The marijuana, psychosis connection

Feb 16, 15 The marijuana, psychosis connection

Increasingly, we are contacted by parents desperate to learn more about the strong association between adolescent marijuana use and psychosis. Their typical and tragic messages go something like this: “We never knew. We thought marijuana wasn’t even addictive and that it was less harmful than alcohol. Why did nobody tell us?”

So, we’ve decided to revisit this issue periodically with a guide to reputable research conducted around the world — and writing we’ve compiled here on drthurstone.com.

Update, Feb. 16, 2015: Today, in one of the world’s most prominent medical journals, Lancet Psychiatry, a team of 23 scientists published a large study showing that people who smoked high-grade marijuana — about 16 percent THC with no CBD, which is similar to average U.S. varieties of marijuana — were five times more likely than non-users to have a psychotic disorder. Weekend users were three times more likely than non-users to have a psychotic disorder.

Use of only this “typical” pot — a substance also consistent with what Colorado adults routinely divert to teens in this state — was responsible for 24 percent of those adults presenting with first-episode psychosis to the psychiatric services in south London.

“This paper suggests that we could prevent almost one quarter of cases of psychosis if no-one smoked high potency cannabis,” stated Sir Robin Murray, professor of Psychiatric Research at the Institute of Psychiatry at King’s College and senior researcher on the study. “This could save young patients a lot of suffering and the Health Services a lot of money.”

England is telling the world it cannot afford these exorbitant tolls on life and public healthcare costs. The United States should, at the very least, bother to calculate these cases and costs before pressing ahead with marijuana legalization.

What is psychosis?

First, here’s a refresher on psychosis published here May 23, 2012, after researchers at the Royal College of Surgeons in Ireland showed how marijuana use during adolescence causes specific changes in regions of the brain associated with psychosis and the psychotic disorder schizophrenia.

As I explained:

“Psychosis is a medical term that describes auditory and visual hallucinations. Simply put, people who are psychotic are delusional. They may see or hear things that aren’t real. Their minds often play terrible tricks on them that surface as extreme paranoia and anxiety. There are different psychotic disorders, but people tend to be most familiar with schizophrenia — which is one of the most emotionally difficult diagnoses for me to deliver to young people and their families.

“The first study revealing the link between adolescent marijuana use and the development of psychosis in early adulthood was released in Sweden in 1988. Since then, six other large studies have been conducted. Like that first Swedish investigation, they have shown a two-to-four-fold increase in the development of psychosis in young adults who used marijuana during adolescence. These studies have controlled for more than 60 variables, including gender, family history of psychosis, pre-existence of psychosis and the use of other substances along with marijuana. All of these studies have reinforced the relationship between adolescent marijuana use and the development of psychosis.”

Marijuana use and brain abnormalities

Northwestern University researchers’ findings were published in December 2013 in the journal Schizophrenia Bulletin and supported by grants from the National Institutes of Health and the National Institute on Drug Abuse. Their report is titled, “Cannabis-Related Working Memory Deficits and Associated Subcortical Morphological Differences in Healthy Individuals and Schizophrenia Subjects.” Its authors are Matthew J. Smith, Derin J. Cobia, Lei Wang, Kathryn I. Alpert, Will J. Cronenwett, Morris B. Goldman, Daniel Mamah, Deanna M. Barch, Hans C. Breiter and John G. Csernansky. You can learn more about the study from a statement issued by Northwestern University

While this study did not examine the onset of psychosis, it did show adolescent marijuana use was associated with structural changes in the brain consistent with the structures observed in people who suffer from schizophrenia, which includes psychosis.

From a summary of the research issued by the university:

“Teens who were heavy marijuana users — smoking it daily for about three years — had abnormal changes in their brain structures related to working memory and performed poorly on memory tasks, reports a new Northwestern Medicine® study.

“A poor working memory predicts poor academic performance and everyday functioning.

“The brain abnormalities and memory problems were observed during the individuals’ early twenties, two years after they stopped smoking marijuana, which could indicate the long-term effects of chronic use. Memory-related structures in their brains appeared to shrink and collapse inward, possibly reflecting a decrease in neurons.

