Neurobiology of Heroin Addiction and of Methadone Treatment

ADDICTION AND THE BRAIN

There are eight families of addictive drugs, which are different in many ways, but similar in one important respect — whether it is nicotine or alcohol or cocaine or heroin, some people lose control and become compulsive users. The hallmark of addiction is compulsive use. Addiction is “a behavioral pattern of drug use, characterized by overwhelming involvement with the use of a drug (compulsive use), the securing of its supply, and a high tendency to relapse after withdrawal” (J. H. Jaffe, 1985).

Recent years have seen great advances in our understanding of this compulsive behavior. As all behavior is rooted in the brain, our new knowledge about addiction comes directly from basic brain research.

Every addictive drug used by people is also self-administered by rats and monkeys. If we arrange matters so that when an animal presses a lever, it gets a shot of heroin into a vein, that animal will press the lever repeatedly, to the exclusion of other activities (food, sex, etc.); it will become a heroin addict. A rat addicted to heroin is not rebelling against society, is not a victim of socioeconomic circumstances, is not a product of a dysfunctional family, and is not a criminal. The rat’s behavior is simply controlled by the action of heroin (actually morphine, to which heroin is converted in the body) on its brain.

We are beginning to learn why a laboratory animal (or a person) uses these drugs. A bundle of nerve cells (neurons) deep in the brain, the so-called mesolimbic dopaminergic pathway, is the main site of action of opiates like heroin — and also, interestingly, of all other addictive drugs. We call this the “reward pathway”. It mediates feelings of pleasure and satisfaction. Within the reward pathway, opiates indirectly cause dopamine neurons to release their dopamine. These dopamine neurons are held constantly in check by inhibitory neurons. Opiates act on those inhibitory neurons, shutting them down, removing the inhibition and thus allowing the dopamine neurons to run wild. Inhibition of inhibition causes stimulation.

An analogy may help. Dopamine, in that part of the brain, could be called a “pleasure hormone”; its release causes feelings of satisfaction, of euphoria. The dopamine neurons are held constantly in check by another neurotransmitter released from inhibitory neurons. If a dopamine neuron is like the accelerator pedal in a car, the inhibitory neuron is like the brake pedal, keeping the car from going too fast. Then endorphin neurons, in turn, hold the inhibitory neurons in check, prevent too much braking action and tend to let the car speed up. The net result is to keep the speed just right. A complicated way to run a car, a complicated way to run a brain; but an efficient way to maintain precise control. Thus, in short, opiates like heroin, mimicking the endorphins, cause more dopamine release, cause euphoria; but they do so in an uncontrolled way, overriding the natural controls.

We have learned the structure of the mu opioid receptors, on which the endorphins — and also, of course, opiates like morphine (from heroin) and methadone — act. These receptors are the locks that are unlocked by the endorphin (or opiate) keys. We know exactly how each of the several hundred amino acids in the receptor protein is positioned. Seven segments span the nerve cell membrane, back and forth, forming the staves of a barrel. A molecule of an endorphin (or morphine or methadone), passing from a blood capillary onto a neuron, would drop into the pocket in the middle of the barrel. When the molecular key drops into the lock, it changes the shape of the receptor, and a “signal” is sent to the inside of the cell. That “signal” triggers big chemical changes, which make that neuron less active, so it releases less of its neurotransmitter. The neurons containing mu opioid receptors, which are activated by endorphins or opiates, are the ones that hold the dopamine neurons in check, as already described, and the net result is to stimulate the release of more dopamine.

Our normal feelings of satisfaction, our good moods, are controlled by the regulation of dopamine release by endorphins acting on mu opioid receptors, as described. Heroin is rapidly converted in the body to morphine and 6-acetylmorphine, which act on these same receptors in the brain. The brain responds with feelings of euphoria, but the dopamine stimulation is excessive — far greater than when under the fine-tuned natural control of the endorphins. The brain adapts to this changed condition. It becomes less sensitive to opioids through several mechanisms I shall not discuss here. There are two important consequences of this adaptation. First, more heroin is now required to produce the desired “high”; and second, the system has become less sensitive to the endorphins, so that without heroin, there is insufficient dopamine release, and an uncomfortable feeling we describe as “dysphoria” (and the addict calls “sick”). Thus, after repetitive use of heroin, at increasing dosages, the addict has become tolerant and dependent, and undergoes withdrawal disturbances if the heroin is abruptly terminated.

TWO KEY QUESTIONS ABOUT ADDICTION

FIRST KEY QUESTIONWhy do some people become addicted in the first place, and others not? Why do some people not even like the psychoactive effects of an addictive drug and therefore never start using it? Why can some people use such a drug in moderation and never go on to heavy use and addiction? This extreme variability among people is typical for every addictive drug, from nicotine and alcohol to cocaine and heroin. Might there be some people whose reward pathway is defective in some way from birth, who can only feel “normal” on an opiate, for example, and who discover this the first time they encounter heroin?

