A lot of people are talking about a new study showing a 40% increase risk of "psychosis", which I first heard news of in this story, from the Daily Mail:
A single joint of cannabis raises the risk of schizophrenia by more than 40 percent, a disturbing study warns.
The Government-commissioned report has also found that taking the drug regularly more than doubles the risk of serious mental illness.
Overall, cannabis could be to blame for one in seven cases of schizophrenia and other life-shattering mental illness, the Lancet reports.
Something sounds a little off. Let's see what this Lancet study says.
Ok, first we see it is a meta-analysis, which means one should be cautious as the quality of the study is highly dependent on their design and inclusion criteria. Their findings were as follows.
There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1·41, 95% CI 1·20-1·65). Findings were consistent with a dose-response effect, with greater risk in people who used cannabis most frequently (2·09, 1·54-2·84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding effect was present for both psychotic and affective outcomes.
Woah! Reefer Madness might have been right? Now, we have a modest effect, but a statistically significant dose-response relationship between marijuana use and psychosis. This is very interesting. What was the design?
Studies were included if they were population-based longitudinal studies, or case-control studies nested within longitudinal designs. We excluded cohorts of people with mental illness or substance-use-related problems, studies of prison populations, and RCTs of cannabis for medical use
Ok, I'm still with ya here. Reasonable criteria, good, good. How did they define "psychosis":
Diagnostic outcomes for psychosis included schizophrenia, schizophreniform, schizoaffective, or psychotic disorders, non-affective or affective psychoses, psychosis not otherwise specified, psychotic symptoms, delusions, hallucinations, or thought disorder. Presence of delusions, hallucinations, or thought disorder was a requirement for all psychosis outcomes. Affective, mood, or bipolar disorder, affective disorder not otherwise specified, depression, suicidal ideation or suicide attempts, anxiety, neurosis, and mania were included for affective outcomes.
Here a slight problem, which the authors acknowledge, is that intoxication effects or descriptions of intoxication effects could lead to false positive psychosis diagnosis. But that's ok, science is tough, you do what you can.
Their search criteria were good etc., so what were the results exactly? Well this one figure is probably the most important:
What this shows is the odds ratios from studies of psychosis in marijuana users for those that have ever smoked marijuana, with confidence intervals, compiled into this meta-analysis. The dose response one is similar but shows a bigger effect. Overall the odds ratios of these studies is 1.41 with a 95% CI of 1.20-1.65 which you can view as upper and lower limits of the probable size of this effect. Stunning no? Should we be convinced this is a real effect?
First of all, the statement that "just one joint" increases risk by 41% is absurd. The study here is of those who have tried marijuana once or more, not of people who have only tried it once. So already, the Daily Mail and every other news organization is way off. Second, I think we're ultimately seeing a post-hoc ergo propter hoc argument, and a dose-response that's more characteristic of the population studied than a real pharmacologic effect. Now, why do I think this is bogus?
Well for one, people with serious mental illness often do drugs. Lots of drugs. And not just marijuana. Marijuana is actually pretty low down on the list. In other words, people with schizophrenia and other serious mental health problems are at high risk of addiction. And this will necessarily confound their study.
The authors assert that this is not the problem, that is, mental health susceptibility is not the cause of the marijuana use but rather, marijuana use is increasing the probability of psychosis. Their reasoning is that the cohorts excluded populations that already had a diagnosis of schizophrenia or other psychotic disorder, so they are studying people who showed no signs of mental illness, then became mentally ill. This is well and good, and absolutely the right thing to do, otherwise you would immediately see a huge effect simply because people with serious mental health problems are at high risk of addiction. But, is the assumption still valid?
Well, no. And my answer lies in smoking. Yes, plain old cigarettes. Do you have any idea how much schizophrenics smoke? Tons. It's unbelievable. In fact, approximately 90% of schizophrenics smoke, and of schizophrenics who smoke, 90% of them started smoking before onset of their illness. Further, evidence of a dose response effect, 68% of schizophrenics are heavy smokers, compared to 11% of the smoking population.
