Opioids' Addictive Potential
Origins of the craving/reward cycle
Summary:Not all people who take a particular drug become addicted, in fact most do not.
Drugs which reach the brain faster have a higher addiction liabilitythan those that reach the brain more slowly. Drugs which produce a greater intensity of euphoria and have a shorter duration have higher addiction liabilities.
The one property all
addictive substances share is an ability to manipulate the brain's natural reward circuitand
release dopamine. Increased dopamine activity also prompts the creation of a lasting memory associating the pleasurable feelings with drug use. From that point on, previously neutral stimuli will
evoke or "trigger" memories of the reward experience.
reward circuitry becomes increasingly dulled and desensitizedas the addiction progresses, while the
ability to resist drug use evaporates. Eventually the
drug loses its ability to reward, yet the
Addictive Potential not Addictive
Don't think of the drug as addictive rather see it as having the potential to lead to addiction. That's because addictiveness is more accurately a property of the brain not the drug. Most people who take drugs, even opioids, don't develop addiction.
Some properties of a drug raise the potential for addiction. First, drugs with the potential to lead to addiction all facilitate the release of dopamine and produce a feeling of euphoria. Drugs which reach the brain faster have a higher addiction liability than those that reach the brain more slowly, such as time released drugs. Drugs which produce a greater intensity of euphoria and have a shorter duration have higher addiction liabilities.
Opioids such as methadone, which is slow acting, produces a low level of euphoric response and has a long duration of action; has a lower addiction potential than heroin, which is fast acting, produces a high euphoric response and is short acting.
Addiction Hijacks the Reward System
The one property all addictive substances share is an ability to manipulate the brain's natural reward circuit in order to induce feelings of pleasure or relieve distress.1,2
The reward circuit is designed to reinforce life-sustaining activities, such as eating and sex.1 Engaging in these activities stimulates neurons just above the brainstem to release dopamine into an area of the brain called the nucleus accumbens (NA).3,4 The increased dopamine activity in the NA causes feelings of euphoria.3 Through this reward process, humans and other animals are taught to favor and therefore prioritize behaviors essential for their survival.2
Increased dopamine activity also prompts the creation of a lasting memory associating the pleasurable feelings with the circumstances and setting under which they occur. In effect, these memories (also called conditioned associations) supplement the brain's positive reinforcement of certain behaviors.3
From that point on, previously neutral stimuli will evoke or "trigger" memories of the reward experience.3
In the case of opioids, when the opioid molecule binds to mu receptors in the brain, it initiates the same biochemical sequence and dopamine release normally reserved for rewarding life-sustaining behaviors.3
Ironically, because the brain rewards opioid use in this same way, opioid use is positively reinforced just as though it were critical to survival. This "feeling" that opioid use is essential for survival is postulated as being responsible for many of the behavioral symptoms associated with opioid addiction.
How Addiction Takes Hold in the Brain
The rewarding effects of drugs of abuse come from large and rapid upsurges in dopamine, a neurochemical critical to stimulating feelings of pleasure and to motivating behavior. The rapid dopamine "rush" from drugs of abuse mimics but greatly exceeds in intensity and duration the feelings that occur in response to such pleasurable stimuli as the sight or smell of food, for example. Repeated exposure to large, drug-induced dopamine surges has the insidious consequence of ultimately blunting the response of the dopamine system to everyday stimuli. Thus the drug disturbs a person's normal hierarchy of needs and desires and substitutes new priorities concerned with procuring and using the drug. 5
Drug abuse also disrupts the brain circuits involved in memory and control over behavior. Memories of the drug experience can trigger craving as can exposure to people, places, or things associated with former drug use. Stress is also a powerful trigger for craving. Control over behavior is compromised because the affected frontal brain regions are what a person needs to exert inhibitory control over desires and emotions. 5
That is why addiction is a brain disease. As a person's reward circuitry becomes increasingly dulled and desensitized by drugs, nothing else can compete with them food, family, and friends lose their relative value, while the ability to curb the need to seek and use drugs evaporates. Ironically and cruelly, eventually even the drug loses its ability to reward, but the compromised brain leads addicted people to pursue it, anyway; the memory of the drug has become more powerful than the drug itself.5
- Cam* J, Farr© M. Mechanisms of disease: drug addiction. N Engl J Med. 2003;349:975-986.
- Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ. 2001;164:817-821.
- Kosten TR, George TP. The Neurobiology of Opioid Dependence: implications for treatment. Science & Practice Perspectives. 2002;1:13-20.
- National Institute on Drug Abuse and National Institutes of Health. Lesson 1. The brain what's going on in there? The Brain: Understanding Neurobiology Through the Study of Addiction Accessed April 27, 2005.
- National Institute on Drug Abuse and National Institutes of Health. The Essence of Drug Addiction.