An interesting study this week from the American Journal of Epidemiology entitled “Early Cannabis Use and Estimated Risk of Later Onset of Depression Spells: Epidemiologic Evidence From the Population-based World Health Organization World Mental Health Survey Initiative” – you can read the paper on the Medscape website  (you need to create an account- click here – but it’s free). After registering you can find the paper by putting “Early Cannabis Use and Estimated Risk” into their search box.

Before we go any further let’s restate a simple precautionary principle which really applies to all drugs, not just cannabis, which is children and young teenagers really shouldn’t be using them. The reason for this is simple and obvious; young brains are still developing and drugs tinker about with the workings of the brain.

So really to look for some kind of negative impact on young drug users – especially heavy young users – is a bit like fishing in a bucket, they’re looking for something they expect to find. So it’s perhaps something of a surprise that their conclusion is:

The association between early-onset cannabis use and later risk of a depression spell was studied … The overall association was modest … , was statistically robust in 5 countries, and showed no sex difference. The association did not change appreciably with statistical adjustment for mental health problems, except for childhood conduct problems, which reduced the association to nonsignificance.

Not quite the result which might have been expected from a bucket fishing expedition, although the last bit is  more interesting than it sounds at first.

One limitation of the study was:

This study did not allow differentiation of levels of cannabis use; this issue deserves consideration in future research.

Which is a somewhat odd thing not to have looked at in all honesty.

The study used data collected by the World Health Organisation which surveyed subjects from 17 countries, so the claim that the overall association was “statistically robust in 5 countries” needs to balanced by the statement that it  was not statistically robust in 12 countries.

The paper begins by stating that several studies have shown a link between early onset cannabis use whilst other haven’t. The aim of the study then was to look at the data collected around the world by the WHO to test the hypothesis that there is, indeed, a causal link between early onset cannabis use and depression later in life.

Here, with community samples from diverse countries, we estimated whether cannabis onset by the middle of adolescence (before age 17 years) is followed by greater risk of first onset of a depression spell, with due attention to sex and age variations.

Now, there are some important observations to be made at this point:

We used a local area matching approach  to constrain the effects of geographic variation in enforcement of cannabis laws, local jurisdictional variation in subnational law, and other socially shared local area variations that might confound cannabis-depression estimates and which also account for potential geographic variation in odds of exposure to cannabis use.

Of course as an illegal activity cannabis use is more likely to be linked with overall risky activities and young people are unlikely to be using cannabis with any guidance from more experienced adults, they are more likely to associate with other deviant sub-cultures and be alienated from mainstream society; all this is one of the main arguments against prohibition. The study also seems to be based on the assumption that strong law enforcement will have a simple impact on the rates of use and the consequences of that use, but read on.

It’s worth mentioning as a criticism that the study clearly avoided any consideration of the possibility that different strains of cannabis might have different impacts on adolescent development. Cannabis is not a simple drug in the sense that its composition varies greatly between strains and under the rule of prohibition there has been a claimed move away from high CBD strains in some areas which might have an impact on mental health.

Furthermore, we considered an array of possibly confounding mental health problems, including childhood conduct problems. Childhood conduct problems and early rule violations have been described to precede early peer rejection, affiliation with drug-using peers, early-onset cannabis use, and subsequent low self-esteem and mood disturbances and thus are important confounding variables.

There is something rather worrying about the way this is written, the implication being that youthful rebellion and non-conformity is somehow a form of mental illness.  As it reads it seems to justify the authoritarian mind-set that young kids who push against authorities laws are destined to be social outcasts and that this is a natural thing, not something created by the social constraints imposed on these young people.

The study drew on data collected by the WHO between 2001 and 2006 in the Americas (Colombia, Mexico, the United States), Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, Ukraine), the Middle East and Africa (Israel, Lebanon, Nigeria, South Africa), Asia (Japan and 2 separate surveys carried out in Beijing and Shanghai, China), and Oceania (New Zealand) and involved 85,088 respondents, so it was a big survey.

The results were

Early-onset cannabis use was moderately associated with later onset of a depression

Of tobacco use they claim

Tobacco smoking and a depression spell after age 16 years were associated too modestly for tobacco to function as an important confounder here

Robust (what a cynic might call the expected “right” result) were seen in Germany, Ukraine, Nigeria, South Africa, and New Zealand, with the strongest associations being seen in South Africa and Nigeria.

Worthy of special note is this observation that:

Estimations for Lebanon, Japan, and China failed because early-onset cannabis use was rare there.

