Tuesday, November 23, 2010

Marijuana And Mental Illness

I decided to gather together links and summaries of various scholarly articles on marijuana and mental illness, mostly because they are too scattered for me to easily find, and I had someone that needed them.

This study performed a reanalysis of the 1969 Swedish conscript study:
An association between use of cannabis in adolescence and subsequent risk of schizophrenia was previously reported in a follow up of Swedish conscripts. Arguments were raised that this association may be due to use of drugs other than cannabis and that personality traits may have confounded results. We performed a further analysis of this cohort to address these uncertainties while extending the follow up period to identify additional cases.
The followup study found that reanalysis of the data with more modern statistical techniques, as well as additional followup data from those conscripts, found that the association was still present:

Results: Cannabis was associated with an increased risk of developing schizophrenia in a dose dependent fashion both for subjects who had ever used cannabis (adjusted odds ratio for linear trend of increasing frequency 1.2, 95% confidence interval 1.1 to 1.4, P<0.001), and for subjects who had used only cannabis and no other drugs (adjusted odds ratio for linear trend 1.3, 1.1 to 1.5, P<0.015). The adjusted odds ratio for using cannabis >50 times was 6.7 (2.1 to 21.7) in the cannabis only group. Similar results were obtained when analysis was restricted to subjects developing schizophrenia after five years after conscription, to exclude prodromal cases. 

Conclusions: Cannabis use is associated with an increased risk of developing schizophrenia, consistent with a causal relation. This association is not explained by use of other psychoactive drugs or personality traits relating to social integration.["Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study," British Medical Journal (2002) 325:1199]
Prodromal: a person who has early symptoms of the disease.  This is an issue because people with mental illness are more likely to self-medicate using alcohol, marijuana, and other drugs.  The conclusion that marijuana users were more likely to develop schizophrenia turned out to be true even for those persons who exhibited no prodromal symptoms before beginning marijuana use.

This study performed a longitudinal study in New Zealand and found that:
Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for. … Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). The youngest cannabis users may be most at risk because their cannabis use becomes longstanding. ["Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study," British Medical Journal (2002) 325:1212]
This paper, from the British Journal of Psychiatry in 2004, also concluded that marijuana roughly doubles the risk of schizophrenia. From the abstract:
On an individual level, cannabis use confers an overall twofold increase in the relative risk for later schizophrenia. At the population level, elimination of cannabis use would reduce the incidence of schizophrenia by approximately 8%, assuming a causal relationship. Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis. ["Causal association between cannabis and psychosis: examination of the evidence," British Journal of Psychiatry (2004) 184:110-117]

This metastudy examined existing published studies of mental illness and marijuana:
Results On an individual level, cannabis use confers an overall twofold increase in the relative risk for later schizophrenia. At the population level, elimination of cannabis use would reduce the incidence of schizophrenia by approximately 8%, assuming a causal relationship. Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis.

Conclusions Cases of psychotic disorder could be prevented by discouraging cannabis use among vulnerable youths. Research is needed to understand the mechanisms by which cannabis causes psychosis. ["Causal association between cannabis and psychosis: examination of the evidence," British Journal of Psychiatry (2004) 184: 110-117]

There’s unquestionably a genetic component. This Schizophrenia Bulletin (2008) paper tells us:
Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength, but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. … Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. ["Gene-Environment Interplay Between Cannabis and Psychosis," Schizophrenia Bulletin (2008), 34:6 1111-1121]
Recent studies continue to recognize a causal connection:

Cross-sectional studies document an association between cannabis use and psychotic symptoms, and longitudinal studies suggest that early exposure to cannabis confers a close to two-fold increase in the risk of developing schizophrenia. Pharmacological studies show that cannabinoids can induce a full range of transient positive, negative, and cognitive symptoms in healthy individuals that are similar to those seen in schizophrenia. There is considerable evidence that in individuals with an established psychotic disorder such as schizophrenia, exposure to cannabis can exacerbate symptoms, trigger relapse, and worsen the course of the illness. Only a very small proportion of the general population exposed to cannabis develop a psychotic illness. It is likely that cannabis exposure is a ‘component cause’ that interacts with other factors to ‘cause’ schizophrenia or other psychotic disorder, but is neither necessary nor sufficient to do so alone. ["Cannabinoids and psychosis," International Review of Psychiatry (2009), 21:2  152-162]

