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1.
J Environ Sci (China) ; 85: 82-93, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471034

RESUMO

Cannabis is increasingly used for both medicinal and recreational purposes with an estimate of over 180 million users annually. Canada has recently legalized cannabis use in October 2018, joining several states in the United States of America (e.g., Colorado, California, and Oregon) and a few other countries. A variety of cannabis products including dry flowers, edibles, and oil products are widely consumed. With high demand for cannabis products worldwide, the quality of cannabis and its related products has become a major concern for consumer safety. Various guidelines have been set by different countries to ensure the quality, safety, and efficacy of cannabis products. In general, these guidelines require control of contaminants including pesticides, toxic elements, mycotoxins, and pathogens, as well as residual solvents in regard to cannabis oil. Accordingly, appropriate analytical methods are required to determine these contaminants in cannabis products for quality control. In this review, we focus on the current analytical challenges and method development for detection of pesticides and toxic elements in cannabis to meet various guidelines.


Assuntos
Cannabis/química , Poluentes Ambientais/análise , Praguicidas/análise , Oligoelementos/análise , Estados Unidos
4.
Adv Exp Med Biol ; 1162: 1-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31332731

RESUMO

Marijuana/cannabinoid research has been transformed into mainstream science during the last half-century. Evidence based research and remarkable biotechnological advances demonstrate that phytocannabinoids and endocannabinoid (eCBs) acting on cannabinoid receptors (CBRs) regulate various aspects of human physiological, behavioral, immunological and metabolic functions. The distribution and function of the components of the endocannabinoid system (ECS) in the central nervous system (CNS) and immune processes have garnished significant research focus with major milestones. With these advances in biotechnology, rapid extension of the ECS research in the periphery has gained momentum. In this chapter, we review the components and tissue distribution of this previously unknown but ubiquitous and complex ECS that is involved in almost all aspects of mammalian physiology and pathology.


Assuntos
Canabinoides/farmacologia , Endocanabinoides/fisiologia , Receptores de Canabinoides/fisiologia , Animais , Cannabis/química , Humanos , Distribuição Tecidual
5.
Adv Exp Med Biol ; 1162: 151-165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31332738

RESUMO

The Cannabis plant has been used for many of years as a medicinal agent in the relief of pain and seizures. It contains approximately 540 natural compounds including more than 100 that have been identified as phytocannabinoids due to their shared chemical structure. The predominant psychotropic component is Δ9-tetrahydrocannabinol (Δ9-THC), while the major non-psychoactive ingredient is cannabidiol (CBD). These compounds have been shown to be partial agonists or antagonists at the prototypical cannabinoid receptors, CB1 and CB2. The therapeutic actions of Δ9-THC and CBD include an ability to act as analgesics, anti-emetics, anti-inflammatory agents, anti-seizure compounds and as protective agents in neurodegeneration. However, there is a lack of well-controlled, double blind, randomized clinical trials to provide clarity on the efficacy of either Δ9-THC or CBD as therapeutics. Moreover, the safety concerns regarding the unwanted side effects of Δ9-THC as a psychoactive agent preclude its widespread use in the clinic. The legalization of cannabis for medicinal purposes and for recreational use in some regions will allow for much needed research on the pharmacokinetics and pharmocology of medical cannabis. This brief review focuses on the use of cannabis as a medicinal agent in the treatment of pain, epilepsy and neurodegenerative diseases. Despite the paucity of information, attention is paid to the mechanisms by which medical cannabis may act to relieve pain and seizures.


