Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans

Background. We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug.Method. We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words : cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy.Results. Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls.Conclusions. Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.

Background: While long-term cessation is an outcome of interest in adult smokers, little is known about discontinuing smoking in adolescent smokers. The objective was to identify the predictors of the occurrence of smoking discontinuation in novice smokers.Methods: Data were available for 620 adolescent smokers participating in a longitudinal study on the natural course of nicotine dependence. Data on smoking discontinuation (i.e., stopping smoking for !12 consecutive months) were collected in 20 cycles over five years from grade 7 to 11 (1999)(2000)(2001)(2002)(2003)(2004)(2005). Data on 37 potential predictors representing a wide range of demographic, psychosocial, health, lifestyle, smoking-related, and context-related characteristics were collected once, 2 to 3 times, or 20 times. Pooled logistic regression was used to test the association between each potential predictor and smoking discontinuation, adjusting for potential confounders.Results: Forty percent of 620 participants discontinued smoking during follow up. Conclusions: Both individual and context-level factors were associated with smoking discontinuation. Impact: Programs and policy targeting novice adolescent smokers may be more effective if factors associated with long-term smoking discontinuation are taken into consideration. In particular, young smokers may need help with dependence symptoms, body weight issues, family functioning, and polysubstance use. Cigarette package warnings may be effective in helping adolescents discontinue smoking. Cancer Epidemiol Biomarkers Prev; 23(6); 1090-101. Ó2014 AACR.

Recebido: 06out13Aceito: 26set14 Publicado: 13nov14 Revisado por AnônimosResumo. O conhecimento das alterações cognitivas decorrentes do consumo regular de cannabis é deficiente, em particular no que se refere a sua influência de ordem emocional. Neste estudo é revisado como o uso da cannabis pode levar a alterações neurológicas e perceptuais, em especial quanto ao reconhecimento de emoções e de situações ameaçadoras. São encontradas evidências de dessensibilização na percepção de estímulos estressores, fator de relevância potencial nas discussões sobre o desenvolvimento de psicopatologias e dependência da substância. Palavras-chave. Cannabis; Percepção emocional; Psicopatologias; Dependência.Abstract. The knowledge of cognitive changes related to the regular consumption of cannabis is restricted, particularly concerning to emotional changes. In this study it is reviewed how the use of cannabis can lead to neurological and perception alterations, particularly in what concerns to recognizing emotions and threatening situations. Evidence suggest that it occurs desensibilization of perception related to potentially stressing stimuli that may be relevant for psychopathology development and for addiction to this substance. Keywords. Cannabis; Emotional perception; Psychopathology; Addiction.Contato: carolina.bueno@usp.br Revisão CannabisEstima-se que cerca de 8,8 % da população brasileira já experimentou maconha, sendo que, dentre esses usuários, 31,89 % faz uso da substância mais de 3 vezes por semana (OBID, 2005). Um estudo de âmbito nacional mostrou que cerca de 2,1 % da população brasileira fez uso de maconha nos 12 meses anteriores à pesquisa (Jungerman et al., 2010), sendo que as regiões Sul e Sudeste exibem maior número relativo de usuários. Dentre as substâncias presentes na maconha destacam-se o cannabidiol (CBD) e o delta-9-tetraidrocanabinol (THC) como principais mediadores de seu efeito. As alterações fisiológicas e farmacodinâmicas causadas pelo CBD ainda são pouco compreendidas, sabendo-se que este atua na via endocanabinoide sem alterações sobre o psiquismo, ou seja, sem efeitos psicotrópicos (Iuvone et al., 2009). A substância pode, no entanto, realçar, inibir ou ser indiferente à ação desencadeada pelo THC, dependendo da dose e da região encefálica analisada (Hayakawa et al., 2008;Malone et al., 2009). O THC é uma molécula capaz de se ligar a receptores canabinoides do tipo 1 (CB1) e do tipo 2 (CB2) levando a efeitos psicotrópicos. Os receptores CB1 são possivelmente os receptores acoplados a proteína G mais abundantes no encéfalo, presentes em alta concentração no hipocampo, algumas regiões olfatórias, caudado-putamen, núcleo accumbens, substância negra pars reticulata (SNr), globo pálido e na porção horizontal da banda diagonal de Broca. Algumas regiões do encéfalo apresentam densidade moderada desse receptor como neocórtex, núcleo basal da amígdala, hipotálamo medial e núcleo do trato solitário; enquanto outras, como o tálamo e o tronco encefálico apresentam baixa densidade do receptor (SvíZenská...