195 research outputs found

    Hypothesizing that a Pro-Dopaminergic Regulator (KB220z(™) Liquid Variant) can Induce “Dopamine Homeostasis” and Provide Adjunctive Detoxification Benefits in Opiate/Opioid Dependence

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    In order to explore the initiation of detoxification of addictive patients to opiates/opioids (along with some other anti-withdrawal agents), we developed a protocol to be utilized in treatment centers particularly with heavily dependent opiate/opioid subjects. Out of 17 subjects, only three received Buprenorphine/Naloxone (Bup/nx) along with KB220Z. In this pilot, we first used a dose of KB220Z of 2 oz twice daily before meals along with clonidine and benzodiazepines and other anti-nausea and sleep aids including Gabapentin. The dose of KB220Z was maintained for 6 days in five individuals. In a second scenario, we utilized a higher dose of 4 oz every 6 hours, over a 6-day period. The higher dose was employed in another 12 patients. It is noteworthy that only 3 people have relapsed utilizing these two protocols during the first two weeks of the study, allowing for the remaining 82% to be maintained on KB220Z. The patients have been maintained without any additional Bup/nx for a minimum of 120 days and in one subject, 214 days. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates utilizing data from the Clinical opiate Withdrawal Scale (COWS) pre and post KB220Z. We are in the process of testing this hypothesis in multiple treatment centers across the United Sates. While this does not constitute an acceptable controlled experiment, it does provide some preliminary evidence that agrees with an earlier study. Moreover, because of the utilization of standard detoxifying agents in this detoxification protocol, we cannot make any inference to KB220Z’s effects. However, out of 17 subjects, only three required Bup/nx suggesting an interesting finding. If further confirmed in larger studies, the utilization for opiate/opioid detoxification may provide a novel way to eliminate the need for addictive opioids during withdrawal and detoxification. This paradigm shift may translate to a reduction in utilizing powerful and addictive opioids like buprenorphine and methadone (especially in these patients at high genetic risk for addiction) as not only detoxifying agents, but also maintenance drugs. While extensive research is required, this pilot paves the way for future investigations that could assist in the reduction of addictive opiate/opioid use and mortalities amongst both the young and old in America

    Hypothesizing Synergy between Acupuncture/ Auriculotherapy and Natural Activation of Mesolimbic Dopaminergic Pathways: Putative Natural Treatment Modalities for the Reduction of Drug Hunger and Relapse

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    Acupuncture is a very ancient form of healing which predates recorded history. The philosophy is rooted in the Taoist tradition which goes back over 8000 years. To date this practice although used world-wide to treat addictive behaviors has not been generally accepted or scientifically proven. There are however many positive reports in the literature in its effectiveness in reducing symptoms of withdrawal from alcohol, heroin and cocaine. In addition, due to known neuro-chemical mechanisms associated with acupuncture, especially its role in pain relief and endogenous opioid function, clinical benefits in reward dependence behaviors seem parsimonious. In this review article we are hypothesizing synergy between acupuncture/auriculotherapy and natural activation of mesolimbic dopaminergic pathways to reduce drug hunger and prevent relapse. Following a review of the literature involving both of these modalities the scientific and clinical community is encouraged to carry out translational research in large randomized double-blinded placebo controlled investigations coupling these two anti-craving treatment modalities

    Sugar addiction: the state of the science.

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    PURPOSE: As obesity rates continue to climb, the notion that overconsumption reflects an underlying 'food addiction' (FA) has become increasingly influential. An increasingly popular theory is that sugar acts as an addictive agent, eliciting neurobiological changes similar to those seen in drug addiction. In this paper, we review the evidence in support of sugar addiction. METHODS: We reviewed the literature on food and sugar addiction and considered the evidence suggesting the addictiveness of highly processed foods, particularly those with high sugar content. We then examined the addictive potential of sugar by contrasting evidence from the animal and human neuroscience literature on drug and sugar addiction. RESULTS: We find little evidence to support sugar addiction in humans, and findings from the animal literature suggest that addiction-like behaviours, such as bingeing, occur only in the context of intermittent access to sugar. These behaviours likely arise from intermittent access to sweet tasting or highly palatable foods, not the neurochemical effects of sugar. CONCLUSION: Given the lack of evidence supporting it, we argue against a premature incorporation of sugar addiction into the scientific literature and public policy recommendations.Wellcome Trust (Senior Fellowship award)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00394-016-1229-

    Mesolimbic opioid-dopamine interaction is disrupted in obesity but recovered by weight loss following bariatric surgery

