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

Visit the aatod conference website for more details…www.aatodconference.com.

@aatod1984
  • 3/28 Expanding Access to #Methadone in Correctional Facilities will focus on opportunities to expand access to methadone in correctional facilities, including recent developments with the SAMHSA 2024 final rule on the use of methadone.

Register ➡️ bit.ly/3Vz1RPE
  • Invitation to SAMHSA Webinars on 42 CFR Part 8 💻 

On February 2, 2024, the final rule for 42 CFR Part 8 was published. The effective date for these regulations is April 2, 2024, with an implementation date of October 2, 2024. 

In preparation for implementation of the revisions, SAMHSA will provide two preliminary webinars for OTPs.  The first will focus on administrative areas; the second will focus more on clinical content. These will be held on March 20th (from 2-3pm EST) and March 27th, 2024 (from 2- 3pm EST).  

REGISTER ➡ https://conta.cc/3TF9CSQ

View the final rule ➡ https://lnkd.in/e_iu-AtG.

There will be an opportunity to receive an overview of the rule changes and discuss with SAMHSA the implications of the changes. 

We encourage you to attend these important meetings to assist you in determining how you will need to prepare for full implementation of these regulations. 

This webinar series will be moderated by Mark W. Parrino, MPA (AATOD President). Speakers include Yngvild Olsen, MD, MPH (Director - CSAT), Robert Baillieu, MD, MPH, FAAFP (Physician and Senior Advisor - SAMHSA/CSAT, and Patti Juliana, PhD, LCSW
(Director - CSAT’s Division of Pharmacologic Therapies).

The presentations will be followed by Q&A, and these webinars will become available to the public for On-Demand viewing via the AATOD website. Certificates of Attendance will be provided per request.
  • Don’t miss out on the chance to show your support, share your products/services and secure your sponsorship at the AATOD 2024 Conference, �The world’s premier training conference event for the Treatment of Opioid Use Disorder. #aatod2024

The 2024 AATOD Conference will attract over 1,600 physicians, social workers, nurses, counselors, program administrators, executive directors, and other treatment providers from many countries. The registrants are decision-makers with purchasing power for their treatment centers and are looking for new products, services, and information to improve their patient treatment.

To become an exhibitor today —> https://bit.ly/48ZKMRX
  • TREATING OPIOID USE DISORDER: SO MUCH MORE THAN MEDICATION

💻 View the latest Conference Video Message from AATOD's President, Mark W. Parrino bit.ly/48y815w,
for the most up-to-date details regarding the upcoming #aatod2024 Conference -
The world's premier training conference event for the treatment of Opioid Use Disorder. #OUD 

Registration ➡️ www.aatodconference.com
  • TREATING OPIOID USE DISORDER: SO MUCH MORE THAN MEDICATION #aatod2024

TODAY is the last day to take advantage of the discounted registration rate. #aatod2024 is the world’s premier training conference event for the treatment of #OUD.

For registration and hotel information ➡️ bit.ly/3Ue57Q6.

We look forward to seeing you in Las Vegas!
  • #aatod2024 Conference Update. Comprehensive Listing/Descriptions of Workshops, Posters, and Hot Topic Roundtable Conference Sessions are now available ➡️ http://bit.ly/3Ue57Q6.

The workshop committee is pleased to present a dynamic workshop lineup that includes extremely rich and diverse educational content for all disciplines. You will hear from experts who will share the latest research and developments relating to opioid use disorders and treatment. The workshop lineup will include state of the art information on diverse areas of focus such as patient care and best practices, building community partnerships and collaborations, public policy and regulatory changes, workforce development, quality assurance, and financial reimbursement. There will be workshops that focus on emerging treatment trends and developments such as the fentanyl epidemic, mobile opioid treatment programs, regulatory changes, expansion of treatment services in rural areas, integrating treatment with the corrections systems, and integrating harm reduction initiatives. For those newer to the field or those who want a refresher on the basics, we have once again included a “Foundations” track which will include selections on the fundamentals of medication assisted treatment.

