A new candidate for ADHD medication: Amantadine and the rise of non-stimulants

It is well known that ADHD diagnoses and substance abuse problems are closely associated. It is estimated that substance abuse problems including dependence are up to twice as common among individuals with ADHD, which is not surprising given the impulsivity factor involved in ADHD. The problem is that until recently, most medications for ADHD have belonged to the stimulant category and as many, including us, have written before it is probably not the best idea ever to give drugs that have a relatively large abuse probability to people who are relatively likely to develop substance abuse problems. Right?

We’ve already written about atomoxetine and bupropion, two drugs with relatively low abuse potential (since patients don’t actually feel “high” from them) that are being successfully used in treating ADHD. But there is little doubt that the type of effect seen among patients who are using stimulants (like adderall, ritalin, etc.) isn’t being observed among patients taking non-stimulant medications. All of this means that patients on non-stimulants are getting less bang but with less risk. A dopamine agonist by the name of amantadine might change all of that according to a recent study.

Amantadine versus stimulants for ADHD treatment

Fourty children between the ages of 6 and 14 were enrolled in the study conducted in a psychiatric hospital in Iran. The kids were randomized into two groups a methylphenidate (ritalin) and amantadine group. Over a six week period the kids were assessed four times – at intake and then every two weeks -using an instrument that parents and teachers (who didn’t know what medication the kids were getting) would use to rate the child’s behavior on the 18 ADHD symptoms listed in the DSM-IV.

Amantadine may soon offer a new non-stimulant medication option for ADHD treatmentThe final findings were very encouraging (see picture): The kids in both conditions improved greatly over the 6 weeks of the study and no difference was found between the two medications. the children in the amantadine condition actually suffered less side effects and significantly so when looking at side effects common to stimulant medication such as decrease in appetite and restlessness. While more studies are obviously needed, this randomized trial shows that amantadine is not only safe, but it may be safer than at least some stimulant medications while also providing the same effect on ADHD symptoms. Given that approximately 30% of patients don’t respond well to stimulants and that some families are afraid of giving stimulant medications to their children, at least partially because of the risk of substance abuse issues, non-stimulant medications can be an attractive alternative, and it seems like amantadine can deliver.

Final thoughts from Dr. Jaffe on ADHD medications and amantadine

One of the main reservations I have about the notion of using this medication for ADHD is that NMDA receptors are very important in learning, so it may be that we’re helping to resolve attention problems but making it more difficult to actually create memories that are crucial for learning. More research is necessary to see if these decreases in impulsivity are accompannied by improvements, and not reductions, in learning ability.

So, if you’re considering medicating a child who has been diagnosed with ADHD, I strongly support the notion given the difference that medication has made in my own life. However, I urge you to be educated and to consider non-stimulant options, especially as more are researched and as that treatment option becomes more available, less costly, and less likely to lead to abuse of the drug. With prescription drug abuse one of the fastest growing problems in the U.S., being careful is just sound advice.

Citation:

Mohammad-Reza Mohammadi, Mohammad-Reza Kazemi, Ebtehal Zia, Shams-Ali Rezazadeh, Mina Tabrizi, Shahin Akhondzadeh (2010) Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial. Human Psychopharmacology.

Some parkinson work showing effect of amantadine: http://www.springerlink.com/content/76r5wxux8wn52rq5/fulltext.pdf

Obesity, drug addiction, and dopamine

Eating junk-food can be addictive, and apparently, it causes brain changes that look eerily similar to drug addiction. That’s the message not only from the rapidly fattening waistlines of Americans everywhere, but also from the Johnson and Kenny labs at the Scripps Institute.

Food and drug addiction

The idea that obesity is caused by a compulsive pattern of eating, and that there could be a similarity between such compulsive eating and drug addiction isn’t super new. In fact, Dr. Volkow from NIDA seemed to make research into this association her goal when taking  the helm of the addiction research kingdom.

When you think about it, the notion isn’t far-fetched: Drug addicts continue to take drugs, in increasing amounts, even though they’d often like to stop (at some point) and in the face of negative consequences and the common loss of other important life functions (like family, work, etc.). Obese individuals are quite the same, eating more and more food regardless of their desire to adopt a healthier diet and in-spite of ridicule, low self-esteem, and decreased functioning that often accompanies extreme weight gain.

The research by Johnson and Kenny examined whether exposure to the kind of high-fat, super high-calorie foods that floods the junk-food market are responsible for creating food-addicts in a similar way to drugs that alter the brain in ways that make stopping more difficult.

Dopamine, reward, and junk-food

The study took three groups of rats and gave them either the regular chow diet lab animals are used to or the worse kind of birthday party food: bacon, sausage, cheesecake, pound cake, frosting and chocolate. You can imagine the party going on in the rat cages that got to eat that! Of the two groups that got to eat the crazy-fat food, one had unlimited access while the other got to binge for only one hour a day.