Assuntos
Canabidiol/farmacologia , Cannabis , Dronabinol/farmacologia , Maconha Medicinal/farmacologia , Humanos
11.
Forensic Sci Int ; 301: 331-340, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202146

RESUMO

The structural identification and the monitoring of the relative concentrations of a wide range of major (3) and minor secondary (16) metabolites used as marker substances for profiling of cannabis resin using GC-FID at the Swedish National Forensic Centre (NFC) has facilitated the mapping of their chemical and physical behaviors over a period of 48months whilst stored under different conditions (exposure to light, exposure to air, temperature). In all cases the behavior of this group of sesquiterpenes, sesquiterpenoids, cannabinoids and waxes could be directly related to their chemical lability/functionality. In particular, the identification of homologue triads for both Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) together with a group of seemingly chemically inert substances (for example, cannabicyclol(CBL) and the waxes (n-alkanes)) has created new tools for the establishment of common origins between samples of cannabis resins aged under different conditions. Since sampling of the resin blocks in NFC's method for profiling of cannabis resin is made below the surface, the effects of light incursion were found to be negligible. The effects of exposure to air (and indirectly temperature) were found to be more significant, not unexpectedly as many of the observed transformations were based on oxidation or rearrangement processes.


Assuntos
Canabinoides/química , Cannabis/química , Resinas Vegetais/química , Manejo de Espécimes/métodos , Cromatografia Gasosa , Escuridão , Luz , Temperatura Ambiente
12.
Phytochemistry ; 164: 162-171, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31151063

RESUMO

In addition to the psychoactive constituents that are typically associated with Cannabis sativa L., there exist numerous other specialized metabolites in this plant that are believed to contribute to its medicinal versatility. This study focused on two such compounds, known as cannflavin A and cannflavin B. These prenylated flavonoids specifically accumulate in C. sativa and are known to exhibit potent anti-inflammatory activity in various animal cell models. However, almost nothing is known about their biosynthesis. Using a combination of phylogenomic and biochemical approaches, an aromatic prenyltransferase from C. sativa (CsPT3) was identified that catalyzes the regiospecific addition of either geranyl diphosphate (GPP) or dimethylallyl diphosphate (DMAPP) to the methylated flavone, chrysoeriol, to produce cannflavins A and B, respectively. Further evidence is presented for an O-methyltransferase (CsOMT21) encoded within the C. sativa genome that specifically converts the widespread plant flavone known as luteolin to chrysoeriol, both of which accumulate in C. sativa. These results therefore imply the following reaction sequence for cannflavins A and B biosynthesis: luteolin ► chrysoeriol ► cannflavin A and cannflavin B. Taken together, the identification of these two unique enzymes represent a branch point from the general flavonoid pathway in C. sativa and offer a tractable route towards metabolic engineering strategies that are designed to produce these two medicinally relevant Cannabis compounds.


Assuntos
Cannabis/química , Flavonas/biossíntese , Cannabis/metabolismo , Flavonas/química , Flavonas/metabolismo , Engenharia Metabólica , Estrutura Molecular
14.
BMC Complement Altern Med ; 19(1): 132, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208410

RESUMO

BACKGROUND: Nigerian Cannabis sativa (hemp) causes male gonadotoxicity by inducing hyperprolactinemia, down-regulation of hypothalamic-pituitary-testicular axis, and oxidative stress. Benin republic hemp has been preferred by illicit users in Nigeria but its effect on male fertility is not understood. This study determined and compared the compositions of Benin republic hemp ethanol extract (BHE) and Nigerian hemp. The effects of BHE on semen parameters, reproductive hormones, and anti-oxidant status, and the possibility of bromocriptine (prolactin inhibitor) to abolish hemp-induced toxicities in rats were also investigated. METHODS: Thirty-six male Wistar rats were blindly randomized into 6 oral treatment groups (n = 6 each). Groups I (control) and II received normal saline and bromocriptine (3 mg/kg) respectively. Groups III and IV received 2 mg/kg of BHE alone and in combination with bromocriptine respectively, while groups V and VI received 10 mg/kg BHE alone and in combination with bromocriptine respectively. Comparisons among the groups were done by one-way analysis of variance, followed by post-hoc Tukey multiple comparison test. Statistical significance was considered at p < 0.05. RESULTS: The BHE has no cannabichromene and tetrahydrocannabinol but a very small quantity of cannabinol and higher quantity of fatty acids when compared to Nigerian hemp. Both doses of BHE increased sperm count, morphology and viability but not motility. Co-administration of BHE with bromocriptine lowered sperm count but increased sperm morphology and viability. Bromocriptine and/or BHE caused reduction in the plasma prolactin level, increase in the plasma superoxide dismutase activity, but no significant change in the plasma gonadotropin releasing hormone, follicle stimulating hormone (except for the increase in rats that received bromocriptine+ 10 mg/kg BHE), luteinizing hormone, estradiol, malondialdehyde and glutathione peroxidase. The 10 mg/kg BHE or bromocriptine+BHE (both doses) increased total anti-oxidant capacity and catalase. CONCLUSIONS: The BHE improves semen parameters by reducing plasma prolactin and enhancing plasma anti-oxidant status. Its pro-fertility potential might be associated with its deficiency in the widely known gonadotoxic phytocannabinoids.


