Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: Role of enhanced brain reward functional connectivity and homeostasis redeeming joy

Background Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. Case presentations We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid “bad dreams” remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. Results The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient’s regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. Conclusions These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies

Long Term Suboxone™ Emotional Reactivity As Measured by Automatic Detection in Speech

Addictions to illicit drugs are among the nation’s most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states (“true ground emotionality”) in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of “true” emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate “true ground” emotionality in long-term buprenorphine/naloxone combination (Suboxone™). We found in long-term SUBX patients a significantly flat affect (p<0.01), and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.United States. Dept. of Defense. Assistant Secretary of Defense for Research & Engineering (Air Force Contract FA8721-05-C-0002

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

Background and aims: Many patients presenting multiple behaviors including drug and food abuse as well as other pathological repetitive unwanted activities such as gambling, self-mutilation and paraphilias may not be appropriately diagnosed. Here we present a case of a male presenting many of these seemingly diverse behaviors and finally diagnosed with reward deficiency syndrome (RDS) by his attending physician. Methods: The use of the dopamine agonist, ropinirole after two weeks showed improvement in terms of sexual behavior but tolerance set in and was discontinued especially when an infraction occurred with the patient's insurance. In this article, we carefully explore the potential of ropinirole to downregulate dopamine receptors causing adenylate cyclase receptor supersensitivity and tolerance a feature of neurotransmitter cross-talk. Based on previous scientific evidence showing KB220Znutrigenomic amino-acid therapy (NAAT) to rapidly (post one-hour) activate dopaminergic pathways in both the pre-frontal cortex cingulate gyrus (relapse loci) and ventral tegmental area-caudate-accumbens-putamen (craving and emotion loci) the patient was prescribed NAAT. Results and discussion: Within one week of utilization the repetitive paraphilia was eliminated. There were also a number of other positive effects such as enhanced focus that persisted even after the patient stopped using KB220Z suggesting neuroplasticity (e.g. altruistic thoughts). However, these observed profound benefits require more in-depth study, especially in a large cohort against a placebo. While this report focused on a rapid response rather than long-term benefits previously associated with NAAT, it is somewhat encouraging and longer term required follow-up and larger placebo controlled studies are warranted before any definitive conclusions could be gleaned from this case report

Systematic evaluation of "compliance" to prescribed treatment medications and "abstinence" from psychoactive drug abuse in chemical dependence programs: data from the comprehensive analysis of reported drugs.

This is the first quantitative analysis of data from urine drug tests for compliance to treatment medications and abstinence from drug abuse across "levels of care" in six eastern states of America. Comprehensive Analysis of Reported Drugs (CARD) data was used in this post-hoc retrospective observational study from 10,570 patients, filtered to include a total of 2,919 patients prescribed at least one treatment medication during 2010 and 2011. The first and last urine samples (5,838 specimens) were analyzed; compliance to treatment medications and abstinence from drugs of abuse supported treatment effectiveness for many. Compared to non-compliant patients, compliant patients were marginally less likely to abuse opioids, cannabinoids, and ethanol during treatment although more likely to abuse benzodiazepines. Almost 17% of the non-abstinent patients used benzodiazepines, 15% used opiates, and 10% used cocaine during treatment. Compliance was significantly higher in residential than in the non-residential treatment facilities. Independent of level of care, 67.2% of the patients (n = 1963; P<.001) had every treatment medication found in both first and last urine specimens (compliance). In addition, 39.2% of the patients (n = 1143; P<.001) had no substance of abuse detected in either the first or last urine samples (abstinence). Moreover, in 2010, 16.9% of the patients (n = 57) were abstinent at first but not at last urine (deteriorating abstinence), the percentage dropped to 13.3% (n = 174) in 2011; this improvement over years was statistically significant. A longitudinal analysis for abstinence and compliance was studied in a randomized subset from 2011, (n = 511) representing 17.5% of the total cohort. A statistically significant upward trend (p = 2.353×10-8) of abstinence rates as well as a similar but stronger trend for compliance ((p = 2.200×10-16) was found. Being cognizant of the trend toward drug urine testing being linked to medical necessity eliminating abusive screening, the interpretation of these valuable results require further intensive investigation

