Researchers Discover Impaired Neuronal Activity in Occasional Users of Stimulant Drugs

 

By stimulant drugs they mean cocaine, amphetamines (given to our children as Adderall), or similar drugs (which the study classifies as Adderall and maybe Ritalin).

Subjects were all 18-24 year old college students. Occasional users were characterized as having taken stimulants an average of 12 to 15 times. The “stimulant naïve” control group included students who had never taken stimulants.
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The brain images of the occasional users showed consistent patterns of diminished neuronal activity in the parts of the brain associated with anticipatory functioning and updating anticipation based on past trials.

I have been Adderall since I went back to school a few years back. In my lost youth I quite liked stimulants of almost any variety. I can't imagine what all of this has done to my brain.

There are three pieces here - a summary from Constance Scharff at Psychology Today, the original press release as posted for Drug Discovery and Development Magazine, and the citation and abstract from the Journal of Neuroscience.

Cocaine and Stimulants Literally Damage Your Brain

A hard wiring of the brain may be the reason some people become addicts.

Published on April 14, 2014 by Constance Scharff, Ph.D. in Ending Addiction for Good

Scientists using functional magnetic resonance imaging (fMRI) have discovered impaired neuronal activity in occasional users of stimulant drugs. An internal hard wiring of the brain may be the reason some people become prone to drug addiction. The implication of the study is the possibility of using brain pattern activity to identify people who are at risk before they become addicted or when they exhibit addictive type behavior.

At the University of California, San Diego School of Medicine researchers recorded brain activity via fMRI. The participants were given instructions to press a button when they saw a specific image, but not if they heard a sound in 288 trails measuring reaction times and errors on the assigned task. The study compared the brains of young adults between the ages of 18 and 25 years old that occasionally used cocaine, amphetamines or similar drugs to those of a “stimulant naïve” control group.The reaction times of occasional users were actually faster on the first part of the trials, implying more impulsiveness compared to the control group. On the next part, the same group made more mistakes, which became worse as the tasks became more difficult. The difference in the two groups of people was notable.

“We used to think that drug addicts just did not hold themselves back but this work suggests that the root of this is an impaired ability to anticipate a situation and to detect trends in when they need to stop,” said Katia Harlé, a postdoctoral researcher and the study’s lead author.

Next, the researchers want to discover whether this impaired neuronal activity is permanent or can be re-wired.

It may be possible to “exercise” weak areas of the brain, where attenuated neuronal activity is associated with higher tendency to addiction.

This would offer hope of early intervention thus preventing the damage that stimulants can cause to brain function and the measurable difference of physical reaction performance.

Not using any stimulant drug is the best choice to make as even casual or occasional users risk the possibility of addiction later on. Make the right choice and just don’t start! But, if you have recently used cocaine or stimulants, consider seeking professional advice if you need help quitting. Our brains are not something to mess with!

Here is the original press release about this study, as it was posted in Drug Discovery and Development Magazine. Below that is the original abstract and citation from the Journal of Neuroscience.

Stimulant Drugs Can Impair Neuronal Activity

Date: March 25, 2014
Source: UC San Diego School of Medicine


Researchers at the University of California, San Diego School of Medicine have discovered impaired neuronal activity in the parts of the brain associated with anticipatory functioning among occasional 18- to 24-year-old users of stimulant drugs, such as cocaine, amphetamines and prescription drugs such as Adderall.

The brain differences, detected using functional magnetic resonance imaging (fMRI), are believed to represent an internal hard wiring that may make some people more prone to drug addiction later in life.

Among the study’s main implications is the possibility of being able to use brain activity patterns as a means of identifying at-risk youth long before they have any obvious outward signs of addictive behaviors.

The study is published in the Journal of Neuroscience.

“If you show me 100 college students and tell me which ones have taken stimulants a dozen times, I can tell you those students’ brains are different,” said Martin Paulus, professor of psychiatry and a co-senior author with Angela Yu, PhD, professor of cognitive science at UC San Diego. “Our study is telling us, it’s not ‘this is your brain on drugs,’ it’s ‘this is the brain that does drugs.’”

