This study deals with the impact of the legislative bill that enabled the creation of a regulated cannabis market in Uruguay as a means to combat organized crime in the country. This study will also explore the hypothesis that this legislative bill changed the legal character of criminality as well as reformulating narcotic issues from being a criminal issue into a public health issue. Analyzing the very specific case of Uruguay’s current narcotic policies becomes a means to explore the ideas that constitute Law Nr 19.172 “Marijuana and its derivatives” which might be indicative of the attitudes in society regarding criminality. This ties into the new iteration of the dichotomy between law and democracy as a result of this legislative reform in Uruguay and the possible new role of legal theory in a democratic country which is discussed in this article.

Purpose: Marijuana is the most widely used illicit drug in the United States. However, marijuana and cannabinoid derivatives have potential therapeutic uses. Studies in cannabis users have yielded contradictory results with regard to long-term effects on cognitive functions. There is no prospective study assessing this issue, and such studies may raise ethical issues in humans, whereas mice have been shown to exhibit similar cannabinoid-mediated behaviors as humans. The purpose of this study was to assess the consequences of chronic administration of Δ9-THC, the major psychoactive component of marijuana, in a mouse memory model. Methods: In Experiment 1, the dose-response relationship of Δ9-THC was assessed in the object recognition task, a well-documented rodent memory model. In Experiment 2, mice were treated repeatedly with either escalating doses of Δ9-THC or vehicle for one week, and then challenged with the drug to assess whether tolerance had developed. Results: Acute Δ9-THC dose-dependently interfered with memory as assessed in the object recognition task (ED50 95% C.I. = 0.5 (0.1 to1.7) mg/kg). No tolerance to the memory disruptive effects of 1 mg/kg Δ9-THC was evident after chronic treatment. Conclusions: Considerably low doses of Δ9-THC impaired memory. The failure of chronic Δ9-THC to produce tolerance in this model was surprising considering that a similar dosing regimen has been reported to produce tolerance in non-mnemonic behaviors. The results suggest that memory is particularly sensitive to the disruptive effects of Δ9-THC and chronic cannabis use is likely to elicit persistent impairment of cognitive function. Caution should be applied in advocating chronic use of medicinal cannabinoids. Potential solutions lie in reinforcing education on the harm caused by cannabis use and availability of alternative solution to cannabis users, especially among youth that have shown to be more vulnerable to this drug.

EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 molar ratio of 5.4 and 0.37, respectively, with no difference in CB1 receptor expression. To test the hypothesis that CRIP1a modulates CB1 receptor signaling, G-protein and effector activity were examined with and without full, partial and inverse agonists. [35S]GTPgS binding, which measures G-protein-coupled receptor (GPCR)-mediated G-protein activation, showed that CRIP1a inhibited constitutive CB1 receptor activity, as indicated by the decreased effect of the inverse agonist SR141716A. CRIP1a also decreased CB1 receptor-mediated G-protein activation by high efficacy agonists, whereas moderate and low efficacy agonists were unaffected. In experiments varying Na+ concentration, CRIP1a decreased spontaneous G-protein activation at low Na+ concentrations, where spontaneous GPCR activity is highest. This effect was eliminated by pertussis toxin pre-treatment, indicating that CRIP1a only inhibits GPCR-mediated activity. To determine whether CRIP1a modulates receptor adaptation, hCB1-HEK (±CRIP1a) cells were pretreated with WIN or THC. Both ligands desensitized CB1 receptor-mediated G-protein activation, but desensitization was unaffected by CRIP1a. In contrast, CRIP1a attenuated downregulation of CB1 receptor binding sites by WIN, but not THC. Downstream, CRIP1a attenuated constitutive CB1 receptor-mediated inhibition of cAMP, as indicated by elimination of SR141716A-stimulated cAMP, without affecting agonist-induced cAMP inhibition. Constitutive inhibition was not due to endocannabinoids because LC-ESI-MS-MS did not detect endocannabinoids in hCB1-HEK (±CRIP1a) cells. To determine whether effects of CRIP1a were conserved among cell types, Chinese Hamster Ovary cells expressing CB1 receptors were stably co-transfected with CRIP1a, and had a CRIP1a/CB1 receptor molar ratio of 15 and 1900 with and without CRIP1a over-expression, respectively. In this model, CRIP1a inhibited constitutive CB1 receptor-mediated G-protein activity, but activation by agonists was enhanced, suggesting CRIP1a effects were dependent on stoichiometry of CRIP1a/CB1 receptor or cell type. Overall, these results indicate that CRIP1a decreases constitutive CB1 receptor activity, modulates agonist efficacy, and inhibits CB1 receptor downregulation, in a ligand- and cellular environment-dependent manner.

