Is marijuana addictive? You can bet your heroin on that!

marijuana“Is marijuana addictive?” seems to be the ultimate question for many people. In fact, when discussing addiction, it is rare that the addiction potential for marijuana doesn’t come up.

Some basic points about marijuana:

The active ingredient in marijuana, THC, binds to cannabinoid receptors in the brain (CB1 and CB2). Since it is a partial agonist, it activates these receptors, though not to their full capacity. The fact that cannabinoid receptors modulate mood, sleep, and appetite is why you get the munchies and feel content and why many people use it to help with sleep.

But how is marijuana addictive? What’s the link to heroin?

What most people don’t know is that there is quite a bit of interaction between the cannabinoid receptor system (especially CB1 receptors) and the opioid receptor system in the brain. In fact, research has shown that without the activation of the µ opioid receptor, THC is no longer rewarding.

If the fact that marijuana activates the same receptor system as opiates (like heroin, morphine, oxycontin, etc.) surprises you, you should read on.

The opioid system in turn activates the dopamine reward pathway I’ve discussed in numerous other posts (look here for a start). This is the mechanisms that is assumed to underlie the rewarding, and many of the addictive, properties of essentially all drugs of abuse.

But we’re not done!

Without the activation of the CB1 receptors, it seems that opiates, alcohol, nicotine, and perhaps stimulants (like methamphetamine) lose their rewarding properties. This would mean that drug reward depends much more heavily on the cannabinoid receptor system than had been previously thought. Since this is the main target for THC, it stands to reason that the same would go for marijuana.

So what?! Why is marijuana addictive?

Since there’s a close connection between the targets of THC and the addictive properties of many other drugs, it seems to me that arguing against an addictive potential for marijuana is silly.

Of course, some will read this as my saying that marijuana is always addictive and very dangerous. They would be wrong. My point is that marijuana can not be considered as having no potential for addiction.

As I’ve pointed out many times before, the proportion of drug users that become addicted, or dependent, on drugs is relatively small (10%-15%). This is true for almost all drugs – What I’m saying is that it is likely also true for marijuana (here is a discussion of physical versus psychological addiction and their bogus distinction).

Citation:

Ghozland, Matthes, Simonin, Filliol, L. Kieffer, and Maldonado (2002). Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors. Journal of Neuroscience, 22, 1146-1154.

Why the addiction-brain connection has to be part of the addiction treatment picture

Dr. Dodes recent article, apparently trying to blow up the myth of addiction as a neurophysiological disorder, sounded persuasive, although its underpinning was oversimplified and it’s understanding of the brain-science involved in addiction, and other associated mental health disorders, was lacking. Hopefully, by presenting a more complete picture of the evidence for a brain-aspect to addiction, I can un-bias the discussion somewhat. I, for one, don’t believe that neuroscience will ever be the only factor important in addiction – an individual’s environment, social influences, and other factors will always end up playing important parts as well – still, I think that to dismiss all of the evidence for biological factors at play in the development of addiction is foolhardy. Especially when there’s so much of it that was glossed over in Dr. Dodes’ introduction.

Pleasure center activation is only part of the picture in addiction

Firstly, supporters of the notion that addiction is, at least partly, an outcome of specific brain function point not only to pleasure center activation, but also to a whole host of findings showing genetic variability that is either protective from, or a risk factor for, dependence on drugs and likely also behavioral addiction like eating disorders, compulsive gambling, and maybe sex addiction as well (you can start out looking up ALDH2-2 variability and alcoholism and cocaine addiction, DRD4 and stimulant addiction, and many more).

While it is true that all those who consume addictive substance activate the brain similarly, there are considerable differences in the specific of that activation in reaction to drugs. Some release more dopamine while others have more “active” versions of specific important receptors; neurotransmitter recycling is quick in some, but not all, and drug metabolism is different in different individuals in ways that have been shown to be important not just for addiction risk, but also for the probability of treatment success. Just look at the nicotine and CPY26 literature for an example. It’s right there.

Additionally an entire body of literature exists that shows differential activation, as well as structural differences, between addicts and non-addicts in regions as varied as the OFC, PFC, Insula, and more. This is not to mention a slew of evidence that shows different behavioral test performance on risk-taking, impulsivity, and delay-discounting, all personality variables highly associated with addiction. If one simply ignore all of this evidence, it may be easy to believe that there is no biological explanation for these phenomena, but that’s just wrong.

To say that mesolimbic activation (what the good doctor called “pleasure centers”) is the only evidence for physiological factors in addiction is dismissive at best.

