Co-exposure of cannabinoids with amphetamines and biological, behavioural and health outcomes: a scoping review of animal and human studies.

RATIONALE: The growing prevalence of psychostimulant (including amphetamine) use and associated health harms, with limited treatment options, present a global challenge. There is an increasing availability and medical applications of cannabinoids, and growing interest in their therapeutic potential for addictive disorders. OBJECTIVES: The objective of this study is to review available data regarding cannabis/cannabinoid co-use or exposure on amphetamine-related outcomes. METHODS: Towards the present scoping review, we systematically searched four databases (Medline, Web-of-Science, CINAHL Plus and PsycInfo) using cannabis/cannabinoid and amphetamine text-terms identifying peer-reviewed, English-language studies published in 2000-2020 involving multiple methods approaches among both human and animal study samples, assessing the association of co-use/administration of cannabis/cannabinoids products with non-medical amphetamines on biological, behavioural or health outcomes. RESULTS: Twenty-five articles were included. Pre-clinical studies (n = 15) found mostly protective effects of single or repeated cannabinoids administration on rodents in amphetamine addiction models, amphetamine-induced models of human mental disorders (e.g. schizophrenia) and amphetamine-induced neurotoxicity. Human studies (n = 10) were more heterogeneously designed (e.g. cross-sectional, case-control, longitudinal) and assessed natural ongoing cannabis and methamphetamine use or dependence, showing mostly enhanced harms in a diversity of outcomes (e.g. mental health, methamphetamine use, cognition). CONCLUSIONS: While human studies suggest cannabis use as an adverse risk factor among non-medical amphetamine users, pre-clinical studies suggest therapeutic potential of cannabinoids, especially cannabidiol, to alleviate amphetamine addiction and harms, including treatment outcomes. Given increasing psychostimulant harms but lack of care options, rigorous, high-quality design studies should aim to translate and investigate pre-clinical study results for potential therapeutic benefits of cannabinoids for amphetamine use/abuse in human subjects.

Nitrogen leaching and Tifway bermudagrass response to simultaneous nutrient and pre-emergence herbicide applications.

Pre-emergence (PRE) herbicides are commonly applied simultaneously with fertilizers to turfgrass; however, the influence of PRE herbicides on nitrogen (N) uptake and leaching from turfgrass remains unclear. The hypothesis of this study was that PRE herbicides applied simultaneously with N fertilizers increase N leaching from Tifway 419 bermudagrass [Cynodon dactylon (L.) Pers. × C. transvaalensis Burtt-Davy, 'Tifway'] above that from fallow soil. A nutrient leaching study was conducted from June 2017 through June 2019 in Fort Lauderdale, FL. Treatments consisted of indaziflam (25 g a.i. ha-1 ), prodiamine (540 g a.i. ha-1 ), and oxadiazon (4,480 g a.i. ha-1 ); a nontreated turfgrass control (turfgrass fertilized but not treated with PRE herbicides); and a fallow soil. Fertilizer (15-2-12) was applied every 60 d at 49 kg N ha-1 , and PRE herbicides were applied every 120 d. Pre-emergence herbicides resulted in a 3.6- and 5.5-fold increases in NO3 -N concentration compared with fallow soil during June 2017 and January 2018, respectively, whereas fallow soil resulted in increased NO3 -N concentration during 10 mo and ranged from 3.8- to 15-fold greater than that from turfgrass plots. Turfgrass plots resulted in reduced N leaching of ∼7% during 5 mo compared with fallow soil and did not result in increased N leaching during any month. Cumulative N leached from turfgrass plots ranged from 75 to 120 kg ha-1 and did not differ from fallow soil. Turfgrass growth rate and N uptake were not influenced by PRE herbicide. The results indicated that fertilizers applied with PRE herbicides does not result in increased N leaching or reduced N uptake.

Co-exposure of cocaine and cannabinoids and its association with select biological, behavioural and health outcomes: A systematic scoping review of multi-disciplinary studies.

