Alkohol: godt eller skidt?

Transkript

1 Alkohol: godt eller skidt? Skadelige effekter Gavnlige effekter

2 Mange SKADELIGE effekter af alkohol Institut for Neurovidenskab og Farmakologi

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5 Ny genstandsgrænse anbefalet af SHS: 1 genstand dgl (12 g alkohol; kvinder) Institut for Neurovidenskab og Farmakologi 2 genstande dgl (24 g alkohol; mænd)

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7 Danske unge har stadig Europa-rekord i druk ESPAD's 2015 undersøgelse foretaget blandt 48 Europæiske lande. Danmark har største andel af årige, som har drukket tæt de seneste 30 dage (>5 genstande): 1. Danmark: 56 procent 2. Østrig: 53 procent 3. Cypern: 51 procent

8 Danske unge har stadig Europa-rekord i druk ESPAD's 2015 undersøgelse foretaget blandt 48 Europæiske lande. Danmark har største andel af årige, som har drukket tæt de seneste 30 dage (>5 genstande): 1. Danmark: 56 procent 2. Østrig: 53 procent 3. Cypern: 51 procent og drukket mest: 1. Danmark: 9% 2. Estland: 6-7% 3. Sverige: 6%

9 Alkohol særligt skadeligt for teenager hjerner T a Saline a 1 0 gikg EtOH 2 0 g/kg EtOH Højt alkoholforbrug à øget risiko for senere afhængighed c - g L o w c v) : ;. Iṉ Hjerner først modne hos 21-årige à Rotteforsøg viser, at unge rotters hukommelse tager mere skade af alkohol end voksnes n Adolescent Adult Fig. 2. Mean (+SEM) total distance swam in the water maze during spatial memory training. EtOH. ethanol. Markwiese et al. (1998) Alcohol Clin Exp Res 22:416-21

10 Alkohol særligt skadeligt for teenager hjerner T a Saline a 1 0 gikg EtOH 2 0 g/kg EtOH Højt alkoholforbrug à øget risiko for senere afhængighed c - g L o w c v) : ;. Iṉ Hjerner først modne hos 21-årige à Rotteforsøg viser, at unge rotters hukommelse tager mere skade af alkohol end voksnes n Adolescent Adult Fig. 2. Mean (+SEM) total distance swam in the water maze during spatial memory training. EtOH. ethanol. Markwiese et al. (1998) Alcohol Clin Exp Res 22:416-21

11 Enkelte GAVNLIGE effekter af alkohol Institut for Neurovidenskab og Farmakologi

12 Holahan et al Texas-studium I: Let og moderat alkohol indtagelse giver lavere dødelighed Ukorrigeret Korrigeret Afholdende: 0 genstande Light: <1 genstande Moderate: 1-<3 genstande Heavy: >3 genstande Afholdenhed + heavy drinking: 50% øget mortalitet vs. Let og moderat alkoholindtagelse Fig. 1. Cumulative hazard of mortality across 20 years by baseline alcohol consumption group membership for an initial model controlling for age and gender. Fig. 2. Cumulative hazard of mortality across 20 years by baseline alcohol consumption group membership for a model controlling for all covariates.

13 Vin, øl eller anden spiritus??

14 Holahan et al Texas-studium II: Vin eller anden alkohol lige god! Institut for Neurovidenskab og Farmakologi Ukorrigeret Korrigeret FIGURE 1. Cumulative hazard of mortality across 20 years among moderate drinkers by proportion of ethanol from wine consumption for an initial model controlling only for overall daily ethanol consumption (n = 457) FIGURE 2. Cumulative hazard of mortality across 20 years among moderate drinkers by proportion of ethanol from wine consumption for a full model controlling for sociodemographic, behavioral, and health status factors, as well as for overall daily ethanol consumption (n = 457)

15 Er der gavnlige effekter af antioxidanter i rødvin? Antioxidanter (resveratrol og flavonoider) har gavnlige effekter: Dyremodeller for cancer og andre sygdomme, hvor antioxidanter sprøjtes ind i høje doser Problem: resveratrol har lav biotilgængelighed og kort t 1/2 Franske paradoks: Formentlig pga gavnlig moderat alkoholindtagelse og ikke rødvins-antioxidanter Sidste ord ikke sagt i den sag!

