Scheduling of new psychoactive substance the Swiss way: A review and critical analysis.

Since the introduction of the European Early Warning System in 2005, >700 new psychoactive substances (NPS) have been listed. This review article presents for the first time the Swiss narcotic law in perspective of scheduling of NPS, and compares it to the regulations of the German speaking neighbours Austria and Germany. The Swiss way is a fast and effective way for scheduling NPS, with the purpose to restrict drug trafficking and for controlling the NPS drug market: the legal basis for scheduling substances of abuse is the "Law about narcotics and psychotropic substances" (BetmG, SR 812.121), which includes the "narcotic law directory (BetmVV-EDI, SR 812.121.11) suitable for listing all controlled substances. The BetmVV-EDI, SR 812.121.11 contains seven indices, with index e specifically designed for the fast scheduling of NPS. Newly appearing NPS can either be controlled under a structure analogues definition or by listing single substances. The list of single substances is updated at least once per year, and structure analogues definitions can be implemented, in order to keep track with new developments on the NPS market. The latest version from November 30th 2018 contains ten different structure analogue definitions and 207 single substances. Requirements to list NPS are their appearance on the NPS market, suspected psychotropic effects and their suggestions by Forensic professionals. As soon as substances are newly placed, on Schedule I of the 1961 Convention or Schedule II of the 1971 Convention by the Commission on Narcotic Drugs of the World Health Organization they can easily be transferred from index e to index a-d of the BetmVV-EDI, SR 812.121.11. The Austrian law uses a structure analogue and single substances approach (introduced in 2012, one update in 2016), whereas the German NPS law (established in 2016, no update yet) only lists two structure-analogue-definitions. All three legislations have defined which core structures, kinds and sites of substitutions are regulated.

Consistency Between Opioid-Related Mortality Trends Derived From Poison Center and National Vital Statistics System, United States, 2006-2016.

OBJECTIVES: To determine the association between poison center opioid exposure calls and National Vital Statistics System (NVSS) deaths. METHODS: We categorized Centers for Disease Control and Prevention NVSS mortality and the Researched Abuse, Diversion and Addiction-Related Surveillance System poison center program cases from 2006 to 2016 by International Classification of Diseases, Tenth Revision, codes (heroin [T40.1]; natural or semisynthetic opioids [T40.2]; methadone [T40.3]; synthetic opioids, other than methadone [T40.4]). We scaled rates by 100 000 population and calculated Pearson correlation coefficients. Sensitivity analysis excluded polysubstance cases involving either heroin or synthetic opioids as well as natural and semisynthetic opioids. RESULTS: The NVSS mortality and poison center program exposure rates showed similar trends from 2006 to 2012, and diverged after 2012 for all opioids combined, natural and semisynthetic opioids, and synthetic opioids (r = -0.37, -0.12, and 0.30, respectively). Sensitivity analysis with removal of heroin or synthetic opioid polysubstance deaths markedly improved correlations for all opioids combined and natural and semisynthetic opioids (r = 0.87 and 0.36, respectively). CONCLUSIONS: The NVSS mortality and poison center exposure rates showed similar trends from 2006 to 2012 then diverged, with sensitivity analysis suggesting polysubstance cases also involving heroin or illicit fentanyl as the cause. Public Health Implications. The NVSS and poison center program may provide complementary data when trends diverge. Public health interventions must include both licit and illicit opioids for maximal impact.

Allergy to illicit drugs and narcotics.

Despite their frequent use, allergy to illicit drugs and narcotics is rarely reported in literature. We present a review of the different classes of drugs of abuse that might be involved in allergies: central nervous system (CNS) depressants (such as cannabis, opioids and kava), CNS stimulants (cocaine, amphetamines, khat and ephedra) and hallucinogens such as ketamine and nutmeg. Diagnosis of drug and narcotic allergy generally relies upon careful history taking, complemented with skin testing eventually along with quantification of sIgE. However, for various reasons, correct diagnosis of most of these drug allergies is not straightforward. For example, the native plant material applied for skin testing and sIgE antibody tests might harbour irrelevant IgE-binding structures that hamper correct diagnosis. Diagnosis might also be hampered due to uncertainties associated with the non-specific histamine releasing characteristics of some compounds and absence of validated sIgE tests. Whether the introduction of standardized allergen components and more functional tests, that is, basophil activation and degranulation assays, might be helpful to an improved diagnosis needs to be established. It is anticipated that due to the rare character of these allergies further validation is although necessary.

Phentermine: an appetite-suppressant amphetamine classified as a narcotic in France. Is a combination with topiramate on the horizon?