“The study also shows the marijuana-related brain abnormalities are correlated with a poor working memory performance and look similar to schizophrenia-related brain abnormalities. Over the past decade, Northwestern scientists, along with scientists at other institutions, have shown that changes in brain structure may lead to changes in the way the brain functions.

“This is the first study to target key brain regions in the deep subcortical gray matter of chronic marijuana users with structural MRI and to correlate abnormalities in these regions with an impaired working memory. Working memory is the ability to remember and process information in the moment and — if needed — transfer it to long-term memory. Previous studies have evaluated the effects of marijuana on the cortex, and few have directly compared chronic marijuana use in otherwise healthy individuals and individuals with schizophrenia.

“The younger the individuals were when they started chronically using marijuana, the more abnormally their brain regions were shaped, the study reports. The findings suggest that these regions related to memory may be more susceptible to the effects of the drug if abuse starts at an earlier age.

‘The study links the chronic use of marijuana to these concerning brain abnormalities that appear to last for at least a few years after people stop using it,’ said lead study author Matthew Smith, an assistant research professor in psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. ‘With the movement to decriminalize marijuana, we need more research to understand its effect on the brain.'”



Marijuana use and schizophrenia

Today, people championing marijuana legalization and generally looking to explain away the potential harms of using this addictive drug are trumpeting research conducted at Harvard University that found no causal link or association between adolescent marijuana use and development of schizophrenia. The preliminary study, published December 2013 in the journal Schizophrenia Research, is titled, “A Controlled Family Study of Cannabis Users With and Without Psychosis.” Its authors are Ashley C. Proal, Jerry Fleming, Juan A. Galvez-Buccollini, Lynn E. DeLisi.

For the purposes of this guide, it is important to note:

  • the main finding is that it’s not cannabis use alone, but, rather, an interplay between use and an underlying genetic vulnerability that may cause schizophrenia. This is consistent with previous research findings.
  • researchers acknowledge the limitations of this study. They compared four groups of research subjects ranging in size from 32 to 87 people. The researchers concede this sample size may not be large enough to detect actual differences. Indeed. For example, one study that found marijuana use was linked to a fourfold risk of developing psychosis involved 45,570 people and followed them for a 15-year period (See “Lancet. 1987 Dec 26;2(8574):1483-6. “Cannabis and schizophrenia. A longitudinal study of Swedish conscripts”.
  • this study is cross-sectional, not longitudinal. Longitudinal research — such as the 1987 study cited above — is needed to prove or disprove causal associations between marijuana use and psychosis and/or schizophrenia.
  • this research does not diminish repeated and widespread findings of strong association between adolescent marijuana use and psychosis. And while psychosis is not necessarily schizophrenia, it would be foolish to believe psychosis isn’t worth worrying about and guarding against.

Research previously cited on DrThurstone.com

Bertha Madras, a professor at Harvard University’s School of Medicine, summarizes the findings of Large M, et al., Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry. 2011 Jun;68(6):555-61.

“Persistent cannabis users show neuropsychological decline from childhood to midlife.” Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS, McDonald K, Ward A, Poulton R, Moffitt TE. Researchers found permanent declines in IQ from adolescent onset of marijuana use to age 38. The decline included all four indices of IQ: working memory, processing speed, perceptual reasoning and verbal comprehension, and is consistent with research examining the drug’s link to psychosis.

Causal association between cannabis and psychosis: examination of the evidence

This 2004 study — so it’s a decade old — published in the British Journal of Psychiatry, is the peer-reviewed research of Louise Arsenault of the Institue of Psychiatry, King’s College London; Mary Cannon, Division of Psychological Medicine, Institute of Psychiatry, King’s College London; John Witton, National Addiction Centre, Institute of Psychiatry, King’s College London; and Robin M. Murray, Institute of Psychiatry, King’s College London. Among its findings: “On an individual level, cannabis use confers an overall twofold increase in the relative risk for later schizophrenia.”

In a subsequent interview Mr. Murray granted in 2005, he is quoted as saying: “…A majority of the population can abuse as much cannabis as they like and don’t come to much harm. But a vulnerable minority, about 25 percent of the population, is prone to psychotic reactions if they take regular cannabis.”

