Efectes de l'abstinència tabàquica sobre la termoregulació durant l'activitat física

La situació de fumador actiu 1 hora abans de la pràctica d’activitat física pot alterar la resposta termoreguladora, comprometen de forma significativa els mecanismes vasodilatadors cutànis de pèrdua de calor i provocar una resposta hemodinàmica anormal durant l’exercici. L’efecte additiu de la nicotina i de l’activitat física d’alta intensitat pot fer augmentar la temperatura central al pertorbar els mecanismes de pèrdua de calor mitjançant la redistribució del flux vascular cutani. A més, durant exercicis perllongats com els exercicis de resistència, i en ambients calorosos, el consum actiu de cigarretes podria actuar com a factor limitant en el rendiment esportiu, i poder incrementar el risc d’induir hipertèrmia.

Factores de adherencia al tratamiento en pacientes dependientes de cannabis

Introducción: En los últimos años se ha producido un aumento del consumo de cannabis en la población general, estando más extendido en los jóvenes entre 15 y 34 años, y en los hombres más que en las mujeres. Igualmente se ha producido una disminución en la edad de inicio del consumo. Por otro lado van detectándose aumento de las demandas de tratamiento por esta adicción en los centros especializados. Objetivo: valorar la adherencia al tratamiento de la población que consulta por problemas derivados del consumo de cannabis. La atención se realiza dentro de un Programa Específico para estos consumidores. Material y métodos: Se realiza una revisión de 74 pacientes que solicitan tratamiento en el centro, durante el periodo de tiempo de dos años. La adherencia al tratamiento se mide en términos de asistencia a visitas médicas/psicológicas posteriores. Se contabilizan visitas realizadas a dos semanas, un mes, tres meses y seis meses desde la primera demanada. Se tiene en cuenta la coexistencia de otro trastorno psiquiátrico, utilizando para esto la entrevista clínicadisgnóstica y las entrevistas semiestructuradas SCID-I y SCID-II. Resultados: De los 74 pacientes incluídos en el estudio, 22% son mujeres y el 78% son hombres. El 74% continúan tratamiento a los tres meses, y el 64% a los seis meses de haberlo iniciado. Hay que señalar que del total de la muestra, el 55% no son consumidores de otras sustancias de abuso, excepto nicotina, que en este caso correspondería al 100% de los pacientes admitidos a tratamiento. El 23% de estos pacientes presentan de forma comórbida a la dependencia de cannabis un diagnóstico de Trastorno Psicótico. Conclusiones: Dentro de las conclusiones de este estudio, podemos destacar que: existe elevada comorbilidad psiquiátrica en pacientes con diagnóstico de Trastorno por dependencia de cannabis; las mujeres abandonan el programa de tratamiento con mayor frecuencia que los varones; el hecho de no existir comorbilidad psiquiátrica es un factor de abandono temprano del tratamiento; los pacientes con diagnóstico comórbido de Trastorno psicótico mantienen la adherencia en su totalidad a los seis meses del inicio; los pacientes que solicitan tratamiento a menor edad tienden a abandonarlo antes; y la alta prevalencia de consumo de tabaco en las personas dependientes de cannabis.

Delta9-tetrahydrocannabinol decreases somatic and motivational manifestations of nicotine withdrawal in mice

The possible interactions between Delta9-tetrahydrocannabinol (THC) and nicotine remain unclear in spite of the current association of cannabis and tobacco in humans. The aim of the present study was to explore the interactions between these two drugs of abuse by evaluating the consequences of THC administration on the somatic manifestations and the aversive motivational state associated to nicotine withdrawal in mice. Acute THC administration significantly decreased the incidence of several nicotine withdrawal signs precipitated by mecamylamine or naloxone, such as wet-dog-shakes, paw tremor and scratches. In both experimental conditions, the global withdrawal score was also significantly attenuated by acute THC administration. THC also reversed conditioned place aversion associated to naloxone precipitated nicotine withdrawal. We have then evaluated whether this effect of THC was due to possible adaptive changes induced by chronic nicotine on CB1 cannabinoid receptors. The stimulation of GTPS-binding proteins by the cannabinoid agonist WIN 55,212-2 and the density of CB1 cannabinoid receptor binding labelled with [3H] CP-55,940 were not modified by chronic nicotine treatment in the different brain structures investigated. Finally, we evaluated the consequences of THC administration on c-Fos expression in several brain structures after chronic nicotine administration and withdrawal. c-Fos was decreased in the caudate putamen and the dentate gyrus after mecamylamine precipitated nicotine withdrawal. However, acute THC administration did not modify c-Fos expression under these experimental conditions. Taken together, these results indicate that THC administration attenuated somatic signs of nicotine withdrawal and this effect was not associated to compensatory changes on CB1 cannabinoid receptors during chronic nicotine administration. In addition, THC also ameliorated the aversive motivational consequences of nicotine withdrawal.

Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

Rationale: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. Objectives: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: Animals were only exposed once to nicotine. The acute administration of low (0.05, sc) or high (0.8 mg/kg, sc) doses of nicotine produced opposite effects in the elevated plus-maze, i.e., anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, ip), and the cannabinoid agonist, 9-tetrahydrocannabinol (0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, 9-tetrahydrocannabinol failed to modify nicotine anxiolytic-like responses, but attenuated its anxiogenic-like effects. In addition the association of non-effective doses of 9-tetrahydrocannabinol and nicotine produced clear anxiolytic-like responses. Conclusions: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice, and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.

Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice

The involvement of μ-opioid receptors in different behavioral responses elicited by nicotine was explored by using μ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of μ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that μ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior

Emerging evidence suggests that the hypocretinergic system is involved in addictive behavior. In this study, we investigated the role of these hypothalamic neuropeptides in anxiety-like responses of nicotine and stress-induced reinstatement of nicotine-seeking behavior. Acute nicotine (0.8 mg/kg, s.c.) induced anxiogenic-like effects in the elevated plus-maze and activated the paraventricular nucleus of thehypothalamus (PVN) as revealed by c-Fos expression. Pretreatment with the hypocretin receptor 1 (Hcrtr-1) antagonist SB334867 orpreprohypocretin gene deletion blocked both nicotine effects. In the PVN, SB334867 also prevented the activation of corticotrophinreleasing factor (CRF) and arginine-vasopressin (AVP) neurons, which expressed Hcrtr-1. In addition, an increase of the percentage of c-Fos-positive hypocretin cells in the perifornical and dorsomedial hypothalamic (PFA/DMH) areas was found after nicotine (0.8 mg/kg,s.c.) administration. Intracerebroventricular infusion of hypocretin-1 (Hcrt-1) (0.75 nmol/1 l) or footshock stress reinstated a previouslyextinguished nicotine-seeking behavior. The effects of Hcrt-1 were blocked by SB334867, but not by the CRF1 receptor antagonistantalarmin. Moreover, SB334867 did not block CRF-dependent footshock-induced reinstatement of nicotine-seeking while antalarmin was effective in preventing this nicotine motivational response. Therefore, the Hcrt system interacts with CRF and AVP neurons in the PVN and modulates the anxiogenic-like effects of nicotine whereas Hcrt and CRF play a different role in the reinstatement of nicotineseeking.Indeed, Hcrt-1 reinstates nicotine-seeking through a mechanism independent of CRF activation whereas CRF mediates the reinstatement induced by stress.

Nicotine-induced antinociception, rewarding effects and physical dependence are decreased in mice lacking the preproenkephalin gene

It has been shown previously that the endogenous opioid system may be involved in the behavioral effects of nicotine. In the present study, the participation of endogenous enkephalins on nicotine responses has been investigated by using preproenkephalin knock-out mice. Acute nicotine-induced hypolocomotion remained unaffected in these mice. In contrast, antinociception elicited in the tail-immersion and hot-plate tests by acute nicotine administration was reduced in mutant animals. The rewarding properties of nicotine were then investigated using the place-conditioning paradigm. Nicotine induced a conditioned place preference in wild-type animals, but this effect was absent in knock-out mice. Accordingly, in vivo microdialysis studies revealed that the enhancement in dopamine extracellular levels in the nucleus accumbens induced by nicotine was also reduced in preproenkephalin-deficient mice. Finally, the somatic expression of the nicotine withdrawal syndrome precipitated in nicotine-dependent mice by mecamylamine was significantly attenuated in mutant animals. In summary, the present results indicate that endogenous opioid peptides derived from preproenkephalin are involved in the antinociceptive and rewarding properties of nicotine and participate in the expression of physical nicotine dependence.