University: Charles University in Prague Faculty: First Faculty of Medicine Psychiatric clinic, Center for Addictology School Year…….2012/2013…… ABSTRACT DIPLOMA WORK Name …………………Bc. Kristýna Piskáčková....………………………………….… Branch of study: Addictology Matriculation Year: …………2006….………… Thesis supervisor: Mgr. Jaroslav Vacek The number of pages:……80…………… Diploma Thesis Title: Obtaining cannabis drugs by adolescents: the comparison of the wards experience from facilities for foreigners with the selected facilities for wards with Czech nationality The goal of the diploma thesis is to determine the ways and circumstances of obtaining hemp drugs by adolescent users - wards of selected facilities for juveniles. Theoretical part mainly deals with issues such as cannabis drugs, usage patterns, cannabis distribution patterns, drug market and school facilities system for the performance of residential care and protective upbringing. The research part first deals with research questions, methods of data creation, then with the help of data analysis are given the answers to research questions. The used method of obtaining data is semi-structured interview. The survey was conducted with 16 participants. The sample only consists of one gender - male. Their age is from 15 to 18. Participant's statements are kept and...

INTRODUÇÃO: O instrumento escolhido para coleta de informações em uma investigação científica tem de ser capaz de traduzir, com boa precisão, a realidade estudada. Neste estudo, foi analisado o desempenho de um questionário para avaliar o consumo de drogas na prisão confrontando o relato dos entrevistados com a análise toxicológica de urina. METODOLOGIA: Foi realizado um estudo observacional transversal em setembro de 2007, numa unidade prisional masculina, localizada no estado de São Paulo. Os detentos foram entrevistados e submetidos à coleta de urina para detecção qualitativa de canabinóides e de cocaína, utilizando análise por imunoensaio enzimático. Foram selecionadas duas questões; a primeira sobre uso de drogas e, a segunda, mais específica, que identifica o padrão de uso da maconha e da cocaína na prisão. Para avaliar a capacidade destas questões em identificar corretamente os indivíduos que usam drogas na prisão, foram comparadas as respostas com os resultados de exame de urina (padrão ouro) e calculadas a sensibilidade e a especificidade. Entrevistador, período em que foi realizada a entrevista, faixa etária dos entrevistados, tempo de presídio, situação prisional, relação existente entre o delito cometido e as drogas, duração da pena atual e o resultado das análises toxicológicas da urina foram escolhidos como fatores com potencial para interferir nos resultados. RESULTADOS: Participaram da pesquisa 337 detentos, com idade média de 30,4 anos, cumprindo pena média de 10,1 anos, que estão em média há 16,7 meses no presídio e que, em sua maioria não cometeram delitos relacionados a drogas (73,3%). A prevalência obtida pela análise toxicológica da urina foi de 61,4% para maconha e 7,7% para cocaína. Combinar as questões melhorou o desempenho do questionário. Dos 260 entrevistados identificados, pelo questionário, como usuários de drogas na prisão, 191 tiveram resultado positivo na análise toxicológica da urina e 69, resultado negativo. Dos 76 entrevistados identificados como não usuários de droga na prisão, 21 tiveram resultado positivo na análise toxicológica da urina e 55, resultado negativo (Sensibilidade=90,1% e Especificidade=44,1%). A prevalência para o uso de maconha na prisão, obtida a partir das entrevistas, foi de 77,4% e, para o de cocaína, de 8,8%. Os detentos que não cometeram crimes relacionados a drogas (p=0,011) e os com resultado positivo para a análise da urina para canabinóides (p=0,028) tiveram um desempenho melhor ao responder as questões relacionadas ao uso de cocaína. Os detentos mais novos consomem mais maconha na prisão (80,6%, p=0,000). Já os reincidentes (11,4%, p=0,017) e os que estão há mais tempo no presídio (17,3%, p=0,038) destacaram-se como os que consumem mais cocaína. Os detentos primários (11,3%, p=0,028) e os com resultado positivo na análise da urina para canabinóides (10,2%, p=0,009) apresentaram frequência maior de respostas dissociadas. Apresentaram frequência menor, os que cumprem pena entre 6,33 e 14,62 anos (3,4%, p=0,025). CONCLUSÕES: A concordância entre o relato de consumo de maconha e cocaína na prisão obtida pelo questionário e o resultado do exame toxicológico foi boa para as duas drogas. Combinar as respostas apareceu como uma forma de melhorar a sensibilidade do questionário. / INTRODUCTION: The instrument used for collection of information in scientific research must be able to translate with accuracy the reality under investigation. In this study, we investigated the performance of a questionnaire in assessing drug use in prison compared with toxicological analysis of urine. METHODS: A cross sectional observational study was conducted in September 2007, in a male inmate placed in the state of Sao Paulo. The prisoners were interviewed and underwent urine collection for the detection of cannabinoids and cocaine metabolites trough toxicological analysis (enzyme immunoassay). Two questions were selected, one about drug use in general, and a second one, which was more specific and used to identify the drug consumption pattern in prison. To assess the ability of these questions to correctly identify individuals who currently use drugs in prison, the responses were compared with the urine test (gold standard) and sensitivity and specificity rates were calculated. Interviewer characteristics, total period of interview, age of respondents, time in jail, penalties conditions, relationship between the offense and drug use, total penalty time and urinalysis were considered factors with the potential to affect the results. RESULTS: 337 prisoners completed the questionnaire and provided urine samples for the study. These subjects presented a mean age of 30.4 years, an average time spent in prison of 1 year and 16.7 months, 10.1 years of total penalty time and the majority of them have not committed crimes related to drugs (73.3%). The prevalence based on urine toxicological analysis was 61.4% for marijuana and 7.7% for cocaine. When the answers to the questions were combined to the toxicological results, the assessment for drug consumption trough the questionnaire was improved. Of the 260 respondents identified by the questionnaire as a drug user in prison, 191 presented positive results for toxicological analysis and 69 negative results. Of the 76 respondents identified as non-drug user in prison, 21 presented positive results for toxicological analysis and 55 negative (sensitivity=90.1% and specificity =44.1%). The prevalence of cannabis use in prison taking into account only the interviews was 77.4% and 8.8%, for marijuana and cocaine, respectively. Prisoners who have committed crimes related to drugs (p=0,011) and those with positive urinalysis for cannabinoids (p=0,028) performed better in answering questions related to cocaine use. The younger prisoners consumed more marijuana in prison (80.6%, p=0,000) than their older counterparts. Repeat offenders (11.4%, p=0,017) and those who are in prison for longer (17.3%, p=0,038) time stood out as those who consume more cocaine. First offenders (11.3%, p=0,028) and those with positive urinalysis for cannabinoids (10,2%, p=0,009) showed higher frequency of misleading answers and, less often, those who were serving time between 6.33 and 14.62 years (3.4%, p=0.025). CONCLUSIONS: The agreement between the reporting of marijuana and cocaine consumption in prison obtained by questionnaire with toxicological essay was adequate for both use in general and recent use. Combining responses appeared as a way to improve the sensitivity of the questionnaire.