The conference will continue to be the world’s premier training and education event for the treatment of opioid use disorders.  We hope to see you in Las Vegas!
  • Patient access to OTPs saves lives every day.

AATOD has been working with policymakers and regulatory authorities to increase access to opioid treatment programs (OTPs) though the expansion of mobile vans and Medication Assisted Treatment in correctional facilities in the United States. 

Please support AATOD's mission by making an online donation ➡️ https://bit.ly/3uDOeDC #givingtuesday
  • Lev Facher represented a fair reporting of the current #methadone policy debate that took place at last week’s #STATSummit. 

“Mark Parrino, AATOD’s founder and president, cautioned during the panel that achieving sweeping change might not be so easy. The health system, he argued, is unprepared and even unwilling to make methadone a part of primary care. Potential obstacles, he said, include doctors’ lack of enthusiasm about prescribing methadone; pharmacists’ unwillingness to stock and dispense it; and drug manufacturers’ reluctance to manufacture and distribute it more widely, especially following the lawsuits and criticism many have experienced in the wake of the opioid crisis and the prescription opioid oversupply that accelerated it.” #morethanmedicine #opioidusedisorder #OpposetheMOTAA 

Read More ➡️ bit.ly/3tKb1gy
  • Earn up to 6 LADC & LPC CEU’s at 9th Annual OKATOD Conference, which is convening this Thursday, Oct 12th in Oklahoma City. 

This year, the focus turns to the paramount theme of #harmreduction and its profound role in ushering transformative pathways to #recovery.

Registration is now officially open, and you can secure your tickets promptly ➡️ bit.ly/45l3mm1

For more information, please visit www.okatod.org or send an email to a_rios@oktreatment.com.
  • Join OKATOD, one of AATOD’s state chapters, in Oklahoma City on Oct 12 as they convene their ninth annual OKATOD Conference. This year’s theme is HARM REDUCTION: A TRANSFORMATIVE APPROACH. 

Speakers include Mark Parrino (AATOD President), Maia Szalavitz, Teresa Stephensen, Dr. Larry Lovelace, Angela Harnden, Shajine Blake, and Jason Hall. 

Register ➡️ bit.ly/461CkkG
3/28 Expanding Access to #Methadone in Correctional Facilities will focus on opportunities to expand access to methadone in correctional facilities, including recent developments with the SAMHSA 2024 final rule on the use of methadone.

Register ➡️ bit.ly/3Vz1RPE
3/28 Expanding Access to #Methadone in Correctional Facilities will focus on opportunities to expand access to methadone in correctional facilities, including recent developments with the SAMHSA 2024 final rule on the use of methadone. Register ➡️ bit.ly/3Vz1RPE
2 days ago
View on Instagram |
1/10
Invitation to SAMHSA Webinars on 42 CFR Part 8 💻 

On February 2, 2024, the final rule for 42 CFR Part 8 was published. The effective date for these regulations is April 2, 2024, with an implementation date of October 2, 2024. 

In preparation for implementation of the revisions, SAMHSA will provide two preliminary webinars for OTPs.  The first will focus on administrative areas; the second will focus more on clinical content. These will be held on March 20th (from 2-3pm EST) and March 27th, 2024 (from 2- 3pm EST).  

REGISTER ➡ https://conta.cc/3TF9CSQ

View the final rule ➡ https://lnkd.in/e_iu-AtG.

There will be an opportunity to receive an overview of the rule changes and discuss with SAMHSA the implications of the changes. 

We encourage you to attend these important meetings to assist you in determining how you will need to prepare for full implementation of these regulations. 