Influència del consell nutricional en pacients en tractament de deshabituació tabàquica per minimitzar l'augment de pes

El consum de tabac és causa de pèrdua de salut i la primera causa de mort prematura prevenible en els països desenvolupats. Deixar de fumar aporta grans beneficis per a la salut però hi ha un fet que fa que moltes persones es plantegin no deixar aquest hàbit i és la preocupació pel guany ponderal. Diversos estudis consultats apunten a que es produeix un guany mig de 3-4 kg durant el procés de deshabituació tot i que en un percentatge considerable pot ser superior. Les causes d’aquest guany de pes són degudes a diversos factors: recuperació dels sentits del gust i l’olfacte, l’ansietat, la falta d’activitat física i sobre tot el paper que juga la nicotina. La nicotina augmenta la despesa energètica en l’activitat física, augmenta la termogènesi, incrementa el metabolisme basal, inhibeix la gana, produeix pèrdua de pes, afavoreix el buidament gàstric i recentment s’ha vist en rosegadors que la nicotina regula mecanismes cerebrals a nivell del hipotàlem, això ho fa perquè actua inactivant l’acció de l’enzim adenosine 5′-monophosphate-activated protein kinase (AMPK) provocant una pèrdua de la gana i un augment de la despesa energètica al incrementar la temperatura corporal i accelerar el metabolisme de les grasses. Explicar que la majoria dels efectes tenen una base bioquímica pot ajudar al pacient a comprendre la simptomatologia que pateix en el procés de la deshabituació tabàquica.

Salivary cotinine concentrations in daily smokers in Barcelona, Spain: a cross-sectional study

Background: Characterizing and comparing the determinant of cotinine concentrations in different populations should facilitate a better understanding of smoking patterns and addiction. This study describes and characterizes determinants of salivary cotinine concentration in a sample of Spanish adult daily smoker men and women. Methods: A cross-sectional study was carried out between March 2004 and December 2005 in a representative sample of 1245 people from the general population of Barcelona, Spain. A standard questionnaire was used to gather information on active tobacco smoking and passive exposure, and a saliva specimen was obtained to determine salivary cotinine concentration. Two hundred and eleven adult smokers (>16 years old) with complete data were included in the analysis. Determinants of cotinine concentrations were assessed using linear regression models. Results: Salivary cotinine concentration was associated with the reported number of cigarettes smoked in the previous 24 hours (R2 = 0.339; p < 0.05). The inclusion of a quadratic component for number of cigarettes smoked in the regression analyses resulted in an improvement of the fit (R2 = 0.386; p < 0.05). Cotinine concentration differed significantly by sex, with men having higher levels. Conclusion: This study shows that salivary cotinine concentration is significantly associated with the number of cigarettes smoked and sex, but not with other smoking-related variables.

3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors

Nicotine (NIC), the main psychostimulant compound of smoked tobacco, exerts its effects through activation of central nicotinic acetylcholine receptors (nAChR), which become up-regulated after chronic administration. Recent work has demonstrated that the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has affinity for nAChR and also induces up-regulation of nAChR in PC 12 cells. Tobacco and MDMA are often consumed together. In the present work we studied the in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or combined with a chronic schedule of NIC, on the density of nAChR and on serotonin reuptake transporters. MDMA induced significant decreases in [3H]paroxetine binding in the cortex and hippocampus measured 24 h after the last dose and these decreases were not modified by the association with NIC. In the prefrontal cortex, NIC and MDMA each induced significant increases in [3H]epibatidine binding (29.5 and 34.6%, respectively) with respect to saline-treated rats, and these increases were significantly potentiated (up to 72.1%) when the two drugs were associated. Also in this area, [3H]methyllycaconitine binding was increased a 42.1% with NIC + MDMA but not when they were given alone. In the hippocampus, MDMA potentiated the a7 regulatory effects of NIC (raising a 25.5% increase to 52.5%) but alone was devoid of effect. MDMA had no effect on heteromeric nAChR in striatum and a coronal section of the midbrain containing superior colliculi, geniculate nuclei, substantia nigra and ventral tegmental area. Specific immunoprecipitation of solubilised receptors suggests that the up-regulated heteromeric nAChRs contain a4 and b2 subunits. Western blots with specific a4 and a7 antibodies showed no significant differences between the groups, indicating that, as reported for nicotine, up-regulation caused by MDMA is due to post-translational events rather than increased receptor synthesis.