Drug addiction develops in only some drug users

The notion that not everyone who takes drugs becomes addicted is nothing close to evidence against a brain explanation for addiction. Everyone’s motor–cortex, striatum, and substantia nigra (the areas of the brain responsible for movement) activate in the same way during movement, but only a small group ends up suffering from Parkinson’s or Huntington’s disorders. One fact does not preclude the other but instead may specifically point to the fact the group which develops the disorder has somewhat different neurological functioning. Researchers aren’t concerned with explaining why all individuals can become addicted to drugs, but rather why that small subgroup develops compulsive behavior. A short reading of the literature makes that fact pretty clear. Additionally, while Dr. Dodes’ claims otherwise, imaging technology HAS produced evidence explaining this “mystery”, including differences in the ways addicted smokers respond to smoking-related triggers, and an increased dopamine response in cocaine addicts to cues, and well as to cocaine.

As mentioned in the motor disorder section above, ingestion of chemicals is not at all necessary for brain disorders to occur or indeed develop later in life. Dr. Dodes example of shifting addiction could be used as evidence for an underlying neurological difference just as well as it would serve to make his point… Or even better. If there’s a faulty basic mechanism attached to rewarding behaviors, it doesn’t really matter what the behavior is, does it? Sex addiction, gambling, and more can all be explained using a similar mechanism, though drugs of abuse may just have a more direct impact. I know, I’ve written about them all.

The Vietnam vet heroin story used by Dr. Dodes as evidence that emotional, rather than physiological, factors are responsible for addiction actually fits right in line with the notion of predisposition and underlying differences, and I’m surprised to hear a physician point to group differences as an indicator of no neurobiological basis. Indeed, when it comes to the emotional reactivity associated with drug associated cues, normal learning literature, as well as drug-specific learning research, has revealed over and over that drug-related stimuli activate brain regions associated with drug reward in the same way that natural-reward predictors do for things like food and sex. Once again, these facts are part of the basic understanding of the neuroscience of learning, with or without drug abuse involvement.

My own dissertation work shows that it is very likely that only a subsection of those exposed to nicotine will develop abnormal learning patterns associated with that drug. However, among those, learning about drug-related stimuli (as in “triggers”) continues in an exaggerated manner long after the other “normal” animals have stopped learning. That sort of difference can lead to a seriously problematic behavioral-selection problem whereby drug-related stimuli are attended to, and pursued, more so than other,  non-drug-related ones. If that sounds familiar, it should, since drug users continuously pursue drug-associated activities and exposures in a way that seems irrational to the rest of the world. It just might be due to such a mechanism and others like it.

Some important points about science in Dr. Dodes’ article

One very true fact about mental health pointed out by Dr. Dodes is that diseases like schizophrenia, which used to be explained simply as demon possession and evidence of witchcraft can now be, to a large extent, explained by the study of behavioral neuroscience and cognition. The same is true for bipolar disorder, depression, ADHD, and a host of other such conditions. In fact, the study of psychology has only been able to rely on technological advances that allow us to “see” brain function for a few short decades, leading to incredible advances in the field that I think will continue. The thinking that no such advances have, or will continue to be, made in the study of addiction is, in my opinion short sighted.

As I mentioned above, I don’t for a second think that the entire explanation for drug abuse and addiction will come from neurophysiological evidence. The doctor points out that “If we could take a more accurate image of addiction in the brain, it would encompass much of the history and many of the events that make us who we are.” I agree that we need to advance our technology as well as expand our understanding, but I think that to discount neuroscientific explanations completely is a big mistake.

Choice and control in addiction – Genetics and neuroscience of drug abuse

Dr. Jaffe recently gave an online lecture (webinar) for HealthCentral on the processes involved in choice and control of behavior during addiction and drug abuse. We’ve written quite a bit on here about the neuroscience of impulsivity issues and the genetic predisposition to addiction and this talk really covers some of the most important aspects of this topic. I’m also attaching a link to the presentation materials that go along with this talk so that you can follow along (Wellsphere Webinar 1 – Choice Vs. Control). There was definitely quite a bit of material (on both neuroscience and genetics) that we couldn’t get to, so hopefully having the presentation will help you follow along and learn.

We hope you enjoy!

Control Versus Choice in addiction


Watch live video from HealthCentral on Justin.tv

If you need help finding treatment for your own, or a loved one’s addiction, make sure to give our Rehab-Finder a try: It’s the only evidence-based, scientifically created, tool for finding rehab anywhere in the United States!

Addicts’ brains depressed but normal users… normal.