Now this is kind of astounding. Why don't we say that cigarettes are putting people at risk for psychosis? Just because something follows an event, doesn't mean that event is the cause. The population is choosing the drug, the drug is not creating the population. If you were to do similar study with cigarettes, or booze, you'd find a similar correlation (RR=1.94), and dose response etc (although some articles have suggested a protective effect as well - albeit in older cohorts). Eliminating the cohort that already had the diagnosis would not eliminate the effect, because schizophrenics overwhelmingly start smoking, and other drugs, before the psychotic break that defines the diagnosis.
Similar findings are often shown with alcoholism and early drinking, but suffer from the same assumptions. There are people with a tendency towards addiction, for various reasons, and at earlier ages they engage in drug-seeking behaviors. The mistake is thinking that when they become alcoholic or drug dependent in early life that the drugs caused the behavior, rather than considering the possibility that such behavior existed even before exposure to the drugs. Hell, I knew people growing up that would seek a high from every chemical at hand (long before they had even had access to pot or booze), not because they were addicted to those chemicals, or had even tried them before, but because they were the type that actively seek a high.
Correlation is not causation people. And this particular correlation is a hairy one, due to the tendency towards drug abuse that is characteristic of those suffering from psychotic disorders. I would put little trust in this particular study's conclusions as the more likely phenomenon being studied is the predilection for drug-seeking in adolescents who subsequently become schizophrenic.
1. Theresa HM Moore, Stanley Zammit, Anne Lingford-Hughes, Thomas RE Barnes, Peter B Jones, Margaret Burke and Glyn Lewis, Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review, The LancetVolume 370, Issue 9584, , 28 July 2007-3 August 2007, Pages 319-328.
doi:10.1016/S0140-6736(07)61162-3
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"A single joint of cannabis raises the risk of schizophrenia by more than 40 percent, a disturbing study warns."
At which point I stopped taking any notice of this study. If that claim were true, we would be literally up to our armpits in schizophrenia patients.
Not necessarily. Since the initial risk is something like 1%, then the increased risk is 1.4%.
I guess they looked at the wrong cohorts. Looking at an RCT of cannabis for medical use (in a cannabis naive population) should eliminate this self-selection bias.
I seem to recall reading that schizophrenics also consume large amounts of caffeine. Is that true?
Yet another meta-analysis... Has there ever been any new relationship that was of any importance discovered or confirmed by meta-analysis? (Actually, seriously, it would be interesting to know of some.) I think they should not be allowed in standard scientific journals. They ought to be confined to the "Journal of Meta-Analytical Surmises and Wild Guesses". Or something like that.
Yes, but you never hear about them in the news. It's a selection bias problem. The news media selects for the outrageous, so you only see the worst meta-analyses, since they are frequently the ones saying absurd things.
Thank you for this. I am a non-smoker of any kind who has always been sympathetic to the decriminalization of cannabis, and this report had even me wondering if I should support the War on Drugs.
It's certainly going to prove a very powerful talking point against decriminalization, but now I learn how weak the actual results are, compared to the hype, I suspect the drug warriors have nothing better up their sleeve. If they did, they'd publicize that, and not this.
It's almost like citing the statistics backwards.
Latent schizophrenics often suffer their first break while under the influence of psychoactive drugs. Pot, along with LSD, physical trauma,the death of a loved one, and other intense emotional events can all trigger an initial schizophrenic break in late adolescence. So NATURALLY you would find a correlation. But as Markh so succinctly pointed out in the originating post, to attribute causality to pot is really bad science writing.
Oh no, I'm doomed!
And so am I!
Uhh... no way, man... like, pot doesn't cause... um... wow, pretty flowers... uh, mental illness and stuff...
CHIPS!
<grin>
Jeez, I thought everyone knew that tobacco significantly increased the risk of schizophrenia.
Thanks for giving me someone else to point to, who is saying exactly what I have said about this.
I am a non-smoker of any kind who has always been sympathetic to the decriminalization of cannabis, and this report had even me wondering if I should support the War on Drugs.
Regardless of what the actual dangers are, there is no evidence that prohibition helps. Many (most? all?) of the supporters of drug-law reform hold that position because we believe that reform is necessary to manage the very real risks associated with drug use, not because we believe drug use is harmless.
This really is a question.
Are we looking at people who are self-medicating?
Could people with mental disorders be using drugs, either tobacco or pot or whatever, to treat there disorder?
