neurobiology of opioid addiction & physical health … of opioid addiction & physical health...

1

Neurobiology of Opioid Addiction & Physical Health Impacts Thomas Kosten, M.D. Baylor College of Medicine

1

Faculty Disclosure

• Dr. Kosten—Speakers Bureau: Cephalon, Forest, Reckitt Benckiser; Consultant: Novartis, Bristol-Myers Squibb, Celtic, Alkermes, Synosia, Catalyst, Lannacher, Gerson Lerman Consultants

2

Addiction

• Chemical dependency is a compulsive, pathological, impaired control over drug use, leading to an inability to stop using drugs in spite of adverse consequences

3

Essential Definitions

• Physical Dependence: Pharmacologic effect characteristic of opioids; withdrawal or abstinence syndrome manifest on abrupt cessation of medication

• Tolerance: Pharmacologic effect characteristic of opioids; need to increase dose to achieve the same effect or diminished effect from the same dose

4

Essential Definitions

• Pseudo-Addiction: Pattern of drug-seeking behavior of pain patients receiving inadequate pain management that can be mistaken for addiction; resolves with re-establishing analgesia

5

Neurotransmitters

• Dopamine • Opioid • Glutamate • GABA • Cannabinoid • Norepinephrine

6

Drug Abuse

Acute Effects

• Positive Effects • Reward • Reinforcement

Chronic Effects

• Tolerance • Dependence • Sensitization

7

Drug Abuse

• Addiction • Detoxification-Withdrawal • Craving • Relapse

8

Current Theory: Reward Pathway

• There is reward pathway in the brain which is activated by – Food, water and sex – Nurturing and caring for others – “Thrills” – Exercise

• This reward pathway is also activated by – Drugs, including alcohol – Gambling

• Project Cork

9

Presenter

Presentation Notes

The reward pathway, or pleasure center is activated as part of life and can be activated by drugs, gambling, thrills ( adrenaline junkies, roller coasters, merry go rounds)

Neural Circuitry of Reward

• Present in all animals • Produces pleasure for

behaviors needed for survival:

• eating • drinking • sex • Nurturing Project Cork

10

All drugs of abuse bind to the neural circuitry of reward

11

12

Presenter

Presentation Notes

Slide 30: Summary; addictive drugs activate the reward system via increasing dopamine neurotransmission In this last slide, the reward pathway is shown along with several drugs that have addictive potential. Just as heroin (morphine) and cocaine activate the reward pathway in the VTA and nucleus accumbens, other drugs such as nicotine and alcohol activate this pathway as well, although sometimes indirectly (point to the globus pallidus, an area activated by alcohol that connects to the reward pathway). While each drug has a different mechanism of action, each drug increases the activity of the reward pathway by increasing dopamine transmission. Because of the way our brains are designed, and because these drugs activate this particular brain pathway for reward, they have the ability to be abused. Thus, addiction is truely a disease of the brain. As scientists learn more about this disease, they may help to find an effective treatment strategy for the recovering addict.

13

Presenter

Presentation Notes

Slide 16: Positron emission tomography (PET) scan of a person on cocaine Cocaine has other actions in the brain in addition to activating reward. Scientists have the ability to see how cocaine actually affects brain function in people. The PET scan allows one to see how the brain uses glucose; glucose provides energy to each neuron so it can perform work. The scans show where the cocaine interferes with the brain's use of glucose - or its metabolic activity. The left scan is taken from a normal, awake person. The red color shows the highest level of glucose utilization (yellow represents less utilization and blue shows the least). The right scan is taken from a cocaine abuser on cocaine. It shows that the brain cannot use glucose nearly as effectively - show the loss of red compared to the left scan. There are many areas of the brain that have reduced metabolic activity. The continued reduction in the neurons' ability to use glucose (energy) results in disruption of many brain functions.

1-2 Min 3-4 5-6

6-7 7-8 8-9

9-10 10-20 20-30

Your Brain on Drugs

14

Presenter

Presentation Notes

Slide 7: This is literally the brain on drugs. When someone gets “high” on cocaine, where does the cocaine go in the brain? With the help of a radioactive tracer, this PET scan shows us a person’s brain on cocaine and the area of the brain, highlighted in yellow, where cocaine is “binding” or attaching itself. This PET scan shows us minute by minute, in a time-lapsed sequence, just how quickly cocaine begins affecting a particular area of the brain. We start in the upper left hand corner. You can see that 1 minute after cocaine is administered to this subject nothing much happens. All areas of the brain seem to be functioning normally. But after 3 to 4 minutes [the next scan to the rightl, we see areas highlighted in yellow where cocaine is starting to bind to the striatum [stry-a-tum] of the brain and activate it. At the 5- to 8-minute interval, we see that cocaine is affecting a large area of the brain. After that, the drug’s effects begin to wear off. At the 9- to 10-minute point, the high feeling is almost gone. Unless the abuser takes more cocaine, the experience is over in about 20 to 30 minutes. Scientists are doing research to find out if the striatum produces the “high feeling”and controls our feelings of pleasure and motivation. One of the reasons scientists are curious about specific areas of the brain affected by drugs such as cocaine is to develop treatments for people who become addicted to these drugs. Scientists hope to find the most effective way to change an addicted brain back to normal functioning. Photo courtesy of Nora Volkow, Ph.D. Mapping cocaine binding sites in human and baboon brain in vivo. Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, Macgregor RIR, Hitzemann R, Logan J, Bendreim B, Gatley ST. et al. Synapse 1989;4(4):371-377.

