1 Gene Environment Interaction THC THC THC COMT Pre-adolescence period Cannabis and Psychosis: Transition to Psychosis Amresh Shrivastava, MD,DPM,MRCPsych.FRCPC, Johnston M Ph.D, Terpstra K, MA.Bureau Y Ph.D. Associate Professor of Psychiatry Western University, London, Ontario, Canada , Clinical Syndromes Psychotic disorder Schizophrenia spectrum Substance abuse psychosis Psychosis NOS ARMS Psychosis/schizophrenia Affective disorder Anxiety disorder/ other disorders -1200 BC Indus Valley- five sacred plants 1894 No evidence of mental or moral injuries 1928 Recreational use banned in UK 1942 Removed from American pharmacopeia 1961 60 Nations signed ‘end cannabis in 25 years 1985 THC isolated 1970 Clear evidence of psychological effect 1987 First evidence of link with schizophrenia 1988 CB receptors discovered by Hewlett & Devane 1992 First Endocannabinoid discovered 2000 Agonist shown to reduce plasticity 2002 Effect on long term plasticity 2005 Cannabis based medicine for MS in Canada No vulnerability (1) Biological vulnerability Genetic studies (2) Cannabis induced neurobiological changes Seen in neurochemical and neuroimaging (3) Cognitive dysfunction(4) Seen in memory, executive function, information processing Cognitive dysmetria (4) Excessive THC Psychosocial stress & environmental event External biological events (5) Abstract: Abbreviated: Trajectory Gene Environment Interaction 1 Neurochemical Outcome Dopamine Serotonine Psychosocial unmasking Environmental Unmasking Biological Unmasking Genotype Behavioral traits-correlates Life style factors Risk factors Brain vulnerability Essential etiological factors 1 Family History Conclusion there is robust and consistent association between cannabis consumption Cannabis supposedly cases almost similar neurobiological changes as seen in schizophrenia Association of cannabis , psychosis in Normal individual and cannabis use in Schizophrenia is not clearly known cannabis does not cause any structural changes per say. the alleged role played by the endocannabinoid system in later developmental phases such as the adolescent one, prompted speculation that alterations in the endocannabinoid tone Although the direct pathway of causation from cannabis consumption to development for psychosis is not known, pharmacological as well as behavioral studies intend to develop better intervention and prevention of psychosis which remains critical. Biological Endophenotype Gene PFC Amygdala Brain Maturation CB Receptor Cannabinoids Brain Changes Executive function Information processing Cognitive dyscontrol Dopamine 5 HT Behavioral Changes 2 THC THC THC COMT Pre-adolescence period Adolescence Post adolesence 3 Possible trajectory of Cannabis and related Psychosis ARMS – At risk mental state, THC – Tetrahydro cannabidole,PFC – Prefrontal cortex, COMT – Catechol-o-methyl transferase, 1,2 and 3- different levels biological events Published: Shrivastava A. Johnston M, Terpstra K, Bureau Y.Pathways to Psychosis in Cannabis  Abuse.Clin Schizophr Relat Psychoses. 2013 Mar 14:1-18. [Epub ahead of print]   Shrivastava A. Johnston M, Tsuang M Cannabis use and cognitive dysfunction..Indian J Psychiatry. 2011 Jul;53(3):187-91. doi: 10.4103/0019-5545.86796.