We see a similar dynamic with alcohol. The majority of people who use the substance do not cause harm to themselves or others and do not experience dependence and/or addiction — but surely no one would argue that the minority of users who abuse the drug or develop alcoholism don’t cause great harm to themselves and society at large. In fact, marijuana legalization proponents cite alcohol’s negative impact to justify their reasoning for making cannabis legal.

So while many people can use cannabis without experiencing psychosis or causing harm to themselves and others, we should not ignore or sweepingly dismiss that smaller percentage of marijuana users who cannot — a percentage of people that could grow as marijuana is legalized.



The Arsenault et al study is followed by this extensive list of citations of medical research examining the association between marijuana use and psychosis:

American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM^IV). Washington,DC: American Psychiatric Assocation.

Andreasson, S., Allebeck, P., Engstro« m, A., et al (1988) Cannabis and schizophrenia: a longitudinal study of Swedish conscripts. Lancet, ii, 1483^1485.

Arseneault, L., Cannon, M., Poulton, R., et al (2002) Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ, 325, 1212^1213.

Boydell, J., van Os, J., Lambri, M., et al (2003) Incidence of schizophrenia in south-east London between 1965 and 1997. British Journal of Psychiatry, 182, 45^49.

Cannon, M., Jones, P., Gilvarry, C., et al (1997) Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences. American Journal of Psychiatry, 154, 1544^1550.

Cannon, M.,Caspi, A., Moffitt,T. E., et al (2002) Evidence for early, specific, pan-developmental impairment in schizophreniform disorder: results from a longitudinal birth cohort. Archives of General Psychiatry, 59, 449^457.

Cantwell, R., Brewin, J., Glazebrook, C., et al (1999) Prevalence of substance misuse in first-episode psychosis. British Journal of Psychiatry, 174, 150^153.

D’Souza, C., Cho, H.-S. Perry, E., et al (2004) A cannabinoid model psychosis, dopamine ^ cannabinoid interactions and implications for schizophrenia. In Marijuana and Madness (eds D. J. Castle & R. Murray). Cambridge: Cambridge University Press. In press.

Duke, P. J., Pantelis,C., McPhillips, M. A., et al (2001) Comorbid non-alcohol substance misuse among people with schizophrenia. Epidemiological study in central London. British Journal of Psychiatry, 179, 509^513.

Fergusson, D. M. & Horwood, L. J. (2000) Does cannabis use encourage other forms of illicit drug use? Addiction, 95, 505^520.

Fergusson, D. M., Horwood, L. J. & Swain-Campbell, N. R. (2003) Cannabis dependence and psychotic symptoms in young people. Psychological Medicine, 33, 15^21.

Grech, A., Takei, N. & Murray, R. (1998) Comparison of cannabis use in psychotic patients and controls in London and Malta. Schizophrenia Research, 29, 22.

Hall,W. & Degenhardt, L. (2000) Cannabis use and psychosis: a review of clinical and epidemiological evidence. Australian and New Zealand Journal of Psychiatry, 34, 26^34.

Hall,W. & Degenhardt, L. (2004) Is there a specific ‘cannabis psychosis’? In Marijuana and Madness (eds D. J. Castle & R. Murray). Cambridge: Cambridge University Press. In press.

Hambrecht, M. & Hafner, H. (1996) Substance abuse and the onset of schizophrenia. Biological Psychiatry, 40, 1155^1163.

Hill, A. B. (1965) The environment and disease: association or causation? Proceedings of the Royal Society of Medicine, 58, 295^300.

Johns, A. (2001) Psychiatric effects of cannabis. British Journal of Psychiatry, 178, 116^122.

Johnston, L. D., O’Malley, P. M. & Bachman, J. G. (2002) Monitoring the Future National Results on Adolescent Drug Use: Overview of Key Findings 2001 (NIH Publication No. 02-5105). Bethesda, MD: National Institute of Drug Abuse.

Jones, P., Rodgers, B., Murray, R., et al (1994) Child developmental risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet, 344, 1398^1402.

Kazuo,Y. & Kandel, D. B. (1984) Patterns of drug use from adolescence to young adulthood: II. sequences of progression. American Journal of Public Health, 74, 668^672.

Kraemer, H., Stice, E., Kazdin, A., et al (2001) How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. American Journal of Psychiatry, 158, 848^856.

