Client H was a 27 year old, white female who entered treatment for polysubstance abuse and bipolar disorder November 2008. Her substances of choice were opiates (heroin), stimulants (crack) and benzos (xanax). She weighed 135 lbs, with a 61in height on a small frame, upon arriving in treatment. She entered treatment 2 years following a gastric bypass procedure.
Prior to surgery, Client H weighed 293 lbs. She admitted to abusing alcohol and occasional marijuana use prior to surgery in October of 2006. Client H underwent gastric bypass at 25 years of age. Following the surgery, she found that she could no longer drink sufficient quantities of alcohol to produce the results that she desired and became addicted to the pain medication that she was prescribed for post operative pain.
During the two years that followed her surgery, she progressed from prescription medications to street drugs. She began using cocaine because she found that she had no energy as a result of both the opiates and the probable malnutrition induced by the surgery. Crack was a natural progression from cocaine and heroin use supplemented then replaced prescription opiates.
As of December 2010, Client H has nearly 2 years clean and sober. She relapsed twice during the first 90 days after treatment. Currently, Client H has been using amino acids to manage her bipolar symptoms.
Client M was a 47 year old, white female who entered treatment for polysubstance abuse, bipolar disorder and anxiety disorder. Her substances of choice were alcohol, pain pills and cocaine. Client M entered treatment in February of 2010 weighing 235 pounds three (3) years following lapband surgery in October of 2007.
Prior to surgery she weighed 285 pounds. She has been to treatment five times before and admits to abusing pain pills prior to surgery. Her lowest weight after surgery was 200 pounds.
She currently has 10 months clean and sober and is using amino acids to manager her bipolar symptoms and anxiety.
J is a 44 year old morbidly obese female who suffers from hypertension, type 2 noninsulin dependent diabetes, obstructive sleep apnea and lower extremity venous stasis. In the past she has been hospitalized for recurrent cellulitis and received IV antibiotics. She also suffers from long term chronic low back and knee pain and had been a patient in our pain management program for several years. During this time her pain has been marginally controlled. Her physical examination and radiologic studies suggests degenerative disc disease, facet joint arthropathy and osteoarthritis. Her treatment plan included, weight loss, physical therapy, and interventional modalities. After trying several nonopioid medications and adjuncts, her regimen progressed to include chronic opioid therapy which provided moderate relief and improved function. Her medicinal regimen consisted of pregabalin 75 mg TID, duloxitine 60 mg/day, as well as time-release oxymorphone and one or two rapid onset short acting opioids for episodic breakthrough pain. Her compliance with this regimen had been exceptional with appropriate pill counts. It was common for her to have leftover breakthrough pain pills each month. She reported minimizing the use of breakthrough opioid analgesics because she did not like the way they made her feel. As a result, her breakthrough medications often required no refill. Her random drug screens were always appropriate.
J reported being overweight as far back as she could remember. She suffered from low self esteem which she attributed to being overweight. At the time of the bariatric surgery evaluation her weight was 348 lbs. In the past she had attempted numerous diets with limited success. She smoked tobacco and had seriously attempted to quit “on multiple occasions” without success. She admitted to worrying about the possibility of gaining weight with smoking cessation. Her sister, father and husband smoke cigarettes were all overweight. She has no history of compulsive behaviors other than overeating. J reported overeating especially when anxious or depressed and experienced significant guilt afterwards. She reported that she rarely felt satiated with normal proportions. She had a history of depression for which she was in remission. She had a stable marriage, no children and was employed as a registered nurse in a hospital cancer ward.
Because her weight was contributing significantly to her many medical as well as chronic pain problems, J was evaluated for bariatric surgery. After successfully completing the pre-surgery screening and educational program, J underwent successful gastric bypass surgery and had an uneventful postoperative course. When she followed up at our pain clinic approximately three weeks after her surgery she had already lost fourteen pounds. She continued to lose weight over the next 8 months and though we expected this weight loss to have a positive effect on pain control, J consistently complained of increased knee and back pain and insisted on continuing tid breakthrough medications. She called our clinic on several occasions requesting early appointments due to scheduling conflicts with her work and family obligations. Unlike prior t surgery, J also forgot to bring her pill bottles with her to appointments for counting as is our practice.
