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.

Gambling on marijuana use makes for bad decisions

I just can’t seem to stay away from the marijuana debate, even given the recent defeat of Proposition 19 that aimed to legalize marijuana in California. This article is a short one, but speaks to some of the cognitive issues associated with marijuana use.

A study (see here) conducted by a Wake Forest University team (Including Doctor Linda Porrino) found that habitual marijuana smokers (those who smoked an average of twice a day for seven years) may be bad at detecting negative outcomes.

The experiment used fMRI scanning technology to examine the brain activity of smokers and controls during the Iowa Gambling Task, which uses four decks of cards. Two of the decks yield large, infrequent, rewards as well as losses. The other two decks yield small, more frequent rewards, and less losses. The first two are considered the “bad” decks, and the latter two the “good” decks, because selecting from the small-gain, small-loss, decks will result in more gain overall. The task is considered a pretty good, if complex, measure of risk-taking, decision making, and loss-discounting.

Marijuana users lose money while controls gainThe take-home result from the study: Not only did marijuana smokers take longer to learn how to maximize their rewards, but their decision-making brain regions seemed to show lower overall responding during the task, meaning they were less active while performing the decisions. And as you can see from the graph on the left, while the controls were able to achieve overall gains, the same was not true for the long-term marijuana users even after 100 repetitions. It seems that marijuana smokers’ brains were not as efficient at detecting losses and responding to them. Maybe that’s why marijuana users are the first to claim that marijuana use has no negative outcomes associated with it…

As usual, it is important to note that since the participants in the study were not randomly assigned to long-term marijuana smoking, it’s impossible to know if these deficits are specifically caused by marijuana use or if they were pre-existing. Nevertheless, these results strongly suggest that individuals who engage in long-term use of marijuana are cognitively distinct from those who don’t. I think that plays into the argument that marijuana legalization would not increase use, because if that’s actually true, then there’s something different about individuals who choose to smoke weed and it is not the legal status that matters. I suspect that in actuality, people who currently choose to smoke marijuana long-term are in fact distinct, in some ways, from some of the people who would take up smoking the stuff if it became legal.

Citation:

Christopher T. Whitlowa, Anthony Liguoria, L. Brooke Livengooda, Stephanie L. Harta, Becky J. Mussat-Whitlowb, Corey M. Lamborna, Paul J. Laurientic and Linda J. Porrino (2004). Long-term heavy marijuana users make costly decisions on a gambling task. Drug and Alcohol Dependence, 76, 107-111.

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.

The brain-addiction connection: Alcohol use affects almost everything

Alcohol is the most popular psychoactive substance used in the U.S. and the worldWith statistics showing that at least 50% of adults in the US are regular alcohol drinkers (drinkers who have consumed 12 drinks or more in the past year¹), alcohol clearly remains the drug of choice for most Americans. While moderate alcohol use is not deemed dangerous, and is likely even healthy², it is nevertheless still important to know how chemicals we put in our bodies affect us. Many people know and often hear about alcohol abuse and its effects on the liver, the broad effects of alcohol use on other bodily systems, especially the brain, don’t seem to get that much attention. In the tradition of our other brain-addiction articles, we aim to do just that.

Alcohol use and brain depression

In a nutshell, alcohol depresses the central nervous system, causing the uninhibited, relaxed feeling that even the most casual drinker is familiar with. It does so mainly by interrupting brain communication – suppressing the excitatory nerve pathway (by affecting glutamate) and increasing the inhibitory activity (by affecting GABA).

Glutamate is the major excitatory neurotransmitter in the brain – it’s the one that commonly turns certain brain cells on and increases their firing activity. When alcohol is consumed it inhibits glutamate activity, which diminishes the excitatory effect of glutamate and reduces important relevant functions.

GABA is the major inhibitory neurotransmitter in the brain – it reduces firing activity and generally turns targets off. When alcohol is consumed it enhances GABA’s inhibition, which is always present throughout the brain to some extent, by directly increasing the activity of many GABA releasing neurons.

In short, alcohol use simultaneously suppresses important new brain activity and inhibits ongoing function at the same time, resulting in an intense depressive effect.

Interference with these two neurotransmitters, some of the most common ones found in the brain, is the reason for alcohol’s wide-ranging effects, particularly on the memory, which depends on the activation, by glutamate, of two receptor types – AMPA and NMDA. Without them, there’s no learning- and no memory (blackout anyone?).

The effects of alcohol use on behavior

By interfering with brain function, alcohol use lowers inhibitions, allowing drinkers to be more outgoing (and willing to do things they most likely otherwise wouldn’t). Information processing is also compromised when drinking, mostly due to alcohol’s effects on the cerebral cortex (and glutamate which is responsible for everything from seeing, to hearing, and more). This is the part of the brain which takes in a person’s senses and thoughts, and helps with voluntary muscle movements. Alcohol use causes impaired thoughts, poor judgment, and a higher threshold for pain. What you’re left with is someone who is slower and less thoughtful, but feels stronger and smarter, all while experiencing less pain. This is, of course, a dangerous combination.