The bottom line: Only the rats that got unlimited access to the fat-party food developed compulsive eating habits that resulted in roughly twice the weight gain of the other two groups and the ability to continue eating even in the face of signals for punishment (a light that they were trained to associate with shocks).

When the researchers looked deeper, they found that the brains of these rats suffered a significant reduction in the density of a specific kind of dopamine receptor (D2) in a brain part known as the striatum, the same kind of reduction common in drug addicted people and obese individuals. This receptor type is often thought to be important for regulation of impulses, both physical and otherwise. It therefore makes sense that losing this type of function would cause uncontrollable eating or drug taking.

Are drug- and food-addictions the same?

While this research isn’t saying that compulsive eating, or obesity, are the same as drug addiction, it does strongly suggest that there are common mechanisms in both. More importantly, it reveals a common process that unfolds when over-exposure to the reward, in this case food, occurs. This tells us that there can likely be common pathways to these different addictive disorders, though whether any specific person ended up a food- or drug-addict because of this kind of process is still an open question. I wonder if we’ll see something like this with sex addiction soon…

Citation:

Johnson and Kenny (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature neuroscience, 13, 635-641.

Talking to NIDA about addiction research- Nicotine, cocaine, treatment matching and more

It’s not everyday that I get an invite to speak with NIDA‘s director, Dr. Nora Volkow, and so, even though it required my creative use of some VOIP technology from a living room in Tel-Aviv, I logged onto a conference call led by the leading addiction researcher. When my colleagues, Dirk Hanson and Elizabeth Hartney, were introduced, I knew I was in good company.

Addiction research directions the NIDA way

The call focused on some NIDA interests, including a nicotine vaccine, which Dr. Volkow seemed confident will triumphantly exit phase 3 trials in less than two years and potentially enter the market after FDA approval in three years or less. The vaccine, which seems to significantly and effectively increase the production of nicotine antibodies in approximately 30% of research participants, has shown promise as a tool for smoking cessation in trials showing complete cessation, or significant reduction in smoking among participants that produced sufficient antibodies. Obviously, this leaves a large gap for the 70% of participants for which the vaccine was not effective, but a good treatment for some is much better than no treatment for all. For more on the vaccine, check out Mr. Hanson’s post here.

Aside from the nicotine vaccine (and on a similarly conceived cocaine vaccine), our conversation centered on issues relevant to the suggested new DSM-5 alterations in addiction-related classifications. Dr. Volkow expressed satisfaction at the removal of dependence from the title of addictive disorders, especially as physical dependence is often part of opiate administration for patients (especially pain patients) who are in no way addicted to the drugs. Dr. Volkow also noted that while physical dependence in relatively easy to treat, addiction is not, a matter that was made all the more confusing by the ill-conceived (in her opinion, and in mine) term. Additionally, the inclusion of severity ratings in the new definition, allowing for a more nuanced, spectrum-like, assessment of addiction disorders, seemed to make Dr. Volkow happy in her own, reserved, way.

Treatment matching – rehab search for the 21st century

As most of my readers know, one of my recent interests centers on the application of current technology to the problem of finding appropriate treatment for suffering addicts. I brought the problem up during this talk, and Dr. Volkow seemed to agree with my assessment that the current tools available are nowhere near adequate given our technological advancements. I talked a bit about our upcoming addiction-treatment-matching tool, and I hope that NIDA will join us in testing the utility of the tool once we’re up and running. I truly believe that this tool alone will allow more people to find appropriate treatment increasing the success rate while maximizing our system’s ability to treat addicts.

Involving the greater public in addiction research

It wasn’t until the end of the conversation that I truly understood the reason for the invitation (I’m slow when it comes to promotional issues) – NIDA is looking to move the discussion about it’s goals and directions out of the academic darkness in which they’ve lurked for years, and into the light of online discussion. I’m in no way offended by this, especially since this was exactly my point in starting All About Addiction in the first place. If anything, I’m honored to be included in the select group of people NIDA has chose to carry their message, especially since the conversation was an open, respectful, and data-centered one. I hope more of these will occur in the future.

Resolving confusion about addiction

One of the final points we got to discuss in the too-short hour we had Dr. Volkow on the “phone” had to do with the oft misunderstood concept of physical versus psychological addictions. I’ve written about this misconception in the past, and so I won’t belabor the point here, but it’s time that we gave our brain the respect it deserves by allowing it to join the rank, along with the rest of our body, and the physical realm. We’re no longer ignorant of the fact that our personalities, memories, feelings, and thoughts are driven by nothing more than truly physical, if miniature, happenings in our brains. In the same way that microbe discovery improved our well-being (thank you Pasteur), it’s time the concept of the very physical nature of our psychological-being improves our own conceptualization of our selves.

We are physical, spiritual, and awesome, but only if we recognize what it is that makes “us.”