This webinar series will be moderated by Mark W. Parrino, MPA (AATOD President). Speakers include Yngvild Olsen, MD, MPH (Director - CSAT), Robert Baillieu, MD, MPH, FAAFP (Physician and Senior Advisor - SAMHSA/CSAT, and Patti Juliana, PhD, LCSW
(Director - CSAT’s Division of Pharmacologic Therapies).

The presentations will be followed by Q&A, and these webinars will become available to the public for On-Demand viewing via the AATOD website. Certificates of Attendance will be provided per request.
Invitation to SAMHSA Webinars on 42 CFR Part 8 💻 On February 2, 2024, the final rule for 42 CFR Part 8 was published. The effective date for these regulations is April 2, 2024, with an implementation date of October 2, 2024. In preparation for implementation of the revisions, SAMHSA will provide two preliminary webinars for OTPs.  The first will focus on administrative areas; the second will focus more on clinical content. These will be held on March 20th (from 2-3pm EST) and March 27th, 2024 (from 2- 3pm EST).  REGISTER ➡ https://conta.cc/3TF9CSQ View the final rule ➡ https://lnkd.in/e_iu-AtG. There will be an opportunity to receive an overview of the rule changes and discuss with SAMHSA the implications of the changes. We encourage you to attend these important meetings to assist you in determining how you will need to prepare for full implementation of these regulations. This webinar series will be moderated by Mark W. Parrino, MPA (AATOD President). Speakers include Yngvild Olsen, MD, MPH (Director - CSAT), Robert Baillieu, MD, MPH, FAAFP (Physician and Senior Advisor - SAMHSA/CSAT, and Patti Juliana, PhD, LCSW (Director - CSAT’s Division of Pharmacologic Therapies). The presentations will be followed by Q&A, and these webinars will become available to the public for On-Demand viewing via the AATOD website. Certificates of Attendance will be provided per request.
1 week ago
View on Instagram |
2/10
Don’t miss out on the chance to show your support, share your products/services and secure your sponsorship at the AATOD 2024 Conference, �The world’s premier training conference event for the Treatment of Opioid Use Disorder. #aatod2024

The 2024 AATOD Conference will attract over 1,600 physicians, social workers, nurses, counselors, program administrators, executive directors, and other treatment providers from many countries. The registrants are decision-makers with purchasing power for their treatment centers and are looking for new products, services, and information to improve their patient treatment.

To become an exhibitor today —> https://bit.ly/48ZKMRX
Don’t miss out on the chance to show your support, share your products/services and secure your sponsorship at the AATOD 2024 Conference, �The world’s premier training conference event for the Treatment of Opioid Use Disorder. #aatod2024 The 2024 AATOD Conference will attract over 1,600 physicians, social workers, nurses, counselors, program administrators, executive directors, and other treatment providers from many countries. The registrants are decision-makers with purchasing power for their treatment centers and are looking for new products, services, and information to improve their patient treatment. To become an exhibitor today —> https://bit.ly/48ZKMRX
2 weeks ago
View on Instagram |
3/10
TREATING OPIOID USE DISORDER: SO MUCH MORE THAN MEDICATION

💻 View the latest Conference Video Message from AATOD's President, Mark W. Parrino bit.ly/48y815w,
for the most up-to-date details regarding the upcoming #aatod2024 Conference -
The world's premier training conference event for the treatment of Opioid Use Disorder. #OUD 

Registration ➡️ www.aatodconference.com
TREATING OPIOID USE DISORDER: SO MUCH MORE THAN MEDICATION 💻 View the latest Conference Video Message from AATOD's President, Mark W. Parrino bit.ly/48y815w, for the most up-to-date details regarding the upcoming #aatod2024 Conference - The world's premier training conference event for the treatment of Opioid Use Disorder. #OUD Registration ➡️ www.aatodconference.com
1 month ago
View on Instagram |
4/10
TREATING OPIOID USE DISORDER: SO MUCH MORE THAN MEDICATION #aatod2024

TODAY is the last day to take advantage of the discounted registration rate. #aatod2024 is the world’s premier training conference event for the treatment of #OUD.