Months later a random urine drug screen was repeated. This was appropriate for her controlled release medication, though her breakthrough was absent. Her explanation for this absence was she had not needed it for the several days prior to her appointment and therefore the drug levels must have dropped to undetectable. Several months later another point-of-contact random drug screen was positive for benzodiazepines. At first she insisted that this was an error. However, she finally admitted taking a single clonazepam several days prior to the appointment for anxiety. She said this pill was leftover from a very old prescription that she had failed to discard. Instead of clonazepam. GC/MS confirmation testing which returned several days later was positive for alprazolam metabolites, as well as ethyl glucuronide (ETG), a test indicative of alcohol consumption within the past several days. Though not precisely correlated with the degree of alcohol consumption, her level of 25,000 was well beyond our cutoff of 1000 ng/dl. Since the ingestion of controlled medications and alcohol consumption was a violation of her opioid agreement, J was called and told to come in immediately.
At first J denied the validity of the results, however when confronted with the possibility of clinic discharge she admitted to taking an occasional Xanax that she obtained from a “friend” and “ had an occasional drink” for anxiety. After a long discussion of the dangers of combining benzodiazepines with opioids, especially with coexisting obstructive sleep apnea and reviewing clinical policies with her, J agreed to follow-up ASAP with psychiatry for evaluation and appropriate treatment of her anxiety. She assured us that this would not happen again. She kept her psychiatry appointment the following week and her psychiatrist increased her duloxitine to 90 mg/day, her pregabalin to 100 mg tid, and arranged for her to receive counseling and begin cognitive behavioral therapy. Later that same week our clinic received a message from J stating that her medications had been stolen the previous evening and requesting a replacement prescription. She also reminded us that this had never happened in the past. She was told to bring in a police report. When she arrived, she requested the prescription and became angry when told that she needed to sign in for a full appointment and a discussion of events with her doctor. Her vital signs were significant for an increased heart rate and elevated blood pressure. Her pupils were dilated and she seemed agitated. When told that she needed to provide urine for a repeat drug screen, J became extremely angry, and stated that she had suffered from the flu and had been experiencing diarrhea and GI distress and was probably too dehydrated to provide a urine sample. We explained that this was an absolute requirement, and had her sit in the waiting room and drink water until she was able to do so. The urine she provided was noted to be very dilute, not much above room temperature and negative for all drugs. When confronted with these results, she became upset and finally admitted that her medications had not been stolen but that she had actually overused them and that she had run out early. Furthermore J confessed that she has been going to another pain clinic and obtaining additional opioid medications. She demanded that we just transfer her care there. When we stated that we needed to call them to discuss these events, she broke down and admitted that she felt that she had developed a problem with alcohol and opioids, and had been drinking heavily for the past six months and concealing it from her family. She stated that she tried to quit drinking alcohol after her recent positive urine drug screen but developed “jitters” and nausea. She also admitted that she had been taking Xanax several times a day for the past few months. She had also been overeating constantly. Finally, she confessed that her pain had actually improved along with her weight loss, however she had embellished her symptoms because the pain medications seemed to elevate her mood and she felt that she could not do without them. She admitted that she felt unhappy, that her life was out of control and was experiencing feelings of guilt surrounding her deceptive behavior and recently had been experiencing suicidal ideation. J wanted help and agreed to be immediately admitted to our drug detoxification facility. While in detox, she also admitted that she had recently begun diverting dilaudid while at work and that one of her coworkers recently approached her asking if everything was OK. She felt that it was just a matter of time before she was discovered. She agreed to sign a contract with the state’s recovering nurses program.
While in treatment, J was placed on buprenorphine for pain, embraced the diagnosis of addiction, began going to AA and NA meetings, and obtained a sponsor who is guiding her through the 12 steps of alcoholics anonymous. Her anxiety and depression has improved and she has continued to participate in outpatient cognitive/behavioral therapy. Her weight loss has been slow but steady, and her compliance in our pain clinic has been 100%. She has been participating several times a week in aqua therapy. At this time J continues to take sublingual buprenorphine at a dose of four milligrams every eight hours. Her weight is now 214 lbs and she has signed a five year contract with the impaired nurse monitoring program and is optimistic about being allowed to return to work.
Fifty-five year old man who weighed 423 lbs prior to gastric bypass surgery. He had a BMI of 63. He has done well after surgery and now weighs 180 lbs. He has transferred his food addiction to exercise. He runs jogs and exercises religiously five times per week. He has already run 2 half marathons and plans to run a full marathon (26 miles) in a few months. This is an example of a positive transfer addiction.
