EDITORIAL
Can Cannabis Cause Psychosis? Timothy I Michaels, BA and Vladan Novakovic, MD
Abstract: In recent years, increasing popular support for the medicinal and recreational use of cannabis has led to legalization for both medicinal and recreational purposes in the United States. To the extent that these changes in policy lead to increase widespread use, it is important to consider the association between heavy chronic cannabis use and the onset of psychotic illnesses, such as schizophrenia. This article provides a brief review of evidence that support cannabis use as a risk factor in the complex etiology of psychotic illness. In addition to reviewing psychopharmacology, longitudinal research, and clinical studies, the article addresses the potential implications of current research on public health policy.
O
ver a relatively short period of time, American society has exhibited increasing support for the medicinal and recreational use of cannabis. It is the most commonly used illicit substance in the United States with 12.3% of the population having smoked marijuana in the past 12 months and over 13 million Americans who report smoking on a regular basis. 1 As of November 2014, 23 states and the District of Columbia permit some form of medicinal marijuana use, and by 2015, 4 states, Alaska, Colorado, Oregon, and Washington will have legalized marijuana for recreational use.2 Yet, medical experts are only beginning to understand the risks associated with regular cannabis use; converging evidence suggests that cannabis is a significant risk factor for the onset of schizophrenia and other psychotic illnesses.3,4 One of our patients, John, aged 18 years, had been smoking marijuana since the age of 14. John's smoking had increased from 1 joint to several blunts daily. His parents at first tolerated his use but became alarmed when John experienced command auditory hallucinations giving him instructions to assault his housemaid and warning him of imminent danger coming from his neighbors. After being admitted to an inpatient psychiatric unit, he responded well to medications and therapy. Later on, he continued smoking marijuana only sporadically, but his behavior deteriorated significantly as he became bizarre and disorganized. Schizophrenia, an illness that is characterized by delusions, hallucinations, and odd behavior, is among the top 10 leading causes of disability in the United States.5 It affects approximately 1% of the general population.6 Serious mental illness exerts a toll not only on those suffering directly but also on patients' families, communities, and society as a whole. Despite decades of research that has led to some improvements in treatment, much remains unknown about the specific biological etiology of schizophrenia. Many patients with schizophrenia continue to suffer and are prevented from fully recovering.7 In psychiatry research, cannabis has long been used as a model for understanding psychotic experiences. Acute exposure Department of Psychology, University of Connecticut, Storrs, CT (Michaels), Department of Psychiatry, Mount Sinai School of Medicine, New York, NY. Address correspondence and reprint requests to Timothy I Michaels, BA, Department of Psychology University of Connecticut, 406 Babbidge Road Storrs, CT 06269; E-mail: [email protected] Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/WNF.0000000000000066
to cannabis can result in temporary psychosis, such as paranoia and auditory hallucinations, whereas chronic and heavy use appears to be specifically associated with an increased risk for developing schizophrenia.8,9 Several large studies suggest that 50% of patients admitted to a hospital with cannabis-induced psychosis later developed schizophrenia or another psychotic disorder.10,11 A 2007 review by Moore and colleagues12 reported that those who used cannabis were twice as likely to later develop a psychotic disorder as those who did not use cannabis. Several factors, such as age of exposure, amount of cannabis use, childhood trauma, and a family history of psychotic illness, appear to moderate the link between cannabis and psychosis.13–16 Adolescence may be a particularly sensitive period of increased vulnerability to the effects of cannabis; a study conducted in New Zealand reported that those who used cannabis by the age of 15 years were 4 times more likely to have a diagnosis of schizophrenia than those who used it later in life.4 A Swedish study among military conscripts found a positive linear relation between the amount and frequency of cannabis use and the risk for developing schizophrenia.17 Although no one factor can be identified as being solely responsible for the complex biological changes that lead to psychiatric illness, the interaction of multiple different factors along with environmental influences can significantly contribute toward the onset of psychosis. It is important to note that the direction of the causal link between cannabis and psychosis remains unclear. Does cannabis cause individuals to develop schizophrenia or does being genetically predisposed toward schizophrenia make an individual more likely to abuse cannabis? A recent genetic study with over 2000 participants reported that a genetic liability for schizophrenia increases the likelihood of cannabis use.18 Cannabis use itself may not