Addiction stories – LSD addiction: AN LSD trip down the wrong path

An LSD trip may be fun for a bit, but LSD addiction doesn't sound like any fun at all.**DISCLAIMER: This post has been changed since its original content. Since I Believe the submitted story was fake, I’ve now made this a post about the possibility of developing LSD dependence**

Many of my readers claim that LSD addiction does not exist. Well, They’re simply wrong. LSD dependence (the clinical term for addiction) is certainly out there, though its no doubt rare. To understand why I can make that claim, let’s cover the specifics of what a psychological assessment of dependence requires:

The official definition of addiction

As far as the DSM-IV (the psychological assessment manual) is concerned, dependence on any drug require at least three of the following to occur within a year:

  1. Tolerance, as defined by either of the following:
    • a need for markedly increased amounts of the substance to achieve intoxication or desired effect
    • markedly diminished effect with continued use of the same amount of substance
  2. Withdrawal, as manifested by either of the following:
    • the characteristic withdrawal syndrome for the substance
    • the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms
  3. The substance is often taken in larger amounts or over a longer period than was intended
  4. There is a persistent desire or unsuccessful efforts to cut down or control substance use
  5. A great deal of time is spent in activities to obtain the substance, use the substance, or recover from its effects
  6. Important social, occupational or recreational activities are given up or reduced because of substance use
  7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., continued drinking despite recognition that an ulcer was made worse by alcohol consumption)

Now, I’ve taken more than my share of LSD trips before. Actually, I used to sell acid, among many other drugs in my former life. I knew many people who loved acid, mushrooms, and other hallucinogens (including me) but a few cases stand out in particular.

LSD addiction – Hypotheticals and examples

Given the above definition of substance dependence, any number of combinations of symptoms could qualify someone as being dependent on LSD.

  1. Tolerance buildup for the drug is quick and significant. As anyone who’s ever tried to follow one trip with another knows, the second time requires a lot more acid, and any additional trips increase the amount of LSD needed greatly. Tolerance – Check!
  2. Withdrawal from LSD, especially in the wake of repeated exposures (the multiple trips I was talking about before), includes disorientation, difficulty thinking, fatigue, and sometimes perceptual difficulties (problems with hearing, vision). I’ve experienced this myself, but the best example I’ve seen is of a friend who tried to trip continuously for as long as possible – After about a week and a half, she was eating literally a sheet of acid to feel anything (her boyfriend was a dealer, talk about tolerance). When she stopped because her boyfriend cut her off, she had the hardest time finishing sentences, completing thoughts, or following conversations for nearly three months! Withdrawal – Check!
  3. With the above 2 out of the way, any of the other 5 symptoms can serve to complete the LSD dependence picture. Still, though I’ve never met anyone who tried to stop but couldn’t, I have:
    1. Known people who spent a lot of their time and resources (money) chasing down good acid, paying for it, or preparing for and getting involved in activities that involved LSD.
    2. Many of the people I knew began slacking off at work, sometimes being fired, getting far more lax at school, and neglecting any relationships they had with people who were not involved in their LSD use.
    3. Quite a few of the hard-core LSD users I knew told me time and again that they know their LSD use is causing them difficulties (mostly psychological difficulties) but that fact seemed unable to deter them from buying more acid and continuing down the same path.

So does LSD addiction exist?

Obviously, I believe that LSD dependence exists, though it is no doubt rare. As I’ve stated time and again, I am NOT against the use of drugs. However, I think that drug users’ naive approach to many of these issues, including their constant desire to ignore all signs of the negative consequences of drug abuse, is a big part of the problem here. Ingesting drugs is harmful, but knowing that, I believe people should have the choice to harm themselves, though not others. People with drug problems need help, not jails. Still, to make this a reality, we need to do a much better job of educating ourselves about the true effects of drugs.

I’ve seen LSD destroy lives that took years to rebuild. I’m not talking about people locked away in mental institutions thinking they’re an orange (we’ve all heard that story). But I had friends who became completely unable to live and function in society who gave up friends, significant others, and family for a drug that eventually made them crazy. Some of them are back, some aren’t.

All I’m saying is be careful.

More drug addiction research from CPDD: Teenage smoking, childhood trauma, and marijuana withdrawal

Today, I’ll give a short summary of a few interesting talks I saw at the conference:

  1. Teenage smoking – Children of mothers who used drugs during pregnancy had abnormal stress hormone levels. When assessed over time, their abnormal stress response was associated with an earlier onset (age of first use) of cigarettes smoking and an increased amount and frequency of smoking cigarettes.
  2. Childhood trauma and drug use – Children who experienced excessive childhood trauma had altered brain activity (in the Nucleus Accumbens specifically) and showed increased anxiety. This area, which is important for essentially all learning, was differentially activated in a way that correlated with the amount of childhood trauma.
  3. Marijuana withdrawal and relapse to marijuana use – Marijuana withdrawal, which might soon be added to the APA‘s DSM (in version 5) was characterized as: Increased irritability, restlessness, and misery, reduced sleep quality, sleep duration, and food intake. When tested, restlessness, sleep disturbance, and early wakening were found to be predictors of relapse among participating marijuana users.