A paper that’s about to be published in the journal Science has found at least part of the difference between the brains of addicted individuals and those that use recreationally.

The question as to why only some people get addicted to drugs has been a difficult one to answer. Still, there’s no doubt that only a relatively small fraction of those exposed to drugs develop the compulsive, often destructive pattern of use we associate with addiction. The pattern holds in animal research too – even though all the animals in an experiment get the same amount of drugs, delivered in the same way, only some of them develop addictive drug taking. It seems there’s something different about addicts’ brains, but what is it?

What’s different about addicts’ brains?

We’ve found quite a few things that differentiate addicts’ brains from those of normal research participants. These include lower density of a certain type of dopamine receptor (D2), reduced activity in specific brain parts like the OFC (orbitofrontal cortex) that are important in decision making and behavioral control. Still, if we start with what is supposed to be a pretty similar group of rats and give them all the same drug, for the same time, in the same amounts, why do only some get addicted?

This recent study found that a specific neuronal process called LTD (Long Term Depression), that is important in learning (or what we call plasticity) is suppressed in addicted animals for far longer than in animals that end up not not displaying addictive behavior. Even though all animals displayed this sort of deficiency in LTD right after learning to take drugs, only the addicted animals showed it when tested two months later.

Since the difference was seen in an area of addicts’ brains called the Nucleus Accumbens, a very important area for learning about rewards, it seems likely that it plays an important role in addicts’ inability to change their behavior after they’ve started using drugs. Past research has already identified this as a problem with something we call “reversal learning” but it seems we may have just found at least part of the mechanism.

Now we have to figure out why some animals show this sort of pattern and others don’t. Genetic variability seems like a good place to start here.

Citation:

F. Kasanetz, V. Deroche-Gamonet, N. Berson, E. Balado, M. Lafourcade, O. Manzoni, P. V. Piazza, Transition to addiction is associated with a persistent impairment in synaptic plasticity. Science 328, 1709–1712 (2010).

Know before you speak – Why etiquette is important

You know, I try to write this blog from a completely objective point of you, but guess what – I’m a person, so things take on a personal tone once in a while.

There’s nothing I hate more than readers who come to this site, read a single post, and then decide they know who I am, or what I’m about. It’s taken me more than 13 years to get to this point in terms of my knowledge, experience, and viewpoint on drugs, addiction, and policy issues. It all started with 8 years of some personal “experimentation” with the behaviors I’m talking about. I’d love to say I was doing it for science, but the last three years were far from enjoyable for many around me. Since then I’ve studied statistics, neuroscience, public-health, and psychology. And I’m not done. Staying in the academic world, I keep educating myself on issues related to addiction from every field I have access to.

So please, if you have opinions, share them, but if you want to insult me, make sure you know what you’re talking about, because I’ll tell you if you don’t. Personal attacks are easy to make through an internet connection, but being stupid will leave an obvious stain and will cause me to either remove your comment or just reveal how ridiculous it is. I don’t like making personal attacks on people – not in posts, not in comments, and not in real life. Don’t tell me how you do, or don’t, want me to die because I probably don’t care how you go and I certainly don’t want the experience to be bad.

I know blogs are a little loose, but let’s keep this at least somewhat professional, okay?

The misunderstanding of addiction neuroscience

I just read a comment on another blogger’s post about the neuroscience of sex addiction. The commenter just couldn’t understand why an addict’s behavior could be rationalized by neuroscience when so many other people have little problem, even when exposed to sex, drugs, or whatnot.

It seems simple to me, but I’ve been doing research on this stuff for almost ten years (not including my own time out there using). I want to try this analogy on you and hear what you have to say:

We’re all used to people speaking different languages. We think nothing of the fact that another person can make sounds that mean nothing to us but yet seem to mean so much to others who understand. Our brains are quite the same. People look a lot alike, but small changes in brain structure -through genetics or exposure- can lead to some very significant changes in actual behavior.Our brains all speak slightly different languages.

To me, this makes complete sense, but I’d love to get an idea of what others out there think. For more reading on how our brains differ, check out other AllAboutAddiction posts.

Also, check out this video lecture (it’s long) on the neuroscience of emotions:

About addiction: Animal research, food addiction, policy, and cocaine addiction

Here are this weeks gems when it comes to learning about addiction. As usual, if you click this title’s post, you’ll get a list of our related post as a bonus!

Adventures in Ethics and Science A nice post about the current state of the animal-rights dialog

Addiction InboxMood Foods (and their possible role in food addiction)

Addiction TomorrowAdvocacy and Treatment

PhysOrgAltered reward-based brain-activation in cocaine addiction