This study published in 2009 sought to identify age relationships to psychotic symptoms and substance abuse.  While it found no correlation of frequency of use of marijuana or tobacco and psychotic symptoms, it did find that increase in frequency of marijuana and tobacco use was correlated to onset of psychotic symptoms--suggesting that increases in dosage might be the factor.  From the abstract:
RESULTS: Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of onset, analysis of change in frequency of use prior to onset indicated that progression to daily cannabis and tobacco use was associated with an increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness or prodromal symptoms was the outcome. A gender-by-daily-cannabis-use interaction was observed; progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than in males.
CONCLUSIONS: Pre-onset cannabis use may hasten the onset of psychotic as well as prodromal symptoms. Age at onset is a key prognostic factor in schizophrenia, and discovering modifiable predictors of age at onset is crucial.  ["Association of Pre-Onset Cannabis, Alcohol, and Tobacco Use With Age at Onset of Prodrome and Age at Onset of Psychosis in First-Episode Patients," American Journal of Psychiatry (2009), 166:1251-1257]
Here's a study published 2010 that used siblings to attempt to reduce unmeasured confounding variables:
Results  Duration since first cannabis use was associated with all 3 psychosis-related outcomes. For those with duration since first cannabis use of 6 or more years, there was a significantly increased risk of (1) nonaffective psychosis (adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.5), (2) being in the highest quartile of Peters et al Delusions Inventory score (adjusted odds ratio, 4.2; 95% confidence interval, 4.2-5.8), and (3) hallucinations (adjusted odds ratio, 2.8; 95% confidence interval, 1.9-4.1). Within sibling pairs, duration since first cannabis use and higher scores on the Peters et al Delusions Inventory remained significantly associated.

Conclusions  Early cannabis use is associated with psychosis-related outcomes in young adults. The use of sibling pairs reduces the likelihood that unmeasured confounding explains these findings. This study provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults. ["Association Between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults," Archives of General Psychiatry (May 2010), 67:5]
A chapter from The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes (2009) concludes that there is evidence for brain structure changes in heavy marijuana users that are similar in nature to those measureable in schizophrenics.  From the abstract:

While previous research failed to identify structural brain abnormalities in human cannabis users, more recent studies using high resolution imaging techniques combined with more robust delineations of specifi c brain regions in very heavy cannabis users have revealed evidence of dose-related alterations in regions implicated in schizophrenia. Moreover, these regional brain volumetric reductions are of similar magnitude to those seen in schizophrenia. We discuss the association between cannabis use and the development of cognitive defi cits and psychiatric symptoms in relation to structural brain alterations. We propose that long term heavy cannabis use leads to structural brain changes and associated deleterious functional (cognitive and mental health) sequelae that resemble schizophrenia. These changes may occur not only in individuals who are vulnerable to the development of such disorders, but also in nonvulnerable individuals if cannabis is used heavily for prolonged periods.  ["Structural Brain Alterations in Cannabis Users: Association with Cognitive Deficits and Psychiatric Symptoms," ch. 27, The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes (2009)]

The American Psychiatric Association's May 21, 2010 Psychiatric News reports on upcoming research about to be published, showing that marijuana use both increases psychotic symptoms, and psychotic symptoms increase use of marijuana:

The relationship between marijuana use and positive psychotic symptoms appears to be bidirectional—an increase in use predicts greater symptoms, and increased symptoms predict more use. 

Marijuana use among individuals with schizophrenia is associated with more severe positive psychotic symptoms over time, according to a 10-year longitudinal study posted online May 15 on AJP in Advance.

Researchers found that changes in cannabis use at four follow-up points over the 10-year period were associated with similar direction changes in positive psychotic symptoms of delusions and hallucinations over time; if subjects stopped using cannabis, their symptoms decreased, and if they started or increased use, their symptoms increased. This remained true even after controlling for gender, age, socioeconomic status, other drug use, antipsychotic medication use, and other symptoms.


Kyzernick said...

Well this makes a lot of sense. A psychoactive drug inducing worse cases of psychotic disorders at a faster rate and with a quicker onset seems like a, pardon the pun, no-brainer!

Dom said...

Here's a personal story.

My brother smoked pot most of his adult life. He very gradually descended into a mild case of ... what can I call it? ... craziness. -- violence (mostly verbal, including threats), a tendency to get sucked into religious cults, paranoia, that type of thing. He told me that a number of people, such as doctors, dentists, etc, all asked him to have himself checked for schizophrenia, just based on his conversations. When he got into legal trouble, his lawyer refused to represent him because he suspected he suffered from a kind of mental disturbance. He died a few months ago, and I was shocked to find that so many of his friends had all noticed the same thing.

I don't know if pot will always cause this type of behavrioual change, but I suspect that it did in my brother.

Jonathan Rowe said...

The results, even if true, don't impress me. I don't doubt, pot -- and a whole lot of other things -- can exacerbate problems for a small % of folks on the margins. Isn't that what, most generous to the point of view of the author, the data show?

I haven't yet seen CC blog on the positive effect marijuana use, both medicinal and recreational, has on people's lives. AND the costs of fighting the war on drugs, specifically the war on pot.

Taken together, the case for full legalization for adults seems a no-brainer to me.

Clayton said...

I haven't posted on the "positive effect" because so much of the popular culture is already hyping this aspect just fine. The costs of the war on drugs is very high, no question about it. But an honest discussion of this as public policy requires discussion of the enormous social costs of legalization as well--and that isn't happening.