For registration and hotel information ➡️ bit.ly/3Ue57Q6.

We look forward to seeing you in Las Vegas!
TREATING OPIOID USE DISORDER: SO MUCH MORE THAN MEDICATION #aatod2024 TODAY is the last day to take advantage of the discounted registration rate. #aatod2024 is the world’s premier training conference event for the treatment of #OUD. For registration and hotel information ➡️ bit.ly/3Ue57Q6. We look forward to seeing you in Las Vegas!
2 months ago
View on Instagram |
5/10
#aatod2024 Conference Update. Comprehensive Listing/Descriptions of Workshops, Posters, and Hot Topic Roundtable Conference Sessions are now available ➡️ http://bit.ly/3Ue57Q6.

The workshop committee is pleased to present a dynamic workshop lineup that includes extremely rich and diverse educational content for all disciplines. You will hear from experts who will share the latest research and developments relating to opioid use disorders and treatment. The workshop lineup will include state of the art information on diverse areas of focus such as patient care and best practices, building community partnerships and collaborations, public policy and regulatory changes, workforce development, quality assurance, and financial reimbursement. There will be workshops that focus on emerging treatment trends and developments such as the fentanyl epidemic, mobile opioid treatment programs, regulatory changes, expansion of treatment services in rural areas, integrating treatment with the corrections systems, and integrating harm reduction initiatives. For those newer to the field or those who want a refresher on the basics, we have once again included a “Foundations” track which will include selections on the fundamentals of medication assisted treatment.

The conference will continue to be the world’s premier training and education event for the treatment of opioid use disorders.  We hope to see you in Las Vegas!
#aatod2024 Conference Update. Comprehensive Listing/Descriptions of Workshops, Posters, and Hot Topic Roundtable Conference Sessions are now available ➡️ http://bit.ly/3Ue57Q6. The workshop committee is pleased to present a dynamic workshop lineup that includes extremely rich and diverse educational content for all disciplines. You will hear from experts who will share the latest research and developments relating to opioid use disorders and treatment. The workshop lineup will include state of the art information on diverse areas of focus such as patient care and best practices, building community partnerships and collaborations, public policy and regulatory changes, workforce development, quality assurance, and financial reimbursement. There will be workshops that focus on emerging treatment trends and developments such as the fentanyl epidemic, mobile opioid treatment programs, regulatory changes, expansion of treatment services in rural areas, integrating treatment with the corrections systems, and integrating harm reduction initiatives. For those newer to the field or those who want a refresher on the basics, we have once again included a “Foundations” track which will include selections on the fundamentals of medication assisted treatment. The conference will continue to be the world’s premier training and education event for the treatment of opioid use disorders. We hope to see you in Las Vegas!
2 months ago
View on Instagram |
6/10
Patient access to OTPs saves lives every day.

AATOD has been working with policymakers and regulatory authorities to increase access to opioid treatment programs (OTPs) though the expansion of mobile vans and Medication Assisted Treatment in correctional facilities in the United States. 

Please support AATOD's mission by making an online donation ➡️ https://bit.ly/3uDOeDC #givingtuesday
Patient access to OTPs saves lives every day. AATOD has been working with policymakers and regulatory authorities to increase access to opioid treatment programs (OTPs) though the expansion of mobile vans and Medication Assisted Treatment in correctional facilities in the United States. Please support AATOD's mission by making an online donation ➡️ https://bit.ly/3uDOeDC #givingtuesday
4 months ago
View on Instagram |
7/10
Lev Facher represented a fair reporting of the current #methadone policy debate that took place at last week’s #STATSummit. 

