Pain and Addiction: More Than a Feeling Walter Ling, MD Integrated Substance Abuse Programs (ISAP) UCLA Dept. of Psychiatry Pacific Southwest ATTC Tenth Annual Training and Educational Symposium September 18, 2013 lwalter@ucla.edu www.uclaisap.org California Endowment Center Yosemite A. 1000 North Alameda St. 1

Pain and Addiction: Role of the Opioids Scope of the talk: Addiction: a brain disease On becoming and staying addicted Defining pain: acute and chronic pain Addiction in pain patients: how to tell Opioids: the two faces of Janus Opioids in chronic pain Overcoming addiction and chronic pain

Addiction: A Brain Disease What, Where, and How Our Three Brains Reptilian brain: Survival--feeding, fighting, fleeing, reproducing Limbic brain: memory and emotion—love, attachment, consideration for others, foundation for community and civilization Cortical brain: CEO and operating system--intelligence, intuition, insight flexibility, speed, efficiency, creativity, morality, free will, meaningful life, uniquely human, under construction Reptilian brain: a billion years ago, it does 4 things for survival. Next time we have a road rage, you’re operating your reptilian brain. To keep control: STOP—stop, take 3 deep breaths and smile, really smile, observe inside and out, proceed with reflection. Limbic brain: community and civilization made possible by love and attachment, care and consideration. People who need people are luckiest people..drama queen vs cold fish Cortical brain: CEO, uniquely human free will and creativity and morality. Still not finish, not sure where we are going.

Addiction: Why Do People Take Drugs? People Take Drugs To: Feel Good (Sensation seeking) Feel Better (Self medication) Dopamine One way or the other they like what drugs do to their brain 100 200 300 400 1 2 3 4 5 hr Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 100 200 300 400 500 600 700 800 900 1000 1100 1 2 3 4 5 hr Time After Amphetamine % of Basal Release AMPHETAMINE 100 150 200 250 1 2 3 4 5hr Time After Morphine % of Basal Release Accumbens 0.5 1.0 2.5 10 Dose (mg/kg) MORPHINE 100 150 200 250 1 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE How does it happen? Dopamine

Conditioned Response: Reward Driven Learning, Memory and Behavior Dopamine Dopamine: the brain’s motivational or “feel good” chemical. It makes us want to do it again—to repeat what activates its release Dopamine is also involved in reward-driven learning and memory: conditioning Conditioned Response: Reward Driven Learning, Memory and Behavior 1849-1936 Pavlov’s Dog Conditioned learning incorporates the drug use environment into drug use memories and adds weight –salience—to these memories, giving them higher priority in driving drug use behavior until it takes over everything. Dopamine is key to reward driven learning—conditioned response-- which creates hightened-value memory that determines the behavioral basis of addiction. Slide 2A trigger is a stimulus which has been repeatedly associated with the preparation for, anticipation of or the use of drugs and/or alcohol. These stimuli include drugs, cues, people, things, places, times of day, and emotional states. Conditioned response is reward-driven learning which involves dopamine. Definition of a trigger. (

How the Brain Got Its Addiction You begin with a normal brain and subject it to repeated exposures to drugs: dopamine spikes Repeated reward-driven, salient, learning experiences became encoded as enduring conscious and unconscious memories. The reward-driven salient drug use memories gain higher and higher priority in driving drug use behaviors until they take over everything—extreme take over. This is how the brain got its disease of addiction. How the addict got his brain disease “First the man takes a drink, then the drink takes a drink, then the drinks takes the man”. Japanese proverb Disconnection between the limbic and cortical brain, an extreme take over brain disease

Becoming and Staying Addicted: A Matter of Drugs and Memory Becoming addicted is a matter of drugs Staying addicted is a matter of memory The problem of addiction is not getting off drugs; it’s staying off drugs. Detoxification may be good for a lot of things, but staying off drugs is not one of them To stay off drugs—relapse prevention—you have to deal with drug memories: no memory, no relapse Relapse prevention means substituting drug memories with non-drug memories. Detoxification may be good for a lot of things, staying off drugs is not one of them Next time you talk about substitution therapy, remember it’s the memories, not the drugs, you are trying to substitute.

