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Cannabis and mental illness: it’s complicated!

By Suzi Gage @soozaphone

This blog originally appeared on the Mental Elf site on 11th May 2016.

The use of recreational drugs is seen at much higher rates in populations with mental health problems than in the general population, and this is true for both legal substances such as alcohol and tobacco, as well as prohibited substances like cannabis.

But understanding what these associations mean is problematic:

  • Do the substances cause psychiatric problems?
  • Do people use recreational drugs to self-medicate?
  • Or, is there some other factor earlier in life that can lead to both risk of substance use and mental health problems?

The impact of cannabis (Hamilton, 2016) on mental health (Kennedy, 2015) is of particular interest in the USA, where cannabis is now legal in some states, and decriminalized in a number of others. There is a fear that cannabis use will increase, and therefore there is a pressing need to understand the nature of its association with psychiatric problems.

Blanco and colleagues state that this is their particular motivation for undertaking the research they have just published, to try and understand whether cannabis use predicts later substance use disorders, and also mood and anxiety disorders.

Methods

This study used a very large sample of adults in the USA, measured at 2 time-points, 3 years apart. Cannabis use in the past year was assessed at wave one, and a variety of outcomes were assessed at wave 2. These were cannabis use disorder, alcohol use disorder, nicotine dependence, other drug use disorder, mood disorder (including depressive disorder, bipolar I or II and dysthymia), and anxiety disorder (including panic disorder, social anxiety disorder, specific phobia, and generalized anxiety disorder). These were all assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV.

Regression analyses were used to look at the associations between cannabis and these disorders, before and after adjustment for a variety of other factors that might influence both cannabis use and mental health, and therefore could be confounding the relationship. These were socio-demographic characteristics, family history of substance use disorder, disturbed family environment, childhood parental loss, low self-esteem, social deviance, education, recent trauma, past and present psychiatric disorder, past substance use disorder and history of divorce.

The authors also used propensity score matching to try and further account for these confounders. This is a technique where cannabis users and non-users are matched by their values for the confounding variables, then compared. If confounding is the same between cannabis users and non-users, it cannot therefore drive the associations seen, meaning they’re more likely to be causal, rather than due to other factors (although confounding has to have been known about and measured for this to be the case). The sample size is a lot smaller for these analyses, with 1,254 people in each group.

Cannabis is now legal in some US states, so evidence about it's potential risks is now even more in demand.

Cannabis is now legal in some US states, so evidence about it’s potential risks is even more in demand.

Results

Of the 34,653 participants in the study, only 1,279 (roughly 3.5%) reported having used cannabis in the past 12 months at wave one. Before taking confounders in to consideration, cannabis use at wave one was associated with substance use disorders and mood and anxiety disorders. However, this changed after accounting for the factors the authors believed might confound the relationships.

Across the regressions and the propensity matched analyses, adjustment for confounders attenuated the associations between cannabis use and later mood and anxiety disorders, suggesting that these might be due to confounding. Conversely, associations remained between cannabis use and later substance abuse and dependence. This was particularly strong for cannabis abuse, as might be expected.

  • Cannabis use at wave one was associated with around a 7x increased risk of cannabis abuse or dependence at wave 2
  • Cannabis users also had 2-3x increased risk of alcohol use disorder or any other drug use disorder
  • Cannabis users also had around 1.5x increased risk of nicotine dependence.
Cannabis use was found to increase the risk of various substance use disorders.

Cannabis use was found to increase the risk of various substance use disorders.

Conclusions

The study found evidence that cannabis use predicts substance use disorder, even after adjustment for confounding. However, they also found that associations between cannabis use and later mood and anxiety disorders seemed to be due to confounding, rather than there being a causal association.

The authors concluded:

These adverse psychiatric outcomes [substance use disorders] should be taken under careful consideration in clinical care and policy planning.

After confounders had been taken into account, cannabis use was not found to increase the risk of mood or anxiety problems.

After confounders had been taken into account, cannabis use was not found to increase the risk of mood or anxiety problems.

Strengths and limitations

A strength of this study is the use of a nationwide sample, assessed at two different time points, and that they had a really big sample size. The authors also took steps to try and keep the sample representative, even after drop-out between wave one and wave two. The consideration of confounders is also a strength, although of course causation cannot be ascertained from observational data; a limitation that the authors themselves acknowledge.

