, 2 from which the EBA antigen—being phylogenetically more restricted—is absent. 3 Since this procedure seems attractive, we undertook a retrospective comparative study to better delineate the usefulness of animal skin substrates for the diagnosis, using indirect immunofluorescence, of subepidermal autoimmune bullous diseases. During the last 3 years, we screened over 1500 human serum samples sent to us under the suspicion of a subepidermal autoimmune

La jonction dermo-epidermique et les desmosomes cooperent pour assurer la resistance de la peau, la premiere en ancrant solidement l'epiderme au derme et les seconds en liant les keratinocytes entre eux. Or, les desmosomes et des constituants de la jonction dermo-epidermique (les hemidesmosomes et les fibrilles d'ancrage) sont fortement antigeniques et deviennent la cible d'auto-anticorps dans les trois principales dermatoses auto-immunes bulleuses: les pemphigus, la pemphigoide bulleuse et l'epidermolyse bulleuse acquise. Les antigenes reconnus par les autoanticorps de la pemphigoide bulleuse et de l'epidermolyse bulleuse acquise sont maintenant bien caracterises et leurs genes sont clones