Forty year old female who had a lap gastric bypass for a BMI of 44 five months ago. Post operatively has been non compliant with her vitamins and has begun to smoke and drink coffee excessively. Despite smoking cessation counseling, she continues to use tobacco. She has been explained the increased risk of marginal ulcer in gastric bypass patients who smoke.
Because of these new phenomena it is generally agreed by bariatric surgeons across America that comprehensive physical and psychological pre-operative assessments combined with continued medical care and counseling post-operatively are critical for assuring the best possible outcome for patients who undergo bariatric surgery. Prospective patients may have a previous or current history of various mental health disorders, including binge eating or addictions to cigarettes, alcohol, drugs or other illegal substances; active substance abuse is generally considered a reason to exclude a patient from surgery. However, the pre-surgical screening programs such as genetic testing may in the not too distant future help identify persons affected by such problems [23
] and allow them to receive treatment so that they can overcome the addiction and then be considered for bariatric surgery in the future.
Common dopaminergic mechanism of food and drug craving behavior
Certainly, overeating in obese individuals share similarities with the loss of control and compulsive drug taking behavior observed in drug-addicted subjects. The mechanism of these behaviors is not well understood. However, recent studies by Wang et al. [24
] with positron emission tomography (PET) in drug-addicted subjects documented reductions in striatal dopamine (DA) D2 receptors. In pathologically obese subjects, the same researchers [25
] found reductions in striatal DA D2 receptors similar to that in drug-addicted subjects. Moreover, DA D2 receptor levels were found to have an inverse relationship to the body mass index of the obese subjects. Wang et al [25
] postulated that decreased levels of DA D2 receptors predisposed subjects to search for reinforcers; in the case of drug-addicted subjects, the drug and in the case of the obese subjects, food as a means to temporarily compensate for a decreased sensitivity of DA D2 regulated reward circuits. Understanding the mechanisms involved in food intake will help to suggest strategies for the treatment of obesity. This understanding has been researched by Stice and associates revealing that carriers of the DRD2 A1 allele show a blunted reward circuitry response to palatable food and that carriers of the polymorphisms of the D2 and the D4 genes with a blunted response gain weight in a one-year follow –up [26
Furthermore, diminished dopaminergic neurotransmission contributes to decreased reward and negative eating behaviors in obesity. While Bariatric surgery is the most effective therapy for obesity and rapidly reduces hunger and improves satiety through unknown mechanisms little is known about dopaminergic activity following this surgical procedure. Volkow et al [29
] hypothesized that dopaminergic neurotransmission would be affected after Roux-en-Y-Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG) surgery and that these changes would influence eating behaviors and contribute to the positive outcomes from bariatric surgery. In their study, body weight decreased as expected after surgery. DA D2 receptor availability decreased after surgery. Regional decreases (mean+/−SEM) were caudate 10+/−3%, putamen 9+/−4%, ventral striatum 8+/−4%, hypothalamus 9+/−3%, substantia nigra 10+/−2%, medial thalamus 8+/−2%, and amygdala 9+/− 3%. These were accompanied by significant decreases in plasma insulin (62%) and leptin (41%).
Volkow et al. [29
] points out that decreases in DA D2 receptor availability after RYGB and VSG most likely reflect increases in extracellular dopamine levels. Enhanced dopaminergic neurotransmission may contribute to improved eating behavior (e.g. reduced hunger and improved satiety) following these bariatric procedures. However, it might also reflect a decrease in brain D2/D3 receptor availability in the longer term which will enhance addiction liability and lead to aberrant drug seeking behavior as an addiction transfer or even cross tolerance. These findings may have real importance in explaining in part the increased risk for drug seeking behavior following bariatric surgery. However, it is our hypothesis herein that the real culprit may reside in a condition we have coined called RDS and the genetic antecedents thereof [30
Neurogenetics of RDS as an antecedent to food and drug cravings
One new hypothesis for epidemic obesity is food addiction, which is associated with both substance-use and eating disorders. Emerging evidence has shown that there are many neural, hormonal and genetic pathways and antecedents that are shared. Functional neuroimaging studies have revealed that reinforcing food has characteristics similar to that of drugs of abuse. Moreover many of the brain changes reported for hedonic eating and obesity are also seen in various forms of addiction. A consensus of the literature suggests that overeating and obesity may have an acquired drive like drug addiction with regard to motivation and incentive, craving, wanting, and liking. These behavioral elements occur after early and repeated exposures to stimuli. Liu et al [31
] concluded that the acquired drive for food and the relative weakness of the satiety signal would cause an imbalance between the drive and the hunger/reward centers in the brain and their regulation.