Normal

Cocaine Abuser (10 da)

Cocaine Abuser (100 da)

Your Brain After Drugs

15

Presenter

Presentation Notes

Slide 8: Long-term effects of drug abuse. This PET scan shows us that once addicted to a drug like cocaine, the brain is affected for a long, long time. In other words, once addicted, the brain is literally changed. Let’s see how... In this slide, the level of brain function is indicated in yellow. The top row shows a normal-functioning brain without drugs. You can see a lot of brain activity. In other words, there is a lot of yellow color. The middle row shows a cocaine addict’s brain after 10 days without any cocaine use at all. What is happening here? [Pause for response.] Less yellow means less normal activity occurring in the brain—even after the cocaine abuser has abstained from the drug for 10 days. The third row shows the same addict’s brain after 100 days without any cocaine. We can see a little more yellow, so there is some improvement— more brain activity—at this point. But the addict’s brain is still not back to a normal level of functioning. . . more than 3 months later. Scientists are concerned that there may be areas in the brain that never fully recover from drug abuse and addiction. Photo courtesy of Nora Volkow, Ph.D. Volkow ND, Hitzemann R, Wang C-I, Fowler IS, Wolf AP, Dewey SL. Long-term frontal brain metabolic changes in cocaine abusers. Synapse 11:184-190, 1992; Volkow ND, Fowler JS, Wang G-J, Hitzemann R, Logan J, Schlyer D, Dewey 5, Wolf AP. Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse 14:169-177, 1993.

All drugs of abuse increase dopamine in the nucleus accumbens

• alcohol • cocaine • heroin • marijuana • nicotine

• amphetamines • sedatives • hallucinogens • pcp

16

Definition

• “Addiction is a cycle of spiraling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug taking” George Koob

17

Compulsion to use The brain is altered by abuse of a psychoactive chemical and use becomes the only way to experience feeling good or normal

– No one ever starts drinking or using a drug intending to become an alcoholic or drug addicted

– The focus of life is on obtaining access to, using, and recovering from a chemical that makes you high….OR IN THE END TO AVOID WITHDRAWAL OR FEEL NORMAL

– Everything—social time, job performance, recreational opportunities—are given up or reduced because of this focus

18

Medical History Associated with Substance Abuse

• Medical history findings associated with substance abuse: hepatitis C, HIV, TB, cellulitis, sexually transmitted diseases, elevated liver function tests

• Social history: motor vehicle accidents, DUIs, domestic violence, legal history, loss of property in fire

• Psychiatric history

19

Clinical Assessment: Psychosocial History

• Current psychiatric symptoms • History of addictive disease • Change in social function

– work – family and relationships – recreation

• Medical-legal status

20

Pain and Addiction

• Nearly 1/3 of the US population has used illicit drugs and an estimated 6-15% have a substance abuse disorder of some type

• An individual with chronic pain AND untreated addictive disease WILL NOT get better with an opioid prescription

21

Pain History

• Provocative or Palliative Features • Quality • Radiation • Severity • Timing

22

Predictors of Opioid Misuse

• Behavior that Suggests Addiction – Multiple episodes of prescription “loss” – Repeatedly seeking prescriptions from other clinicians or

from the emergency rooms without informing prescriber, or after warnings to desist

– Evidence of deterioration in the ability to function at work, in the family , or socially, which appears to be related to drug use

– Repeated resistance to changes in therapy despite clear evidence of adverse physical or psychological effects from the drug

– Positive urine drug screen-other substance abuse

23

Predictors of Opioid Misuse

• Dangerous Behavior – Motor vehicle crash/arrest related to opioid or

illicit drug or alcohol intoxication effects – Intentional overdose or suicide attempt – Aggressive/threatening/belligerent behavior in

the clinic

24

Define Your Role in Medication Prescribing

25

Patient Medication Agreement

• A patient medication agreement establishes clear expectations between physician and patient and specifies – purpose of opioid therapy – side effects – treatment goals – physician’s role in responsible opioid prescribing – patient’s role in responsible opioid use

26

Opioid Agreement

• Opioid prescriptions are provided by only one Provider

• Patients agree not to ask for opioid medications from any other doctor without the knowledge and assent of the provider

• Patients agree to keep all scheduled medical appointments

• Urine drug screens will be obtained as indicated

27

Opioid Agreement

• Patients agree to comply fully with all aspects of the treatment program including behavioral medicine and physical therapy if recommended

• A prohibition on use with alcohol, other sedating medications or illegal medications

• Agreement not to drive or operate heavy machinery until medication-related drowsiness is cleared

