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.

Marc Lewis, Ph.D. - Addiction as Self-Medication

This brief post at the Psychology Today blog, Addicted Brains (A neuroscientist examines life on drugs) by Marc Lewis, Ph.D., looks at the "self-medication" model of addiction, the perspective that most addictions are based in efforts to numb feelings that are perceived as too overwhelming to experience. This is a model to which I adhere, mostly based on my own experience.

Lewis is the author of Memoirs of an Addicted Brain: A Neuroscientist Examines his Former Life on Drugs and co-editor of Emotion, Development, and Self-Organization: Dynamic Systems Approaches to Emotional Development.
 

Addiction as Self-Medication

Brain patterns formed by trauma sometimes need fixing—at any price

 

Published on August 22, 2012 by Marc Lewis, Ph.D. in Addicted Brains

A while back I promised to survey the three most common models of addiction—disease, choice, and self-medication—and say something about the advantages and disadvantages of each. I got hung up on the choice model for a few posts: there’s so much there to think about. But now let’s look at self-medication as the essence of addiction.

The self-medication model seems to be the kindest of the three. It has the advantage of the disease model, in absolving the addict of excessive blame, but it has the additional advantage of avoiding the stigma of “disease” and all that goes with it. In fact, it gives control (agency) back to the addict, who is, after all, acting as his or her own physician. Whereas the disease model places agency in the hands of others and casts the addict as a passive victim. Furthermore, the self-medication model just might be the most accurate of the three.

The idea is simple: trauma is the root cause. Trauma includes abuse, neglect, medical emergencies, and other familiar categories, but it also includes emotional abuse, and above all loss. Loss of a parent during childhood or adolescence can take many forms, including divorce, being sent away from home (in my case) or the shutting down of one or both parents due to depression or other psychiatric problems. Trauma is often followed by post-traumatic stress disorder (PTSD), which includes partial memory loss, intrusive thoughts, anxiety and panic attacks, avoidance of particular places, people, or contexts, emotional numbing or a sense of deadness, and overwhelming feelings of guilt or shame. But if that’s not bad enough, PTSD is about 80% comorbid with other psychiatric conditions—depression and anxiety disorders being chief among them.

A famous study using a huge sample (17,000) looked at Adverse Childhood Experiences (ACEs) in relation to subsequent physical and mental problems. The results of the study are nicely summarized in the Sept. 25/2011 issue of The Fix. Take-home message: the relationship between trauma and addiction is unquestionable. An ACE score was calculated for each participant, based on the number of types of adverse experience they reported during childhood or adolescence. The higher the ACE score, the more likely people were to end up an alcoholic, drug-user, food-addict, or smoker (among other things). Here are two graphic examples:



 

These figures, which are likely to be low estimates, show a 500% increase in the incidence of adult alcoholism, and a 4,600% increase in the incidence of IV drug use, predicted by early adverse experiences. Despite criticisms of the study, based mostly on retrospective self-reporting, these correlations are huge and they are meaningful, and follow-up prospective studies are finding similar results.

So how does self-medication work? There must be something about PTSD, depression, and anxiety that gets soothed by drugs, booze, binge-eating, and other addictive hobbies. Again, it’s not complicated. PTSD, depression, and anxiety disorders all hinge on an overactive amygdala—one that is not controlled or “re-oriented” by more sophisticated (and realistic) appraisals coming from the prefrontal cortex and anterior cingulate cortex (ACC). That traumatized amygdala keeps signalling the likelihood of harm, threat, rejection, or disapproval, even when there is nothing in the environment of immediate concern. In fact, this gyrating amygdala lassos the prefrontal cortex, foisting its interpretation on the orbitofrontal cortex (and ventral ACC) rather than the other way around (which we might loosely call emotion regulation). The whole brain is dominated by limbic imperialism—making it a less-than-optimal neighbourhood in which to reside.

At the very least, drugs, booze, gambling and so forth take you out of yourself. They focus your attention elsewhere. They may rev up your excitement and anticipation of reward (in the case of speed, coke, or gambling) or they may quell anxiety directly by lowering amygdala activation (in the case of downers, opiates, booze, and maybe food). The mechanisms by which this happens are various and complex. But addicts and ex-addicts (like me) know what it feels like. If we find something that relieves the gnawing sense of wrongness, we take it, we do it, and then we do it again.

So, according to the self-medication model, addictive behaviours “medicate” depression, anxiety, and related feelings. But is that the whole story? I don’t think so, and I’ll get into why in my next post.