In France, extra restrictions have been placed on this appetite-suppressant drug. Phentermine is widely used in many countries despite its multiple adverse effects and lack of proven efficacy in preventing complications of obesity.

Multiple drug intolerance syndrome: prevalence, clinical characteristics, and management.

BACKGROUND: Population-based data on the demographics and clinical characteristics of patients with multiple unrelated drug class intolerances noted in their medical records are lacking. OBJECTIVES: To provide population-based drug "allergy" incidence rates and prevalence, and to identify individuals with multiple drug intolerance syndrome (MDIS) defined by 3 or more unrelated drug class "allergies," and to provide demographic and clinical information on MDIS cases. METHODS: Electronic medical record data from 2,375,424 Kaiser Permanente Southern California health plan members who had a health care visit and at least 11 months of health care coverage during 2009 were reviewed. Population-based drug "allergy" incidence rates and prevalence were determined for 23 unrelated medication classes. RESULTS: On January 1, 2009, 478,283 (20.1%) health plan members had at least one reported "allergy." Individuals with a history of at least 1 "allergy" and females, in general, reported higher population-based new "allergy" incidence rates. Multiple drug intolerance syndrome was present in 49,582 (2.1%). The MDIS cases were significantly older, 62.4 ± 16.1 years; heavier, body mass index 29.3 ± 7.1; and likely to be female, 84.9%, compared with average health plan members. They had high rates of health care utilization, medication usage, and new drug "allergy" incidence. They sought medical attention for common nonmorbid conditions. CONCLUSIONS: Multiple drug intolerance syndrome is in part iatrogenic. It is associated with overweight elderly women who have high rates of health care and medication usage. Urticarial syndromes only explain a small fraction of MDIS cases. Multiple drug intolerance syndrome is associated with anxiety, but not predominately with immunoglobulin E (IgE)-mediated allergy or life-threatening illness. Multiple drug intolerance syndrome can be managed by medication avoidance and judicious rechallenge.

Bridging the gap between molecular descriptors and mechanism: cases studies by molecular dynamics simulations.

In recent years, both classification models and quantitative structure-activity relationships (QSARs) have been developed to discriminate the acute toxicity of polar narcotics and uncouplers. One of fundamental issues is how to select and interpret the molecular descriptors used in both methods. In this work, we first employed support vector machine on a dataset containing 155 polar narcotics and 19 uncouplers to filter the predictive hydrophobic and hydrogen bonding descriptors. Molecular dynamics simulations were then conducted to investigate the behavior of salicylate and pentachlorophenol molecules in the context of a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. The results demonstrated that their equilibrium properties in the lipid bilayer were closely associated with hydrophobic and hydrogen bonding descriptors. The preferable occupations of these molecules in the lipid bilayer were discussed in terms of their modes of toxic action. The observations from molecular dynamics simulations facilitated to elucidate the mechanism of polar narcotics and uncouplers.

Control of a chemical precursor used in the illicit manufacture of fentanyl as a List I chemical. Final rule.

The Drug Enforcement Administration (DEA) is finalizing the Interim Rule with Request for Comment published in the Federal Register on April 23, 2007. The Interim Rule controlled the chemical N-phenethyl-4- piperidone (NPP) as a List I chemical under the Controlled Substances Act. Clandestine laboratories are using this chemical to illicitly manufacture the schedule II controlled substance fentanyl. No comments to the Interim Rule were received. This Final Rule finalizes the regulations without change.

Abuse liability of prescription opioids compared to heroin in morphine-maintained heroin abusers.

Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as 'I feel a good drug effect' and 'I like the drug.' In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine>or=heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of 'I feel a bad drug effect' and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

Control of a chemical precursor used in the illicit manufacture of fentanyl as a List I chemical. Interim rule with request for comments.

This rulemaking controls the chemical N-phenethyl-4-piperidone (NPP) as a List I chemical under the Controlled Substances Act (CSA) (21 U.S.C. 801 et seq.). Clandestine laboratories are using this chemical to illicitly manufacture the schedule II controlled substance fentanyl. The recent distribution of illicitly manufactured fentanyl has caused an unprecedented outbreak of hundreds of suspected fentanyl-related overdoses, at least 972 confirmed fentanyl-related deaths, and 162 suspected fentanyl-related deaths occurring mostly in Delaware, Illinois, Maryland, Michigan, Missouri, New Jersey, and Pennsylvania. NPP has been identified as the starting material in several seized fentanyl clandestine laboratories. In addition to DEA's concern regarding the deaths associated with illicitly manufactured fentanyl, DEA is extremely concerned about the safety of law enforcement officers encountering these clandestine laboratories. Therefore, DEA is regulating NPP as a List I chemical through this Interim Rulemaking. DEA is soliciting comments on this Interim Rule. This rulemaking will subject handlers of NPP to the chemical regulatory provisions of the CSA and its implementing regulations, including 21 CFR Parts 1309, 1310, 1313, and 1316. This rulemaking does not establish a threshold for domestic and international transactions of NPP. As such, all transactions involving NPP, regardless of size, shall be regulated. This rulemaking also specifies that chemical mixtures containing NPP will not be exempt from regulatory requirements at any concentration. Therefore, all transactions of chemical mixtures containing any quantity of NPP will be regulated and will be subject to control under the CSA.