Defining Pain Pain: An unpleasant sensory and emotional experience arising from actual or potential tissue damage or described in terms of such damage. It is always subjective. Each individual learns the application of the word through experiences related to injury in early life.—IASP IASP = International Association for the Study of Pain Early life -- historical Experience--learned Subjective--private Individual--unique

Acute vs Chronic Pain: Acute Pain Physiological; protective Causes external; obvious Tissue damage; resolution expected within days/wks Symptom of illness Happens TO you Key issue: what pain? Meds/big role vs self Chronic Pain Pathological; non-protective Causes internal; obscured CNS changes; resolution depends on mastery/control Disease & way of life Happens IN you Key issue: what patient? Meds/limited role vs self The Acute pain patient is afflicted; the Chronic patient is transformed. Chronic pain sufferer suffers for nothing

When Pain Becomes Chronic The one certain thing: treatment didn’t work Patient frustrated and lost faith in doctors Patient blamed for not getting better Lost “role”; becomes dependent on others Others must pick up slack and provide support Patient feels neglected when others can’t do all Patient becomes anxious, angry and depressed Patient assumes life style of chronic pain Series of referral letters from surgeon: thank you ..sure will do well; surgery went well, expect return soon; healing fine, seem less than enthused about return to work; despite success, doesn’t seem motivated to return, obviously need psychiatrist.

Defining Addiction in Pain Patients Addiction….is characterized by behavior that includes one or more of the following: impaired Control over drug use, Compulsive use, Continued use despite harm, and Craving AAPM/APS/ASAM Addiction is not taking lots of drugs; it’s taking drugs and acting like an addict. Addicts are addicts not for who they are, but for what they do. The 4 C’s: Control, compulsion, Continued use, Craving; Plus Chronicity

Who’s at Risk and How to Tell? 4 Ways to identify patients at risk History—personal history and family history Screening instruments Behavioral checklists Therapeutic maneuver

Screening Instruments History What predicts addiction? Personal history of drug use Family history of drug use Current addiction to alcohol or cigarettes History of problems with prescriptions Co-morbid psychiatric disorders Same predictors as in non-pain patients Screening Instruments Several clinical tools are available that estimate risk of noncompliant opioid use1,2,3 The results determine how closely a patient should be monitored during the course of opioid therapy3 Scores implying a high risk of misuse are not reasons to deny pain relief3 1 Webster, et alr. Pain Med. 2005;6:432. 2 Coambs, et al. Pain Res Manage. 1996;1:155. 3 Butler, et al. Pain. 2004;112:65.

Opioid Risk Tool (ORT) Administration Scoring On initial visit Mark each box that applies: Female Male Family history of substance abuse Alcohol 1 3 Illegal drugs 2 3 Prescription drugs 4 4 Personal history of substance abuse Alcohol 3 3 Illegal drugs 4 4 Prescription drugs 5 5 Age (mark box if between 16-45 years) 1 1 History of preadolescent sexual abuse 3 0 Psychological disease ADO, OCD, bipolar, schizophrenia 2 2 Depression 1 1 Scoring totals: Administration On initial visit Prior to opioid therapy Scoring 0-3: low risk (6%) 4-7: moderate risk (28%) > 8: high risk (> 90%) Webster, et al. Pain Med. 2005;6:432.

Screener and Opioid Assessment for Patients in Pain (SOAPP) 14-item, self-administered form, capturing the primary determinants of aberrant drug-related behavior Validated over a 6-month period in 175 chronic pain patients Adequate sensitivity and selectivity May not be representative of all patient groups A score of ≥ 7 identifies 91% of patients who are high risk Butler, et al. Pain. 2004;112:65. SOAPP® V.1 – 24Q Butler S et al, Pain, 2005

Aberrant Drug-Taking Behaviors Probably less predictive Aggressive complaining about need for higher dose Drug hoarding during periods of reduced symptoms Requesting specific drugs Acquisition of similar drugs from other medical sources Unsanctioned dose escalation 1 – 2 times Unapproved use of the drug to treat another symptom Reporting psychic effects not intended by the clinician Probably more predictive Selling prescription drugs Prescription forgery Stealing or borrowing another patient’s drugs Injecting oral formulation Obtaining prescription drugs from non-medical sources Concurrent abuse of related illicit drugs Multiple unsanctioned dose escalations Recurrent prescription losses The problem with this is that the good predictors don’t happen very often; the common ones are not very predictive. Passik and Portenoy, 1998