Alcohol use also can influence a person’s cerebellum and limbic system, which control coordination, and emotional regulation, respectively. We’ve all seen those brave-drunks – normally shy individuals who get a little liquid courage in them and are suddenly the life of the party, all while barely being able to put one foot in front of the other. This is a great example of alcohol’s effect on the limbic system as well as the cerebellum. When the limbic system is impaired, individuals often experience memory loss, especially when it comes to emotional states and experiences. Limbic system dysfunction can also lead to individuals experiencing exaggerated feelings (the “I LOVE you, man!” effect). Cerebellum problems lead to a lack of muscle control and fine motor movements – just what you want when you’re trying to steer a car at 65 miles per hour and stay on the road.

The alcohol-sex connection

Due to its effect on the hypothalamus, alcohol use also plays a role in decreasing a person’s sexual desire and performance. The hypothalamus, along with the medulla, plays a role in controlling many regulatory functions of the brain and body. The hypothalamus is the control center for much of the body’s hormone function and governs the autonomic nervous system. The hypothalamus is part of the system than keeps the body in homeostasis, a balanced state that can be considered the “baseline” of system function. In this role, the hypothalamus organizes and controls many complex emotions, feelings and motivational states. The neurons in the hypothalamus produce a number of neurotransmitters which give instructions to different parts of the body.

When this neurotransmitter function get impaired, these systems get depressed, which lowers sexual desire and performance as well as causing individuals to become sleepy- at which point sexual performance doesn’t really matter anymore.

A parting gift – what alcohol abuse may leave users with long-term

As we mentioned above, many people only hear about how alcohol abuse can cause liver damage. But alcohol can do so much more damage than that and since this stuff is commonly used as a solvent (chemistry class anyone?!) that’s not really surprising. There is plenty of emerging research touting the positive effects of moderate alcohol consumption. However, if an individual continuously drinks to excess, there are serious long-term implications for that person’s memory, sex drive, and overall cognitive functions that can, and for more than 27,00 people a year does, end in death. So if alcohol use isn’t a problem for you, enjoy your glass of red wine (or micro-brew), but be aware of the effects; if alcohol abuse is an issue, you might as well keep everything operating as well as possible and stay away altogether.

Citations:

CDC Source: Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2008, table 27.

Charles J. Holahan, Kathleen K. Schutte, Penny L. Brennan, Carole K. Holahan, Bernice S. Moos, Rudolf H. Moos (2010). Late life alcohol consumption and 20-year mortality. Alcohol Clinical & Experimental Research.

Alcohol – Blackouts, Brownouts and how they affect your body

Do you remember what you did last night? Have you ever not remembered what you did after drinking? Drinking alcohol affects the brain and can cause lasting damage including, but not limited to, slips in memory. These memory slips can be due to lack of blood flow to brain areas that are important for memory consolidation and are commonly known as blackouts. Contrary to what popular belief, blackouts often occur in social drinkers and don’t seem to be related to age or level of alcohol dependence.

 

Blackouts and the Blood Alcohol Content (BAC) rate

Amnesia, or memory dysfunction, can begin to occur even with as few as one or two drinks containing alcohol. However, as the amount of alcohol intake increases so does the probability of memory impairment. Although heavy drinking alone will not always cause blackouts, heavy drinking of alcohol on an empty stomach or “chugging” alcoholic drinks often does cause blackouts.

The estimated BAC (blood alcohol content) range for blackouts begins at levels .14%- .20%. Individuals who reached high BAC levels slowly experienced far less common occurrences of blackouts. Additionally, while blackouts lead to forgetting entire events that happened while intoxicated, some individuals experience an inability to recall only parts of an event or episode (these are often called brownouts).

Blackouts can occur to anyone who drinks too much too fast. In a survey of college students, males and females experienced an equal number of blackouts, although men consumed a significantly more alcohol.

Although brain damage could potentially occur from heavy alcohol consumption, there is no evidence that blackouts are caused by brain damage per se. However, if brain damage is caused from excessive alcohol use, some studies show improvements in brain function with as little as a year of abstinence. Regardless of the possibility of reversing any effects, alcohol use causes damage in different areas of the body (including the liver), and those damages have been shown to occur more quickly among females.

Co-authored by Jamie Felzer

 

Citations:

1. White, Aaron M., Signer, Matthew L., Kraus, Courtney L. and Swartzwelder, H. Scott(2004). Experiential Aspects of Alcohol-Induced Blackouts Among College Students, The American Journal of Drug and Alcohol Abuse,30:1,205 — 224

2. Alcohol Alert (2004) . Alcoholic Brain Damage. Alcohol Research & Health, Vol. 27.

About Addiction: DUI, Psychedelics, Smoke, and the Brain!

You know it and love it – here is our weekly post about addiction research, news, and more interesting tidbits from the wonderful world of the internet. I guarantee you’ll know more about addiction, drugs, and the brain, after reading it!

