Monday, December 1, 2014

Overall, anxiety is only one of the factors that contribute to relapse. Although it’s only one of the factors, aiming to ease this emotion in the withdrawal syndrome could make it easier for a drug addict to take control of his or her life once again. Even though the Nucleus Accumbens is an important area of the brain for survival, the reinforcing and rewarding effects of addictive drug intake and the anxiety produced by drug withdrawal, contribute to the addiction cycle, making it really hard to quit drugs. Further research in the action of the Nucleus Accumbens and anxiety in relapse could lead to better treatment designs for the rehabilitation of drug addicts.

Because drug addiction is a disease based on neuro-adaptive changes, we should remember, first of all, to only use prescribed drugs as described by doctors. It may seem as a cliché, but understand that, to their best extent, doctors are professionally trained to understand how your physiological and psychological composition can best match the kind of drug you need, and how and when you should take it. Secondly, if your suffering from drug dependence, and are currently seeking to quit, go to a doctor or special organizations, such as  Hogar Crea and Assmca for assistance.

Possible Treatments

Certain treatments for drug abuse have been proposed based on its relationship with anxiety. For instance, treatments with CRFR1 antagonists have shown promising result in animal subjects by reducing stress induce relapse to drug taking. Specifically, CP-154, 526, a CRFR1 nonpeptide antagonist has significantly reduce stress related relapse in rats. CRFR1 is a receptor located in the Central Nervous System (CNS) and the periphery. This receptor, along with CRFR2, mediates the release of corticotropin- releasing factor, which coordinates homostasis in the body. Now, CRFR1 has been shown to have an important role in anxiety, since research has shown that CRFR1 knockout mice have impaired stress response and present decrease anxiety-like behavior. (Bale et al, 2002)(Boyson et al, 2011) Therefore, a CRFR1 antagonist will be expected reduce anxiety in drug addicts and decrease relapse do to anxiety. However, targeting this receptor to the treatment of addiction has been low in human population.  Nevertheless, high affinity CRFR1 antagonist NB1-34041 has demonstrated efficiency in reducing elevated stress in animal and humans, but further research in its role in drug addiction treatment is necessary. (Cleck et al, 2008)
Antidepressants such as Desipramine (DMI) have shown significant effects in treating cocaine addiction. Research in both animal subjects and human subjects have shown decrease anxiety related relapse. However, recent investigations have shown little positive effects of DMI to crack cocaine withdrawal symptoms, so research in other antidepressants such as modafinil have arisen. Modafinil, has shown to be more promising in clinical trials, but yet the exact mechanism of action is to be further studied. Still, it is known that it inhibit reuptake of dopamine in the brain and activates other neurotransmitters such as glutamate and norepinephrine. (Cleck et al, 2008)(Dackis et al, 2005).

In addition to medical treatments, rehabilitation programs that promote a new life in a positive environment can also decrease anxiety a reduce relapse in drug addicts. A study conducted in rats, showed how enriched environments significantly reduce drug seeking in rats compared to common environments. (Chauvet et al, 2009). Furthermore, many Drug addict programs focus, such as Hogar Crea, focus on identifying anxiety agents that increase craving in drug addicts, as a source of rehabilitation and perseverance in abstinence.

Sunday, November 30, 2014

Nucleus Accumbens (NAcc) and Anxiety

The Nucleus Accumbens is an area within the brain that pertains to a system that involves other brain areas. This system is called the mesolimbic dopaminergic system. Meso means brain and limbic is the region were these systems are found, and dopaminergic because these areas have specialized cells (called neurons) that synthesis and release dopamine. This system is mainly comprised of the Ventral Tegmental Area (VTA) and the Nucleus Accumbens (NAcc).  The VTA, upon receiving stimuli, secrets Dopamine in the NAcc. This secretion of dopamine in the NAcc creates a reinforcing and rewarding effect on the drug that caused the stimuil (Jerlhag et al, 2010; Thorfinn et al, 2012; Nieh et al,2012; Salamone et al, 1997). When we say reinforcing we mean that it will make you want more, and when we say rewarding we mean that the drug will make you feel good and you’ll like it. Although it may seem like something bad because it involves drugs, it is actually critical for survival. This is because food intake and sex have their rewarding and reinforcing effects here. So, imagine that this system doesn’t exist and for the first time you eat something (like when, for the first time, you drink milk from your mother when you are born), if you don’t like or feel any kind of sensation that makes you say “mmmm this is good”, then you’re just not going to be motivated to eat it again. If this occurs with the milk of the mother and her child, what else is he going to eat when he is just a few days old and can’t swallow or take anything else but milk? Nothing, so the survival of the child is threatened. If every newborn in the world were to suddenly be born without this system, then survival of the human race is at stake. Now that we understand how powerful the motivational effects of stimulating the NAcc are in order to secure survival, we can understand why it is so hard for many addicts to stop taking a drug that has its stimulating effects in the NAcc. Now, when we correlate this to anxiety, we must ask ourselves what happens when we like something (we are motivated to get it) that we cannot have and desperately want?. The answer is not that difficult, we may get frustrated and/or stressful. Stress leaves to anxiety which means heightened blood pressure, heightened heart rate, muscle contractions and everything that you get when you’re in a “fight or flight” mode but in a prolonged manner. Prolonged stress can make you feel horrible, like your dying and you can’t do anything about it, and who wants to feel that way? Nobody, so when it gets worst and worst and worst you get to the point where you say enough is enough and if you’re an addict in abstinence you may want to take the drug to alleviate these symptoms. This, and many other factors that go beyond the scope of this blog, are the reason for why so many people that try stopping the use of a drug, which they are addicted to, are not able to continue abstaining (Sinha, 2009; Zhanget al, 2014). Suppose that you managed to absolutely abstain and now your system is free of the drug you were addicted to, what happens if you come in contact with the environment or the drug? To answer this question we must understand that drugs are normally associated to something; it can be a place, a song, a movie, anything to which when you took that drug you were constantly exposed to. For example, people that take their coffee (which act on the same system) when they are reading the newspaper. Every time you read the newspaper, you drink your coffee. The repetition of this pattern creates an association, so the next time that you’re reading your newspaper and you are not having coffee, you will feel like something is missing, and that something is the coffee. But this is not the only thing you will feel, you will also feel the same good sensation that comes when you drink your coffee, even though you’re not drinking it. As expected this good sensation will make you say “why am I not drinking my coffee if it feels so good”, and you’ll get up, if you’re seated, and go get your coffee. If you can’t get your coffee you’ll probably get irritated and anxious. Back to our question, this association practically lasts forever, so even though you haven’t taken the drug for years and years, when you are in presence of that associative thing or place, it will remind you of how taking the drug made you feel, and this my friends is why so many people relapse or, in other words, resume taking the drug (Shimamoto et al, 2014). The anxiety you will feel because you can’t have that great and pleasant stimuli, that the drug gave you, is so powerful that it can make you go back to your old bad habits of taking the drug. Anxiety is only one of the many factors that contribute to relapse and the unsuccessful stopping of drug use in many addicts.