28

Adjuncts and Alternatives to Opioid Therapy

• Antidepressants • NSAIDS • Anticonvulsants • Acetaminophen • Muscle Relaxers • Tramadol • Medications for sleep • Topical Agents

• Heat • Prosthetic supports • Physical therapy • Exercise • Cognitive-behavioral

therapy • Interventional Pain

Management • TENS Unit • Orthopedic Consultation

29

Exercise is important for everyone

30

Don’t Forget to Look at Lifestyle

31

Don’t forget about lifestyle changes

32

Monitoring – Opioid Treatment Guidelines

• Clinicians should reassess patients on COT periodically as warranted by changing circumstances. Monitoring should include documentation of pain intensity and level of functioning, assessment of progress toward achieving therapeutic goals, presence of adverse events, and adherence to prescribed therapies.

33

Urine Drug Screen

• Urine drug screens typically check for evidence of opiate, alcohol, benzodiazepine, cocaine, marijuana, amphetamine and barbiturate use

• Some opiates may need to be specifically requested such as oxycodone, fentanyl, and methadone

35

Length of Time Drugs of Abuse Can Be Detected in Urine • Alcohol 7-12 hours • Amphetamine 48 hours • Barbiturate 24 hours to 3 weeks • Benzodiazepines 3 days to 1 month • Cocaine 3 days • Marijuana 3 days to over 1 month • Opioids 48 hours to 4 days

36

Urine Drug Screens

Parameter Diluted Adulterated

Creatinine Less than 20 ph Less than 3

Greater than 11 s.g. Less than 1.003 nitrite Greater than

500

40

Substances that can be detected with u/a, color check and temperature • Bleach • Table salt • Laundry detergent • Toilet bowl cleaner

41

Aberrant Behavior that Requires Attention

• Aggressive complaining about needing more of the drug

• Drug hoarding during periods of reduced symptoms • Requesting specific drugs • Openly acquiring similar drugs from other medical

sources • Unsanctioned dose escalation or other

noncompliance with therapy on one or two occasions

42

Aberrant Behavior that Requires Attention

• Unapproved use of the drug to treat other symptoms • Reporting psychic effects not intended by the

clinician • Resistance to a change in therapy associated with

adverse effects • Missing appointments • Not following other components of the treatment

plan (physical therapy, exercise, etc)

43

Rationale for a primary care based chronic pain program Patients who do not follow-up with pain

consultation are at high risk for substance abuse diversion psychiatric illness They frequently come back to the primary care

provider demanding opiate therapy for their chronic pain

44

Problems with high risk patients in a typical primary care visit • Time constraints attempting to provide

primary care, adequate pain control, pain education

• Disruptive behavior related to patient attempts to get inappropriate opiate prescriptions

• Increased stress on the primary care providers which further limits their ability to care for other patients in the clinic

45

Pitfalls that need to be (are being) addressed

• The need for a more comprehensive and possibly supervised drug screen for patients at the highest risk for problems

• The need for greater non-narcotic formulary options for pain and/or mechanisms set up for greater dialogue between pharmacy and primary care when attempting non-formulary requests for opioid sparing medications, including antidepressants

• The need for treatment options for patients with Substance abuse with a high degree of denial about their problem and/or who are in need of inpatient services

46

Opioid Related Adverse Effects-Opioid Guidelines • Clinicians should anticipate, identify, and treat

common opioid-associated adverse effects.

47

Opioid Adverse Effects: Therapeutic Complications

• Hyperalgesia • Hypogonadism • Sedation • Cognitive Impairment • Constipation • Nausea/Vomiting • Pruritis • Respiratory Depression • Central Sleep Apnea

48

Effects of Opioid Treatment

• Long-term opioid treatment is associated with the development of tolerance to its analgesic effects

• Evidence is accumulating that opioid treatment may also paradoxically induce abnormal pain sensitivity, including hyperalgesia and allodynia. Thus, increasing opioid doses may not improve pain control and function

49

Is Drug Addiction Treatment Worth The Cost? • Drug addiction treatment is cost-effective in reducing

drug use and its associated health and social costs. – Each dollar invested in treatment yields between $4-7 in

reduced crime, court, and theft costs. – If health care savings are included as well, each dollar

invested in treatment saves up to $12. (Chevron Study) – Medical insurance premiums cost for unlimited treatment

increases costs by only 2 cents per day. (Rand Study)

50

Addiction Treatment Works

• If you apply the same principles to the disease of addiction that you would use to treat any other chronic illness, you will find that the disease of addiction will respond to that treatment just as any other chronic illness would respond.

51

Some Useful Websites

• www.painedu.com • www.projectcork.org • www.asam.com • www.globalrph.com • www.jpain.org • www.ampainsoc.org

52

http://www.painedu.com/

http://www.projectcork.org/

http://www.asam.com/

http://www.globalrph.com/

http://www.jpain.org/

http://www.ampainsoc.org/

neurobiology of opioid addiction & physical health … of opioid addiction & physical health...

Documents