No presente trabalho, foram desenvolvidos e validados dois métodos com o objetivo de determinar os herbicidas paraquat e glifosato, bem como o AMPA, principal metabólito do glifosato, em amostras de maconha apreendidas pela polícia de Campinas, São Paulo. A detecção e quantificação de herbicidas na maconha são necessárias e importantes para alertar o real risco que a droga pode oferecer aos usuários. Existem várias razões que explicam a presença de herbicidas na maconha em vários países, incluindo o Brasil. A eletroforese capilar foi utilizada para determinação dos herbicidas. Um método de detecção direta foi usado para determinar o paraquat e outro, com detecção indireta, para determinar o glifosato e AMPA. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão e recuperação. Os dados da validação atestam que os métodos podem ser utilizados em laboratórios Forense no Brasil. Cento e trinta amostras foram analisadas, sendo que em doze amostras foram detectadas a presença de paraquat em várias concentrações e ainda três amostras forneceram resultados positivos apenas para o glifosato sendo uma delas, detectado a presença concomitante do AMPA. Os valores dos contaminantes encontrados podem representar um risco ao usuário, fazendo-se necessário novos estudos para delineamento sobre os reais efeitos que esses contaminantes podem apresentar aos usuários de Cannabis. / In the present work, two methods were developed and validate, aiming to determinate the herbicides paraquat and glyphosate and his major metabolite AMPA in seizured marijuana samples by the police in Campinas, São Paulo. The determination of herbicides in confiscated samples is necessary and important to alert the real risk of marijuana can offer to the users. There are many reasons that explain the presence of herbicides in marijuana in several countries, including Brazil. Capillary electrophoresis was used to determinate the studied herbicides. A method with direct detection was used to determinate paraquat and indirect detection to determinate glyphosate and AMPA. The developed methods showed good linearity, precision, accuracy, and recovery. Therefore, it can be applied in Forensics labs in Brazil. One hundred and thirty samples were analyzed, and twelve of them result positive for paraquat in several concentrations and three samples showed positive to glyphosate and one of them, detected the presence of AMPA. The values of the contaminants found, can offer a risk to the users, making it necessary new studies to know the real effects that such contaminants can offer to the Cannabis users.

