If you were to read the opening couple of pages of most natural or alternative treatment books on ADHD, you would likely find some version of the following argument: "Ritalin is chemically similar to cocaine and amphetamines and studies have shown it has a high addiction potential". There actually is a fair amount of truth to that statement, but the latter half leaves out some equally important information concerning the nature of these studies.
This post is not meant to be a pro-stimulant drug message, I certainly do see some apparent risks for many ADHD medications, especially concerning young children and their developing nervous systems. However, I also feel that we should carefully examine the nature of many of these "anti-methylphenidate" studies and evaluate the relevancy of their findings. To facilitate this discussion, I have taken data from a serious of research articles on the topic of habit-forming potentials of methylphenidate (Ritalin, Concerta, Daytrana, etc.) and have attempted to box together some of the overlapping information with relevant conclusions that are, to the best of my ability, as unbiased as possible. Here are some key points worth noting:
- Chemical similarity to cocaine and amphetamines. The chemical structure of methylphenidate is given below. As a comparison, the structure of methamphetamine is also given. I realize that the majority of readers here are not organic chemists, so I have highlighted the similar regions of the two molecules (which is a relatively big overlap as far as chemical structure and function is concerned). The purple/red regions below highlight chemically similar regions between the two drugs, while the green/blue areas show chemical differences. For brevity and simplicity, I have not included the structure of cocaine, because there are fewer obvious similarities between the chemical structures of methylphenidate and cocaine. Just realize that there are chemical and functional similarities between the two drugs.
- A huge factor in a drug's addiction potential rests on how fast the drug can both enter and leave the brain. In short, the faster the entry and the faster the clearance of the drug from the brain, the greater the "high" and the greater the addiction potential. We have seen this before in earlier posts, such as the one on Vyvanse for ADHD treatment. The chart below summarizes some of the key comparisons between methylphenidate and cocaine (most of the data comes from studies by Volkow and coworkers on brain entry and clearance times of cocaine vs. methylphenidate:
We can see from the chart above that cocaine and methylphenidate show similarly quick routes of entry into the brain when administered intravenously (note that this is not the typical route for taking methylphenidate for ADHD patients). However, note that the clearance time from the brain is significantly longer for methylphenidate than cocaine (half-life is a common measuring tool, which refers to the amount of time it takes for half the drug to clear the system). Also note that when methylphenidate is taken in the appropriate manner (orally), the time to arrive at a peak concentration (based on a mammalian model) is significantly longer as well. Both the longer clearance time and times to peak concentrations play a crucial role in reducing the involved "high" and addiction potential for methylphenidate, when compared to drugs such as methamphetamines and cocaine.
- The type of methylphenidate administered may also play a role in the addiction potential. There is a general trend towards prescribing longer-lasting sustained release versions of methylphenidate over the original immediate-release version (although cost is also a factor, with the longer-release versions typically carrying a higher price tag). At the 20 and 40 mg levels, one study showed that the immediate-release version of methylphenidate produced a higher degree of addictive level effects than the longer-release version, although this was based on more qualitative subjective measurements than hard, concrete numerical data.
- On somewhat of an interesting note, it appears that the reinforcing effects of methylphenidate may be much more pronounced in the case of sleep deprivation. One study indicated that methylphenidate only produced reinforcing effects when study participants were limited to 4 hours of sleep the previous night. Given the fact that sleep problems and disturbances are remarkably common in individuals with ADHD, this may actually lend a fair amount of support to potential for abuse among ADHD individuals. However, I personally believe that, based on the other points regarding individuals with ADHD, this population is still relatively "safe" from stimulant medication abuse when the medication is administered and taken in a proper manner.
- We have spoken extensively on the role of Dopamine Transporter (DAT) proteins and their role on governing levels of dopamine, a key neuro-signaling agent which is thought to be critically involved with regards to the onset and symptoms of ADHD. In short, DAT proteins are responsible for shuttling dopamine into and out of neuronal cells and maintaining an overall balance of this important chemical. Individuals with ADHD are thought to have more of these DAT proteins in their brain systems, which results in lower levels of dopamine in the areas between nerve cells, a phenomena which is commonly seen in cases of ADHD and related disorders. DAT proteins are therefore common targets of many ADHD stimulant drugs, which typically act by binding to these DAT proteins and reduce their shuttling effects, which, in turn, helps restore higher dopamine levels in these key regions between nerve cells. It is hypothesized that drugs, even at low doses (such as 20 mg methylphenidate) which bind to and saturate these DAT proteins may contribute to some of the "high" associated with these drugs. However, other findings have contradicted this, with regards to the role of the DAT proteins on "highs" associated with stimulant medications such as methylphenidate.
- Finally, in what may be the most important piece of the puzzle with regards to addictions and ADHD stimulant medications, there was a review done by Kollins which examined the nature of pre-existing studies on the abuse potential of methylphenidate. Kollins noted that a large number of the studies which suggested high addiction potentials for methylphenidate and related subjects gathered their data from non-ADHD individuals. This is important to note, especially considering some of the aforementioned differences between ADHD individuals and non-ADHD individuals with regards to chemical balances (such as the dopamine levels) and hard-wiring issues (such as a higher density of Dopamine Transporter Proteins or DAT's in individuals with ADHD). While this should not be grounds for immediate dismissal of these findings, the lack of studies on actual ADHD patients should raise some serious questions as to whether methylphenidate deserves its "guilty" label with regards to addiction potential. Of course, these studies provide ample evidence to support the assertion that ADHD medications such as methylphenidate can be abused if they are taken by the wrong individuals (non-ADHD patients, such as healthy individuals with few to no signs of ADHD as well as generalized drug abusers), but there appears to be an overall lack of evidence to support the claim that needy patients who do suffer from ADHD will turn into stimulant abusers if they begin to take methylphenidate at prescription-based levels.
- Kollins does conclude with some more relevant (at least in this blogger's opinion) concerns surrounding the use of methylphenidate for ADHD. He questions the impact of methylphenidate and related drugs with regards to:
- Their impact on brain development, especially in young children (a topic in which there is still relatively little conclusive data available).
- How dopamine level changes due to these medications may alter the dopamine system, including the levels of dopamine transporter proteins (DAT proteins).
- The role of early stimulant exposure on latter stimulant abuse (although Kollins notes that early treatment with appropriate stimulants may actually have a protective effect against latter stimulant abuse).
For the most part, I am in agreement with this line of thinking. It is my opinion that we should shift our focus away from the fears of addiction potentials with regards to stimulant medications taken via appropriate doses and methods for ADHD and related disorders, and instead shift our attentions to the effects of these substances on the developing nervous systems of young children. We have seen that methylphenidate has several built-in safety measures with regards to reducing its abuse potential. Furthermore, I personally believe that there are much greater potential risks of stimulant medications with regards to their effects on the critical early neural developmental stages (such as those in the first 5 years of life) than to overall addiction potentials of these substances, and that our research focuses with regards to overall safety of these medications should shift in this direction.