An integrative approach to quality of life measurement, research, and policy

While Quality of Life (QOL) has long been an explicit or implicit policy goal, adequate definition and measurement have been elusive. Diverse objective and subjective indicators across a range of disciplines and scales, and recent work on subjective well-being (SWB) surveys and the psychology of happiness have spurred renewed interest. Drawing from multiple disciplines, we present an integrative definition of QOL that combines measures of human needs with subjective well-being or happiness. QOL is proposed as a multiscale, multi-dimensional concept that contains interacting objective and subjective elements. We relate QOL to the opportunities that are provided to meet human needs in the forms of built, human, social and natural capital (in addition to time) and the policy options that are available to enhance these opportunities. Issues related to de?ning, measuring, and scaling these concepts are discussed, and a research agenda is elaborated. Policy implications include strategies for investing in opportunities to maximize QOL enhancement at the individual, community, and national scales

Significant differences in emotional expressiveness across groups.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069043#pone-0069043-g012" target="_blank">Figure 12</a> shows that the SUBX group had significantly less emotional expressiveness, as measured by length of speech, than both the GP group and the AA group (p<0.0001). It may be difficult to determine the emotion of SUBX patients, both by humans and by the automatic detector, due to flatter affect. The average audio response to “How are you feeling?” was (3.07 seconds; CI: 2.89–3.25). SUBX patients’ responses were significantly shorter (2.39 seconds; CI: 2.05–2.78)) than both the GP (p<0.0001) (3.46; CI: 3.15–2.80) and AA members (p<0.0001) (3.31; CI: 2.97–3.68). In terms of emotional expressiveness as measured by confidence scores, the SUBX group also showed significantly lower scores than both the GP and the AA groups. There was significantly less confidence in SUBX patients’ audio responses (72%; CI: 0.69–0.74) than the GP (p = 0.038) (74%; CI: 0.73–0.76) and AA members (p = 0.018) (75%; CI: 0.73–0.77).</p

Patient Momentary Emotional State collection through the Interactive Voice Response system.

<p>Patient-reported-outcome (PRO) Experience Sampling Method (ESM) data collection places considerable demands on participants. Success of an ESM data collection depends upon participant compliance with the sampling protocol. Participants must record an ESM at least 20% of the time when requested to do so; otherwise the validity of the protocol is questionable. The problem of “hoarding” – where reports are collected and completed at a later date – must be avoided. Stone et al confirmed this concern through a study and found only 11% of pen-and-pencil diaries where compliant; 89% of participants missed entries, or hoarded entries and bulk entered them later. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069043#pone.0069043-Stone2" target="_blank">[58]</a> IVR systems overcome hoarding by time-sampling and improve compliance by allowing researchers to actively place outgoing calls to participants in order to more dynamically sample their experience. Rates of compliance in IVR sampling literature vary from as high as 96% to as low as 40% <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069043#pone.0069043-Hufford1" target="_blank">[59]</a> Subject burden has also been studied as a factor effecting compliance rates. At least six different aspects affect participant burden: Density of sampling (times per day); length of PRO assessments; the user interface of the reporting platform; the complexity of PRO assessments (i.e. the cognitive load, or effort, required to complete the assessments); duration of monitoring; and stability of the reporting platform <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069043#pone.0069043-Hufford1" target="_blank">[59]</a>. Researchers have been known to improve compliance through extensive training of participants <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069043#pone.0069043-Stone2" target="_blank">[58]</a>. Extensive training is impractical for automated ESM systems. Patients were called by the IVR system at designated times thus overcoming hoarding. A simple intuitive prompt: “How are you feeling?” elicited emotional state response (e.g., “I am angry!”); no training was required. The audio response is recorded on the web server for analysis. The IVR system was implemented through the W3C standards CCXML and VoiceXML on a Linux-Apache-MySQL-PHP (LAMP) server cluster.</p