Warren and Gold [32
] pointed out the relationship between obesity and drug abuse in response to a paper by Kalarchian et al. [33
] who found that approximately 66% of the participants had a lifetime history of at least one axis I disorder, and 38% met diagnostic criteria at the time of preoperative bariatric surgery evaluation. In addition, 29% met criteria for one or more axis II disorders. Axis I psychopathology, but not axis II, was positively related to BMI, and both axis I and axis II psychopathology were associated with lower scores on the Medical Outcomes Study 36-item Short-Form Health Survey. It was concluded current and past DSM-IV psychiatric disorder (including a number of addictive behaviors) are prevalent among bariatric surgery candidates and are associated with greater obesity and lower functional health status, highlighting the need to understand potential implications for surgery preparation and outcome.
Certainly, eating behaviors are similar to those of other addictions since both affect the levels of dopamine in the meso-limbic dopaminergic system [34
]. It is well established that there is an increased prevalence in obese individuals carrying the DRD2 Taq A1 allele [35
] and this allele has been linked to low levels of D2 receptors in obese individuals [40
In order to investigate the prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with and without comorbid substance use disorder, Blum et al [44
] investigated a total of 40 patients, from an outpatient neuropsychiatric clinic in Princeton, New Jersey, by genotyping for the presence or absence of the Taq I DRD2 A1 allele. The prevalence of the Taq I A1D2 dopamine receptor (DRD2) alleles was determined in 40 Caucasian obese females and males. In this sample with a mean BMI of 32.35 +/− 1.02, the A1 allele of the DRD2 gene was present in 52.5% of these obese subjects. Furthermore, they found that in the 23 obese subjects possessing comorbid substance use disorder, the prevalence of the DRD2 A1 allele significantly increased compared to the 17 obese subjects without comorbid substance use disorder. The DRD2 A1 allele was present in 73.9% of the obese subjects with comorbid substance use disorder compared to 23.5% in obese subjects without comorbid substance use disorder. Moreover, when we assessed severity of substance usage (alcoholism, cocaine dependence, etc.) increasing severity of drug use increased the prevalence of the Taq I DRD2 A1 allele; where 66.67% (8/12) of less severe probands possessed the A1 allele compared to 82% (9/11) of the most severe cases. Linear trend analyses showed that increasing use of drugs was positively and significantly associated with A1 allelic classification (p < 0.00001). These preliminary data suggest that the presence of the DRD2 A1 allele confirms increased risk not only for obesity, but also for other related addictive behaviors further supporting the commonality between food and drug addiction. Therefore, these individuals use food to raise their dopamine levels initially through positive reinforcement but secondary because of a blunted reward circuitry response to palatable food as pointed out by Stices group [26
] which causes a weak satiety signal leading to weight gain. Certainly it has been shown that the activity of dopamine in the brain can be related to abnormal eating behavior, binge eating and other eating disorders including bulimia [45
]. In terms of genetics and eating disorders there have been a number of association studies linking various type of eating disorders with candidate gene polymorphisms: serotonergic [48
], opiate receptors and peptides [52
] and GABA [58
It is known that many genes are involved in complex behavioral disorders including addictive behaviors Li et al. [61
] performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones. In their gene map they found that all roads lead to two common neurotransmitters glutamate and dopamine.
Thus the key neurotransmitter of addiction, DA, has site specific action regulating the intake of food and it reinforces the effects of food [62
]. As Stice et al. [63
] and others [64
] have suggested dopamine is necessary to begin the meal process. It acts upon the prefrontal area, ventral medial hypothalamus and the arcade nucleus to reduce the intake of food and prevent hyperphagia, which in turn is influenced by leptin, insulin and other hormones [64
]. Blum and Gold [65
] have inferred that disruptions in DA function may predispose certain individuals to addictive behaviors and obesity.