Aberrant Behaviors in Cancer and AIDS However, even a simple count may be very usful. Passik et al. 2003

Probability of positive urine toxicology by number of aberrant behaviors Higher prevalence of SUD among pts on opioids for chronic pain than general population (8.1% current users) Katz N et al, Clin J Pain, 2002

Therapeutic Maneuver: Is the Pain Patient Addicted? Drug-seeking or increased requests for pain medication  Pathology/pain of new source Detailed pain work-up No new pain pathology  Opioid dose Improved functioning Absence of toxicity Unimproved functioning Presence of toxicity Therapeutic dependence Pseudoaddiction Addictive disease

Opioids in Chronic Pain: The Two Faces of Janus Relieve pain Relieve suffering Relieve misery Make you feel better Make you feel good Make you “high”

Use of Opioids for Chronic Pain

Treating Pain with Opioids: What Can We Expect to Achieve? Reduction in pain and suffering Meaningful pain reduction (Analgesia; Pain) Acceptable side effects (Adverse effects; Price) Improved functionality Meaningful functional improvement (Activities; Performance) No unacceptable aberrant behavior (Aberrant behavior; “Pees” The 4 A’s (Passik); the 4 “P’s”

Meaningful Pain Reduction Using a VAS or Numeric scale of 0-10 (4-6= mod pain; 7-10= severe pain) For Moderate pain ( mean=6) Meaningful reduction=2.4 (40%) Very much better=3.5 (45%) For Severe pain (mean=8) Meaningful reduction=4.0 (50%) Very much better=5.2 (56%) M. Soledad Cepeda et al. Proc 10th world Cong on Pain vol 24; pp 601-609 IASP press 2003

Meaningful Functional Improvement: My Favorites Patient perspective of “improvement” Used to do, can’t do now, would like to do again Could be physical, social, recreational With friends, family, church Achievable, enjoyable, and meaningful Hobbies Volunteer work Notice emphasis on new or renewed activities to rebuild a different new memory bank.

Chronic Pain and Suffering: Some Basics Chronic pain hurts, but seldom harms Chronic pain patients are not bothered by pain; they are plagued by suffering. Pain happens to you, suffering happens in you. Pain is the enemy outside; suffering is the demon within. Pain is inevitable and universal, suffering is optional and individual Pain can be likened to how much money you owe; suffering is how poor you feel. Suffering cannot be cured, it can only be conquered and mastered.

Chronic Pain and Addiction: Memory Matters Characterized by aberrant behaviors that persist despite their being destructive and detrimental to one’s best interest. Behaviors are based on a distorted belief system rooted in deeply ingrained learning and memory of past experiences. Both involve brain changes that result in the hyperexcitability of a lower brain and loss of control from a higher rational brain Neither can be gotten rid of but must be overcome with new and different reward-driven learning life experiences creating a new memory bank and a new belief system and new behaviors. We are all created equal, but we don’t sit down at the table with the same hand; hence, different clinical expressions. Series of referral letters from surgeon: thank you ..sure will do well; surgery went well, expect return soon; healing fine, seem less than enthused about return to work; despite success, doesn’t seem motivated to return, obviously need psychiatrist.

Chronic Pain and Addiction: Common Overlapping Features Early trauma Loss of mastery Loss of control Loss of sense of self Cognitive error “Personalization” Over interpretation “Catastrophization” Addiction Early trauma Loss of mastery Loss of control Loss of self-efficacy Cognitive error “Nirvana” Denial

Overcoming Chronic Pain The sufferer of chronic pain is permanently preoccupied by it and suffers as a result. Overcoming chronic pain means learning to overcome suffering, no matter what happens. Be prepared physically and emotionally Actually engage in the act and take charge Reconnect and become engaged with friends and family and community Regain a meaningful balanced life Business adventure as analogy; whether or not you make money depends on what you do after you start to work on it; but it’s chances of making money is a lot better if you go into it believing that you’ll be successful. And of course you have to actually do it.

How Not to Succeed 1. Don’t attend 2. Try not to learn anything 3. Don’t do any of the exercises 4. Don’t try any of the techniques 5. Keep a closed mind 6. Resist change 7. Look and act miserable 8. Tell yourself “nothing will help me” 9. Remain very serious and never smile 10. Don’t share anything (R. N. Jamison)

Relapse: A Three-Character Play Drug memories: …everything, seems to bring memories of you…(Eubie Blake) Cues and triggers: external and internal; craving and desire for love lost—regression & comfort Emotional buildup: justification for use—the internal dialogue making use okay and natural Relapse does not happen by accident.