No presente trabalho, foram desenvolvidos e validados dois métodos com o objetivo de determinar os herbicidas paraquat e glifosato, bem como o AMPA, principal metabólito do glifosato, em amostras de maconha apreendidas pela polícia de Campinas, São Paulo. A detecção e quantificação de herbicidas na maconha são necessárias e importantes para alertar o real risco que a droga pode oferecer aos usuários. Existem várias razões que explicam a presença de herbicidas na maconha em vários países, incluindo o Brasil. A eletroforese capilar foi utilizada para determinação dos herbicidas. Um método de detecção direta foi usado para determinar o paraquat e outro, com detecção indireta, para determinar o glifosato e AMPA. Os métodos desenvolvidos mostraram boa linearidade, precisão, exatidão e recuperação. Os dados da validação atestam que os métodos podem ser utilizados em laboratórios Forense no Brasil. Cento e trinta amostras foram analisadas, sendo que em doze amostras foram detectadas a presença de paraquat em várias concentrações e ainda três amostras forneceram resultados positivos apenas para o glifosato sendo uma delas, detectado a presença concomitante do AMPA. Os valores dos contaminantes encontrados podem representar um risco ao usuário, fazendo-se necessário novos estudos para delineamento sobre os reais efeitos que esses contaminantes podem apresentar aos usuários de Cannabis. / In the present work, two methods were developed and validate, aiming to determinate the herbicides paraquat and glyphosate and his major metabolite AMPA in seizured marijuana samples by the police in Campinas, São Paulo. The determination of herbicides in confiscated samples is necessary and important to alert the real risk of marijuana can offer to the users. There are many reasons that explain the presence of herbicides in marijuana in several countries, including Brazil. Capillary electrophoresis was used to determinate the studied herbicides. A method with direct detection was used to determinate paraquat and indirect detection to determinate glyphosate and AMPA. The developed methods showed good linearity, precision, accuracy, and recovery. Therefore, it can be applied in Forensics labs in Brazil. One hundred and thirty samples were analyzed, and twelve of them result positive for paraquat in several concentrations and three samples showed positive to glyphosate and one of them, detected the presence of AMPA. The values of the contaminants found, can offer a risk to the users, making it necessary new studies to know the real effects that such contaminants can offer to the Cannabis users.

Drug use and misuse by young people is a problem and concern in the Australian and Australian Capital Territory (ACT) communities. There are concerns regarding illicit and licit drugs but licit drug use has been identified as the major area of concern. Young people in the ACT reflect the drug use/misuse patterns and trends of other states. Commonly used drugs by young people are alcohol, tobacco, cannabis and analgesics. Strategies to address the problem of drug use/misuse by young people include intervention and community drug education programs. Peer drug education (as an example of community drug education), trains young people as peer educators to implement drug education programs with younger age groups. A case study analysis based on qualitative, naturalistic and new paradigm research is the research method used in this thesis. An eclectic model of drug education including key components from a variety of drug education models provides a comprehensive overview of peer drug education. The literature review showed the complexity of influences on drug use/misuse. These influences relate to individual, peer, parental and family, community and societal factors. Peer drug education is generally recognised as an effective drug education strategy. Peer drug education programs (Triple T: Teenagers Teaching Teenagers) were conducted in the ACT from 1988-1990. Reports documenting these programs (including evaluation data) and a literative review are the main data analysed for the case study. The case study analysis of five ACT peer drug education programs and one interstate program showed the key planning issues for effective peer drug education were: collaborative decision making as a central concept; detailed planning and liaison with target groups; established structures within schools and communities to support the trained peer educators; team work and small group work as intrinsic and extrinsic factors within the program; clarification of responsibilities and roles of all personnel involved in the program; and facilitators/leaders with attributes and qualities that encourage peer drug educators as social change agents. Analysis of data from the case study reports showed young people can be effective peer drug educators. Residential programs are preferred over non-residential programs. Peer drug education programs are effective in both school and community agencies. The literature review and analysis of reports also indicated that peer drug education needs to focus on establishing positive norms in groups of young people. Collaborative decision making and positive role modelling assist in the establishment of these norms. Peer drug education links to the wider changes occurring in education and health settings. Peer drug education is about collaborative decision making, social justice, development of key competencies and social change. This thesis confirmed the complexity and dynamic nature of peer drug education and there were many questions raised for further research from the literature review and analysis of program reports.