Cocaine use entails severe health- and social-related harms globally. Treatment options for cocaine dependence are highly limited. Benefits of cannabinoids for addiction have been documented, making it opportune to examine existing data on the possible outcomes associated with cannabinoids and cocaine co-use. We conducted a systematic scoping review following the PRISMA guidelines of peer-reviewed, English-language studies published from 2000 to 2021 in four databases (Medline, Web-of-Science, CINAHL Plus, and PsycInfo), assessing the co-exposure of cannabis/cannabinoids with cocaine on behavioural, biological or health outcomes. Both quantitative and qualitative, as well as humans and pre-clinical animals' studies (n=46) were included. Pre-clinical studies (n=19) showed mostly protective effects of cannabidiol (CBD) administration on animal models of addiction (e.g., cocaine-craving, -relapse, and -withdrawal) and cocaine-toxicity. Tetrahydrocannabinol (THC) had more inconsistent results, with both protective and counter-protective effects. Human studies (n=27) were more heterogeneous and assessed natural ongoing cannabis and cocaine use or dependence. Quantitative-based studies showed mostly enhanced harms in several outcomes (e.g., cocaine use, mental health); two available clinical trials found no effect upon CBD administration on cocaine-related treatment outcomes. Qualitative data-based studies reported cannabis use as a substitute for or to alleviate harms of crack-cocaine use. While pre-clinical studies suggest a potential of cannabinoids, especially CBD, to treat cocaine addiction, the few trials conducted in humans found no benefits. Cannabis co-use by cocaine users commonly presents a risk factor, entailing enhanced harms for users. More rigorous, controlled trials are still necessary to investigate cannabinoids' potential considering pre-clinical findings and reported benefits from specific drug users.

Opioid use, regulation, and harms in Brazil: a comprehensive narrative overview of available data and indicators.

BACKGROUND: Global opioid consumption increased multifold post-2000, disproportionately in high-income countries, with severe mortality/morbidity consequences. Latin America features comparatively low opioid availability; Brazil, the region's most populous country, makes an interesting case study concerning opioid use/harms. In this comprehensive overview, we aimed to identify and summarize medical and non-medical data and indicators of opioid availability and use, regulation/control, and harm outcomes in Brazil since 2000. METHODS: We searched multiple scientific databases to identify relevant publications and conducted additional 'grey' literature searches to identify other pertinent information. RESULTS: Despite some essential indicators, opioid-related data are limited for Brazil. Data indicate that population-level availability of prescription opioids represents only a small fraction of use in comparison to high-income countries. However, within Latin America, Brazil ranks mid-level for opioid consumption, indicating relatively moderate consumption compared to neighboring jurisdictions. Brazil has implemented restrictive regulations to opioid prescribing and is considered 'highly restricted' for opioid access. Codeine remains the major opioid analgesic utilized, but stronger opioids such as oxycodone are becoming more common. Professional knowledge regarding medical opioid use and effects appears limited. National surveys indicate increases in non-medical use of prescription opioids, albeit lower than observed in North America, while illicit opioids (e.g., heroin) are highly uncommon. CONCLUSIONS: Overall population-level opioid availability and corresponding levels of opioid-related harms in Brazil remain substantially lower than rates reported for North America. However, the available surveillance and analytical data on opioid use, policy/practice, and harms in Brazil are limited and insufficient. Since existing and acute (e.g., pain-related) needs for improved opioid utilization and practice appear to be substantiated, improved indicators for and understanding of opioid use, practice, and harms in Brazil are required.

The association of psychiatric symptomatology with patterns of alcohol, tobacco, and marijuana use among Brazilian high school students.

BACKGROUND AND OBJECTIVES: Studies have highlighted psychosocial factors associated with drug use among adolescents. Association of specific psychiatric comorbidity with substance use has not been properly established in Brazil. This study aimed to investigate alcohol, tobacco, and marijuana use by 15-18-year-old high school Brazilian students and to estimate associations with psychiatric symptoms. METHODS: A cross-sectional survey of 4,034 students from 128 public and private schools in São Paulo State was carried out using a two-step probability sample. Data were collected through self-report standardized questionnaires including questions on substance use patterns and the Strengths and Difficulties Questionnaire (SDQ). Key outcome variables were past-month use and past-month frequent use of alcohol, tobacco and marijuana. Questionnaires with missing information were excluded, resulting in a final sample of 2,532 adolescents. Weighted data was analyzed through logistic regressions, adjusted by gender and by socio-economic status (SES). RESULTS: Regarding SDQ total score, 43.6% of students had no psychiatric symptoms, 7.9% had subclinical symptoms and 48.5% presented clinically significant symptoms. Respondents with a clinically significant SDQ score were more likely to be past month alcohol (aOR = 1.51; 95%CI 1.22-1.88), tobacco (aOR = 1.82; 95%CI 1.25-2.66), and marijuana (aOR = 1.79; 95%CI 1.21-2.64) users as compared to those with no symptomatology. DISCUSSION AND CONCLUSIONS: Psychopathological symptoms were associated with alcohol, tobacco and marijuana use by 15-18-year-old adolescents. These associations should also be considered when planning public policies of mental health promotion. SCIENTIFIC SIGNIFICANCE: This study discusses the importance of the association between psychopathological symptoms and substance use in a middle-income country, with high level of social inequalities, in a state representative sample. (Am J Addict 2016;25:416-425).