“Mark Parrino, AATOD’s founder and president, cautioned during the panel that achieving sweeping change might not be so easy. The health system, he argued, is unprepared and even unwilling to make methadone a part of primary care. Potential obstacles, he said, include doctors’ lack of enthusiasm about prescribing methadone; pharmacists’ unwillingness to stock and dispense it; and drug manufacturers’ reluctance to manufacture and distribute it more widely, especially following the lawsuits and criticism many have experienced in the wake of the opioid crisis and the prescription opioid oversupply that accelerated it.” #morethanmedicine #opioidusedisorder #OpposetheMOTAA 

Read More ➡️ bit.ly/3tKb1gy
Lev Facher represented a fair reporting of the current #methadone policy debate that took place at last week’s #STATSummit. “Mark Parrino, AATOD’s founder and president, cautioned during the panel that achieving sweeping change might not be so easy. The health system, he argued, is unprepared and even unwilling to make methadone a part of primary care. Potential obstacles, he said, include doctors’ lack of enthusiasm about prescribing methadone; pharmacists’ unwillingness to stock and dispense it; and drug manufacturers’ reluctance to manufacture and distribute it more widely, especially following the lawsuits and criticism many have experienced in the wake of the opioid crisis and the prescription opioid oversupply that accelerated it.” #morethanmedicine #opioidusedisorder #OpposetheMOTAA Read More ➡️ bit.ly/3tKb1gy
5 months ago
View on Instagram |
8/10
Earn up to 6 LADC & LPC CEU’s at 9th Annual OKATOD Conference, which is convening this Thursday, Oct 12th in Oklahoma City. 

This year, the focus turns to the paramount theme of #harmreduction and its profound role in ushering transformative pathways to #recovery.

Registration is now officially open, and you can secure your tickets promptly ➡️ bit.ly/45l3mm1

For more information, please visit www.okatod.org or send an email to a_rios@oktreatment.com.
Earn up to 6 LADC & LPC CEU’s at 9th Annual OKATOD Conference, which is convening this Thursday, Oct 12th in Oklahoma City. 

This year, the focus turns to the paramount theme of #harmreduction and its profound role in ushering transformative pathways to #recovery.

Registration is now officially open, and you can secure your tickets promptly ➡️ bit.ly/45l3mm1

For more information, please visit www.okatod.org or send an email to a_rios@oktreatment.com.
Earn up to 6 LADC & LPC CEU’s at 9th Annual OKATOD Conference, which is convening this Thursday, Oct 12th in Oklahoma City. This year, the focus turns to the paramount theme of #harmreduction and its profound role in ushering transformative pathways to #recovery. Registration is now officially open, and you can secure your tickets promptly ➡️ bit.ly/45l3mm1 For more information, please visit www.okatod.org or send an email to a_rios@oktreatment.com.
6 months ago
View on Instagram |
9/10
Join OKATOD, one of AATOD’s state chapters, in Oklahoma City on Oct 12 as they convene their ninth annual OKATOD Conference. This year’s theme is HARM REDUCTION: A TRANSFORMATIVE APPROACH. 

Speakers include Mark Parrino (AATOD President), Maia Szalavitz, Teresa Stephensen, Dr. Larry Lovelace, Angela Harnden, Shajine Blake, and Jason Hall. 

Register ➡️ bit.ly/461CkkG
Join OKATOD, one of AATOD’s state chapters, in Oklahoma City on Oct 12 as they convene their ninth annual OKATOD Conference. This year’s theme is HARM REDUCTION: A TRANSFORMATIVE APPROACH. Speakers include Mark Parrino (AATOD President), Maia Szalavitz, Teresa Stephensen, Dr. Larry Lovelace, Angela Harnden, Shajine Blake, and Jason Hall. Register ➡️ bit.ly/461CkkG
6 months ago
View on Instagram |
10/10

Invitation to SAMHSA Webinars on 42 CFR Part 8 💻
In preparation for implementation of the revisions, #SAMHSA will provide two preliminary #webinars for #OTPs - administrative areas & clinical content. Register ➡️ https://conta.cc/3TF9CSQ.

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