Identifying Specific Cues and Contexts Related to Smoking Craving for the Development of Effective Virtual Environments

Craving is considered the main variable associated with relapse after smoking cessation. Cue Exposure Therapy (CET) consists of controlled and repeated exposure to drug-related cues with the aim of extinguishing craving responses. Some virtual reality (VR) environments, such as virtual bars or parties, have previously shown their efficacy as tools for eliciting smoking craving. However, in order to adapt this technology to smoking cessation interventions, there is a need for more diverse environments that enhance the probability of generalization of extinction in real life. The main objective of this study was to identify frequent situations that produce smoking craving, as well as detecting specific craving cues in those contexts. Participants were 154 smokers who responded to an ad hoc self-administered inventory for assessing craving level in 12 different situations. Results showed that having a drink in a bar/pub at night, after having lunch/dinner in a restaurant and having a coffee in a cafe or after lunch/dinner at home were reported as the most craving-inducing scenarios. Some differences were found with regard to participants' gender, age, and number of cigarettes smoked per day. Females, younger people, and heavier smokers reported higher levels of craving in most situations. In general, the most widely cited specific cues across the contexts were people smoking, having a coffee, being with friends, and having finished eating. These results are discussed with a view to their consideration in the design of valid and reliable VR environments that could be used in the treatment of nicotine addicts who wish to give up smoking.

Uso del cigarrillo elctrónico en la población adulta de la ciudad de Barcelona: estudio mixto de diseño trasversal y de corte etnográfico

Introducció: Els cigarrets electrònics estan dissenyats per alliberar una solució líquida que conté substàncies químiques i nicotina o altres aromes mitjançant vaporització, i imiten l'estètica de la cigarreta convencional. Van ser dissenyats com a substituts del tabac per poder fumar sense córrer el risc de patir els efectes nocius d'aquest consum. El coneixement sobre aquests productes és molt escàs, i la seva comercialització i ús està creant gran controvèrsia en salut pública a causa dels interrogants sobre els possibles riscos per a la salut dels seus usuaris i no usuaris, la seva eficàcia per a la deshabituació tabàquica, i les possibles interferències del seu ús amb les activitats de control del tabac existents i l'aplicació del CMCT de l'OMS. Segons estudis, l'ús d'aquests dispositius s'ha expandit ràpidament, encara que de moment, no s'ha aconseguit definir un patró d'usuaris de cigarrets/cigarros electrònics ni del seu ús. Objectius: definir el patró sociodemogràfic dels usuaris de cigarrets electrònics i del seu ús en el grup poblacional estudiat, i analitzar la relació entre la dependència a la nicotina i el consum tabàquic amb l'ús d'aquests dispositius. Metodologia: consta de dues fases diferenciades però alhora complementàries constituint un estudi mixt, amb una primera fase quantitativa, en la qual es desenvoluparà un estudi observacional transversal, i una segona fase qualitativa, en la qual es desenvoluparà un estudi de tall etnogràfic. La primera fase, consta d'una primera etapa per reclutar els participants de l'estudi a través dels establiments registrats a la Cambra de Comerç de Barcelona i se'ls administrarà dos qüestionaris sobre les característiques sociodemogràfiques i el consum de tabac i l'ús dels cigarrets electrònics. En la segona etapa es recontactarà amb els participants fumadors i exfumadors per omplir un qüestionari sobre la dependència a la nicotina i al tabac previ a la utilització d'aquests dispositius i actual. A la segona fase, es realitzaran entrevistes en profunditat i es crearà un diari de camp per conèixer els motius pels que utilitzen aquests dispositius i la percepció que tenen sobre ells i el seu ús.

Efficacy of virtual reality for triggering smoking craving: relation with level of presence and nicotine dependence

Virtual Reality environments that reproduce typical contexts associated with tobacco use may be useful for aiding smoking cessation. The main objective of this study was to assess the capacity of eight environments to produce the craving to smoke and determine the relation of craving to nicotine dependence and level of presence. The results show that all the environments were able to generate the desire to smoke; a direct relation was found between sense of presence and craving.

Discriminació nicotínica

Per als que no som fumadors, i a la llarga també per a molts fumadors, l'aplicació de la nova llei antitabac és, si es fa correctament, una bona notícia. Durant massa anys la nicotina ha exercit un fort poder discriminatori sobre els no-fumadors, als quals no s'ha reconegut el dret a poder fer les activitats normals, com treballar, sense fum. Almenys inicialment, però, la llei antitabac continuarà mantenint tot el poder discriminatori de la nicotina, traslladant-lo també cap als fumadors [...].