cause a psychotic break but rather those already likely to develop schizophrenia are at increased risk for using cannabis. The biological complexity of the cannabis plant itself further complicates our ability to understand causality. There are over 70 different cannabinoids in marijuana with delta-9 tetrahydrocannabinol being considered as the main psychoactive compound.19 The concentration of delta-9 tetrahydrocannabinol in confiscated marijuana has steadily increased over the past decade.20 There has also been a marked increase in the recreational use of synthetic cannabis, commonly sold as Spice or K2.21 These compounds typically have a much higher concentration of their psychoactive compound and much less are understood about their biological mechanism of action. In 2012, approximately 11% of U.S. high school seniors reported using synthetic cannabis.22 The use of synthetic cannabis may result in both acute and persistent psychotic experiences.23 Further research is needed to understand the potential harm of this newly available substance. Beyond scientific research and academic debate, the link between cannabis and psychosis has real world implications for public policy and mental health care in the United States. Further steps to legalize cannabis use will inevitably lead to increased availability, thereby facilitating increased use, perhaps among individuals that may not have tried cannabis otherwise. The risks associated with cannabis use are particularly high for adolescents because this is a critical period of development in which the brain is especially susceptible to the potentially harmful effects of
Clinical Neuropharmacology • Volume 38, Number 2, March/April 2015
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
63
Clinical Neuropharmacology • Volume 38, Number 2, March/April 2015
Editorial
cannabis. Although the risk for developing schizophrenia is albeit small, the public needs to be better educated about this issue. Current scientific evidence may not be sufficient to support a complete public policy reversal on cannabis, but it should cause concern among policymakers, health care professionals, and educators. The public needs to be better informed about the risks associated with the widespread use of cannabis. REFERENCES 1. SAMHSA. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. Rockville, MD: Substance Abuse and Mental Health Services Administration;2011. 2. Governing.com. States Laws Marijuana Map (2014). Available from http://www.governing.com/gov-data/state-marijuana-laws-map-medicalrecreational.html. Accessed November 12, 2014. 3. D'Souza DC, Sewell RA, Ranganathan M. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci 2009;259(7):413–431. 4. 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. 5. International Statistical Classification of Diseases and Related Health Problems (ICD–10) [database online]. Geneva, Switzerland: World Health Organization;1992. Updated October 26, 2014. 6. NIMH. What is Schizophrenia? Available at http://www.nimh.nih.gov/ health/topics/schizophrenia/index.shtml Accessed on September 15, 2014. 7. Nadeem Z, McIntosh A, Lawrie S. EBMH notebook: schizophrenia. Evid Based Ment Health 2004;7:2–3. 8. Chopra GS, Smith JW. Psychotic reactions following cannabis use in East Indians. Arch Gen Psychiatry 1974;30(1):24–27. 9. Chopra GS. Studies on psycho-clinical aspects of long-term marihuana use in 124 cases. Int J Addict 1973;8(6):1015–1026.
12. 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. 13. Harley M, Kelleher I, Clarke M, et al. Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence. Psychol Med 2010;40(10):1627–1634. 14. Decoster J, van Os J, Kenis G, et al. Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. Am J Med Genet B Neuropsychiatr Genet 2011;156B(3): 363–369. 15. Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry 1994;51(4):273–279. 16. Bersani G, Orlandi V, Kotzalidis GD, et al. Cannabis and schizophrenia: impact on onset, course, psychopathology and outcomes. Eur Arch Psychiatry Clin Neurosci 2002;252(2):86–92. 17. Manrique-Garcia E, Zammit S, Dalman C, et al. Cannabis, schizophrenia and other non-affective psychoses: 35 years of follow-up of a population-based cohort. Psychol Med 2012;42(6): 1321–1328. 18. Power RA, Verweij KJ, Zuhair M, et al. Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatry 2014;19(11):1201–1204. 19. Mechoulam R. Plant cannabinoids: a neglected pharmacological treasure trove. Br J Pharmacol 2005;146(7):913–915. 20. Mehmedic Z, Chandra S, Slade D, et al. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci 2010;55(5): 1209–1217. 21. Johnson LA, Johnson RL, Alfonzo C. Spice: a legal marijuana equivalent. Mil Med 2011;176(6):718–720.
10. 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.
22. National Institute of Drug Abuse (NIDA). DrugFacts: Spice (“Synthetic Marijuana”). Updated December 2012. Available at http://www. drugabuse.gov/publications/drugfacts/spice-synthetic-marijuana. Accessed on August 1, 2014.
11. Niemi-Pynttäri JA, Sund R, Putkonen H, et al. Substance-induced psychoses converting into schizophrenia: a register-based study of 18,478 Finnish inpatient cases. J Clin Psychiatry 2013;74(1):94–99.
23. Every-Palmer S. Synthetic cannabinoid JWH-018 and psychosis: an explorative study. Drug Alcohol Depen 2011;117(2–3): 152–157.