DUI because you think you’re sober? Check your BAC

Science Daily– A study found that people recover their subjective feeling of sobriety before they recover functions important for driving, showing that the perception of intoxication is a bad indicator of ability to drive. A BAC of 0.02 doubles the relative risk of a motor vehicle crash among 16- to 20-year old males and this increases to nearly 52 times when the BAC is between 0.08 percent and 0.10 percent. It seems that portable BAC monitors might be a good idea to reduce DUI accidents.

Psychedelics and High-Tech Pills

Common Dreams– Scientists are giving psychedelics another look as a possible tool in psychotherapy. Many psychedelics like LSD and MDMA have been used in psychological-treatment settings before and the Swiss apparently think we should be giving them another turn. The researchers there focus on the effects of psychedelics on the brain systems involved in depression mainly. Who knows, maybe you’ll be given a little LSD or MDMA pill before beginning a weekly therapy session in the future. Probably not in the U.S. though…

Magic “smart” pill– How wonderful would it be if there was technology that alerted you as to when you are supposed to take a pill? A “smart pill” which would text individuals when they need to take it is being tested in the UK, so it may be a reality in the future! Just think about it, all those people who have to take some sort of ADHD pill won’t forget now that their pill sends signals to their phone – “Don’t forget to take meeeee!!!”

Cigarette Smoke

Science Daily– According to physician-scientists at New York-Presbyterian Hospital exposure to even low-levels of cigarette smoke, including second hand smoke, may put people at risk for future lung disease such as lung cancer and chronic obstructive pulmonary disease (COPD). While research showing that second hand smoke is dangerous isn’t new, this new group showed alterations in the genetic functioning of cells in the airway of those exposed. The researchers do point out that the alterations are less pronounced than in heavy smokers but say that even such low levels of smoke exposure can increase disease risk.

Brain Chemistry and regulation of cocaine intake

NIDA–  A regulatory protein, called MeCP2, that is found in the brain and best known for its role in a rare genetic brain disorder may play a critical role in cocaine addiction by regulating cocaine intake and perhaps in determining vulnerability to addiction. The researchers here found a complement to earlier NIDA research showing that as brain miRNA-212 levels increase, cocaine intake decrease. Apparently, it’s the balance between miRNA-212 and MeCP2 that is important.

Is the drinking age getting lower and lower? Teenage alcoholism

How young do kids start drinking?We’ve already mentioned that kids tend to get in quite a bit of trouble during their teen years (see here). Well, adolescence is also a time when the brain is developing and therefore is at a high risk for damage, especially when alcohol abuse enters the picture.

Early use means more alcoholism later

While the risk taking can be playful and harmless, when it involves alcohol and drugs the consequences of use at an early age can be long-lasting. The earlier a person begins drinking the higher the reported rates of alcoholism later in life. During this time, when an adolescent’s brain is changing, they are less likely to be able to inhibit themselves, let alone anticipate the future. Those with hyperactive, disruptive, antisocial personalities are at the greatest risk for alcohol abuse at early ages, putting their already somewhat compromised brains at an even greater risk.

Teens, like adults, report feeling more at ease when under the effects of alcohol, which makes it easy to understand why they would want to continue. Less like (some) adults, teens rarely consider the negative consequences of their actions, a fact that has at least a little to do with their still developing brain structures. But there are consequences to alcohol abuse and they can be dire – over 5000 kids die each year as a result of underage drinking.

Young bodies and early alcohol damage

Before these young adults are truly mature, their intake of alcohol may not be properly resolved by their bodies because their regulatory systems are not fully developed and can be further taxed by the intake of alcohol. Alcohol abuse in a young age can have a lasting effect on brain development resulting in impairments for many years to follow. Reproductive organs and other important maturation factors may also be stunted due to a consumption of alcohol during a vital time (especially when binge drinking). As with most people who drink, regardless of the age, liver enzymes are elevated soon after the heavy drinking begins, meaning the body is less able to ward off other toxins.

Parents and alcoholism

Children of parents who drink more and view drinking with a laid back opinion are more likely to drink more as well. This may not be a problem as long as responsible consumption is discussed, but my guess is that it rarely is. Also, kids who have older friends are more likely to begin drinking at an earlier age. Teens that have become addicted to alcohol need help specifically tailored to their age group that does not remove them from their normal home and school setting. It’s been shown that isolating these kids, or specifically grouping them together, may do more harm than good.

Often, adolescents with alcohol abuse problems are also using other drugs, and they may be suffering from other psychological disorders. All of the issues need to be treated at the same time in order to effectively treat the entire person. No matter what the issue(s), the sooner they are dealt with the more effective the results.

Teenage alcoholism is a problem, and one that we shouldn’t be ignoring.

Co-authored by: Jamie Felzer

Citations:

“Adolescent Brain Development, Decision making, and Alcohol Abuse and Dependence” NIAAA Research. November 2007.

“Why do Adolescents drink, What are the Risks, and How can Underage Drinking be prevented?” Alcohol Alert. January 2006, 67