Assuntos
Antioxidantes/metabolismo , Canabinoides/análise , Cannabis/química , Dronabinol/análise , Fármacos para a Fertilidade Masculina/farmacologia , Extratos Vegetais/farmacologia , Prolactina/metabolismo , Sêmen/efeitos dos fármacos , Animais , Canabinoides/farmacologia , Dronabinol/farmacologia , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Masculina/análise , Masculino , Extratos Vegetais/análise , Ratos , Sêmen/metabolismo
15.
Psychiatr Danub ; 31(Suppl 2): 162-170, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31158117

RESUMO

The influence of cannabis use on the occurrence, clinical course and the treatment of the first psychotic episode (FEP) is well documented. However, the exact link is still not clearly established. The aim of this article is to review and report the noticed increase in the number of hospitalizations of young people with a clinical appearance of severe psychotic decompensation following cannabis consumption and to show the clinical challenges in treatment of the FEP. The case study describes the clinical course of a five selected patients with a diagnosis of the FEP and positive tetrahydrocannabinol (THC) urine test who were hospitalized in a similar pattern of events. They all have a history of cannabis consumption for at least 6 years in continuity and were presented with severe psychomotor agitation, disorganisation, confusion and aggression at admission. Although the chosen drug to treat all patients was atypical antipsychotic and benzodiazepines, the course of the disorder and the clinical response to therapy were noticeably different in each patient. The clinical presentation of FEP in cannabis users can be atypical and highly unpredictable from mild psychotic symptoms to severe substance intoxication delirium. In clinical practice clinicians treating new onset psychosis need to be watchful for cannabis and synthetic cannabinoids induced psychosis. Pharmacotherapeutic interventions include prompt and adequate use of the benzodiazepine, second-generation antipsychotic, and mood-stabilizers. Further research in the pharmacotherapy of cannabis-induced psychosis is required.


Assuntos
Cannabis , Alucinógenos , Abuso de Maconha , Psicoses Induzidas por Substâncias , Transtornos Psicóticos , Adolescente , Antipsicóticos/uso terapêutico , Cannabis/efeitos adversos , Humanos , Abuso de Maconha/complicações , Psicoses Induzidas por Substâncias/tratamento farmacológico
18.
JAMA ; 322(2): 145-152, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31211826