Treating Chronic Pain and Relapse Prevention: Forget It? Addiction is memory; so is chronic pain No memory, no relapse; no memory, no suffering Both are brains transformed—cannot be gotten rid of, can only be conquered and controlled Both require memory substitution Behavior creates experience, experience creates memory, memory creates belief systems, belief systems determine new behavior, new behavior determines new outcome. Change your memory, change your brain, change your brain, change your life. The only way to have your life turn out different is to act differently. And we learn how learning and memory is the basis of relapse, which is what makes addiction a chronic relapsing brain disease. The protein Delta-Fos B produced after repeated exposure; once produced, switches on, regulates genes in Nu accumbens making it sensitive to glutamate which increases sensitivity to drugs. Everybody knows what craving is but no one can really define it. But we all know it has to do with relapse, triggered by drugs.cues, and stress. It began with the abused drugs increases DA in the mesolimbic reward circuit but it doesn’t stay there. With conditioned responses it became learned and is stored in memory and gives it added meaning and value; “value added memory” so to speak. Learning and memory extend beyond mesolimbic circuitry into dorsal striatum. Repeated esposure sensitize the neuronal circuitry not only increase the magnitude of the response but also gives it added value (salience) maiking it more desirable and moving from “liking” it from the drug effect into “wanting” it more and more and pretty soon it becomes all that matters is to seek drug and use. Craving: A strong desire or urge.

Creating Non-Drug Memories: The Old Fashion Way Experience–activities—leads to protein synthesis Protein synthesis activates new gene expressions Gene expressions create new brain connections New brain connections produce new memories New non-drug memories create non-drug belief systems that determine behaviors that determine how life turns out. The only way to change your life is to do things differently so they will turn out different. Forgetting old drug memories and creating non-drug memories the old fashion way.

Preventing Relapse: Eight Steps to a Drug-Free Life Sound physical health Sound mental health Stay off drugs and stay busy Take care of business: out of jail and on the job Take personal responsibilities Live in harmony with family and friends Be a good member of the community Search for a meaning in life. First ready yourself, then put the house in order, then govern the country, then conquer the world—Confucius If there be righteousness in the heart, there will be beauty in the character; If there be beauty in the character, there will be harmony in the home; if there be harmony in the home there will be order in the nation; if there be order in the nation, there will be peace in the world.

Spirituality, Mindfulness, and a Meaningful Life In a Nutshell Mindfulness of motivation: Doing good for someone else is better than feeling good yourself; it’s the true path to happiness. Mindfulness of wisdom: Conventional reality is an illusion; Inherent reality is emptiness. All things follow the laws of impermanence and non-self. Nothing lasts forever, nothing can be possessed, and you can’t take anything with you. To be successful in mindfulness you have to have a pretty sense of yourself, like what am I? Why am I here? Is there some purpose for me being here. Is it a miracle or a meaningless accident? If you think about it with all the things going around in the universe, the chance of your being here is nothing short of a true miracle, and that goes for everybody who is here. That alone should make us see ourselves differently and treat eachother differently. Then the two pillars of the mindfulness meditations will begin to make sense.

What Are We? Unique or Random? Thank you Thank you Thank you You are either a unique special being endowed with the dimensions of consciousness –your mind– and moral capacity, or are a random, accidental collections od DNAs and Genes with no purpose other than the biological imperative of reproduction. Your contribution to humanity, if any, is at best an acciedent waiting to happen—a mutaton--; and when it happens, what will you do? Chances are you wouldn’t matter but someone will try to pattern it and make a profit. Only you can decide, but whatever you decide will impact on the way you see yourself and treat others. To the Dalai Lama, some how it doesn’t make sense that the brightest of us who have learned and know so much about the mysteries of our brains and minds can accommodate the life view that things like the meaning of life and good and evil don’t matter. As we the Thais embark on a mission of helth reform. I hope we will remember that understanding of addiction as a brain disease should not just inform us, but should change us. In that respect I believe our tradition of humanistic aprroach to care based oncontemplative science has aleady put us ahead of the curve. I very much look forward to be part of that enterprise. Again, thank you for the opportunity to share with you a few of my thoughts.