Association of methamidophos and sleep loss on reproductive toxicity of male mice.

This study investigated the effects of organophosphate exposure on the male reproductive system of mice submitted to chronic sleep loss condition. Adult Swiss mice were distributed into 4 groups: control; methamidophos (MTP); sleep restriction (SR); and MTP+SR. The dose of methamidophos was 0.002 mgkg(-1)day(-1) (half of the Acceptable Daily Intake). Sleep restriction condition was 21 h day(-1) during 15 days. In relation to control group, MTP treatment induced a significant reduction of 12% on morphologically normal spermatozoa in both MTP and MTP+SR groups. In addition, the absolute and relative weights of the seminal vesicles were decreased (MTP, -34%; MTP+SR, -45%). Epididymal fat was reduced in SR groups (SR, -64%; MTP+SR, -58%). Plasma testosterone levels were significantly decreased in MTP and SR groups, and progesterone levels were increased 8 times in MTP+SR in comparison with the control group. The corticosterone levels were unaffected by MTP or SR conditions. Thus, low dose MTP exposure resulted in deleterious effects on the male reproductive system. Sleep loss associated with MTP potentiated the effect on steroidogenesis, mainly in terms of progesterone levels.

Neurobiologia da Cannabis: do sistema endocanabinoide aos transtornos por uso de Cannabis / Neurobiology of Cannabis: from the endocannabinoid system to cannabis-related disorders

OBJETIVOS: Diante das lacunas na efetividade das terapêuticas para transtornos por uso de Cannabis, a droga ilícita mais consumida no mundo, este trabalho propõe-se a rever os conhecimentos sobre o substrato neuroanatômico, biomolecular e celular do sistema endocanabinoide, descrever os mecanismos de neuroplasticidade dependente dos canabinoides e relacioná-los com a neurobiologia dos transtornos por uso de Cannabis (abuso e dependência). MÉTODOS: Recorreu-se às bases de dados Medline, Scopus e ISI Web of Knowledge; as palavras-chave pesquisadas foram "Cannabis", "neurobiology", "endocannabinoid system", "endocannabinoids", "receptors, cannabinoid", "neuronal plasticity", "long-term synaptic depression", "long-term potentiation", "marijuana abuse" e "tetrahydrocannabinol". Foram incluídos 80 trabalhos nesta revisão. DISCUSSÃO: A distribuição neuroanatômica, celular e biomolecular do sistema endocanabinoide adequa-se perfeitamente às suas funções de neuromodulação (via neuroplasticidade e metaplasticidade), nomeadamente em vias relacionadas aos transtornos por uso de substâncias. Os canabinoides exógenos perturbam essas funções. CONCLUSÃO: O sistema endocanabinoide contribui para a definição de setpoints em diversas vias neuronais, incluindo vias cruciais na instalação de transtornos por uso de substâncias; com o uso de Cannabis, esses setpoints tornar-se-ão mais permissivos, facilitando os transtornos por uso de Cannabis. Os avanços no entendimento da neurobiologia da Cannabis abrem uma janela de oportunidades para novas estratégias terapêuticas nos transtornos por uso de Cannabis.

OBJECTIVES: Given the challenges arising from the poor effectiveness of therapies for Cannabis-related disorders, the most commonly used illicit drug in the world, this paper aims to review the present knowledge about the neuroanatomic, biomolecular and cellular substrate of the endocannabinoid system, describing the mechanisms of cannabinoid-dependent neuronal plasticity and relating them with the neurobiology of Cannabis-related disorders (abuse and dependence). METHODS: Medline, Scopus and ISI Web of Knowledge were searched for the keywords "Cannabis", "neurobiology", "endocannabinoid system", "endocannabinoids", "receptors, cannabinoid", "neuronal plasticity", "long-term synaptic depression", "long-term potentiation", "marijuana abuse" and "tetrahydrocannabinol". Eighty studies were included in this review. DISCUSSION: The neuroanatomical, cellular and biomolecular characterization of the endocannabinoid system serves perfectly its neuromodulatory neuroplastic and metaplastic functions, particularly in pathways related to substance-related disorders. Exogenous cannabinoids disrupt these functions. CONCLUSION: The endocannabinoid system contributes to the definition of setpoints in several neuronal pathways, including pathways critical for the development of substance-related disorders; with Cannabis use these setpoints become more permissive, facilitating Cannabis-related disorders. The advances in understanding the neurobiology of Cannabis open a window of opportunities for new therapeutic strategies in Cannabis-related disorders.