RESUMO

Importance: Recent evidence suggests that cannabis use during pregnancy is increasing, although population-based data about perinatal outcomes following in utero exposure remain limited. Objective: To assess whether there are associations between self-reported prenatal cannabis use and adverse maternal and perinatal outcomes. Design, Setting, and Participants: Population-based retrospective cohort study covering live births and stillbirths among women aged 15 years and older in Ontario, Canada, between April 2012 and December 2017. Exposures: Self-reported cannabis exposure in pregnancy was ascertained through routine perinatal care. Main Outcomes and Measures: The primary outcome was preterm birth before 37 weeks' gestation. Indicators were defined for birth occurring at 34 to 36 6/7 weeks' gestation (late preterm), 32 to 33 6/7 weeks' gestation, 28 to 31 6/7 weeks' gestation, and less than 28 weeks' gestation (very preterm birth). Ten secondary outcomes were examined including small for gestational age, placental abruption, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference (RD) and relative risk (RR) of outcomes associated with cannabis exposure and control for confounding. Results: In a cohort of 661 617 women, the mean gestational age was 39.3 weeks and 51% of infants were male. Mothers had a mean age of 30.4 years and 9427 (1.4%) reported cannabis use during pregnancy. Imbalance in measured maternal obstetrical and sociodemographic characteristics between reported cannabis users and nonusers was attenuated using matching, yielding a sample of 5639 reported users and 92 873 nonusers. The crude rate of preterm birth less than 37 weeks' gestation was 6.1% among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95% CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98% (95% CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95% CI, 1.45-1.61]), placental abruption (1.6% vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3% vs 13.8%; RR, 1.40 [95% CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95% CI, 1.13-1.45]). Conclusions and Relevance: Among pregnant women in Ontario, Canada, reported cannabis use was significantly associated with an increased risk of preterm birth. Findings may be limited by residual confounding.


Assuntos
Cannabis , Resultado da Gravidez/epidemiologia , Adolescente , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Ontário/epidemiologia , Distribuição de Poisson , Gravidez , Nascimento Prematuro/epidemiologia , Análise de Regressão , Estudos Retrospectivos , Autorrelato , Estados Unidos , Adulto Jovem
19.
Plant Sci ; 284: 108-116, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084863

RESUMO

Cannabinoids are terpenophenolic compounds produced by Cannabis sativa L., which accumulate in storage cavities of glandular trichomes as a part of the exudates. We investigated if tetrahydrocannabinolic acid synthase and cannabidiolic acid synthase, which are involved in the last step of cannabinoid biosynthesis, are also secreted into Cannabis trichome exudates. The exudates were collected by microsuction from storage cavities of Cannabis glandular trichomes and were subjected for proteomic and metabolomic analyses. The catalytic activity of the exudates was documented by cannabigerolic acid biotransformation studies under hydrophobic conditions. Electrophoretic separations revealed protein bands at ˜65 kDa, which were further identified as tetrahydrocannabinolic acid synthase and cannabidiolic acid synthase. The accumulation of the enzymes in trichome exudates increased substantially during the flowering period in the drug-type Cannabis plants. The content of cannabinoids increased significantly after incubating hexane-diluted trichome exudates with cannabigerolic acid. In this study, we showed that Cannabis glandular trichomes secrete and accumulate cannabinoid synthases in storage cavities, and the enzymes able to convert cannabigerolic acid under hydrophobic trichome-mimicking conditions. Metabolite profiling of the exudates revealed compounds with hydrophilic, osmoprotective and amphiphilic properties, which may play a role in providing a necessary aqueous microenvironment, which enables enzyme solubility and biocatalysis under hydrophobic conditions of glandular trichomes.


Assuntos
Canabinoides/metabolismo , Cannabis/metabolismo , Oxirredutases Intramoleculares/metabolismo , Tricomas/metabolismo , Exsudatos e Transudatos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Osmorregulação
20.
Plant Sci ; 284: 67-72, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084880

RESUMO

Cannabis sativa (cannabis) produces a resin that is valued for its psychoactive and medicinal properties. Despite being the foundation of a multi-billion dollar global industry, scientific knowledge and research on cannabis is lagging behind compared to other high-value crops. This is largely due to legal restrictions that have prevented many researchers from studying cannabis, its products, and their effects in humans. Cannabis resin contains hundreds of different terpene and cannabinoid metabolites. Many of these metabolites have not been conclusively identified. Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary. As a consequence, there is concern about lack of consistency with regard to the terpene and cannabinoid composition of different cannabis 'strains'. Likewise, claims of some of the medicinal properties attributed to cannabis metabolites would benefit from thorough scientific validation.


Assuntos
Cannabis/metabolismo , Terpenos/metabolismo , Canabinoides/biossíntese , Cannabis/genética , Variação Genética , Genoma de Planta , Genótipo , Técnicas de Genotipagem , Redes e Vias Metabólicas
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