Animal models of food addiction
Interestingly, animal models have shown that the predisposition to food addiction in offspring was caused by feeding rat mothers junk food consisting of fatty, sugary, and salty snacks during pregnancy and lactation [67
]. Rat offspring showed increased weight gain and BMI compared to controls, while their mothers displayed bingeing and overeating junk food [67
]. These observations may have relevance to pregnant mothers following Bariatric surgery in terms of diet in order for them to have healthy children with normal appetites and weight. While a healthy diet during pregnancy is advocated, the problem may be more complex. One must also consider the potential effect of hypodopaminergic genetics in the pregnant mother which could oppose the advocacy of a healthy diet in the long term. Avena et al. [68
] found clear evidence that sugar has addictive attributes since it releases both opioids and dopamine, which are characteristic of addiction neurochemicals. Moreover, the same authors [68
] classified sugar as an addictive substance because it follows the typical addiction pathway that according to Blumenthal and Gold [69
] and Liu et al [31
] consists of binging, withdrawal, craving and cross –sensitization. In fact cross-sensitization was observed in rats showing the movement from sugar to drugs [70
]. Surprisingly recent work by Cantin et al. [71
] found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative (Saccharin). Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories. Most importantly Koob and Le Moal [72
] suggest that sensitization and cross tolerance are necessary for the initiation of any form of addiction and as such sugar fits this model.
In terms of withdrawal it is of interest that the withdrawal from sugar induces imbalances in both acetylcholine and dopamine similar to opiate withdrawal. Specifically, Avena et al [73
] found that rats undergoing withdrawal from sugar bingeing using microdialysis revealed a concomitant increase in extracellular acetylcholine and decrease in dopamine release in the nucleus accumbens shell. The findings suggest that a diet of bingeing on sucrose and chow followed by fasting creates a state that involves anxiety and altered accumbens dopamine and acetylcholine balance. This is similar to the effects of naloxone, suggesting opiate-like withdrawal. This may be a factor in some eating disorders.
While there are similarities between food and drugs in terms of addictiveness others have argued its validity as a model of obesity on the basis that food per se is not a psychoactive drug [74
]. With that said, the Columbia University Seminar on Appetitive Behavior, the obesity epidemic proposed various causes, one of which is the concept of “food Addiction”. This concept has been vigorously debated in the media [75
] as well as in the scientific community [76
The criteria in the Diagnostic & Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) pertaining to substance abuse have been also applied to food addiction in humans by Gearhardt et al. [78
]. In terms of sugar being considered a psychoactive substance there are clinical accounts in which self-identified food addicts use food to self-medicate; they often eat in order to escape a negative mood state [79
]. The authors further assert that overeating can be described as an addiction to refined foods that conforms to the DSM-IV criteria for substance use disorders. Reports by self-identified food addicts illustrate behaviors that conform to the 7 DSM-IV criteria for substance use disorders [79
]. This commonality notion has been confirmed by studies showing that food craving in normal weight and obese patients activates areas of the brain similar to those indicated in drug seeking [25
In a recent review by Nicole Avena [81
] where she summarized evidence for “food addiction” using animal models of binge eating she adequately defined bingeing, withdrawal and craving
by presenting evidence using an animal model of sucrose or glucose bingeing.
Avena et al [82
] performed analysis using gene array expression and PANTHER
on 152 unique genes resulting in a total of 193 assignments sorted into 20 categories. It is noteworthy that sucrose binge eating group compared to ad libitum sucrose group resulted in differential gene expression clusters. These findings seems to be convergent when one considers the neurotransmitters involved in the brain reward circuitry (e.g. serotonin; endorphins; GABA; Dopamine; Cannabinoids; Acetylcholine) specifically the brain reward cascade [83
] and RDS [30
]. Interestingly Avena et al found significant differences between binge and ad libitum sucrose groups in a number of neurotransmitter pathways for example: Cholinergic Receptor-CREB signaling( P < 0.001677); Leptin Receptor –ELK-SRF signaling (P < 0.001691); Dopamine D2 Receptor –AP-1/CREB/ELK-SRF signaling (P<0.003756); Serotonin-Fos signaling (P< 0.00673); Cannabinoid –AP1/EGR signaling (p<0.015588) and Opioid receptor –CREB/ELK-SRF/Stat3 signaling (P < 0.01823). These findings of significant differences in neurotransmitter genes in the binge eating group compared to the ad libitum group provides important evidence to suggest involvement of brain reward circuitry in binge eating per se. These results in animals may have relevance to binge eating in humans which is a subtype of RDS.