Overcoming qEEG Abnormalities and Reward Gene Deficits during Protracted Abstinence in Male Psychostimulant and Polydrug Abusers Utilizing Putative Dopamine D2 Agonist Therapy: Part 2

Abstract

Background: It is well established that in both food- and drug-addicted individuals there is “dopamine resistance” associated with the DRD2 gene A1 allele. Based on earlier studies, evidence is emerging wherein the potential of utilizing a natural, nonaddicting, safe, putative D2 agonist may play a significant role in the recovery of individuals with reward deficiency syndrome, including those addicted to psychoactive chemicals. Findings: Positive outcomes demonstrated by quantitative electroencephalographic (qEEG) imaging in a randomized, triple-blind, placebo-controlled, crossover study involving oral Synaptose Complex KB220Z? showed an increase of alpha waves and low beta wave activity in the parietal brain region. Using t statistics, significant differences observed between placebo and Synaptose Complex KB220Z? consistently occurred in the frontal regions after week 1 and then again after week 2 of analyses (P = 0.03). This is the first report to demonstrate involvement of the prefrontal cortex in the qEEG response to a natural putative D2 agonist (Synaptose Complex KB220Z?), especially evident in dopamine D2 A1 allele subjects. Independently, we have further supported this finding with an additional study of 3 serious polydrug abusers undergoing protracted abstinence who carried the DRD2 A1 allele. Significant qEEG differences were found between those who received 1 dose of placebo compared with those who were administered Synaptose Complex KB220Z?. Synaptose Complex KB220Z? induced positive regulation of the dysregulated electrical activity of the brain in these addicts. The results are indicative of a phase change from low amplitude or low power in the brain to a more regulated state by increasing an average of 6.169 mV² across the prefrontal cortical region. In the first experiment we found that while 50% of the subjects carried the DRD2 A1 allele, 100% carried ≥ 1 risk allele. Specifically, based on the proposed addiction risk score for these 14 subjects, 72% had moderate-to-severe addiction risk. Similar findings were obtained by repeating the experiment in 3 additional currently abstinent polydrug abusers carrying the DRD2 A1 allele. Conclusion: This seminal work will provide important information that may ultimately lead to significant improvement in the recovery of individuals with psychostimulant and polydrug abuse problems, specifically those with genetically induced dopamine deficiency. Based on this small sample size, we are proposing that with necessary large populations supporting these initial results, and possibly even additional candidate genes and single nucleotide polymorphisms, we may eventually have the clinical ability to classify severity according to genotype and possession of risk alleles, along with offering a safe, nonaddicting, natural dopaminergic receptor agonist that potentially upregulates instead of downregulates dopaminergic receptors, preferably the D2 subtype.     

Characteristics of analytically confirmed 3-MMC-related intoxications from the Swedish STRIDA project

Abstract

Background. 3-Methylmethcathinone (3-MMC) is a synthetic cathinone stimulant structurally related to the new psychoactive substance (NPS) mephedrone (4-methylmethcathinone, 4-MMC). We describe a case series of analytically confirmed intoxications involving 3-MMC presented to emergency departments in Sweden and included in the STRIDA project. Study design. Observational case series of consecutive patients with self-reported or suspected use of NPS presenting to hospitals in Sweden between August 2012 and March 2014. Methods. NPS analysis was performed by a liquid chromatography–mass spectrometry (MS)/MS method that is updated with new substances as they appear. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. Results. 3-MMC was detected in 50 (6.4%) of the 786 cases included in the STRIDA project during the 20-month study period, with the peak occurring in August 2013. The age range of patients testing positive for 3-MMC was 17–49 years (median 24) and 76% of them were men. The 3-MMC concentration in serum ranged between 0.002 and 1.49 μg/mL (median, 0.091) and between 0.007 and 290 μg/mL (median, 3.05) in urine. Co-exposure to other NPS and/or traditional drugs was very common, and 3-MMC mono-intoxication was found in only 4 (8%) cases. The most frequent clinical features were tachycardia (48% of cases) and agitation (42%). Other features included a reduced level of consciousness (32%), dilated pupils (24%), hallucinations (20%), diaphoresis (12%), seizures (8%), and hyperthermia (6%). Most patients (60%) needed hospital care for only 1 day but in 8% for 3 days or longer. Conclusion. The majority of patients with analytically confirmed 3-MMC exposure had sympathomimetic features similar to those associated with mephedrone intoxication. However, the high incidence of co-exposure to other drugs makes the clinical interpretation difficult. Nevertheless, 3-MMC was associated with a high admittance rate to intensive care (30%), and detected in two cases with a fatal outcome, suggesting that 3-MMC is a harmful drug.     