When studies are very large, as this one is, it can be hard to get really accurate measures, because of the amount of time it takes to interview 35,000 people! It is particularly impressive that the outcome measures are all according to DSM-IV criteria. However, as all these measures were taken from an Alcohol Use Disorder interview, the measures of mood and anxiety may be less good (the interview has weaker test-retest reliability for mood and anxiety disorders than for substance use disorders).

The rate of cannabis use in this study (roughly 3.5%) seems very low; the UN’s World Drug Report in 2011 (UNODC, 2011) put previous-year cannabis use in the USA at 13.7%. The data used in the Blanco study were collected in 2001, so perhaps cannabis rates have increased since then. It is notoriously hard to monitor rates of illicit drug use as people may not be keen to honestly report their use; indeed, this may be a problem in this study too, meaning people might be misclassified.

The use of other substances at wave one isn’t necessarily adequately controlled for; pre-existing substance use disorders are controlled for, but less extreme use of a substance isn’t. So these participants that are using cannabis might also be smoking cigarettes, drinking alcohol, or using other illicit drugs. There’s no way to know from this study which came first, and this makes it difficult to know whether cannabis is causing the associations seen, or whether it could be another substance, for example.

While the use of propensity score matching is perhaps a stronger method to assess causation than simply adjusting for confounders, the technique cannot take in to account confounders that vary over time, as these could vary differently between cannabis users and non-users, and still be confounding the association despite being the same at one time point.

Although the authors rightly highlight that associations of cannabis use with later substance use disorders are robust to confounding, their conclusions don’t highlight that adjustment actually reduced the association between cannabis use and later mood and anxiety disorders to the null. I think this is a really interesting finding, and maybe should have been made more of.

Why did the authors not make more of their finding that cannabis use does not increase the risk of depression or anxiety?

Why did the authors not make more of their finding that cannabis use does not increase the risk of depression or anxiety?

Summary

This is a well designed study on a really large sample, and provides useful information about associations between cannabis use and later substance use disorders, as well as suggesting that perhaps associations between cannabis use and mood and anxiety disorders might be due to other factors, rather than due to cannabis causing these outcomes. It still doesn’t really tell us why cannabis use might increase the risk of substance use disorders, and doesn’t tell us that cannabis is causing this increase of risk.

Links

Primary paper

Blanco C, Hasin DS, Wall MM, et al. (2016) Cannabis Use and Risk of Psychiatric Disorders: Prospective Evidence From a US National Longitudinal Study. JAMA Psychiatry.Published online February 17, 2016. doi:10.1001/jamapsychiatry.2015.3229. [PubMed abstract]

Other references

Hamilton I. (2016) Cannabis: what do we know and what do we need to know? The Mental Elf, 17 Mar 2016.

Kennedy E. (2015) High potency cannabis and the risk of psychosis. The Mental Elf, 24 Mar 2015.

UNODC (United Nations Office on Drugs and Crime) (2011) UN World Drug report 2011. United Nations.

Photo credits

– See more at: http://www.nationalelfservice.net/mental-health/substance-misuse/cannabis-and-mental-illness-its-complicated/#sthash.U9604663.dpuf

Researching abroad: Cannabis and decision making in the Big Apple

by Michelle Taylor @chelle_bluebird

Setting off for TARGs 2013 annual retreat to Cumberland Lodge in Great Windsor Park, I was looking forward to hearing a talk from an invited guest speaker. Gill had flown in from Columbia University to talk to the group about a recent drug administration study her lab group had completed. The research being conducted by their lab was very different to the epidemiological research that I am used to. Now don’t get me wrong, I thoroughly enjoy the research that I do, but these studies sounded new and exciting. After listening to the talk, the evening activities began with dinner and a quiz. Luckily, I ended up on the same quiz team as Gill, giving me the opportunity to ask more about her research. I decided to grab the bull by the horns and offer my help in one of her future studies, and so my trip to the Big Apple began…

central park 1Nine months later I was on my way to Heathrow for a two month stint collecting data on a cannabis administration study. I was both excited and apprehensive. I have never lived more than a 3 hour drive away from family, and have always been in a city where I have known people. I didn’t know whether I would get homesick, or whether I would make friends on my trip abroad. These feelings of apprehension soon disappeared in the first few hours of my first day at the New York Psychiatric Institute. Everyone I met was so friendly and welcoming, even the many morning commuters who stopped to help the lone Brit who was obviously puzzled by the subway map at 7.30am.