Industrial hemp (Cannabis sativa) is a highly productive crop that is well suited to cultivation in Canada. To better understand the development of bast (phloem) fiber secondary walls and to facilitate reverse genetics screening for improved germplasm, I undertook two sets of microarray experiments. The first compared transcript expression in stem peels at three positions along the length of the stem. The second set of microarray experiments compared transcript expression in adjacent tissue layers along the radial axis of the stem. The transcripts that were enriched in fiber-producing tissues in both studies were consistent with a dynamic program of cell wall deposition. Detailed qRT-PCR analysis of specific lignification genes identified the best targets for reverse genetics. Finally, as a first step towards establishing a virally induced gene silencing (VIGS) system, I identified viruses that produced visual symptoms of infection, although qRT-PCR failed to confirm the infection / Plant Biology

Anhand einer prospektiven epidemiologischen Verlaufsstudie an einer repräsentativen Bevölkerungsstichprobe von ursprünglich 14- bis 17jährigen Jugendlichen (N=1395) werden die Häufigkeit und die Verlaufsmuster des Konsums, des Mißbrauchs und der Abhängigkeit von Cannabis untersucht. Die Jugendlichen wurden persönlich mit Hilfe eines Interviews befragt, wobei als diagnostisches Instrument das M-CIDI mit seinen DSM-IV Algorithmen verwendet wurde. Die Ergebnisse aus der Basiserhebung ergaben, daß 1995 etwa 20% aller 14- bis 17jährigen - in der Mehrzahl wiederholt - Cannabis probiert hatten und 6% der Population einen regelmäßigen Gebrauch aufweisen. Die Einjahres-Inzidenz (= Auftreten neuer Fälle) für den Cannabisgebrauch der nun 15- bis 19jährigen betrug zum Zeitpunkt der Nachuntersuchung 20,1% für die Männer und 16,3% für die Frauen. Für den regelmäßigen Gebrauch wurden Inzidenzraen von 12% (Männer) und 8,4% (Frauen) ermittelt. Die Stabilität des Konsumverhaltens zwischen der Basis- und der Nachuntersuchung war relativ hoch un stieg mit höherem Initialkonsum an. Angesichts der hohen Gebrauchsrate von 32,4% bei den 15- bis 19jährigen bei der Nachuntersuchung ergab sich im Vergleich zu anderen psychotropen Substanzen eine relativ niedrige Prävalenz für Mißbrauch und Abhängigkeit (4%). Das Vorliegen einer Diagnose bei der Erstuntersuchung weist allerdings eine relativ hohe Stabilität über die Nachuntersuchungskette auf. / The paper examines the prevalence, incidence and stability patterns of cannabis use and dependence in a prospective epidemiological study of a random community sample of adolescents, aged 14 to 17 years (N=1395) at time 1. Assesments are based on personal interviews by trained clinical psychologists using the computerized DSM-IV lifetime and 12-month change version of the M-CIDI. Results indicate that in 1995 every fifth person aged 14 to 17 years had used cannabis at least once and 6% reported regular use. The 12-month incidence rates (i.e. proportion of the sample reporting first cannabis use in the last year) among subjects, 15 to 19 years of age at time 2, was high, with 20,1% of males and 16,3% of females reporting first use. The incidence of regular use was 12,0% (males) and 8,4% (females). The stability of consumption patterns from time 1 to time 2 was high. Increasing with higher initial consumption. Given the reexamined samples overall high cannabis consumption rates of 32,4%, the prevalence of clinically manifest DSM-IV abuse and dependence was low in comparison to other psychologic drugs (4%). However there was remarkable diagnostic stability over time in this age group of those with an initial diagnosis at time 1 receiving a diagnosis again at time 2.