Japan is known to have low levels of cannabis use, China is probably also low, but Lebanon is quite a different situation. In the 90’s (the time period in which the young people studied grew up) Lebanon was emerging from a long and highly destructive war, it is also a major producer of cannabis (hash) and levels of use there are very, very high. Now it could be that the well established social norms of Lebanon work to prevent young people getting stoned, but given the trauma the society went through with the war which only ended in 1990 it would seem unlikely that young people did not come across cannabis very often. Whatever the reason for the data failing there may be, the lack of early onset of use probably wasn’t it.

Persistency of cannabis use into the 12 months prior to assessment did not appear to alter the size of the cannabis-depression association.

Which would seem to suggest that continuing to use didn’t make the problem worse.

Moreover, statistical adjustment for a broad array of precannabis, concurrent, and postcannabis mental health problems in a conditional logistic regression model did little to attenuate the originally observed association

Which would seem to indicate that other mental illness isn’t a factor. So what about the idea that early rule breaking leads to greater social exclusion hence more cannabis use then more depression?

To study the possibility of confounding by a propensity to commit early violations of social norms, we created an index of childhood conduct problems as described in Appendix Table 1 and reestimated the cannabis-depression association with this index in the model, along with terms for age, age squared, and sex. This was possible for all but 4 countries, which did not administer this assessment. Based on data from the 13 countries that administered the childhood conduct problems assessment, and prior to statistical adjustment for this index of early norm violations, the aRR for the estimated cannabis-depression association was modest at 1.18 (95% CI: 1.02, 1.37; P = 0.02). With statistical adjustment for the index of early norm violations, the estimated cannabis-depression association dropped towards the null value and lacked statistical significance

So what do they make of all this?

The general summary evidence from this cross-site research with representation of all world regions suggests that there might be a modest but statistically robust sex- and age-adjusted association linking early-onset cannabis use with later occurrence of a depression spell.

Hardly the clear-cut answer prohibition campaigners would have wanted to read, but it all takes an unexpected turn:

In most prior research on the hazards of cannabis use, the “controls” have been drawn from the total population, without taking into account the fact that in many places cannabis smoking is a violation of social norms.

What they would seem to be talking about is the impact of the legal regime on societies, not the existence or otherwise of some kind of anti-cannabis “social norm”.

Unless early propensity for norm violations of this type can be taken into account, or unless norm violation has no association with the hazards of interest, other research teams may find what has been observed here—namely, an initial statistically robust signal of cannabis-related harm that would disappear when cases and controls were selected with attention to the norm-violation distribution or when the propensity toward norm violation was held constant.

Which would seem to be some comment about the effect of prohibition on the well being of young cannabis users, although it’s phrased in such a way as to be almost incomprehensible.

We found evidence for an association between early cannabis use and later depression spells for 5 individual countries (Germany, Ukraine, Nigeria, South Africa, and New Zealand), representing both developed and developing countries. It is difficult to explain why in some countries the association was significant, while in others it was not. A high prevalence of early cannabis use in a particular country was not a clear explanation for a significant relation. For example, the United States and New Zealand had the highest prevalences of early cannabis use,  but only in New Zealand was the association significant. On the contrary, in South Africa and Nigeria, the prevalence of early cannabis use was low,  while the aRR was large and significant. It might be that in these countries the deviancy of cannabis use influences the incidence of a later depression spell.

If the deviancy of cannabis use is high anywhere it would be in the USA, also rates of cannabis use in South Africa are also high. However, what this conclusion seems to be saying is that if a correlation exists, it isn’t between the age of onset of cannabis use, but (in some way) it’s deviancy index if such a thing exists. Eventually we get there:

The cannabis-depression association was highest in the oldest age group. This might be explained by the fact that the oldest age group had more time to develop depressive symptoms. Another explanation might be the higher prevalence of cannabis use in younger age cohorts,  which makes early cannabis use more normative in younger cohorts and therefore less deviant, with fewer negative consequences (e.g., discrimination, criminalization, use in segregated subcultures), thereby lowering the likelihood of deleterious mental effects such as depressive symptoms. In addition, a shorter duration of cannabis exposure among the younger cohorts could explain this finding, although controlling for persistence of cannabis use in this study did not alter the association.

So what this suggests is that perhaps the more “deviant”  – ie the more illegal – the cannabis use of a young person is, the greater the risk of later depression later in life. If you want to study the effects of cannabis use on young people, the effect of the law is a serious confounding issue which should be taken into account.

Now there’s a surprise. Not.