yankeesI was to spend the next six weeks collecting data for a study examining the neuro-behavioural mechanisms of decisions to smoke cannabis at the Substance Use Research Center in the New York Psychiatric Institute at Columbia University. This research centre is unique; it is one of the largest drug administration centre in the world and has licenses to administer a wide variety of drugs, including cannabis, cocaine and heroin. This means that much of the research conducted here is cutting edge. The aim of the study that I would be working on was to shed light on how and why drug abusers repeatedly make decisions to take drugs despite substantial negative consequences. The study used brain imaging (fMRI) to examine the neural and behavioural processes involved in decisions to self-administer cannabis, compared to decisions to eat food, in regular cannabis users. We also examined the influence of drug and food cues on the processes underlying these decisions. To do this, participants were recruited as inpatients and stayed with us in the lab for a week. Data collection for this study is still ongoing, but I will be sure to write another blog post with what we found when the results are available.

coney_2I found this research fascinating and it was a pleasure to be involved in the work carried out in this department. The experience was made even more enjoyable by the people I was working with. There were many office conversations about the British and American slang that was being used, many lunchtime trips to Chipotle (an American fast food restaurant that I am definitely missing since my return to the UK), and several Friday evening trips to the local Irish bar. One office memory that will always stick in my mind was meeting a very accomplished researcher in the field of my PhD, a researcher that was definitely someone I should be impressing. Upon entering this individuals office on an extreme
ly hot New York day, the fan was turned to the meeting area and the smell of cannabis filled the room as the flow of air reached me (I had been administered the drug to a participant earlier that afternoon). Probably not the best first impression I have ever made!

milkshakeI did, of course, take every opportunity to explore New York. I was lucky enough to get tickets to watch the New York Yankees beat the Boston Red Sox at the Yankee Stadium, which was also one of the last games played by baseball-legend Derek Jeter. I made several trips to the American Natural History Museum (my favourite type of museum, and this one cannot be done in a day), and while there saw a live spider show, a 3D film about Great White Sharks and a full T-Rex skeleton. The glorious weather allowed for several leisurely strolls around Central Park. And, of course, the American food definitely needs a mention. If anyone reading this takes a trip over the Atlantic, I would definitely recommend visiting Big Daddy’s Diner for what could be the best milkshake on the planet. And don’t be shy about trying a hotdog from one of the carts that can be found on nearly every street corner. The reason there are so many of them is that they’re delicious! I would also recommend a trip to the Russian Tea Rooms for caviar afternoon tea, an evening at the New York Metropolitan Opera (if that’s your cup of tea), and a trip to Coney Island.

t_rexAlthough it was daunting going abroad for that length of time to begin with, I don’t think I would be having those feelings again and I would definitely jump at any opportunity to work in a different environment in the future. I am very grateful that I am a PhD student in a large working group like TARG, as without this I probably would not have come across opportunities such as this one. This experience has taught me the importance of inter-disciplinary research, and the need for several fields contributing evidence to a much larger research question. Since this trip, I have been successful in a fellowship application allowing me 9 months in a different department at the University of Bristol, an application that I probably would not have made if it wasn’t for my experience at the Columbia University. I am an epidemiologist and do not have any plans to change that; however I do plan to conduct more interdisciplinary research in the future. I would like to that Gill (and everyone in her lab group) for welcoming me and making this trip possible. I look forward to hopefully working with you again in the future…

High potency cannabis and the risk of psychosis

By Eleanor Kennedy @Nelllor_

This blog originally appeared on the Mental Elf site on 24th March 2015

shutterstock_27220114

Smoking higher-potency cannabis may be a considerable risk factor for psychosis according to research conducted in South London (Di Forti, et al., 2015).

Cannabis is the most widely used illicit drug in the UK and previous research has suggested an association between use of the drug and psychosis, however the causal direction and underlying mechanism of this association are still unclear.

This recent case-control study published in Lancet Psychiatry, aimed to explore the link between higher THC (tetrahydrocannabinol) content and first episode psychosis in the community.

To compare the impact of THC content on first episode psychosis, participants were asked whether they mainly consumed skunk or hash. Analysis of seized cannabis suggests that skunk has THC content of between 12-16%, while hash has a much lower THC content ranging from 3-5% (Potter, Clark, & Brown, 2008; King & Hardwick, 2008).

Cannabis hash and skunk have very different quantities of the active THC component.

Methods

The researchers used a cross-sectional case-control design. Patients presenting for first-episode psychosis were recruited from a clinic in the South London and Maudsley NHS Foundation Trust; patients who had an identifiable medical reason for the psychosis diagnosis were excluded. Control participants were recruited from the local area using leaflets, internet and newspaper adverts. There were 410 case-patients and 370 controls recruited.