Malmberg, A., Lewis, G., David, A., et al (1998) Premorbid adjustment and personality in people with schizophrenia. British Journal of Psychiatry, 172, 308^313.

Mathers, D. C. & Ghodse, A. H. (1992) Cannabis and psychotic illness. British Journal of Psychiatry, 161, 648^653.

McCreadie, R. G. (2002) Use of drugs, alcohol and tobacco by people with schizophrenia: case ^ control study. British Journal of Psychiatry, 181, 321^325.

Menezez, P.R., Johnson, S., Thornicroft, G. et al (1996) Drug and alcohol problems among individuals with severe mental illnesses in south London. British Journal of Psychiatry, 168, 612^619.

Miller, P., Lawrie, S. M., Hodges, A., et al (2001) Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia. Social Psychiatry and Psychiatric Epidemiology, 36, 338^342.

Murray, R., Grech, A., Phillips, P., et al (2003) What is the relationship between substance abuse and schizophrenia ? In The Epidemiology of Schizophrenia (eds R. Murray, P. Jones, E. Susser, et al), pp. 317^342. Cambridge: Cambridge University Press.

Patton, G. C., Coffrey, C., Carlin, J. B., et al (2002) Cannabis use and mental health in young people: cohort study. BMJ, 325, 1195^1198.

Phillips, L. J., Curry, C.,Yung, A. R., et al (2002) Cannabis use is not associated with the development of psychosis in an‘ultra’ high-risk group. Australian and New Zealand Journal of Psychiatry, 36, 800^806.

Poulton,R.,Caspi,A.,Moffitt,T.E.,et al (2000) Children’s self-reported psychotic symptoms and adult schizophreniform disorder: a 15 -year longitudinal study. Archives of General Psychiatry, 57, 1053^1058.

Regier, D., Farmer, M. E., Rae, D. S., et al (1990) Comorbidity of mental disorders with alcohol and other drug abuse: results from the epidemiologic catchment area (ECA) study. Journal of the American Medical Association, 264, 2511^2518.

Robins, L. N. & Regier, D. A. (1991) Psychiatric Disorders in America: the Epidemiologic Catchment Area Study. New York: The Free Press.

Rothman, K. J. & Greenland, S. (1998) Modern Epidemiology (2nd edn). Philadelphia, PA: Lippincott- Raven.

Silva, P. A. & Stanton,W. R. (1996) From Child to Adult: the Dunedin Multidisciplinary Health and Development Study. Auckland: Oxford University Press.

StataCorp (2003) Stata Statistical Software: Release 8.0. Texas: Stata Corporation.

Sterne, J. A. C., Bradburn, M. J. & Egger, M. (2001)
Meta-analysis in StataTM. In Systematic Review in HealthCare: Meta Analysis in Context (eds M. Egger, G. D. Smith & D.G. Altman), pp. 347^369. London: BMJ Books.

Susser, M. (1991) What is a cause and how do we know one? A grammar for pragmatic epidemiology. American Journal of Epidemiology, 133, 635^648.

Thornicroft, G. (1990) Cannabis and psychosis. Is there epidemiological evidence for an association? British Journal of Psychiatry, 157, 25^33.

Tien, A.Y. & Anthony, J. C. (1990) Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. Journal of Nervous and Mental Disease, 178, 473^480.

van Os, J., Bak, M., Bijl, R.V., et al (2002) Cannabis use and psychosis: a longitudinal population-based study. American Journal of Epidemiology, 156, 319^327.

Verdoux, H. (2004) Cannabis and psychosis proneness. In Marijuana and Madness (eds D. J. Castle & R. Murray). Cambridge: Cambridge University Press.

Verdoux, H., Gindre, C., Sorbara, F., et al (2003) Effects of cannabis and psychosis vulnerability in daily life: an experience sampling test study. Psychological Medicine, 33, 23^32.

Wheatley, M. (1998) The prevalence and relevance of substance use in detained schizophrenic patients. Journal of Forensic Psychiatry, 9, 114^129.

Zammit, S., Allebeck, P., Andreasson, S., et al (2002) Self-reported cannabis use as a risk factor for schizophrenia: further analysis of the 1969 Swedish conscript cohort. BMJ, 325, 1199^1201.

1 Comment

  1. Well done! Thank you so much for this comprehensive report!

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