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    Obesity is a growing burden to health and the economy worldwide. Obesity is associated with central mu-opioid receptor (MOR) downregulation and disruption of the interaction between MOR and dopamine D-2 receptor (D2R) system in the ventral striatum. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying 20 healthy non-obese and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability were measured using positron emission tomography (PET) with [C-11]carfentanil and [C-11]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed on obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. In the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but the unaltered association in dorsal caudate (r = .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss. Bariatric surgery and concomitant weight loss recover the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioral interventions for treating obesity

    Animal models of compulsive eating behavior

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    In industrialized nations, overeating is a significant problem leading to overweight, obesity, and a host of related disorders; the increase in these disorders has prompted a significant amount of research aimed at understanding their etiology. Eating disorders are multifactorial conditions involving genetic, metabolic, environmental, and behavioral factors. Considering that compulsive eating in the face of adverse consequences characterizes some eating disorders, similar to the way in which compulsive drug intake characterizes drug-addiction, it might be considered an addiction in its own right. Moreover, numerous review articles have recently drawn a connection between the neural circuits activated in the seeking/intake of palatable food and drugs of abuse. Based on this observation, “food addiction” has emerged as an area of intense scientific research and accumulating evidence suggests it is possible to model some aspects of food addiction in animals. The development of well-characterized animal models would advance our understanding of the etiologic neural factors involved in eating disorders, such as compulsive overeating, and it would permit to propose targeted pharmacological therapies. However, to date, little evidence has been reported of continued food seeking and intake despite its harmful consequences in rats and mice

    Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic

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    Background The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations. We show 50 case reports derived from two independent treatment centers in Florida that suggest the commonality between food and drug addictions. In an attempt to provide data from this cohort, many participants did not adequately respond to our questionnaire. Discussion We propose that dopamine agonist therapy may be of common benefit. Failure in the past may reside in too powerful D2 agonist activity leading to D2 receptor downregulation, while the new methodology may cause a reduction of “dopamine resistance” by inducing “dopamine homeostasis.” While this is not a definitive study, it does provide some additional clinical evidence that these two addictions are not mutually exclusive. Conclusion Certainly, it is our position that there is an overlap between food- and drug-seeking behavior. We propose that the studies focused on an effort to produce natural activation of dopaminergic reward circuitry as a type of common therapy may certainly be reasonable. Additional research is warranted