I am reminded of an infamous piece of abused science that said that long-term lesbian relationships were five times more likely to involve spouse abuse than heterosexual couples. Turned out the psycologist responsible was not only a public relations writer for a anti-gay-rights organisation (one of the smaller ones, not something big like FRC or FotF), but had very deliberatly done a bit of selection bias... by taking her 'sample' from a gay counceling service.
The paper never got into a respectable journal. It got into some far-right pseudoscience place though. Something family something.
I really need to keep better notes.
Now Nature's doing it:
http://www.nature.com/news/2007/070723/full/070723-11.html
Write to them!
Jim, it has been suggested for tobacco at least that the nicotine does help schizophrenics with symptoms. Interestingly, schizophrenics have trouble with the normal saccade movements of the eye - they fail to accurately track something like a pendulum swinging - and cigarettes improve their ability to visually track again.
Here's a review on the topic.
However, nicotine and cannabis are not both acting the same in these cases. If anything cannabis aggravates schizophrenia and makes them susceptible to relapse - as do most other drugs that are frequently abused by schizophrenics. Smoking, oddly, seems to help.
In addition, a case study of this sort is impossible to do accurately in the first place--because cannabis is a controlled substance. People can't be relied on to tell the truth about their use of it. We don't even know how many people use marijuana regularly--don't even know what cohort we are purporting to study.
Lotsa comments at Bad Science:
http://www.badscience.net/?p=476
Nicotine is not the only pharmacologically active substance in tobacco smoke. Carbon monoxide is pharmacologically active, it binds quite strongly to heme, and so modifies the activities of essentially all heme containing enzymes. Two very important ones are nitric oxide synthase and soluble guanylyl cyclase. The main source and receptor for nitric oxide.
I suspect that some of the effects of tobacco which appear to be beneficial (reduction in Parkinson's for example) may be mediated through the CO as a NO mimetic. CO is a signaling molecule in its own right, but considerably less well understood than NO.
I would suspect that tobacco use would help with schizophrenia too, because CO is a NO mimetic.
wait...
what?
Nice post. There are classes of linear models (e.g. marginal structural models) that attempt to control for an individuals latent propensity towards some exposure (e.g. drug seeking behavior). Last I check there were several different estimators and procedures for fitting such models, and I know they have been successfully applied to observational data of HIV treatment schedules (Jamie Robins and colleagues, I don't have the citation on me). I'm not familiar with the particulars of meta-analysis, but it seems a somewhat inappropriate method when the potential for unobserved confounders is so high.
Jim Ramsey -
Yes, it has a lot to do with self-medicating. I am not schizo, but I have been diagnosed mildly bipolar and ADHD, though I suspect that the symptoms of bipolar are actually the result of congenital insomnia, i.e. lifelong sleep deprivation. Regardless, the symptoms are there and marijuana has been a huge help. Also, coffee and cigs have been a huge help with the ADHD, along with the very occasional use of methamphetimine in the past (ingested rather than smoked or snorted, which makes a huge difference in how addictive it becomes, I quit altogether when I started feeling like I should use it more often than I was).
I also use dimenhydramine (generic Dramamine), as I am trying to smoke a lot less weed. Still use the occasional toke, when things are rough. Really looking forward to getting health insurance in a couple of months, so I can quit self-medicating altogether, or at least mostly - I love my coffee.
I listened to a BBC interview on Radio 3 with one of the authors of this study. His claims were nothing like as alarmist as the Daily Mail's of course. He pointed out that there does seem to be some evidence that use of cannabis can exacerbate an underlying psychosis. Arguable maybe, but defensible I think. He also added it was probably not a good idea for someone with a psychosis to use cannabis. I doubt many mental health professionals would disagree with that.
"H pointed out that there does seem to be some evidence that use of cannabis can exacerbate an underlying psychosis." Not really clear from this study.
Remember those old stories - every heroine addict started on cannabis, smoke cannabis you will become a heroine addict?
Same faulty reasoning.
All addiction starts with food....
All this shows as far as I can see is that people who do not become psychotic are slightly less likely to try cannabis.