16 Persistent cannabis users show neuropsychological decline from childhood to midlife Madeline H. Meier a,b,1, Avshalom Caspi a,b,c,d,e, Antony Ambler e,f, HonaLee Harrington b,c,d, Renate Houts b,c,d, Richard S. E. Keefe d, Kay McDonald f, Aimee Ward f, Richie Poulton f, and Terrie E. Moffitt a,b,c,d,e a Duke Transdisciplinary Prevention Research Center, Center for Child and Family Policy, b Department of Psychology and Neuroscience, and c Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708; d Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710; e Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King s College London, London SE5 8AF, United Kingdom; and f Dunedin Multidisciplinary Health and Development Research Unit, Department of Preventive and Social Medicine, School of Medicine, University of Otago, Dunedin 9054, New Zealand Edited by Michael I. Posner, University of Oregon, Eugene, OR, and approved July 30, 2012 (received for review April 23, 2012) Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents. neuropsychological test performance after a period of abstinence from cannabis. There are two commonly cited potential limitations of this approach. One is the absence of data on initial, precannabis-use neuropsychological functioning. It is possible that differences in test performance between cannabis users and controls are attributable to premorbid rather than cannabis-induced deficits (17 20). A second limitation is reliance on retrospectively reported quantity, frequency, duration, and age-of-onset of cannabis use, often inquired about years after initiation of heavy use. A prospective, longitudinal investigation of the association between cannabis use and neuropsychological impairment could redress these limitations and strengthen the existing evidence base by assessing neuropsychological functioning in a sample of youngsters before the onset of cannabis use, obtaining prospective data on cannabis use as the sample is followed over a number of years, and readministering neuropsychological tests after some members of the sample have developed a pattern of long-term cannabis use. To our knowledge, only one prospective, longitudinal study of the effects of cannabis on neuropsychological functioning has been conducted (21), and, in this study, the sample was small and the average duration of regular cannabis use was only 2 y. In the present study, we investigated the association between persistent cannabis use prospectively assessed over 20 y and Proc Natl Acad Sci U S A. 2012

17 p =.03 p =.0002 p =.73 p = Full-Scale IQ Child IQ Adult IQ Full-Scale IQ Child IQ Adult IQ Infrequent Cannabis Use at Age 38 (n=17) Frequent Cannabis Use at Age 38 (n=19) Infrequent Cannabis Use at Age 38 (n=13) Frequent Cannabis Use at Age 38 (n=20) Adolescent-Onset (Used Cannabis Weekly Before Age 18) Adult-Onset (Did Not Use Cannabis Weekly Before Age 18) Fig. 3. Postcessation IQ among former persistent cannabis users. This figure is restricted to persistent cannabis users, defined as study members with two or more diagnoses of cannabis dependence. Shown is full-scale IQ in childhood and adulthood. IQ is plotted as a function of (i) age of onset of at least weekly cannabis use and (ii) the frequency of cannabis use at age 38 y. Infrequent use was defined as weekly or less frequent use in the year preceding testing at age 38 y. Median use among infrequent and frequent adolescent-onset cannabis users was 14 (range: 0 52) and 365 (range: ) d, respectively. Median use among infrequent and frequent adult-onset cannabis users was 6 (range: 0 52) and 365 (range: ) d, respectively. IQ decline was apparent even after cessation of cannabis use for adolescent-onset former persistent cannabis users. Error bars = SEs. Ø Personer med tidligere langvarigt misbrug af cannabis under teenageårene el som voksne Ø Alle testet ved alder 38 år, men stoppede alle med hashrygning før IQ-testen Ø Selv mindre hyppig hashrygning før 18 års alderen giver fald i IQ testet som 38-årig Proc Natl Acad Sci U S A. 2012

18 Genterapi: En fremtidig behandlingsform ved stofafhængighed? Rat brain Genterapi Normal Sagittal hjerne view Woldbye et al Brain

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20 OPTOGENETIK: En hel ny metode til at regulere hjerneaktivitet Opsin gener, der responderer på lys indsat i neuroner via viral vectors Opsiner reagerer på lys med excitation (Na+pumpe) eller inhibition (Cl--pumpe) Lyslederkabler implanteres i specifikke hjerneregioner Axelsen T et al. (2015) Ugeskr Læger Zhang et al. (2010) Nature Protocols

21 OPTOGENETIK: En hel ny metode til at regulere hjerneaktivitet Axelsen T et al. (2015) Ugeskr Læger Opsin gener, der responderer på lys indsat i neuroner via viral vectors Opsiner reagerer på lys med excitation (Na+pumpe) eller inhibition (Cl--pumpe) Lyslederkabler implanteres i specifikke hjerneregioner Zhang et al. (2010) Nature Protocols

22 BLA Glu NAc Blåt lys Stuber et al. (2011) Nature 475: