Kann Cannabis das Risiko für schizophrene Psychosen erhöhen?

Zusammenfassung

Hintergrund: Cannabis wurde in den letzten Jahren zunehmend als einer der wichtigsten umweltbezogenen Risikofaktoren für die Entstehung von schizophrenen Psychosen diskutiert. Dies ist hauptsächlich auf folgende Beobachtungen zurückzuführen: 1. Bei hohen Dosen kann Cannabis auch bei gesunden Personen vorübergehend akute psychotische Symptome auslösen. 2. Patienten mit schizophrenen Psychosen missbrauchen Cannabis deutlich häufiger als altersvergleichbare gesunde Kontrollpersonen.

Fragestellung: Es ist weiterhin umstritten, ob Cannabis kausal an der Entstehung von schizophrenen Psychosen beteiligt ist. In der vorliegenden Arbeit wurden deshalb die wichtigsten Evidenzen, die für oder gegen einen kausalen Zusammenhang zwischen Cannabiskonsum und Auslösung schizophrener Psychosen sprechen, gesichtet und kritisch überprüft.

Methodik: Systematische Literaturrecherche in den Datenbanken PubMed, ISI Web of Science und PsycINFO zu den Schlüsselwörtern cannabis, marijuana, THC, hashish, psychosis, schizophrenia.

Schlussfolgerungen: Es zeigte sich, dass ein kausaler Zusammenhang zwar nicht eindeutig belegbar, aber doch zumindest plausibel ist. Die Ergebnisse wiesen auch darauf hin, dass der Konsum von Cannabis insbesondere bei einem niedrigen Einstiegsalter das Risiko für schizophrene Psychosen erhöht.

Abstract

Background: In recent years, cannabis has been increasingly discussed as one of the most important environmental risk factors for developing schizophrenic psychoses. This is mainly due to the following observations. (i) Cannabis at high doses can cause acute transient psychotic symptoms even in healthy individuals. (ii) Patients with schizophrenia abuse cannabis more often than age-matched healthy controls.

Objectives: It is still controversial whether cannabis use can cause schizophrenic psychoses that would not have occurred otherwise. In our review, we have critically evaluated the evidence for a causal link between cannabis use and schizophrenic psychoses.

Methods: A systematic literature review in PubMed, ISI Web of Science and PsycINFO was carried out using the following keywords: cannabis, marijuana, THC, hashish, psychosis, schizophrenia.

Conclusions: We have concluded that although a causal relationship between cannabis use and schizophrenic psychoses cannot be definitely proven, the available evidence strongly supports its plausibility. Furthermore, the results of the review indicate that cannabis might cause psychosis especially in individuals with a predisposition for schizophrenia and in adolescents with an early onset of cannabis use.

Schlüsselwörter

Cannabis - Schizophrenie - Psychose - Kausalität - Review

Key words

cannabis - schizophrenia - psychosis - causal inference - review

• Literatur

• 1 Annual Report 2010 on the State of the Drugs Problem in Europe. Press Release; 2010
• 2 Deutsche Beobachtungsstelle für Drogen und Drogensucht. Press Release; 2010
• 3 BZgA: Bundeszentrale für gesundheitliche Aufklärung. 2010
• 4 Pabst A, Piontek D, Kraus L et al. Substanzkonsum und substanzbezogene Störungen. Ergebnisse des Epidemiologischen Suchtsurveys 2009. Sucht 2010; 56: 327-336
• 5 Koskinen J, Lohonen J, Koponen H et al. Rate of cannabis use disorders in clinical samples of patients with schizophrenia: a meta-analysis. Schizophr Bull 2010; 36: 1115-1130
• 6 Drewe M, Drewe J, Riecher-Rossler A. Cannabis and risk of psychosis. Swiss Med Wkly 2004; 134: 659-663
• 7 Smieskova R, Allen P, Simon A et al. Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study. Hum Brain Mapp 16.09.2011; (Epub ahead of print)
• 8 Wobrock T, Falkai P. Sertindol in der Schizophreniebehandlung. Eine kritische Übersicht. Die Psychiatrie 2007; 4: 117-125
• 9 Gouzoulis-Mayfrank E. Duale Diagnose Psychose und Sucht. Fortschr Neurol Psychiatr 2006; 74:  528-547
• 10 Rätsch C. Enzyklopädie der psychoaktiven Pflanzen. Aarau: AT Verlag; 2002
• 11 Iversen L. Cannabis and the brain. Brain 2003; 126: 1252-1270
• 12 Castle DJ, Murray R, D’Souza DC. Marijuana and madness. Cambridge: Cambridge University Press; 2012
• 13 Dean B, Sundram S, Bradbury R et al. Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience 2001; 1031: 9-15
• 14 Zavitsanou K, Garrick T, Huang XF. Selective antagonist [H-3]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog Neuro-Psychoph 2004; 28: 355-360
• 15 D’Souza DC, Perry E, MacDougall L et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 2004; 29: 1558-1572
• 16 Morrison PD, Zois V, McKeown DA et al. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med 2009; 3910: 1607-1616
• 17 Solowij N. Cannabis and Cognitive Functioning. Cambridge: Cambridge University Press; 1998
• 18 Ranganathan M, D’Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology 2006; 188: 425-444
• 19 Johns A. Psychiatric effects of cannabis. Br J Psychiatry 2001; 178: 116-122
• 20 D’Souza DC, Sewell RA, Ranganathan M. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci 2009; 259: 413-431
• 21 Association AP. Diagnostic and statistical manual of mental disorders (4th ed.). Text revision (DSM-IV-TR). Washington: American Psychiatric Association; 2000
• 22 WHO. Internationale Klassifikation psychischer Störungen: ICD 10. 1992
• 23 Hasin D, Hatzenbuehler ML, Keyes K et al. Substance use disorders: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) and International Classification of Diseases, 10th ed. (ICD-10). Addiction 2006; 101 (Suppl. 01) 59-75
• 24 Saunders JB. Substance dependence and non-dependence in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD): can an identical conceptualization be achieved?. Addiction 2006; 101 (Suppl. 01) 48-58
• 25 Hasin D, Samet S, Nunes E et al. Diagnosis of comorbid psychiatric disorders in substance users assessed with the Psychiatric Research Interview for Substance and Mental Disorders for DSM-IV. Am J Psychiatry 2006; 163: 689-696
• 26 Arendt M, Rosenberg R, Foldager L et al. Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases. Br J Psychiatry 2005; 187: 510-515
• 27 Smith DE. Acute and Chronic Toxicity of Marijuana. J Psychedel Drug 1968; 2: 37-47
• 28 Schwartz RH. Marijuana: an overview. Pediatr Clin North Am 1987; 34: 305-317
• 29 Verdoux H, Sorbara F, Gindre C et al. Cannabis use and dimensions of psychosis in a non-clinical population of female subjects. Eur Psychiat 2002; 17: 180s-181s
• 30 Barnwell SS, Earleywine M, Wilcox R. Cannabis, motivation, and life satisfaction in an internet sample. Subst Abuse Treat Prev Policy 2006; 1: 2
• 31 Zammit S, Moore TH, Lingford-Hughes A et al. Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br J Psychiatry 2008; 193: 357-363
• 32 Talamo A, Centorrino F, Tondo L et al. Comorbid substance-use in schizophrenia: relation to positive and negative symptoms. Schizophr Res 2006; 86: 251-255
• 33 Solowij N, Battisti R. The chronic effects of cannabis on memory in humans: a review. Curr Drug Abuse Rev 2008; 1: 81-98
• 34 Martin-Santos R, Fagundo AB, Crippa JA et al. Neuroimaging in cannabis use: a systematic review of the literature. Psychol Med 2010; 40: 383-398
• 35 Treffert DA. Marijuana use in schizophrenia: a clear hazard. Am J Psychiatry 1978; 135: 1213-1215
• 36 Turner WM, Tsuang MT. Impact of substance abuse on the course and outcome of schizophrenia. Schizophr Bull 1990; 16: 87-95
• 37 Martinez-Arevalo MJ, Calcedo-Ordonez A, Varo-Prieto JR. Cannabis consumption as a prognostic factor in schizophrenia. Br J Psychiatry 1994; 164: 679-681
• 38 Yucel M, Bora E, Lubman DI et al. The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample. Schizophr Bull 2012 38: 316-330
• 39 Rabin RA, Zakzanis KK, George TP. The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis. Schizophr Res 2011; 128: 111-116
• 40 Loberg EM, Hugdahl K. Cannabis use and cognition in schizophrenia. Front Hum Neurosci 2009; 3: 53
• 41 Meijer JH, Dekker N, Koeter MW et al. Cannabis and cognitive performance in psychosis: a cross-sectional study in patients with non-affective psychotic illness and their unaffected siblings. Psychol Med 2012; 42: 705-716
• 42 Coulston CM, Perdices M, Tennant CC. The neuropsychology of cannabis and other substance use in schizophrenia: review of the literature and critical evaluation of methodological issues. Aust N Z J Psychiatry 2007; 41: 869-884
• 43 Hill AB. The Environment and Disease: Association or Causation?. Proc R Soc Med 1965; 58: 295-300
• 44 McLaren JA, Silins E, Hutchinson D et al. Assessing evidence for a causal link between cannabis and psychosis: a review of cohort studies. Int J Drug Policy 2010; 21: 10-19
• 45 Andreasson S, Allebeck P, Engstrom A et al. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 1987; 2 (8574) 1483-1486
• 46 Tien AY, Anthony JC. Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. J Nerv Ment Dis 1990; 178: 473-480
• 47 van Os J, Bak M, Hanssen M et al. Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol 2002; 156: 319-327
• 48 Arseneault L, Cannon M, Poulton R et al. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002; 325 (7374) 1212-1213
• 49 Fergusson DM, Horwood LJ, Ridder EM. Tests of causal linkages between cannabis use and psychotic symptoms. Addiction 2005; 100: 354-366
• 50 Wiles NJ, Zammit S, Bebbington P et al. Self-reported psychotic symptoms in the general population: results from the longitudinal study of the British National Psychiatric Morbidity Survey. Br J Psychiatry 2006; 188: 519-526
• 51 Kuepper R, van Os J, Lieb R et al. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ 2011; 342: d738
• 52 Hambrecht M, Hafner H. Substance abuse and the onset of schizophrenia. Biol Psychiatry 1996; 40: 1155-1163
• 53 Hambrecht H, Häfner H, Riecher-Rössler A. „Weiche“ Drogen: eine Ursache von Schizophrenie?. Münch Med Wschr 1996; 138: 430-431
• 54 Large M, Sharma S, Compton MT et al. Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry 2011; 68: 555-561
• 55 Wetzler S, Marlowe DB. The diagnosis and assessment of depression, mania, and psychosis by self-report. J Pers Assess 1993; 60: 1-31
• 56 Degenhardt L, Hall W, Lynskey M. Testing hypotheses about the relationship between cannabis use and psychosis. Drug Alcohol Depend 2003; 71 (01) 37-48
• 57 Ajdacic-Gross V, Lauber C, Warnke I et al. Changing incidence of psychotic disorders among the young in Zurich. Schizophrenia Research 2007; 95 (01) 9-18
• 58 Bundesamt für Gesundheit. Press Release; 2005
• 59 Frisher M, Crome I, Martino O et al. Assessing the impact of cannabis use on trends in diagnosed schizophrenia in the United Kingdom from 1996 to 2005. Schizophr Res 2009; 113 (02) 123-128
• 60 Arseneault L, Cannon M, Witton J et al. Causal association between cannabis and psychosis: examination of the evidence. Brit J Psychiat 2004; 184: 110-117
• 61 Zammit S, Allebeck P, Andreasson S et al. Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 2002; 325 (7374) 1199
• 62 Hickman M, Vickerman P, Macleod J et al. Cannabis and schizophrenia: model projections of the impact of the rise in cannabis use on historical and future trends in schizophrenia in England and Wales. Addiction 2007; 102 (04) 597-606
• 63 Macleod J, Oakes R, Copello A et al. Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. Lancet 2004; 363 (9421) 1579-1588
• 64 Macleod J, Davey Smith G, Hickman M. Does cannabis use cause schizophrenia?. Lancet 2006; 367 (9516) 1055
• 65 Leweke FM, Giuffrida A, Wurster U et al. Elevated endogenous cannabinoids in schizophrenia. Neuroreport 1999; 10 (08) 1665-1669
• 66 Chambers RA, Krystal JH, Self DW. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol Psychiatry 2001; 50 (02) 71-83
• 67 Kuepper R, Morrison PD, van Os J et al. Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines. Schizophr Res 2010; 121 (01) 107-117
• 68 Howes OD, Kambeitz J, Kim E et al. The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment: Meta-analysis of Imaging Studies. Arch Gen Psychiatry 02.04.2012; (Epub ahead of print)
• 69 Egan MF, Goldberg TE, Kolachana BS et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98 (12) 6917-6922
• 70 Estrada G, Fatjo-Vilas M, Munoz MJ et al. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Acta Psychiatr Scand 2011; 123 (06) 485-492
• 71 Bilder RM, Volavka J, Lachman HM et al. The catechol-O-methyltransferase polymorphism: Relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology 2004; 29 (11) 1943-1961
• 72 Meyer-Lindenberg A. Imaging genetics of schizophrenia. Dialogues Clin Neurosci 2010; 12 (04) 449-456
• 73 Caspi A, Moffitt TE, Cannon M et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry 2005; 57 (10) 1117-1127
• 74 Costas J, Sanjuan J, Ramos-Rios R et al. Interaction between COMT haplotypes and cannabis in schizophrenia: a case-only study in two samples from Spain. Schizophr Res 2011; 127 (01) 22-27
• 75 van Winkel R, van Beveren NJ, Simons C. AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder. Neuropsychopharmacology 2011; 36 (12) 2529-2537
• 76 Zammit S, Spurlock G, Williams H et al. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br J Psychiatry 2007; 191: 402-407
• 77 Zammit S, Owen MJ, Evans J et al. Cannabis, COMT and psychotic experiences. Br J Psychiatry 2011; 199: 380-385
• 78 Henquet C, Rosa A, Delespaul P et al. COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of ‘switching on’ hallucinations in the flow of daily life. Acta Psychiatr Scand 2009; 119 (02) 156-160
• 79 Henquet C, Rosa A, Krabbendam L et al. An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 2006; 31 (12) 2748-2757
• 80 Casadio P, Fernandes C, Murray RM et al. Cannabis use in young people: The risk for schizophrenia. Neurosci Biobehav Rev 2011; 35 (08) 1779-1787
• 81 Lorenzetti V, Lubman DI, Whittle S et al. Structural MRI findings in long-term cannabis users: what do we know?. Subst Use Misuse 2010; 45 (11) 1787-1808
• 82 Yucel M, Zalesky A, Takagi MJ et al. White-matter abnormalities in adolescents with long-term inhalant and cannabis use: a diffusion magnetic resonance imaging study. J Psychiatry Neurosci 2010; 35 (06) 409-412
• 83 Moore TH, Zammit S, Lingford-Hughes A et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370 (9584) 319-328
• 84 Boydell J, van Os J, Caspi A et al. Trends in cannabis use prior to first presentation with schizophrenia, in South-East London between 1965 and 1999. Psychol Med 2006; 36 (10) 1441-1446
• 85 Schubart CD, Sommer IE, van Gastel WA et al. Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr Res 2011; 130 (01) 216-221
• 86 Bhattacharyya S, Morrison PD, Fusar-Poli P et al. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology 2010; 35 (03) 764-774
• 87 Zuardi AW, Hallak JE, Dursun SM et al. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol 2006; 20 (05) 683-686
• 88 Roser P, Vollenweider FX, Kawohl W. Potential antipsychotic properties of central cannabinoid (CB (1)) receptor antagonists. World J Biol Psychia 2010; 11 (02) 208-219
• 89 Coulston C, Perdices M, Henderson AF et al. Cannabinoids for the Treatment of Schizophrenia? A Balanced Neurochemical Framework for Both Adverse and Therapeutic Effects of Cannabis Use. Schizophr Res Treatment 2011; 2011: 501726
• 90 Leweke FM, Koethe D, Gerth CW et al. The endocannabinoid modulator cannabidiol as an antipsychotic. Results from the first controlled randomized clinical trial in acute schizophrenia. Biol Psychiat 2005; 57 (08) 135s-135s
• 91 Morgan CJ, Curran HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry 2008; 192 (04) 306-307
• 92 Morgan CJ, Schafer G, Freeman TP et al. Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study. Br J Psychiatry 2010; 197 (04) 285-290
• 93 Ashton CH. Pharmacology and effects of cannabis: a brief review. Br J Psychiatry 2001; 178: 101-106
• 94 Murray RM, McDonald C, Bramon E. Neurodevelopmental impairment, dopamine sensitisation, and social adversity in schizophrenia. World Psychiatry 2002; 1 (03) 137-145
• 95 Jockers-Scherubl MC, Wolf T, Radzei N et al. Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31 (05) 1054-1063
• 96 Grech A, Van Os J, Jones PB et al. Cannabis use and outcome of recent onset psychosis. Eur Psychiatry 2005; 20 (04) 349-353