Sunday, April 5, 2009

Ritalin and Cocaine: Similarities and Differences

We have previously investigated some of the similarities between the chemistry and modes of action of Ritalin and cocaine. In this past post, however, we looked more at the rates of uptake and metabolism of the two drugs and investigated a side-by-side structural comparison.

I was originally planning on continuing with posts on Daytrana, which is very similar to the more common ADHD medications Ritalin and Concerta (it is actually comprised of the same chemical agent, methylphenidate. However, I recently saw an interesting article on the topic of methylphenidate, cocaine and nicotine, and the mechanism of interaction between these different stimulants. As a result, in lieu of the Daytrana postings, I would like to discuss these findings in the next couple of posts.

Here are seven key points to be aware of regarding the similarities and differences between methylphenidate and cocaine:

  1. SIMILARITY: Uptake patterns into the brain: Both methylphenidate and cocaine enter the brain at similar rates and target similar specific regions of the brain. When injected, around 7.5% of the injected compound makes it into the brain tissue for each compound at similar rates (peak uptake only takes around 2 to 8 minutes for cocaine and 4 to 10 minutes for methylphenidate in the injected form, oral administration, which will be discussed later, is significantly longer, especially for methylphenidate). The most favored target region of the brain is the striatum for both cocaine and methylphenidate (see brain diagram below). In fact, several studies have indicated that the two drugs share a number of target binding sites within the brain, to the point where the ADHD medication methylphenidate has actually been used as a treatment option for cocaine abuse.

  2. Brain Regions Targeted by each drug: In addition to similar uptake patterns in the brain between the two drugs, there is a relatively large degree of overlap for particular brain regions targeted. However, there is at least one notable exception, which bears relevance to our discussion. On an interesting note, the method of delivery not only affects the speed of uptake of a drug (injected is almost always faster than snorted, which is almost always faster than ingested), but also the actual brain regions targeted by the drug. For example, another brain region, called the Nucleus Accumbens (see image below for approximate location) is targeted by cocaine and injected methylphenidate. However, when methylphenidate, such as Ritalin, Concerta or Metadate is taken orally, this nucleus accumbens region is not targeted (at least not anywhere near the level of injection).

    The nucleus accumbens is believed to play an important role in the addiction potential of a number of drugs, including many stimulant medications. Thus, proper use of the methylphenidate medication actually bypasses a key brain region believed to be critically involved in the "high" or addiction process of a stimulant drug. This highlights a major difference in the pharmacology between Ritalin and cocaine.
  3. Key Difference between methylphenidate and cocaine: Rate of clearance from the striatum region of the brain: As mentioned in an earlier post, the addiction potential of a drug is typically correlated to the rate of exit or clearance from the brain. In other words, drugs that linger in the brain's receptors for extended periods of time are often much less addicting than ones which exhibit a short and rapid spike in their brain levels and then a quick drop-off in their concentration in the brain. In the striatum, the rate of clearance takes about 90 minutes for methylphenidate, and only 20 minutes for cocaine. If we go by peak concentration duration (i.e. the amount of time the highest concentration typically lasts in the brain before going back down), we see that methylphenidate's peak lasts around 15 to 20 minutes, while cocaine's is a fleeting 2 to 4 minutes. In both cases, the higher dissipation of the drug from high levels in the brain is much more pronounced in cocaine, giving this drug a much more addiction-worthy effect over methylphenidate (even when methylphenidate is abuses and either snorted or injected, it still cannot match the rates of clearance of cocaine).

  4. Potency of the two drugs: The following may seem surprising at first. With regards to specific brain targets, methylphenidate is almost twice as potent as cocaine. We have discussed at length the role of the dopamine transporter protein (DAT), and its role in ADHD and related disorders. Essentially, this DAT protein is responsible for retaining a proper balance of the important brain chemical dopamine in and out of nerve cells. For individuals with ADHD, this balance is often skewed, typically with too much dopamine being taken up into the neuron cells and not enough in the gaps between the cells. Many stimulant medications remedy this problem by essentially binding to and plugging up the dopamine transporter proteins in the nervous system, which inhibits their abilities to shuttle dopamine into the cells. As a result of this medication-effected correction, dopamine balance can be somewhat restored. As a frame of reference, based on some of the current literature, it takes often takes at least a 60% saturation of these dopamine transporters with a drug to elicit the "high" (of course, there is a significant degree of variation between individuals).

    With regards to potency, we see that both cocaine and methylphenidate love to bind to these dopamine transporter proteins. To shut down the function of these dopamine transporter proteins to 50% of their original function (a common way of measuring the potency of a drug in pharmaceutical and laboratory testing), a 640 nanomolar concentration was needed for cocaine, while only a 390 nanomolar concentration was needed for methylphenidate to do the trick. If you're not familiar with these units of concentration, don't worry. These numbers work out to very small amounts (around the neighborhood of only 0.001 grams of drug per liter of fluid). I just put the numbers out there to show that only about half the amount of methylphenidate was needed to share the same effects with cocaine (i.e. the methylphenidate is approximately twice as potent for this particular process).