SECOND KEY QUESTION: Since withdrawal discomfort is now readily controlled with various medications, so that an addict can be brought without difficulty to an abstinent state, why doesn’t that solve the problem? Why is relapse so common? Is it because of innate deficiencies in the reward pathway, or because chronic exposure to an opiate has caused irreversible changes? In either case, there may be addicts who can not function normally on their own supply of endorphins but require some opiate (like methadone) to occupy the receptors.

Source:
Neurobiology of Heroin Addiction and of Methadone Treatment
By: Avram Goldstein, M.D.
Professor Emeritus of Pharmacology, Stanford University

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Online registration is still available. We look forward to welcoming you to Las Vegas!
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  • Conference Program Spotlight - Exhibits
The #aatod2024 Conference will attract over 1,600 physicians, social workers, nurses, counselors, program administrators, executive directors, and other treatment providers from many countries. Visit the AATOD Exhibit Hall for networking opportunities, to learn about new products & services and for guidance on how to improve patient treatment ➡️ bit.ly/3yi8T1M.
  • May 7, 2024 = #NationalFentanylAwarenessDay #JustSayKNOW
➡️ fentanylawarenessday.org

As many of you know, the #aatod2024 Conference is just one week away. Our impressive conference program consists of 2 Pre-Conference sessions, 4 Poster Author sessions and 1 Hot Topic Roundtable addressing the urgent problem of illicit fentanyl. These educational sessions are open to all conference attendees. 

Please visit our conference program for more details ➡️ bit.ly/3Ue57Q6
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  • 📣 Announcing the AMAZING Line-Up of Plenary Speakers

💻 View the #aatod2024 Conference Video Message from Ann Jamieson, MS,LADC/MH - AATOD’s Plenary Chair.

😊 We couldn’t be more excited about what we have in store for you next week in the spectacular city of Las Vegas where we will convene our conference!

🎤 You will not want to miss the three impressive plenary sessions that have been organized to deliver you extraordinary presentations for your educational purposes. These Plenary Sessions will cover a range of topics that highlight our conference theme, “Treating Opioid Use Disorder: So Much More Than Medication.” We have packed a lot of information into the plenary sessions and are excited to present the policies and strategies in Nevada and nationally.

Join us in Las Vegas by registering for the #aatod2024 Conference ➡️ www.aatodconference.com.
  • Register for the #aatod2024 Conference ➡️ www.aatodconference.com

⭐️ Conference Program Spotlight ⭐️
We know that opioid use disorder (OUD) knows no geographic boundaries. And, while there are countless initiatives, projects, policy reviews, opportunities, and challenges here in the United States, others around the world are facing and dealing with these same issues as well as successes that will be shared at the conference. 
 
Because we believe it is important and imperative to understand the good and essential work that is being done world-wide, Dr Maremmani and Mike Rizzi (AATOD International Chair) invite you to not only come to the conference but to join us at our Sunday (5/19) International Symposium. Respected international colleagues will address responses and findings related to treatment, recovery, and research in their countries. There will also be a special International Workshop on Tuesday, 5/21.
Welcome to Las Vegas. We invite you to attend this evening’s AATOD Board meeting ➡️ bit.ly/4apbmVt #aatod2024
Welcome to Las Vegas. We invite you to attend this evening’s AATOD Board meeting ➡️ bit.ly/4apbmVt #aatod2024
2 days ago
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Join us for the highly acclaimed 8-hour clinician’s course which convenes on Sunday, May 19, 2024 ➡️ bit.ly/3UOKtVi
#aatod2024
Join us for the highly acclaimed 8-hour clinician’s course which convenes on Sunday, May 19, 2024 ➡️ bit.ly/3UOKtVi #aatod2024
3 days ago
View on Instagram |
2/10
📰 AATOD Unites Global Leaders in Opioid Use Disorder Treatment for Pivotal Las Vegas Summit 
➡️https://prn.to/3wEvR2G #OUD #somuchmorethanmedication #aatod2024
📰 AATOD Unites Global Leaders in Opioid Use Disorder Treatment for Pivotal Las Vegas Summit ➡️https://prn.to/3wEvR2G #OUD #somuchmorethanmedication #aatod2024
4 days ago
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3/10
💻 Welcome Message from Dr. Dinita Smith, Psy.D, MSW - #aatod2024 Conference Chair Thank you to our generous Conference Sponsors, Hosts, Exhibitors, Keynote Speakers, Presenters, Volunteers, and the entire Conference Planning Committee. Online registration is still available. We look forward to welcoming you to Las Vegas!
4 days ago
View on Instagram |
4/10
Post & Hashtag 📸 
We would love to hear about your #aatod2024 conference experience on social media.
Post & Hashtag 📸 We would love to hear about your #aatod2024 conference experience on social media.
5 days ago
View on Instagram |
5/10
Conference Program Spotlight - Exhibits
The #aatod2024 Conference will attract over 1,600 physicians, social workers, nurses, counselors, program administrators, executive directors, and other treatment providers from many countries. Visit the AATOD Exhibit Hall for networking opportunities, to learn about new products & services and for guidance on how to improve patient treatment ➡️ bit.ly/3yi8T1M.
Conference Program Spotlight - Exhibits The #aatod2024 Conference will attract over 1,600 physicians, social workers, nurses, counselors, program administrators, executive directors, and other treatment providers from many countries. Visit the AATOD Exhibit Hall for networking opportunities, to learn about new products & services and for guidance on how to improve patient treatment ➡️ bit.ly/3yi8T1M.
6 days ago
View on Instagram |
6/10
May 7, 2024 = #NationalFentanylAwarenessDay #JustSayKNOW
➡️ fentanylawarenessday.org