Researchers gathered data on participants’ cannabis use in terms of lifetime history and frequency of use as well as type of cannabis used, i.e. skunk or hash. Participants were also asked about their use of other drugs including alcohol and tobacco, as well as providing demographic information.

Results

The case-patients and control participants were different in a couple of key areas (note: psychosis is more common in men and in ethnic minorities):

Case patients Control participants 
Male 66% 56%
Age 27.1 years 30.0 years
Caribbean or African ethnic origin 57% 30%
Completed high level of education 57% 90%
Ever been employed 88% 95%
Lifetime history of ever using cannabis 67% 63%

Participants with first episode psychosis were more likely to:

  • Use cannabis every day
  • Use high-potency cannabis
  • Have started using cannabis at 15 years or younger
  • Use skunk every day

A logistic regression adjusted for age, gender, ethnic origin, number of cigarettes smoked, alcohol units, and lifetime use of illicit drugs, education and employment history showed thatcompared to participants who had never used cannabis:

  • Participants who had ever used cannabis were not at increased risk of psychosis
  • Participants who had used cannabis at age 15 were at moderately increased risk of psychotic disorder
  • People who used cannabis or skunk everyday were roughly 3 times more likely to have diagnosis of psychotic disorder

A second logistic regression was carried out to explore the effects of a composite measure of cannabis exposure which combined data on the frequency of use and the type of cannabis used.Compared with participants who had never used cannabis:

  • Individuals who mostly used hash (occasionally, weekends or daily) did not have any increased risk of psychosis
  • Individuals who smoked skunk less than once a week were nearly twice as likely to be diagnosed with psychosis
  • Individuals who smoked skunk at weekends were nearly three times as likely to be diagnosed with psychosis
  • Individuals who smoked skunk daily were more than five times as likely to be diagnosed with psychosis

The population attributable factor (PAF) was calculated to estimate the proportion of disorder that would be prevented if the exposure were removed:

  • 19.3% of psychotic disorders attributable to daily cannabis use
  • 24.0% of psychotic disorders attributable to high potency cannabis use
  • 16.0% of psychotic disorders attributable to skunk use every day

These findings raising awareness among young people of the risks associated with the use of high-potency cannabis

Conclusions

The results of this study support the theory that higher THC content is linked with a greater risk of psychosis, with daily use of skunk conferring the highest risk. Recruiting control participants from the same area as the case participants meant that the two groups were more likely to be matched on not only demographic factors but also in terms of the actual cannabis that both groups were consuming.

The study has some limits, such as the cross-sectional design which cannot be used to establish causality. Also the authors have not included any comparison between those who smoke hash and those who consume skunk so no conclusions can be drawn about the relative harm of hash.

Media reports about the study have mainly focussed on the finding that ‘24% of psychotic disorders are attributable to high potency cannabis use’. This figure was derived from a PAF calculation which assumes causality and does not allow for the inclusion of multiple, potentially interacting, risk factors. Crucially the PAF depends on both the prevalence of the risk factor and the odds ratio for the exposure; the PAF can be incredibly high if the risk factor is common in a given population.

In this case, the prevalence rate of lifetime cannabis use was over 60% in both participant groups. According to EMCDDA, the lifetime prevalence of cannabis use in the UK is 30% among adults aged 15-64, so it is arguable that this study sample is not representative of the rest of the UK. The authors themselves note that “the ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies”, which is a more accurate interpretation than media reports claiming that “1 in 4 of all new serious mental disorders” is attributable to skunk use.

Future studies looking at the relationship between cannabis and psychosis should also aim to differentiate high and low potency cannabis. Longitudinal cohort studies are particularly useful as they have the same advantages as a case-control design but data about substance use could be more reliable as ‘lifetime use’ can be gathered from multiple measurements collected at a number of time points across the lifetime.

This innovative study is the first to distinguish between different strengths of cannabis in this way.

Links

Primary study

Di Forti M. et al (2015). Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study (PDF). The Lancet Psychiatry, 2(3), 233-238.

Other references

King L, & Hardwick S. (2008). Home Office Cannabis Potency Study (PDF). Home Office Scientific Development Branch.

Potter DJ, Clark P, & Brown MB. (2008). Potency of Delta(9)-THC and other cannabinoids in cannabis in England in 2005: Implications for psychoactivity and pharmacology (PDF). Journal of Forensic Sciences, 53(1), 90-94.