GUEST POST: dazed & confused about cannabis?

Our research director shares some insight on cannabis before legalization later this year.

August 27, 2018

Cannabis is going to be recreationally legalized in Canada on October 17, 2018. This means that a lot of Canadians may, for the first time, be asking, “should I try cannabis”? I’m going to give you the answer to that question (sort of). But before I do that I want to mention my personal favourite part of NeuroCAM: personalized medicine.

A lot of our current treatments for brain disorders are based on the idea that they should work for everyone. But the fact is, they don’t. This may come as a shock to some (#sarcasm), but everyone’s brain is different. Since my brain is wired differently than your brain, there can be some very scientifically valid reasons why what works for you does jack all for me. Personalized medicine is all about trying to understand who you are as an individual, using that information to predict how you might respond to particular treatments, and most importantly, why? So, this leads back to the original question.

Should you try cannabis? Cannabis has some well-documented benefits for a number of conditions, but it also increases your risk for a number of other disorders. There are a whole bunch of articles to explain why cannabis is great for you, and why it’s terrible for you, so how do you know which to believe? Well, since your brain is unique, you could start by thinking about how people similar to you (like family, or BFFs), and how people different than you (arch enemies for example) respond to cannabis to get some insight.

What is one of the most obvious differences between people? The sexes. Men and women differ in the way that their endocannabinoid system (what cannabis operates on) is wired in their brains. This means that the effects of cannabis for men could be different than for women. For example, as you might guess, a stressful childhood can have some bad consequences for your brain. Well, it turns out that in a rat study, teenage cannabis use actually protect females from these negative effects, while cannabis had negative effects for non-stressed females1. So, it looks like that while cannabis was good for women in one case, it was bad for them in another. You may notice this is a theme….

There are also big genetic differences in how the endocannabinoid receptors in our brain operate. One study found that in one genotype, anxiety was correlated with a larger amygdala2 (a brain structure important for emotions). In contrast, the other genotype didn’t show this correlation but instead found a correlation between reward-related brain activity and increased impulsivity2. This suggests that knowing your genotype for this gene could help inform whether cannabis use could put you at risk for anxiety, or at risk for addiction. Indeed, another rat study found that the addicting effects of cocaine operated through endocannabinoids3,4. Since people with Attention Deficit-Hyperactivity Disorder (ADHD) often have increased reward-related brain activity, this means that people with ADHD who use cannabis are at an increased risk for addiction, and indeed, an estimated 34-46% of people seeking cannabis use disorder treatment have co-morbid ADHD5. On the flipside, cannabis could be a possible treatment for ADHD, as it has some similar effects as ADHD medications on dopamine pathways6,7,8. Again, for some people cannabis may be therapeutic, though with some risk for addiction.

So, coming back to the original question: should you use cannabis or not? The answer, of course, is that it’s complicated. I highlighted a number of interesting studies that showed how cannabis can promote different effects in different people. But science on cannabis has not gotten to the place where we can reliably predict how one is going to respond to a joint (hence why we need more personalized medicine research). For some people, it could do amazing things for their mental health and assist with inflammation. For others, it could lead to addiction problems. It all depends on the way your specific brain is wired. Until neuroscientists can integrate personalized medicine into cannabis treatments, if you want to try Canadian cannabis this October, be like a scientist. Be open-minded, be careful*, be skeptical, and try some experiments.

P.S. Will Canadian stoners now celebrate 420 on 1017?

*Part of being careful is being open and honest with medical professionals, therapists, and other clinicians about your experience with cannabis.

References

Zamberletti, E., Prini, P., Speziali, S., Gabaglio, M., Solinas, M., Parolaro, D., & Rubino, T. (2012). Gender-dependent behavioral and biochemical effects of adolescent delta-9-tetrahydrocannabinol in adult maternally deprived rats. Neuroscience, 204, 245-257.
Hariri, A. R., Gorka, A., Hyde, L. W., Kimak, M., Halder, I., Ducci, F., … & Manuck, S. B. (2009). Divergent effects of genetic variation in endocannabinoid signaling on human threat-and reward-related brain function. Biological psychiatry, 66(1), 9-16.
Giuffrida, A., Parsons, L. H., Kerr, T. M., De Fonseca, F. R., Navarro, M., & Piomelli, D. (1999). Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nature neuroscience, 2(4), 358.
Pan, B., Hillard, C. J., & Liu, Q. S. (2008). Endocannabinoid signaling mediates cocaine-induced inhibitory synaptic plasticity in midbrain dopamine neurons. Journal of Neuroscience, 28(6), 1385-1397.
Notzon, D. P., Pavlicova, M., Glass, A., Mariani, J. J., Mahony, A. L., Brooks, D. J., & Levin, F. R. (2016). ADHD is highly prevalent in patients seeking treatment for cannabis use disorders. Journal of attention disorders, 1087054716640109.
Gessa, G., Melis, M., Muntoni, A., & Diana, M. (1998). Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. European journal of pharmacology, 341(1), 39-44.
French, E. D., Dillon, K., & Wu, X. (1997). Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport, 8(3), 649-652.
French, E. D. (1997). Δ9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neuroscience letters, 226(3), 159-162.

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