As many of you know, the #aatod2024 Conference is just one week away. Our impressive conference program consists of 2 Pre-Conference sessions, 4 Poster Author sessions and 1 Hot Topic Roundtable addressing the urgent problem of illicit fentanyl. These educational sessions are open to all conference attendees. 

Please visit our conference program for more details ➡️ bit.ly/3Ue57Q6
May 7, 2024 = #NationalFentanylAwarenessDay #JustSayKNOW ➡️ fentanylawarenessday.org As many of you know, the #aatod2024 Conference is just one week away. Our impressive conference program consists of 2 Pre-Conference sessions, 4 Poster Author sessions and 1 Hot Topic Roundtable addressing the urgent problem of illicit fentanyl. These educational sessions are open to all conference attendees. Please visit our conference program for more details ➡️ bit.ly/3Ue57Q6
1 week ago
View on Instagram |
7/10
You won’t want to miss these 3 POWERFUL Plenary Sessions ready to set the stage in Las Vegas less than 2 weeks. Register today for the #aatod2024 Conference, the world's premier training conference event for the Treatment of Opioid Use Disorder ➡️www.aatodconference.com⬅️
You won’t want to miss these 3 POWERFUL Plenary Sessions ready to set the stage in Las Vegas less than 2 weeks. Register today for the #aatod2024 Conference, the world's premier training conference event for the Treatment of Opioid Use Disorder ➡️www.aatodconference.com⬅️
You won’t want to miss these 3 POWERFUL Plenary Sessions ready to set the stage in Las Vegas less than 2 weeks. Register today for the #aatod2024 Conference, the world's premier training conference event for the Treatment of Opioid Use Disorder ➡️www.aatodconference.com⬅️
You won’t want to miss these 3 POWERFUL Plenary Sessions ready to set the stage in Las Vegas less than 2 weeks. Register today for the #aatod2024 Conference, the world's premier training conference event for the Treatment of Opioid Use Disorder ➡️www.aatodconference.com⬅️
2 weeks ago
View on Instagram |
8/10
📣 Announcing the AMAZING Line-Up of Plenary Speakers 💻 View the #aatod2024 Conference Video Message from Ann Jamieson, MS,LADC/MH - AATOD’s Plenary Chair. 😊 We couldn’t be more excited about what we have in store for you next week in the spectacular city of Las Vegas where we will convene our conference! 🎤 You will not want to miss the three impressive plenary sessions that have been organized to deliver you extraordinary presentations for your educational purposes. These Plenary Sessions will cover a range of topics that highlight our conference theme, “Treating Opioid Use Disorder: So Much More Than Medication.” We have packed a lot of information into the plenary sessions and are excited to present the policies and strategies in Nevada and nationally. Join us in Las Vegas by registering for the #aatod2024 Conference ➡️ www.aatodconference.com.
2 weeks ago
View on Instagram |
9/10
Register for the #aatod2024 Conference ➡️ www.aatodconference.com

⭐️ Conference Program Spotlight ⭐️
We know that opioid use disorder (OUD) knows no geographic boundaries. And, while there are countless initiatives, projects, policy reviews, opportunities, and challenges here in the United States, others around the world are facing and dealing with these same issues as well as successes that will be shared at the conference. 
 
Because we believe it is important and imperative to understand the good and essential work that is being done world-wide, Dr Maremmani and Mike Rizzi (AATOD International Chair) invite you to not only come to the conference but to join us at our Sunday (5/19) International Symposium. Respected international colleagues will address responses and findings related to treatment, recovery, and research in their countries. There will also be a special International Workshop on Tuesday, 5/21.
Register for the #aatod2024 Conference ➡️ www.aatodconference.com ⭐️ Conference Program Spotlight ⭐️ We know that opioid use disorder (OUD) knows no geographic boundaries. And, while there are countless initiatives, projects, policy reviews, opportunities, and challenges here in the United States, others around the world are facing and dealing with these same issues as well as successes that will be shared at the conference. Because we believe it is important and imperative to understand the good and essential work that is being done world-wide, Dr Maremmani and Mike Rizzi (AATOD International Chair) invite you to not only come to the conference but to join us at our Sunday (5/19) International Symposium. Respected international colleagues will address responses and findings related to treatment, recovery, and research in their countries. There will also be a special International Workshop on Tuesday, 5/21.
2 weeks ago
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10/10

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