To back up your contention that cnnibis is causing schizophrenia, one has to look at the onset of marijuana use and the onset of schizophrenic symptoms. Initiation of cannibis use is most commonly in the 15-18 year old age group while schizophrenia is most commonly diagnosed in the 18-25 age group in men and slightly later in women. This could be taken as evidence that cannibis may be causitive, but it is still weak because there is no really good research into the prodromal changes in schizophrenia and how they may change drug-using behavior. What is needed is some kind of prospective study of high risk individuals, but that would need a fairly accurate method of determining at-risk individuals, something that would be difficult to do for many reasons.
There are innumerable documented reports indicating that marijuana triggers hysterical and often violent insanity among police, prosecutors, and politicians.
pbutler, you are right. Somebody should research this phenomenon. Perhaps a meta-analysis?
Mark and others:
Can we clarify this - this is "40% increased risk", expressed as odds ratios. But what is the conversion to "how much more likely"?
As Mark Liberman has cogently explained over at Language Log
http://itre.cis.upenn.edu/~myl/languagelog/archives/004767.html
Odds ratio numbers are often misleading, as they are typically reported in the media, and "processed" by the public as "you are 40% more likely to be diagnosed schizophrenic if you are a cannabis user"
Can someone reasonably stats-literate deconvolute the numbers and give us the corresponding "how much more likely" figure?
Dr Aust. I actually goofed in this article and wrote Relative Risk as well when it was an odds ratio reported - probably because in this instance they are somewhat equivalent and because I was duped by the reporting into thinking in terms of an RR.
Luckily in this instance - in the case of a small percentage effect - reporting the odds ratio does not present a large amount of confusion compared to a relative risk. The overall risk of schizophrenia in the population is about 1.0 (odds are 1 in 99 for schizophrenia or 3 in 97 for all psychosis). This study increases the odds by 40% (1.4/98.6 = 0.014 and 4.2/95.8 = 0.043) In both cases the odds, since they are low, approximate percent risk, so the Relative risk is not significantly different from the odds ratio. Now, no one should think that the risk of schizophrenia or psychosis becomes 40% with smoking weed, instead the odds relative to non-smokers increases by 40%.
Odds ratios become really confusing when the initial risk is high, but at a low risk like this they approximate the relative risk, so there should not be too much confusion. Still I apologize for replicating the same mistake as the article that I was being critical of.
Thanks Mark. Very clear.
Mark Liberman's piece gave a link to this which I found enlightening:
http://www.bmj.com/cgi/content/full/316/7136/989
Back to the main subject: does anyone have the comparable odds ratios for schizophrenia to hand for:
(i) smoking (i.e. if we just take the "correlation" and ignore the idea of self-medication)
(ii) "heavy" smoking (>20 day)
(ii) heavy drinking
(iii) being male
(iv) being born in the Winter
Dr Aust -
I will try to find the study, but don't have it on hand and it's been a few years. It wasn't claiming any causation, but merely compiled statistics for substance abuse among people with schizophrenia and bipolar disorder. I will try to list the stats I remember - estimates only.
Heavy Smoking - 75%
Daily drinking (not necc. heavy) - 67%
Daily Marijuana use - 65%
Other illicit drug abuse - 42%
I don't know about the ratio of male/female, but I seem to recall that schizophrenics are more likely to be male, but not by much.
Try search string; "substance abuse" schizophrenia statistics
Were the studies done in a country with legalized cannabis? I got the impression they weren't.
Better questions to ask are... Do Rastafarians in Jamaica, who use marijuana more for spiritual reasons and less for self-medication, experience higher rates of mental health problems than non-smokers in the same country and of the same religion? What about other countries where the substance is legal, specifically, countries where aceess to mental health is easy to get and cannabis is legal?
It is impossible to do a large pop. study like this without a slew of confounds, but the best way to reduce them from the start would be to pick a country/area with:
A. easy access to mental health facilities for all income levels
B. little or no stigma against seeking these services
C. legalized or decriminalized cannabis
D. relatively static use of cannabis rates over time (easier to find in a location with legal cannabis)
After that we just use regression to statistically eliminate the differences between users and non-users and control for use rates. We'd have to control for age, gender, and race. Hell, we'd have to control for a LOT of things, but I think a better study could easily be done. Now I just need that elusive government grant...
