EXPERT REACTION: Smoking dope just once as a teen could change your brain

The results of this study suggest that even in small doses, cannabis use can result in structural brain changes, most notably increased grey matter volume. 

Given that adolescence is a time of rapid brain maturation/reorganisation, any changes which are induced by external forces such as cannabis or alcohol use rather than normal developmental factors must be viewed with some concern.

The study also noted a large degree of overlap between low-dose users and non-users, suggesting that some individuals may be more at risk than others, although it is not yet possible to identify those at-risk. 

As a consequence, the overall results suggest that cannabis, like alcohol and other recreational drugs, should be avoided until brain development/maturation is complete; that is, until at least the age of 21.

Paradoxically, the finding that low-dose cannabis use can increase grey matter volume may have therapeutic implications.  Previous studies have suggested that some individuals suffering from some disorders (e.g. major depressive disorder) have reduced grey matter volume, thus, low dose  cannabis use, under medical supervision, may have the potential to reverse this reduction, although a significant amount of research needs to be conducted before such a conclusion can be verified either way.

While many past survey-based studies have found that using cannabis before the age of 16 is linked to a range of adverse outcomes, this new research by Catherine Orr and colleagues increases our understanding of how and why this may occur.  In particular, it provides biological evidence that, even when used only once or twice, cannabis use can adversely impact the brains of young teenagers.

It is, however, important to note that the study found only a small number of cognitive functions and behaviours to be associated with these cannabis use-related brain alterations, with many of the assessed cognitive functions and behaviours being unaffected. 

It is also important, as noted by the researchers, that further research is conducted to ensure findings can be replicated in larger and more diverse samples.

More in-depth investigation of the concurrent use of cannabis, alcohol and nicotine on the adolescent brain is also important, to increase our understanding of the individual and combined impacts of these substances on normal brain development and function.   

This is an interesting finding of increased gray matter volume in the brains of young people who tried cannabis once or twice when they were 14. The data are from a small subset of a much larger multi-centre study that was focused on different issues.

The findings are an association, and the direction of cause cannot be determined by this study.

It may be other factors, such as the age at which nicotine or alcohol were first tried, or other personality or environmental characteristics that were not reported in the study that may lead to early experimentation that are causal to the gray matter volume changes, if the effect is real.

Note that the same effect was not apparent in 16-year-olds who tried cannabis once or twice. The sample sizes are relatively limited and the relative low rate of replication of the findings (e.g., https://www.bbc.com/news/science-environment-39054778) means that we need  replication in other samples before we can be confident that the association exists.

Furthermore, the significance levels were not corrected for the large number of comparisons made, which has led to positive findings in a MR brain imaging in a dead salmon brain.

It is also unclear what significance an increase in gray matter volume may have. Is it good or bad? In the past, decreases in gray matter volume were associated with alcoholism and schizophrenia, for example.

This study raises more questions than it answers at this stage.

Along with stress, THC exposure is one of the most prominent risk factors for schizophrenia. In general the earlier the use, the greater the risk.

Therefore this paper imaging teenage brains exposed to THC is an important contribution, especially as sample numbers are relatively large for imaging studies and this is a non-standard population.

The first cohort of THC-exposed and non-exposed teens is well matched. The study design has been careful to include a second longitudinal cohort examining baseline brain structures. This allows not only the ability to examine whether there is change from baseline (assumed to be mediated by THC) but, perhaps even more importantly, allows the reader to assess whether the brains of those who chose to use cannabis were somehow different to start with; i.e do those who use drugs belong to a separate “risk taking” population.

This definitely strengthens the interpretations of these findings - that it is the drug rather than a prior alteration in risk taking individuals driving the findings.

An increase in grey matter is counter to most findings in THC users and schizophrenia, where most brain volume imaging studies reveal decreases. It is difficult for the authors to determine mechanism driving this initial volume increase and follow up scans on those who become dependent would be very informative.

Limitations:

The issue of scanner variation is not insignificant and perhaps requires the delta GMVs [gray matter volume] data to be re-examined with users and controls matched at the same site. The data in cohort two, however, are longitudinal and presumably at the same site so this is perhaps less of an issue.

Another possible limitation is the active nature of use; i.e. was use recent or proximal to the scan. A drug urine screen could be suggested to control for this.

An increase in brain volumes of course may still be a benign feature related to the pharmacology of CB1 receptor activation in various brain regions, i.e. greater dendritic densities, glial hypertrophy or increased glial number, increased spine numbers. These are all dynamic events and presumably able to come back to some sort of equilibrium in the absence of stimuli, in this case THC. The minimal exposure associated with these findings is perhaps the most important result as it speaks to the long-standing nature of these effects on the adolescent brain.

I think this is a well conducted study that makes an important contribution to our knowledge about adolescent brains.