    Dopamine, opioid and serotonin neurotransmission in behavioral addictions

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    Behavioral addictions are psychiatric disorders, in which the object of addiction is not a drug but instead behavior itself, such as gambling or eating. Behavioral addictions share clinical features with substance use disorder, including tolerance against behavior, continued behavior despite negative consequences, withdrawal symptoms and craving. However, little is known about the pathophysiology of these disorders. Behavioral addictions may also serve as a model to investigate the brain reward system at its purest form, without confounding chemical properties of misused drugs. The aim of this study was to investigate brain neurotransmitter function in behavioral addictions. Brain dopamine, opioid and serotonin systems were investigated in pathological gambling (PG), in binge eating disorder (BED) and in a control group using positron emission tomography (PET). PET scans were performed using [18F]fluorodopa to target presynaptic dopamine synthesis rate; [11C]carfentanil to label μ-opioid receptors (MORs); and [11C]MADAM to label serotonin transporter. Statistical analyses covered betweengroup comparisons in all three groups, intraregional PET tracer correlations in the PG and the control groups, and correlations between impulsivity and tracer binding in the PG and the control groups. BED patients showed decreased nucleus accumbens dopamine synthesis, wide-spread decreases in MOR binding, and regionally selective increases and decreases in SERT binding, whereas PG patients failed to show any changes in relation to controls. The changes were independent from possible confounding factors. Dopamine synthesis rate correlated positively with MOR binding in the basal ganglia in both PG and control groups. Impulsivity correlated inversely with SERT binding in the prefrontal cortex in controls. This association was lost in PG, and instead, midbrain MOR binding was related both with impulsivity and nucleus accumbens dopamine synthesis rate. The results of this study indicate that phenotypically distinct behavioral addictions differ also by their neurobiology. Importantly, the findings contrast with previously published results in substance addictions, indicating individual neurobiology in distinct addiction disorders. Whether the observed neurotransmitter alterations in BED and altered relationship between receptor densities and impulsivity in PG reflect predisposing pathophysiology or a neural adaptation remains to be established.Aivojen dopamiini-, opioidi- ja serotoniinitoiminta toiminnallisissa riippuvuuksissa Toiminnalliset riippuvuudet ovat psykiatrisia sairauksia, joissa riippuvuuden kohde ei ole kemiallinen aine vaan toiminta tai käytösmalli, kuten esimerkiksi rahapelaaminen tai syöminen. Toiminnallisilla riippuvuuksilla ja päihderiippuvuuksilla on paljon yhteisiä piirteitä, mukaan lukien sietokyvyn nousu, riippuvuuden kohteena olevan toiminnan jatkaminen huolimatta epäedullisista seurauksista, vieroitusoireet ja himo. Kuitenkaan toiminnallisten riippuvuuksien patofysiologiaa ei juurikaan tunneta. Toiminnallisia riippuvuuksia voidaan käyttää myös mallina tutkittaessa aivojen palkkiojärjestelmää puhtaimmillaan ilman päihteiden aiheuttamaa kemiallista sekoittavaa vaikutusta. Tämän tutkimuksen tarkoituksena oli tarkastella aivojen välittäjäaineiden toimintaa toiminnallisissa riippuvuuksissa. Aivojen dopamiini-, opioidi- ja serotoniinijärjestelmiä tutkittiin peliriippuvuudessa, ahmintahäiriössä ja kontrolliryhmässä positroniemissiotomografialla (PET). PET-kuvauksissa [18F]fluorodopa kuvasi presynaptista dopamiinin tuotantokykyä, [11C]karfentaniili sitoutui μ-opioidireseptoriin (MOR) ja [11C]MADAM puolestaan sitoutui serotoniinin takaisinottajaan (SERT). Tilastollisessa analyysissa tarkasteltiin kaikkien ryhmien välisiä eroja merkkiaineiden sitoutumisessa. Lisäksi peliriippuvuudessa ja kontrolliryhmässä tarkasteltiin eri merkkiaineiden sitoutumisen välisiä riippuvuussuhteita ja impulsiivisuuden ja merkkiaineiden sitoutumisen riippuvuussuhteita. Ahmintahäiriössä dopamiinin tuotantokyky oli alentunut accumbens-tumakkeessa, MOR-sitoutuminen oli alentunut laaja-alaisesti aivojen eri osissa ja SERT-sitoutumisessa nähtiin alueellisesti vaihtelevia sitoutumisen nousuja ja laskuja, kun taas peliriippuvuus ei eronnut kontrolleista minkään merkkiaineen osalta. Muutokset eivät johtuneet mahdollisista sekoittavista tekijöistä. Dopamiinin tuotantokyky korreloi tyvitumakkeiden MORsitoutumisen kanssa sekä peliriippuvuudessa että kontrolleilla. Impulsiivisuus korreloi otsalohkon SERT-sitoutumisen kanssa kontrolliryhmässä, mutta tämä riippuvuussuhde ei ilmennyt peliriippuvuudessa, jossa sen sijaan keskiaivojen MOR-sitoutuminen korreloi sekä impulsiivisuuden että accumbens-tumakkeen dopamiinin tuotantokyvyn kanssa. Tämän tutkimuksen tulokset osoittavat, että ilmiasultaan erilaiset toiminnalliset riippuvuudet eroavat myös neurobiologisesti toisistaan. Lisäksi tulokset poikkeavat aiemmin julkaistuista tuloksista päihderiippuvuuksissa, mikä tarkoittaa yksilöllisen neurobiologisen taustan ilmenemistä eri riippuvuussairauksissa. Edelleen jää selvitettäväksi, heijastavatko hermovälittäjäaineiden muutokset ahmintahäiriössä sekä hermovälittäjäaineiden ja impulsiivisuuden riippuvuussuhteiden muutokset peliriippuvuudessa altistavaa patofysiologiaa vai hermostollista mukautumista

    Molecular Mechanisms of Drug-Induced Plasticity

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    Substance-use disorders (SUDs) are a significant societal burden. Like many other conditions, SUDs are characterized by chronic relapse after periods without symptoms. Alterations in synaptic plasticity have been documented after acute and addiction-related behavioral exposures to drugs of abuse. These synaptic alterations are persistent and similar to the chronic relapse state of patients with SUDs, suggesting that reversing these synaptic alterations may prevent relapse. Additionally, many of these synaptic features of addiction mirror those found in other forms of learning and memory. These features suggest that the etiology of this disorder stems from persistent modifications in corticolimbic synaptic plasticity mediated by drug-induced alterations in addiction-related gene (ARG) expression. Understanding the regulation of addiction-related genes and their impact on synaptic plasticity and behavior may inform new pharmacological treatments that reverse these aberrant drug-evoked forms of plasticity in favor of remission

    Future newborns with opioid-induced neonatal abstinence syndrome (NAS) could be assessed with the genetic addiction risk severity (GARS) test and potentially treated using precision amino-acid enkephalinase inhibition therapy (KB220) as a frontline modality instead of potent opioids

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    In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids
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