Sunday, April 20, 2014

420: How Marijuana Messes With the Brain

Thankfully, I'm only late to the party by 4 days. I wanted to save this post for 4/20 for obvious reasons.

On April 16 in the Journal of Neuroscience, a study was published by Gilman et al. entitled "Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users." Using MRI scans on 20 young adults (age 18-25) who qualified as casual recreational marijuana users and 20 non-using controls who were matched for gender, age, ethnicity, education and handedness, the researchers tested for three things (to quote from the abstract for brevity): (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). The researchers also controlled for alcohol use and cigarette smoking.

Their basic conclusions were that there is an association between casual marijuana use and density of gray matter in the left nucleus accumbens as well as the amygdala. The density, as well, correlated with higher use of marijuana as reported by the subjects.

Let us keep in mind, first, that this was a cross-sectional study. As Ryan Smith suggests: "While the correlative relationship reported here is statistically strong, a longitudinal study design is necessary to make the causative claims throughout the first 29 paragraphs and abstract of this manuscript."

While I partially sympathize with this statement, as correlation does not equal causation (nothing new, right?), I think the researchers have reason to believe that the association is causal, although as they suggest at the end of the study, it has not been conclusively verified. It has already been established that cannabis use is associated with working memory impairment, but there was still a need to establish a potential association between cannabis use and the neural circuitry. As such, we should see this new study in the context of another study published in Schizophrenia Bulletin by Smith et al. entitled "Heavy marijuana users have abnormal brain structure, poor memory." This study from December examined heavy marijuana users as opposed to casual users and found that there is an association between heavy use of cannabis and brain abnormalities as well as poor performance on memory tasks.

Thus, Ryan Smith's objection to the test may be seen as unnecessary. While a longitudinal study would effectively falsify or validate the causal relationship, showing that degree of use is correlated with degree of abnormality/impairment is good enough for supposition (I say this as a matter of opinion because, the way I see it, it seems less likely that having more problems causes you to smoke more weed. I think degree would be unrelated in such a relationship).

However, there are other objections to be made, namely relating to the funding the research received. Funding parties include the National Institute of Drug Abuse and the Office of National Drug Control Policy. This suggests potential funding bias, although practically we cannot make such an assertion. I would honestly be surprised, however, that this study was biased by its funding given the context of established associations between cannabis and cognitive impairment/brain abnormalities.

Although, that's the politics of science, and at this point the only thing that can be done is replication of the findings; but to close, that's not exactly a hard thing to do, considering that this study - to a smaller degree - replicated the results of previous studies. When will it end? 

Thank you very much for reading.

*For supplementary reading on marijuana's negative health effects, I highly recommend this infographic from Healthline.*

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Gilman, J., Kuster, J., Lee, S., Lee, M., Kim, B., Makris, N., van der Kouwe, A., Blood, A., & Breiter, H. (2014). Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users. Journal of Neuroscience, 34 (16), 5529-5538 DOI: 10.1523/JNEUROSCI.4745-13.2014

Meier, M., Caspi, A., Ambler, A., Harrington, H., Houts, R., Keefe, R., McDonald, K., Ward, A., Poulton, R., & Moffitt, T. (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of the National Academy of Sciences, 109 (40) DOI: 10.1073/pnas.1206820109

ResearchBlogging.orgSmith, M., Cobia, D., Wang, L., Alpert, K., Cronenwett, W., Goldman, M., Mamah, D., Barch, D., Breiter, H., & Csernansky, J. (2013). Cannabis-Related Working Memory Deficits and Associated Subcortical Morphological Differences in Healthy Individuals and Schizophrenia Subjects. Schizophrenia Bulletin, 40 (2), 287-299 DOI: 10.1093/schbul/sbt176


  1. There are several things we should keep in mind with these studies. Large subject research designs allow only for inferences to be made from a sample to the population-- all individual variability is lost. For example, there are probably some casual marijuana smokers who have normal brain volume in the amygdala and nucleus accumbens, or perhaps higher densities than some of those in the control group, but these individual differences are lost in the mean comparisons. Also, I am not quite sure that doing a longitudinal study would add any argument to the causal relation here. I could be wrong, but I always have thought that in order to establish a causal relation, you need to randomly assign people to conditions and control for all extraneous variables. Perhaps there is a third variable at play here (e.g. the behaviors that marijuana smokers engage in cause these brain changes, not necissarily the neurochemical effects of marijuana). I am not saying that these findings are null and void, I just like to air on the side of skepticism.