One difficulty with "full legalization for adults" is that it is interpreted by minors as a stamp of approval for marijuana.

Rich Rostrom said...

The most valuable medical application of marijuana is as an antinausea drug and appetite enhancer for people undergoing chemotherapy.

Suppose cannabinol was legalized as a pharmaceutical, and advertised the way other drugs are advertised.

The advertisements always include a list of known side effects.

For cannabinol, the advertisements would have to state: "Use of cannabinol poses an increased risk of schizophrenia and other psychotic conditions."

I wonder how many people would take it, if it wasn't already "known" as "safe".

Rorschach said...

My story is an almost exact duplicate of Dom's. My older brother began smoking pot at age 15 and has never stopped. His criminal history started at age 17 and has had periodic minor brushes with the law repeatedly since then. His mental state has steadily deteriorated over his lifetime. He is now 54 years old, chronically unemployed, paranoid, delusional, and violent. He has only a vague contact with reality. And yes, I blame his drug use.

Epsilon Given said...

It's important to understand the side effects of each and every drug. Whether or not marijuana is legalized, it will always be around, and always available.

I wouldn't touch the stuff for religious and intellectual reasons; I have only recently become aware of the history of mental illness in my family. Because marijuana is so readily available, it's important that I make sure my children know what could happen to them, and quite likely would happen to them, if they use marijuana.

Furthermore, because I can accept medical uses for things, knowing this side-effect of marijuana is very important to me: I now know that if I were to use marijuana as an anti-nausea treatment during chemotherapy, I could very well end up schizophrenic afterwards.

Whether or not marijuana is made legal, it's still important to make connections like this!

Tcaufman said...

So you are all saying that cannabis causes and/or worsens mental illness? If so, then it appears that "Reefer Madness" lives on in this variation of "marijuana causes insanity." For many years now, those seeking power, control, or profits have been spewing out this variation of this particular Big Lie about cannabis. Just follow the money and you will find sponsorship of these false and biased "studies" by adolescent treatment centers, Big Pharma-created associations, ad nauseum. There are new more truthful studies that show cannabis use actually ameliorates schizophrenia and other forms of mental illness. I am sorry for the difficulties of your family members, but you cannot blame the cannabis herb.

Clayton said...

Care to share the studies that that it "actually ameliorates schizophrenia"? Odd that I didn't find any when I was searching for "cannabis schizophrenia." The studies above are generally published in highly respected journals, and while not perfect (as no epidemiological study is), the use of longitudinal studies is persuasive.

Care to provide some evidence that the studies above were funded by people with financial interests?

Tcaufman said...

Understand well that if a study is to occur, somebody has to pay for it. The biggest funding sources by far are Big Pharma and governments through their grant processes. Big Pharma has interest in keeping the lid on marijuana studies. Imagine a simple weed with medicinal effects that far outweigh their highly touted and profitable pharmaceutical agents! Our government, also has hundreds of billions in asset forfeiture money and tax money which is now rolling through the coffers of law enforcement, the court system and political contributions from moneyed interests also wishes to discredit and destroy the legalization movement. These two powerful industrial-complexes are hell-bent on keeping marijuana illegal and inaccessible to the general population.

When you read studies from Harvard for example know they
benefit from Courts sending kids to cannabis “addiction” treatment centers
most unfortunate since Rehab may increase drug use actually

Still, some opposing research does appear:
Australian researchers believe cannabis, a drug [formerly] believed to increase the risk of psychosis, may also be able to reverse psychotic behaviour.

455 people with schizophrenia published in Schizophrenia Research in July. The research showed that patients who smoked marijuana had faster brain processing speed, greater verbal ability and better memory than patients who didn't smoke — not attributes usually associated with being high.

Being left-handed puts you at significant risk but left-handed people should not be worried by the links between handedness and schizophrenia. "There are many factors which make individuals more likely to develop schizophrenia and the vast majority of left-handers will never develop a problem.

...alcohol has been found to increase the risk of psychosis by 800% for men and 300% for women.
alcoholic psychosis may be irreversible

schizophrenia rates . . . is not correlated with population use rates of marijuana.

Perhaps the strongest piece of evidence to cast doubt on a causal connection between marijuana and schizophrenia is a long flat-line trend in the disease.
"If anything, the studies seem to show a possible decline in schizophrenia from the '40s and the '50s," says Dr. Alan Brown, a professor of psychiatry and epidemiology at Columbia University.

June 2005 study at University of Southern California, found that marijuana use was in fact associated with lower levels of depression. both heavy pot smokers and moderate users reported less depression than did nonusers.


If cannabis isn't for you, then don't use it. But our current prohibition is causing much damage and destruction. It's not marijuana that is kicking down doors in the middle of the night, suppressing medical research nor killing innocent grandmothers like Kathryn Johnston and 30,000 others in Mexico, it's our drug laws. We don't need to keep supporting drug cartels, prison overcrowding or police corruption. DEMAND REFORM.