  5. Difference between Ritalin and Cocaine: DAT saturation levels and perceived high: The relative saturation of these dopamine transporters are also believed to play a role in the "high" of stimulant drugs such as methylphenidate and cocaine. However, research by Volkow and coworkers found that while the level of saturation of the dopamine transporters with cocaine correlated with the "high" associated with this drug, the methylphenidate drug tells a different story. As mentioned previously, the reinforcing effects of a drug including the "high" typically correlate with the rate of clearance from the brain.

    We have also seen that methylphenidate clears much more slowly than cocaine. However, in the case of methylphenidate, the diminished effects of the the high occurred long before the drug had fully cleared from the dopamine transporter. In other words, there appears to be a relatively strong connection between the binding of cocaine to the dopamine transporter proteins and the perceived "high" but the effects are much less pronounced with methylphenidate. This highlights a major difference between methylphenidate and cocaine and at least suggests the possibility of a difference in mechanisms between the two stimulants.

  6. Divergence in metabolic patterns between methylphenidate and cocaine: Furthering this issue a bit more, there is some evidence that the pathway of the two drugs is almost identical for the first part of the journey into the system, but their modes of action split off at some point when it comes to dopamine transporter occupancy and the corresponding reinforcement effects (see sketch below).


  7. Difference between methylphenidate and cocaine: Drug lingering and tolerance: The persistence of methylphenidate on the dopamine transporter proteins may result in more than its reduction of abuse potential. It also appears that this "lingering" of the drug on these dopamine transporter proteins may also play a significant role in the phenomena of tolerance to methylphenidate.

    Acute tolerance to methylphenidate is nothing new. Newer formulations of the drug (Concerta, Metadate) were designed in part to address the problem of the reappearance of ADHD symptoms by ramping up and releasing increased levels of the drug throughout the day. This is important, because, the effects of methylphenidate appear to be best felt when its levels are climbing or building up, and not stabilizing (i.e. you do not want a constant level of methylphenidate throughout the day, but rather a constantly increasing one to maintain the same effects). Essentially, this is "micro-tolerance" to methylphenidate and is seen on a daily level. The ideal dosing strategy for methylphenidate typically entails a morning dosage which is approximately 50% of an evening dosage, i.e. a "ramping" effect of the drug throughout the day is often needed to maintain the desired results.

    It is suggested that this tolerance to methylphenidate may be due, at least in part to its continued presence and relatively slow clearance in specific areas, such as on the dopamine transporter proteins. Other faster-clearing drugs, such as cocaine, do not exhibit this property. However, given the fact that cocaine tolerance is also common, it is unlikely that the whole "dopamine transporter saturation" theory can fully address the issue of tolerance for stimulant drugs. Volkow and coworkers explored this role of blocking dopamine transporters with methylphenidate and the perceived high in greater detail. Nevertheless, at least in this blogger's personal opinion, the lingering effect of methylphenidate still plays some degree of significance to the process of tolerance to the drug, and the need for ramping its dosage to treat disorders such as ADHD.

Add to Technorati Favorites

35 comments:

Anonymous said...

Learn about a new way to treat ADHD:

www.adhdfree.net

Anonymous said...

Awesome. Thanks!

comprar un yate said...

No doubt, the chap is totally fair.

John Scott said...

I think that this is a very accurate summation in principle (if not in every detail, which it possibly may be,I don't have that expertise), of the differences of cocaine and ritalin, from what I have already read on the subject. If you were to snort Ritalin, it might come closer to approximating cocaine, but even then would probably not be as intense. See the ADHD book, Overcoming ADHD Without Medication which talks about this subject. Also, the Association for Natural Psychology has a page on Ritalin and Cocaine, although this page is more detailed.

muebles vicalvaro said...

Quite useful info, much thanks for the post.

Anonymous said...

I haven't Been able to read all of your blogs yet, but hopefully - if you haven't already - you can consider the symmetric tonic neck reflex as a major foundational cause for many ADHD symptoms. If a child does not crawl very much as an infant, or used walkers, play pens, johnny jumpers, etc., and did not have ample opportunity to crawl for about 6 months, then a major development was unable to mature. Thus the reflex controls the body rather than any learned voluntary control, including an accurate relationship with gravity. These kids are chronically uncomfortable and have no way if knowing or expressing this; they assume this is life. There are solutions... 32 weeks of crawling exercises to mature the reflex. Worth a try to help the child feel comfortable enough in their own skin to be able to at least sit or be still and calm inside. Major in the foundation of ALL other development.... ALL other development. Perhaps post info on this to help get the word out, and let parents know there are root solutions to try before the insanity of meds.

Anonymous said...

I have been on ADD/ADHD meds for years and used Nicotine, Caffeine, Dexedrine, Adderall (abused that one med) and even did coke and smoked crack and meth a few times as a late teen and Ritalin and Focalin crank me up in a specific way that is much more potent than any stimulant, it is more or less a paranoid feeling that getting off my ass and doing something can fix and I coked it hardcore outside of IV use and I agree, there is an aspect to Ritalin and focalin that make them much stronger than the others...