It just feels like such an injustice to me that neurotic far-right hypocrites who commit worse crimes and never have to piss for their employment make up these ridiculous studies to try and make the fact that they take the general public's amendments and privacy rights away look better. It really just makes me sick. Also, thank you so much for the challenging article, I greatly appreciate it.
With the actual climate of confusion and mis(dis)information is always good when many people take their time to read and comment an article like this. Greetings by Ministry of Cannabis, a cannabis seedbank, based in Amsterdam, The Netherlands.
Cannabis causes schizophrenia when someone who is already predisposed to it smokes a LOT of it.
My uncle was a total pothead at a certain point he started locking family members up with various weapons and the docter had to tell him to stop (he went back to normal after he quit), and my other uncle was diagnosed with it after Nam.
40% after just one joint is bullcrap, the psych wards would be full of schizos.
This actually is a good study. It helps prove we should outlaw birth and all forms of procreation!! According to the tenets of these studies, 100% of all deaths are caused by births!! So sex is bad, m'kay?
Let's not forget, thanks to the political classes, any attempt to study the effects of cannabinoid substances on the human body is a blatant violation of U.S. Federal Law. All these wackos are doing is confessing to a big-time crime. Thank the Drug War for that!
I was addicted of smoking(nicotine)alcohol and drugs too for 14 years and after 14 years i admitted that i am powerless over addiction.Then i joined a N.A group and at last i done it now, i am sober.I will work for people who are addicted like me to sober living.I will fight for that.I got some more power from this blog and comments.Thank you.
I work with people with mental illness. From my experience with people with schizophrenia, marijuana does have a direct effect on psychosis. My clients with schizophrenia often fall into deep psychosis after heavy use of marijuana (or any dopamine stimulating drug, for that matter). THC interferes with GABA's ability to inhibit dopamine production, and dopamine is what is inhibited by antipsychotics, so THC can exacerbate or trigger psychosis. Despite the low numbers of people in these studies that actually become schizophrenic, the results are clear and staggering. Trust me, I have no reason to be bias, this is not my study. I work with people who suffer from schizophrenia, and my concern is their well-being. So for those who are paranoid that the govt is out to get you and limit your freedoms, I ensure you, from my experience, this is legit.
I work with people with mental illness. From my experience with people with schizophrenia, marijuana does have a direct effect on psychosis. My clients with schizophrenia often fall into deep psychosis after heavy use of marijuana (or any dopamine stimulating drug, for that matter). THC interferes with GABA's ability to inhibit dopamine production, and dopamine is what is inhibited by antipsychotics, so THC can exacerbate or trigger psychosis. Despite the low numbers of people in these studies that actually become schizophrenic, the results are clear and staggering. Trust me, I have no reason to be bias, this is not my study. I work with people who suffer from schizophrenia, and my concern is their well-being. So for those who are paranoid that the govt is out to get you and limit your freedoms, I ensure you, from my experience, this is legit.
I have a 17 yr daughter that started smoking pot and a year later ended up in the hospital. Dr called her condition to be bipolar with schizophrenic tendencies. I always wondered if the pot smoking had anything to do with her condition. Until this happened she was always a healthy and never had any kind of episodes. I'm so glad to have found this artical.
1 joint = 40% increase. That means my chances of going schitz have increased by about 999888777000111%. WOW, you'd think I'd have it buy now. Who said that? What? Is someone following me?
I never had symptoms till starting antipsychotics. Now I have migraines nausea vomiting, I never I repeat never have appetite. I also developed muscle problems like I have had a cramp in my elbow for almost a year. The doctors did a biopsy and genetic testing they found the medication to have caused a cellular dysfunction in my muscles and most likely throughout the rest of my body and organs that is responsible for my symptoms and their is no cure. The genetic testing ruled out all known muscle diseases caused by genetics or genetic mutations, or inheritance, the medication is probably the cause. Basically this medicine is given to people who don�t have good health care it is billed as a cure. All patients are labeled for life with this diagnosis and there is no way to prove you do not have the illness in that respect is not a very scientific diagnosis. In science for a theory to be accepted and it still doesn�t mean it is 100 percent guaranteed to be true, there has to be the possibility to disprove it, this is not the case with schizophrenia. I wont comment on the effectiveness of synthetic thc on treating the antipsychotic induced cellular disfunction symptoms. heres to keeping people alive.