In the study, 18- to 24-year-old college students were shown either an X or an O on a screen and instructed to press, as quickly as possible, a left button if an X appeared or a right button if an O appeared. If a tone was heard, they were instructed not to press a button. Each participant’s reaction times and errors were measured for 288 trials, while their brain activity was recorded via fMRI.

Occasional users were characterized as having taken stimulants an average of 12 to 15 times. The “stimulant naïve” control group included students who had never taken stimulants. Both groups were screened for factors, such as alcohol dependency and mental health disorders, which might have confounded the study’s results.

The outcomes from the trials showed that occasional users have slightly faster reaction times, suggesting a tendency toward impulsivity. The most striking difference, however, occurred during the “stop” trials. Here, the occasional users made more mistakes, and their performance worsened, relative to the control group, as the task became harder (i.e., when the tone occurred later in the trial).

The brain images of the occasional users showed consistent patterns of diminished neuronal activity in the parts of the brain associated with anticipatory functioning and updating anticipation based on past trials.

“We used to think that drug addicts just did not hold themselves back but this work suggests that the root of this is an impaired ability to anticipate a situation and to detect trends in when they need to stop,” said Katia Harlé, a postdoctoral researcher in the Paulus laboratory and the study’s lead author.

The next step will be to examine the degree to which these brain activity patterns are permanent or can be re-calibrated. The researchers said it may be possible to “exercise” weak areas of the brain, where attenuated neuronal activity is associated with higher tendency to addiction.

“Right now there are no treatments for stimulant addiction and the relapse rate is upward of 50%,” Paulus said. “Early intervention is our best option.”

* * * *

Full Citation:
Harlé, KM, Shenoy, P, Stewart, JL, Tapert, SF, Yu, AJ, and Paulus, MP. (2014, Mar 26). Altered Neural Processing of the Need to Stop in Young Adults at Risk for Stimulant Dependence. Journal of Neuroscience; 34(13): 4567-4580; doi: 10.1523/JNEUROSCI.2297-13.2014

Altered Neural Processing of the Need to Stop in Young Adults at Risk for Stimulant Dependence

Katia M. Harlé, Pradeep Shenoy, Jennifer L. Stewart, Susan F. Tapert, Angela J. Yu, and
Martin P. Paulus,

Author contributions: M.P.P. designed research; K.M.H. and P.S. analyzed data; K.M.H., P.S., J.L.S., S.F.T., A.J.Y., and M.P.P. wrote the paper.

Abstract

Identification of neurocognitive predictors of substance dependence is an important step in developing approaches to prevent addiction. Given evidence of inhibitory control deficits in substance abusers (Monterosso et al., 2005; Fu et al., 2008; Lawrence et al., 2009; Tabibnia et al., 2011), we examined neural processing characteristics in human occasional stimulant users (OSU), a population at risk for dependence. A total of 158 nondependent OSU and 47 stimulant-naive control subjects (CS) were recruited and completed a stop signal task while undergoing functional magnetic resonance imaging (fMRI). A Bayesian ideal observer model was used to predict probabilistic expectations of inhibitory demand, P(stop), on a trial-to-trial basis, based on experienced trial history. Compared with CS, OSU showed attenuated neural activation related to P(stop) magnitude in several areas, including left prefrontal cortex and left caudate. OSU also showed reduced neural activation in the dorsal anterior cingulate cortex (dACC) and right insula in response to an unsigned Bayesian prediction error representing the discrepancy between stimulus outcome and the predicted probability of a stop trial. These results indicate that, despite minimal overt behavioral manifestations, OSU use fewer brain processing resources to predict and update the need for response inhibition, processes that are critical for adjusting and optimizing behavioral performance, which may provide a biomarker for the development of substance dependence.

Gee, ya think?

In my experience, almost all addictions begin as attempts to self-medicate pain, sometimes physical but often emotional. This is why I don't buy into the "disease model" of addiction.

However, what these researchers are suggesting is a little different. After the first high, which if you ask most addicts was the best high, they are no longer seeking a high as much as trying to avoid the pain of not being high. What they don't mention here is that over time it takes more and more drug to get near the desired original high, but it's nearly impossible to ever reach that state again because the brain is forever altered with the first administration of the drug.

Anyway, this is still interesting research.