64
www.clinicalneuropharm.com
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Can Cannabis Cause Psychosis? Timothy I Michaels, BA and Vladan Novakovic, MD
Abstract: In recent years, increasing popular support for the medicinal and recreational use of cannabis has led to legalization for both medicinal and recreational purposes in the United States. To the extent that these changes in policy lead to increase widespread use, it is important to consider the association between heavy chronic cannabis use and the onset of psychotic illnesses, such as schizophrenia. This article provides a brief review of evidence that support cannabis use as a risk factor in the complex etiology of psychotic illness. In addition to reviewing psychopharmacology, longitudinal research, and clinical studies, the article addresses the potential implications of current research on public health policy.
O
ver a relatively short period of time, American society has exhibited increasing support for the medicinal and recreational use of cannabis. It is the most commonly used illicit substance in the United States with 12.3% of the population having smoked marijuana in the past 12 months and over 13 million Americans who report smoking on a regular basis. 1 As of November 2014, 23 states and the District of Columbia permit some form of medicinal marijuana use, and by 2015, 4 states, Alaska, Colorado, Oregon, and Washington will have legalized marijuana for recreational use.2 Yet, medical experts are only beginning to understand the risks associated with regular cannabis use; converging evidence suggests that cannabis is a significant risk factor for the onset of schizophrenia and other psychotic illnesses.3,4 One of our patients, John, aged 18 years, had been smoking marijuana since the age of 14. John's smoking had increased from 1 joint to several blunts daily. His parents at first tolerated his use but became alarmed when John experienced command auditory hallucinations giving him instructions to assault his housemaid and warning him of imminent danger coming from his neighbors. After being admitted to an inpatient psychiatric unit, he responded well to medications and therapy. Later on, he continued smoking marijuana only sporadically, but his behavior deteriorated significantly as he became bizarre and disorganized. Schizophrenia, an illness that is characterized by delusions, hallucinations, and odd behavior, is among the top 10 leading causes of disability in the United States.5 It affects approximately 1% of the general population.6 Serious mental illness exerts a toll not only on those suffering directly but also on patients' families, communities, and society as a whole. Despite decades of research that has led to some improvements in treatment, much remains unknown about the specific biological etiology of schizophrenia. Many patients with schizophrenia continue to suffer and are prevented from fully recovering.7 In psychiatry research, cannabis has long been used as a model for understanding psychotic experiences. Acute exposure Department of Psychology, University of Connecticut, Storrs, CT (Michaels), Department of Psychiatry, Mount Sinai School of Medicine, New York, NY. Address correspondence and reprint requests to Timothy I Michaels, BA, Department of Psychology University of Connecticut, 406 Babbidge Road Storrs, CT 06269; E-mail: [email protected] Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/WNF.0000000000000066
to cannabis can result in temporary psychosis, such as paranoia and auditory hallucinations, whereas chronic and heavy use appears to be specifically associated with an increased risk for developing schizophrenia.8,9 Several large studies suggest that 50% of patients admitted to a hospital with cannabis-induced psychosis later developed schizophrenia or another psychotic disorder.10,11 A 2007 review by Moore and colleagues12 reported that those who used cannabis were twice as likely to later develop a psychotic disorder as those who did not use cannabis. Several factors, such as age of exposure, amount of cannabis use, childhood trauma, and a family history of psychotic illness, appear to moderate the link between cannabis and psychosis.13–16 Adolescence may be a particularly sensitive period of increased vulnerability to the effects of cannabis; a study conducted in New Zealand reported that those who used cannabis by the age of 15 years were 4 times more likely to have a diagnosis of schizophrenia than those who used it later in life.4 A Swedish study among military conscripts found a positive linear relation between the amount and frequency of cannabis use and the risk for developing schizophrenia.17 Although no one factor can be identified as being solely responsible for the complex biological changes that lead to psychiatric illness, the interaction of multiple different factors along with environmental influences can significantly contribute toward the onset of psychosis. It is important to note that the direction of the causal link between cannabis and psychosis remains unclear. Does cannabis cause individuals to develop schizophrenia or does being genetically predisposed toward schizophrenia make an individual more likely to abuse cannabis? A recent genetic study with over 2000 participants reported that a genetic liability for schizophrenia increases the likelihood of cannabis use.18 Cannabis use itself may not cause a psychotic