Acute behavioural disturbance associated with phenibut purchased via an internet supplier

Abstract

Context. Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet. Case Details. A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 μg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 μg/ml. Discussion. Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances.     

Diagnostic and psychodynamic aspects of sexual addiction appearing as a non‐paraphiliac form of compulsive sexual behaviour

Background: In recent decades, the diagnosis of sexual or love addiction has increasingly become part of the spectrum of addiction medicine. Although it does not figure under this name in either the BNO‐10 or DSM‐IV, the present scientific position is that it can be regarded as a compulsive sexual behaviour disorder that does not show the criteria of paraphilia.

Method: A case report.

Results: In the case of the 61‐year‐old patient we observed, the problems of an extramarital relationship play a central part in the syndrome with a serious conflict situation and prolonged personal and family crisis. This sexual addiction can be interpreted as identification with the father and also as the means of masculine identity. The sexual behaviour meets the criteria of addiction. Follow‐up will decide the stability of the diagnosis. In connection with this case, the authors attempt a psychodynamic analysis of triangular relationships destabilizing couple relationships.     

Chronic promethazine misuse and the possibility of dependence: a brief review of antihistamine abuse and dependence

Objective: Misuse of centrally acting antihistamines is potentially a significant under-recognised issue contributing to problems of abuse and dependence, with the potential to complicate management of other mental disorders. This article considers this problem with the aim of increasing practitioner awareness.

Method: This article considers the literature relating to abuse of centrally acting antihistamines and presents a unique case, with features suggesting of psychological and physiological dependence following prolonged misuse of promethazine.

Results: Increased understanding of the potential problem of centrally acting antihistamine abuse and consideration of the possibility of a dependence syndrome associated with promethazine.

Conclusions: The need for vigilance for abuse potential of promethazine and other centrally acting antihistamines by doctors and pharmacists is emphasised.     

Expert Knowledge in Palliative Care on the World Wide Web: Palliativedrugs.Org

ABSTRACT.?

In my last Internet-related article, I speculated that social networking would be the coming wave in the effort to share knowledge among experts in various disciplines. At the time I did not know that a palliative care site on the World Wide Web (WWW), palliativedrugs.com, already provided the infrastructure for sharing expert knowledge in the field. The Web site is an excellent traditional formulary but it is primarily devoted to “unlicensed” (“off-label”) use of medications in palliative care, something we in the specialty often do with little to support our interventions except shared knowledge and experience. There is nothing fancy about this Web site. In a good way, its format is a throwback to Web sites of the 1990s. In only the loosest sense can one describe it as “multimedia.” Yet, it provides the perfect forum for expert knowledge and is a “must see” resource. Its existing content is voluminous and reliable, filtered and reviewed by renowned clinicians and educators in the field. Although its origin and structure were not specifically designed for social or professional networking, the Web site's format makes it a natural way for practitioners around the world to contribute to an ever-growing body of expertise in palliative care.     

Physician Reported Incentives and Disincentives for Referring Patients to Hospice

Previous research has affirmed the key role of the physician in the decision to use hospice. Yet at least 1/4 of the physicians who have the opportunity to discuss hospice with a terminally ill patient never do so, and those that do so are selective. The present study used a qualitative approach to investigate the factors considered by the physician when deciding to discuss hospice with a patient. Participants were 17 practicing physicians who had referred patients to the one certified hospice in the geographic area of the study. Data were gathered by means of semi-structured interviews, which were audiotaped and transcribed for thematic analysis. The final categorization of data divided themes along two dimensions: a content dimension and a second dimension called incentives and disincentives. It is proposed that the physician’s proactive stance toward disclosure of the terminal diagnosis and perception of hospice as an opportunity for death with dignity create a culture within which the work that is necessary to make the other factors favorable toward use of hospice is accomplished.     

远程医疗与"互联网+"一体化发展现状与前景展望

随着计算机和互联网技术的迅速发展,远程医疗中的远程会诊、远程教学、远程手术及影像会诊、心电会诊、紧急救治、国际交流蓬勃开展,其不仅解决了大部分疑难重症患,而且促进了医学继续教育的持续发展,提高了经济和社会效益,若得到政策的进一步支持其应用前景将十分广阔.