    1. "I just like to air on the side of skepticism."

      As do I, Anon. I think I gave the wrong context in what I said: a longitudinal study would effectively prove that there is a probably a causal relationship between marijuana use and brain abnormality, because a longitudinal study would eliminate any cross-sectional confounders.

      This wouldn't, however, prove that marijuana use is responsible for the abnormalities or vice versa. That would require a test such as what you described. All things considered, the causal relationship may not be "proven" so to speak, but there is great reason to pursue it further because of the associations that have already been established. With degree, marijuana use is correlated with these abnormalities, so there's something to be said for it.

  2. Heya, Lex. I'm just curious: why do you think they only used 20 casual users, and 20 non-users? That sample size seems a bit small, but maybe there's a reason behind it I don't know about. Care to share your thoughts?

    1. You're right -- the sample size is small (generally, the sample should be 25 or 30 at least). There are many reasons for a small sample size. For any study involving human research, it can be a bit sketchy, and thus it may be seen as ethical to start with a small sample. In addition, researchers need the money for the MRI scans and anything else they use in the study. Just as well, we can figure that it might be difficult to get drug users to participate in a study such as this. It depends on where the sample comes from.

      However, when studies such as these are successful, bigger funds and bigger support are going to follow up, and more researchers are going to attempt to replicate the results with bigger samples now that there shows some promise.

  3. First and foremost we all know marijuana messes with the brain in one way or another. Yes we already know that it may cause memory loss. But if it does all these things why are we legalizing it in states for medical/recreational use? Did you know there is a study out there that also says "mushrooms" may grow back brain cells and help with depression? All these drugs that they try and keep illegal are actually helping people with abnormalities. Alcohol is one of the worst drugs known to man and that's the most legal drug. Every prescription drug has side effects. So marijuana may cause memory loss? Oh well! So instead of focusing on the negative effects of it look more towards the positive.

    1. You've raised a common line of argumentation, so I'll have to address it line by line:

      "But if it does all these things why are we legalizing it in states for medical/recreational use?"

      There are a few reasons for this. What little research had been done on the effects of marijuana were on its potential for medicinal uses, and little was known about the harmful side effects it posed until after it had been legalized more widely. Once a drug is legalized, we can do more research on it to gather more knowledge. That being said, I know there are plenty of other negative side effects to marijuana, such as on heart attacks, pulmonary and respiratory functions, etc. It also, if I recall correctly, has 50% more carcinogens than cigarettes.

      In addition, the misconception that marijuana is harmless has led to mass social mobility in favor of its legalization, and when your constituents are shouting for legalization, it's bound to happen.

      "Did you know there is a study out there that also says "mushrooms" may grow back brain cells and help with depression?"

      Well for one, I would have to see this study. Who conducted it? What funding did they receive? Sample size? Methodology? Were the findings replicated? A lot of unanswered questions.

      "All these drugs that they try and keep illegal are actually helping people with abnormalities."

      Well we can't conclusively say that given the lack of hard evidence, but at the same time, there are benefits to nearly anything. If your argument is that marijuana is helping people with abnormalities: it might, but it has also been shown to have a positive correlation with abnormalities as well; so what's the tradeoff, if there is one?

      "Alcohol is one of the worst drugs known to man and that's the most legal drug."

      Because we tried criminalizing it and it just didn't work. It's kind of similar to the current situation: nobody wants to pay for the law enforcement to crack down on marijuana anymore because of its popularization. Just because it's legal doesn't mean it's okay.

      "Every prescription drug has side effects."

      But prescription drugs are designed to have a medical benefit. Drugs like alcohol, marijuana, shrooms, etc. were all designed for the side effects they cause (i.e. getting high as a kite). The relationship between prescription drugs and illicit drugs, then, is weak because of what they're made for and what they do.

      "So marijuana may cause memory loss? Oh well!"

      Well you may see it as a worthwhile risk, but that shouldn't stifle others' ability to gain access to that information and make their own decisions based off of it.

      "So instead of focusing on the negative effects of it look more towards the positive."

      Same general response: the fact is that these drugs have been shown to cause harm, and the full extent of their harm is not yet known well enough. A few decades ago, people thought that any side effects of cigarettes were superficial at best. Now, turns out they can cause cancer. That wouldn't have happened had research not been done on it. We need to focus on both the good and the bad to gain a better understanding of what we're legalizing -- because if it turns out to just be a heavy-tar cigarette, then people need to know.

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