Just to weigh in here: I am schizophrenic and I did smoke weed before full blown schizophrenia disease started when I was 18 (now 33.) The author brings up a good point that I did not know though and that is the tobacco use. I smoke like a chimney and have never been able to quite even though I tried eleven times. The first time I tried to quit, for eight months, I was fired from my first job because I was suffering auditory delusions and went quite literally insane on my co-workers...verbally insane that is.
I was a very moderate smoker of marijuana before onset. I would say a joint a week, off an on, for maybe two years.
I also developed a opiate addiction seven years into schizophrenia (still, at that time, un-diagnosed.) It helps with the stress which is a major trigger of schizophrenia, at least for me. No stress equals fewer and more moderate delusions. So the author is also correct to say that schizophrenic people are more likely to develop a drug problem, specifically an opiate addiction for reasons specified; also because I know allot of schizophrenic people with a habit. Sober now, of opiates, for over a year but my delusional tendencies are actually increased while healthy and sober.
I know my situation does not help the case that marijuana does not cause psychosis and in fact adds proof to it. However, being an intelligent person that actually experienced it I could say with personal certainty that it was not the marijuana that caused the anomaly because I see know association with symptoms to usage. Pretty much everyone I know smokes weed from time to time and they are not schizophrenic or have psychotic tendencies to any degree. I haven't smoked weed in five years and still, as I said, suffer from schizophrenia.
"A single joint of cannabis raises the risk of schizophrenia by more than 40 percent, a disturbing study warn"
we begin at 1 % so after one joint were at 1.4 %. i have smoked at least 4 joints a day (shared with 2 - 3 ppl ) for about 2 years now. im to lazy to do the math but doesnt that mean that i should be a schizo right now or become one in a very little ammount of time ?
I work with people with mental illness. From my experience with people with schizophrenia, marijuana does have a direct effect on psychosis.
Let's not forget, thanks to the political classes, any attempt to study the effects of cannabinoid substances on the human body is a blatant violation of U.S. Federal Law. All these wackos are doing is confessing to a big-time crime. Thank the Drug War for that!
Hi,
I am a graduate student in neuropsychiatry. My thesis work is on the biphasic effects of THC. THC, which binds to the CB1 receptor in the CNS, exerts anxiolytic effects at acute or low dose exposure, and anxiogenic effects at high doses or with chronic exposure. One target of an activated CB1R receptor is GSK-3. We know that GSK-3 is highly repressed in the brain, but hyper-active neural GSK-3 has been reported in people with bipolar disorder, and schizophrenia. We have found that at high doses of THC, treatment of mouse brain cells results in an increase in GSK-3 activity, whereas low doses do not (still unpublished). Recently work done by Carron et al has shown a non-canonical internalization of the D2 Dopamine receptor mediated by B-arrestin. We think that the biphasic anxiety effect may be mediated by changing activity of GSK-3 in response to THC, and that people who are predisposed to bipolar or schizophrenia may have a dysregulation in this CB1/GSK-3 signaling. The question of causality is interesting; a sub-set of the bipolar/schizophrenic population will initiate marijuana use to self-medicate, whereas a sub-set of this population will use marijuana prior to the first episode. I am currently using a mouse model to identify 1) how normal GSK-3 signaling changes in response to THC and 2) if aberrant GSK-3 signaling contributes to mood/anxiety behaviors. There are loads of other interesting things I could talk about here but I've already written more than anyone will probably read.
At Zaytoz: it is not a blatant violation of US Federal Law, there are many peer-review papers published on the effects of cannabis and other cannabinoid ligands in humans. Also humans have endogenous cannabinoids, which means that if it was illegal we would all inherently be breaking the law by being alive :)
Sorry I am late responding to this, just came across it today and the topic is kind of my life right now.
I am bipolar and used marijuana after my diagnosis when I was 11. It didn't help the situation at all. Lamictal did though.
I know this is an old thread but it has again become popular in the news. Here is an interview with another Dr. who also has some very good points.
http://blog.norml.org/2011/02/09/dr-mitch-earleywine-ph-d-responds-to-l…