Wednesday, June 24, 2015

Marijuana addiction: Is it even a thing??

Whenever I talk to people about what worries them when it comes to pot, inevitably they bring up addiction. And let me tell you, addiction is a tragic condition that I wish on no one and that needs to be taken seriously. But are we sure cannabis addiction is even a thing? Here’s what I think.

From a neuroscience perspective, we often measure “addictive potential” of a drug as its ability to activate the brain’s reward system. This system consists of a certain group of brain cells releasing the brain chemical dopamine when activated, and is in place to help us pursue natural rewards (food, company, a mate, etc.). The dopamine release is basically the brain’s way of saying “this is good, go after this, get more of it.” What all addictive drugs have in common is that they manage to manipulate the brain into activating this system.

But whether cannabis activates this system is under heated debate. Animal models are certainly looking like it’s the case -- dopamine release left and right. And not only that, but animals are also behaving in ways that suggest reward: There is plenty of evidence for “self-administration” (pressing a lever to receive the drug, sometimes hundreds of times for a single dose -- a measure of how badly an animal wants it and how hard it is willing to work for it), and animals will prefer places where they previously had the drug (a measure of how much they like it). But little-known fact: it actually takes all sorts of tricks to get animals to start self-administering THC, and under certain conditions, they actually avoid places where it was previously given. So yes, there is a convincing case that animals will come to want and like and release dopamine for it -- IF the conditions are made just right.

But when it comes to humans, the picture gets blurry, and inconsistencies abound. I mean, there is no doubt – judging from both the real world and human self-administration studies – that people WILL “press the lever” and like it. But here it isn’t so easily linked to reward system activation. Some studies find that it releases dopamine. Others do not. Or maybe it does, if you happen to be at risk for psychosis. Or if it does, the effect is ever-so-slight, making the clinical relevance questionable. Or maybe there is no effect after all. Nope, looks like there isn't. And what causes this mess is anyone’s guess:  Is dopamine release a real phenomenon that is masked in some studies by “suboptimal experimental design?” Or is there no actual effect, but some studies find something that looks like dopamine release by chance fluctuations in the imaging signal? Either way, a recent review paper concedes that “in man, there is as yet little direct evidence to suggest that cannabis use affects dopamine release or dopamine receptor status in healthy human volunteers.”

So what are we to believe? The animal models, which may or may not apply to actual human experience, and need certain conditions (which may or may not mimic actual human conditions) to work? Or the human brain images, which rely on indirect measures and statistical calculations and can’t seem to agree on the evidence? And does a lack of human dopamine evidence mean that cannabis isn’t addictive, or can addiction exist in the absence of a clean dopamine story? Clearly, my point is that there are more questions than answers. But while I shrug my agnostic shoulders, the National Institute on Drug Abuse  sounds pretty convinced that “contrary to common belief, marijuana can be addictive” – a claim they support using dopamine logic


To me, the evidence here is a draw, and strong assertions may be based on political motivation over evidence. Luckily (for the debate anyway), there is more to addiction than dopamine; for example, the trademark phenomena of tolerance and withdrawal. How’s the evidence shake out on that one? Stay tuned for part II.

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