break but rather those already likely to develop schizophrenia are at increased risk for using cannabis. The biological complexity of the cannabis plant itself further complicates our ability to understand causality. There are over 70 different cannabinoids in marijuana with delta-9 tetrahydrocannabinol being considered as the main psychoactive compound.19 The concentration of delta-9 tetrahydrocannabinol in confiscated marijuana has steadily increased over the past decade.20 There has also been a marked increase in the recreational use of synthetic cannabis, commonly sold as Spice or K2.21 These compounds typically have a much higher concentration of their psychoactive compound and much less are understood about their biological mechanism of action. In 2012, approximately 11% of U.S. high school seniors reported using synthetic cannabis.22 The use of synthetic cannabis may result in both acute and persistent psychotic experiences.23 Further research is needed to understand the potential harm of this newly available substance. Beyond scientific research and academic debate, the link between cannabis and psychosis has real world implications for public policy and mental health care in the United States. Further steps to legalize cannabis use will inevitably lead to increased availability, thereby facilitating increased use, perhaps among individuals that may not have tried cannabis otherwise. The risks associated with cannabis use are particularly high for adolescents because this is a critical period of development in which the brain is especially susceptible to the potentially harmful effects of
Clinical Neuropharmacology • Volume 38, Number 2, March/April 2015
www.clinicalneuropharm.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
63
Clinical Neuropharmacology • Volume 38, Number 2, March/April 2015
Editorial
cannabis. Although the risk for developing schizophrenia is albeit small, the public needs to be better educated about this issue. Current scientific evidence may not be sufficient to support a complete public policy reversal on cannabis, but it should cause concern among policymakers, health care professionals, and educators. The public needs to be better informed about the risks associated with the widespread use of cannabis. REFERENCES 1. SAMHSA. Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings. Rockville, MD: Substance Abuse and Mental Health Services Administration;2011. 2. Governing.com. States Laws Marijuana Map (2014). Available from http://www.governing.com/gov-data/state-marijuana-laws-map-medicalrecreational.html. Accessed November 12, 2014. 3. D'Souza DC, Sewell RA, Ranganathan M. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci 2009;259(7):413–431. 4. 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. 5. International Statistical Classification of Diseases and Related Health Problems (ICD–10) [database online]. Geneva, Switzerland: World Health Organization;1992. Updated October 26, 2014. 6. NIMH. What is Schizophrenia? Available at http://www.nimh.nih.gov/ health/topics/schizophrenia/index.shtml Accessed on September 15, 2014. 7. Nadeem Z, McIntosh A, Lawrie S. EBMH notebook: schizophrenia. Evid Based Ment Health 2004;7:2–3. 8. Chopra GS, Smith JW. Psychotic reactions following cannabis use in East Indians. Arch Gen Psychiatry 1974;30(1):24–27. 9. Chopra GS. Studies on psycho-clinical aspects of long-term marihuana use in 124 cases. Int J Addict 1973;8(6):1015–1026.
12. 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. 13. Harley M, Kelleher I, Clarke M, et al. Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence. Psychol Med 2010;40(10):1627–1634. 14. Decoster J, van Os J, Kenis G, et al. Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. Am J Med Genet B Neuropsychiatr Genet 2011;156B(3): 363–369. 15. Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatry 1994;51(4):273–279. 16. Bersani G, Orlandi V, Kotzalidis GD, et al. Cannabis and schizophrenia: impact on onset, course, psychopathology and outcomes. Eur Arch Psychiatry Clin Neurosci 2002;252(2):86–92. 17. Manrique-Garcia E, Zammit S, Dalman C, et al. Cannabis, schizophrenia and other non-affective psychoses: 35 years of follow-up of a population-based cohort. Psychol Med 2012;42(6): 1321–1328. 18. Power RA, Verweij KJ, Zuhair M, et al. Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatry 2014;19(11):1201–1204. 19. Mechoulam R. Plant cannabinoids: a neglected pharmacological treasure trove. Br J Pharmacol 2005;146(7):913–915. 20. Mehmedic Z, Chandra S, Slade D, et al. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci 2010;55(5): 1209–1217. 21. Johnson LA, Johnson RL, Alfonzo C. Spice: a legal marijuana equivalent. Mil Med 2011;176(6):718–720.
10. 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.
22. National Institute of Drug Abuse (NIDA). DrugFacts: Spice (“Synthetic Marijuana”). Updated December 2012. Available at http://www. drugabuse.gov/publications/drugfacts/spice-synthetic-marijuana. Accessed on August 1, 2014.
11. Niemi-Pynttäri JA, Sund R, Putkonen H, et al. Substance-induced psychoses converting into schizophrenia: a register-based study of 18,478 Finnish inpatient cases. J Clin Psychiatry 2013;74(1):94–99.
23. Every-Palmer S. Synthetic cannabinoid JWH-018 and psychosis: an explorative study. Drug Alcohol Depen 2011;117(2–3): 152–157.
64
www.clinicalneuropharm.com
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