What's Anxiety?

Anxiety is defined as a state of nervousness, fear, apprehension and worrying. Many people, if not everyone, has experience some sort of anxiety in their life due to certain situations that put us  under stress, which could include tests, interviews, recitals and others. A far from the unpleasant sensation, this emotion is fairly important to the human race because it is essential for survival.  When in a dangerous situation our body activates the fight-or-flight response to assure we manage to survive the emergency. Also, anxiety allows us to progress because makes us prepare harder for situations, like studding hard for an exam, preparing for an interview, etc.  So, in small dose anxiety is an important part of our life.  But, when anxiety presents it self in large doses, it could be really harmful for the human being. If anxiety increases outside a curtain level the performance our performance significantly deteriorates making us fail to accomplish a task. We will remember our failure in subsequent situations, which will make us stress even more, and an escalating cycle is created. (Meyer & Quenzer, 2013) This cycle will make us withdrawal from a situation that has caused us anxiety in the past, and this is exactly what prevents addicts from abstaining from a drug. Because when they abstain from the drug they feel an extreme amount of anxiety that can only be stopped by taking the drug. Different studies have confirmed the role of anxiety in drug addiction withdrawal. In a study conducted en 2001-2002, 99.2% of a sample of 408 addicts, reported to relapse to cocaine use in a 5-year term. (Quintero et al, 2011) Also, drugs like mGluR5 antagonist that act on NAc shell in rats specifically suppresses the relapse to heroin-seeking by suppressing anxiety- like behavior. (Lou et al, 2014).
Additionally, to the anxiety felt as a result of drug abuse, they're also different kind of anxiety disorders that exist in our society. Such disorders include Obsessive Compulsive Disorder, Social Anxiety Disorder, Phobias, Generalized Anxiety Disorder, among others. The following video will explain briefly each of the disorders.

Wednesday, November 26, 2014

Introduction to Anxiety, Addiction and Cocaine
Drug addiction has become one of the mayor problems in Puerto Rico. Every day we see news about tragedies and crimes caused by drug related issues. In Puerto Rico 1 out of 50 people between the ages of 15 to 74 years abused drugs in 2008, while 1 out of 50 people suffered from drug dependence this same year. (Assmca, 2008) This large proportion of drug abuse and dependence has leaded the scientific community to question the possible cause of drug addiction. Anxiety has been consider as a predisposition and one of causes of drug addiction. This emotion occurs with a much stronger intensity during youth, which increases the probability that the young try drugs for the first time to inhibit anxiety feelings, and eventually become addicted to the drug. (Stanton, 1988)(Boddapati, 2014Anxiety does not only has a close relationship with the first drug seeking action, it also holds a connection with drug seeking during withdrawal. (Fox et al, 2013) Anxiety plays an important part in making the drug addict use the drug continuously and relapse after abstaining from the drug, as a part of the abstinence syndrome. So, by studding the relationship between anxiety and drug addiction we could discover different treatments or possible cures for drug addiction.
Cocaine is one of the drugs with highest abuse and dependences probabilities due to anxiety. This psicostimulant drug, like every reinforcing drug employs effects in the dopaminergic mesolimbic pathway. This pathway, that extends from the VTA to the Nucleus Accumbens, activates with the drug, reinforcing the act of drug taking and promoting a second use of the drug. When a constant use of the drug has been established the systems adapts to the presence of the drug and reestablish a new balance of receptors and neurotransmitters of which the drug acts upon. This new balance is dependent of the drug, and when restrained of it, causes the opposite of the reinforcing effects, hence causing anxiety and leading to drug intake. (Koob et al, 2001)