Unknown said...

I think, it's a nice idea to post other articles which helps both of you.
Buy Ritalin UK

Anonymous said...

This is an excellent chance to receive some new knowledge. Thank you!!!
Buy Ritalin UK

Unknown said...

This is a great post.I think it will be very usefull to us.

Buy Ritalin

Unknown said...

I just read through the entire article of yours and it was quite good. This is a great article thanks for sharing this informative information.

Buy Ritalin Online

worthmeds said...

I liked it and enjoyed reading it.Keep sharing such important posts.

Methylphenidate Hydrochloride

Obat Kutil Kelamin Herbal said...

information that is very helpful..
nice blog..

Dr Basim Elhabashy said...

your post is too good and very informative. so thanks for posting this blog.

Unknown said...

Your post is very interesting and informative so thanks for posting this blog.

Unknown said...

I'm happy about everything you bring it very interesting and helpful, thanks
Signature:
facebook iniciar sesion gratis - Sitio Oficial iniciado sesión en Facebook lengua española. facebook inicio sesion rápido, facebook iniciar sesion en tu cuenta de entrar facebook

Anonymous said...

No one sees any criminal implications here...? A "drug dealer" gets 5/10 years mandatory for selling cocaine while a "drug rep" or doctor gets...? "Legal" $. Hypocrisy and insjustice

Unknown said...

This article is really fantastic and thanks for sharing the valuable post.
Signature:
i like play games happy wheels online and play happy wheels 2 games and friv4 , girls go games , games 2 girls

Unknown said...

Hi dan,
Thanks for your opinion and I am glad you love it. The function you mention will complete in a few days. Beylikdüzü Escort)

al3ab banat01 said...

العاب بنات يحتوي موقعنا على تشكيلة من العاب تلبيس بنات متجددة باستمرار وكل مايتعلق بصنف العاب بنات تلبيس ومكياج وطبخ ومرحبا بكم في العاب تلبيس 2017
al3ab-banat01

al3ab banat01 said...
This comment has been removed by the author.
City Game online said...

I used to play online flash games
atari breakout||happywheelsgame.in||
happy wheels 3||happy wheels at school||english to spanish translation||happywheelsdemo.in||Pie Face Game
happywheelsunblocked.in || http://slitherioc.com||Happy Wheels|| unblocked games happy wheels


Write my Statement of Purpose said...

I appreciate you for taking your time to investigate the similarities between the chemistry and modes of action of Ritalin and cocaine. You really did a superb and an amazing job. Keep up with the good work.

expertshelp said...

Many people have abused drugs for quite a long time, but then they still can't differentiate between Ritalin and Cocaine. Scientists say that they may have similar side effects to the users, but after reading this blog i realized the difference. Looking for a fundi Its a blog that many should see, and get information on how such drugs deteriorate their health. Thank you for shedding light on that.

Anonymous said...

Great information, and now the differences and similarities are quite obvious to me. Now, could you provide information for how to stop the "crash"? lol.

Unknown said...

Ritalin 10mg (methylphenidate) is used to treat ADHD (Attention Deficit Hyperactivity). Do not confuse ADHD with ADD, it is also known as Attention Deficit Disorder. Buy Ritalin Online

Anonymous said...

Buy Ritalin Online , it is occasionally called ADD. Clinically standard patients with those with ADD or ADHD, Ritalin regularly recommend not only to focus consideration and restore attention, but also to inspire motivation for the goals and purposes required.

jack willium said...

if anyone wants more information about ritalin for sale online visit us.

Moin khan chouhan said...

Buy Drugs Online Find the best shop at affordable price amazingpharmacy.store. Buy Drug Online Pharmacy store and Where To Buy Good Drugs Online.

Buy Ritalin Online said...

Buy Ritalin Online, on the other hand, is pretty simple as it enables you to buy Ritalin without prescription. You just need to register on an authentic online pharmacy and place order for the required number of pills. The procedure is simple and quick and as it only takes 1-2 days for the order to be shipped at your doorstep. so, good luck with your purchase!

Akami Ayurveda said...

I came across through your blog. I found the valuable information about ADHD treatment from your blog.
Ayurveda Detoxification Therapy

Joseph said...

The great content sharing through your blog. Thanks for sharing.
ayurvedic treatment for brain stroke

low rate essay said...

This is so motivating and I really like the way of sharing. should you need low rate essays let us know

Health and Sports said...


buy xanax online

BUY ADDERALL ONLINE

buy Klonopin online

buy-tramadol-online

**CLICK HERE TO BUY ONLINE MEDICINES IN USA**

**ORDER HERE FOR OVERNIGHT DELIVERY**

**GET INSTANT OFFER**

**GET EASILY DISCOUNT ON ALL MEDICINES**

**PLACE YOUR ORDER HERE**
$ - Buy Tramadol Online For Anxiety Disorder Get up to 55% Off - $



ENJOY HERE said...

It appears as if some of the written text on your content are running off the screen. Can someone else please comment and let me know if this is happening to them as well?

야설
오피
횟수 무제한 출장
스포츠마사지
바카라사이트