Full Citation: 
Peraile, I, Granado, N, Torres, E, Gutiérrez-López, MD, Moratalla, R, Colado, MI, O’Shea, E. (2013, Nov). Cocaine potentiates MDMA-induced oxidative stress but not dopaminergic neurotoxicity in mice: implications for the pathogenesis of free radical-induced neurodegenerative disorders. Psychopharmacology, 230 (1): 125 DOI: 10.1007/s00213-013-3142-5

Addicts May Be Seeking Relief from Emotional Lows More Than Euphoric Highs

Nov. 6, 2013 — Cocaine addicts may become trapped in drug binges -- not because of the euphoric highs they are chasing but rather the unbearable emotional lows they desperately want to avoid.

In a study published today online in Psychopharmacology, Rutgers University Behavioral and Systems Neuroscience Professor Mark West, and doctoral student David Barker in the Department of Psychology, in the School of Arts and Sciences, challenge the commonly held view that drug addiction occurs because users are always going after the high. Based on new animal studies, they discovered that the initial positive feelings of intoxication are short lived -- quickly replaced by negative emotional responses whenever drug levels begin to fall.

If these animal models are a mirror into human addiction, Rutgers researchers say that addicts who learned to use drugs to either achieve a positive emotional state or to relieve a negative one are vulnerable to situations that trigger either behavior.

"Our results suggest that once the animals started a binge, they may have felt trapped and didn't like it," said West. "This showed us that negative emotions play an equal, if not more important role in regulating cocaine abuse."

In their study, Rutgers researchers detected high-pitched calls made by laboratory rats when they had the opportunity at the beginning of the six-hour drug binge to self-administer cocaine and rapidly raise their internal drug levels. After that, positive and negative emotions collided and the high-pitched euphoric calls emitted in the beginning of the experiment were absent even though the cocaine usage continued at the same level for several hours. The only time during the rest of the binge that researchers detected any calls was when drug level fell below the level animals wanted, which triggered lower-pitched calls associated with negative feelings.

"We see all the positive, high-pitched calls in the first 35-40 minutes," said Barker. "Then if the animals are kept at their desired level you don't observe either positive or negative calls. But as soon as the drug level starts to fall off, they make these negative calls."

The Rutgers researchers say this animal study may lead to a better understanding of human addiction -- alcohol, tobacco and food -- as well as substance abuse. The reason animal studies are critical in addiction research, they say, is that human responses are not always reliable. Individuals may be too embarrassed to answer truthfully or may just tell the scientist what they think he or she wants to hear.

"It's not that human studies aren't important, they certainly are," said West. "But with these animal studies it is clear that we should be placing just as much importance on the negative as being a trigger for drug abuse and deal with that as well."

Here is the full abstract of the article (which seems to not have been at all about way addiction occurs - the findings discussed above are provenance):

Abstract

Rationale

The drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”) and cocaine both increase the generation of free radicals, and in the case of MDMA, this increase in oxidative stress is involved in the dopaminergic neurotoxicity produced by the drug in mice. Oxidative stress processes are also involved in the pathogenesis of several neurodegenerative diseases.

Objectives

We aimed to determine the consequences of the combined administration of MDMA and cocaine on oxidative stress and dopaminergic neurotoxicity.

Methods

Mice received MDMA (20 mg/kg, i.p.; two doses separated by 3 h) followed by cocaine 1, 3, 6, or 24 h after the second MDMA dose. Mice were killed between 1 h and 7 days after cocaine injection.

Results

MDMA decreased dopamine transporter density and dopamine concentration 7 days later. Cocaine did not alter this neurotoxicity. MDMA produced an increase in the concentration of 2,3-dihydroxybenzoic acid in striatal microdialysis samples and an increase in lipid peroxidation in the striatum which were potentiated by cocaine. MDMA and cocaine given together also increased nitrate and 3-nitrotyrosine levels compared with either drug given alone. On the other hand, MDMA increased superoxide dismutase activity and decreased catalase activity, changes which were prevented by cocaine administration. In addition, cocaine administration produced an increase in glutathione peroxidase (GPx) activity in both saline-treated and MDMA-treated mice.

Conclusions

Cocaine potentiates MDMA-induced oxidative stress but does not produce an increase in the neurotoxicity produced by MDMA, and this lack of potentiation may involve an increase in GPx activity.