Fatal injuries while under the influence of psychoactive drugs: a cross-sectional exploratory study in England.

BACKGROUND: Studies of drug-related mortality rarely describe fatal injuries due to psychoactive drug intoxication (FIUI). The main aim of this study was to determine the nature, extent and pattern of FIUI. METHODS: This observational study covered the period January 1999 to December 2001. Data were provided by members of a study panel of coroners in England using a standard protocol. Sources of data for this study included autopsy protocols, death certificates, hospital records, police reports, toxicology reports and inquest transcripts. Inclusion criteria for this were (i) the mention of one or more psychoactive substances as contributing to fatality; and (ii) the presence of a Controlled Drug at post mortem. RESULTS: A total of 3,803 drug-related deaths of persons aged 16-64 years were reported by the study panel during the three-year period. The study panel accounted for 86% of drug-related deaths in England in this period. There were 147 FIUI cases (119 males, 28 females), giving a proportionate mortality ratio of approximately 4%. The majority of FIUI cases (84%) were aged 16-44 years, with a median age at death of 33 years (Quartile deviation = 7). Fifty-six percent of FIUI occurred in urban areas of England. The population of the study jurisdictions aged 16-64 years contributed 49,545,766 person-years (py) to the study, giving an annual crude rate of 3/1,000,000 person-years (py). Rates for male and females were 4.9 and 1.1/1,000,000 py respectively, giving a male/female rate ratio of 4.5 (95%CI = 2.9-6.8). The rates of intentional and unintentional FIUI were 2 and 1/1,000,000 py respectively. The leading mechanism for intentional FIUI was suffocation while the predominant mechanisms in unintentional FIUI were road traffic accidents and falls. There is a significant difference in the pattern of drug-specific risk between FIUI and fatal poisoning. Risks of intentional FIUI are elevated among Black and Minority Ethnic groups. CONCLUSION: There are differences in the nature, extent and pattern of intentional and unintentional FIUI that should necessitate targeted prevention strategies. Also, there is an opportunity for cross-discipline collaboration between injury prevention specialists and substance abuse/mental health specialists.

Structural alerts--a new classification model to discriminate excess toxicity from narcotic effect levels of organic compounds in the acute daphnid assay.

Quantitative and qualitative structure-activity relationships (QSARs) have a great potential to support the risk assessment of chemicals, provided there are tools available that allow evaluation of the suitability of QSARs for the compounds of interest. In this context, a pragmatic approach is to discriminate excess toxicity from narcotic effect levels, because the latter can be estimated from QSARs and thus have a low priority for experimental testing. To develop a respective scheme for the acute daphnid toxicity as one of the primary ecotoxicological endpoints, 1067 acute toxicity data entries for 380 chemicals involving the daphnid species Daphnia magna were taken from the on-line literature, and quality checks such as water solubility were employed to eliminate apparently odd data entries. For 36 known narcotics with LC50 values referring to D. magna, a reference baseline QSAR is derived. Compounds with LC50 values above a certain threshold defined relative to their predicted baseline toxicity are classified as exerting excess toxicity. Three simple discrimination schemes are presented that enable the identification of excess toxicity from structural alerts based on the presence or absence of certain heteroatoms and their chemical functionality. Moreover, a two-step classification approach is introduced that enables a prioritization of organic compounds with respect to their need for experimental testing. The discussion includes reaction mechanisms that may explain the association of structural alerts with excess toxicity, a comparison with predictions derived from mode of action-based classification schemes, and a statistical analysis of the discrimination performance in terms of detailed contingency table statistics.

Law relating to the classification and regulation of controlled drugs.

Mary, a newly qualified staff nurse, was asked by the night sister to draw up a syringe of morphine for a patient who was in severe pain. She had understood that she should not be doing this on her own, but the night sister said that they were too short of staff to provide another person.

Drug recognition expert evaluations made using limited data.

The Drug Evaluation Classification (DEC) Program is used by Drug Recognition Expert (DRE) officers to determine whether a suspect is under the influence of a drug or drugs at the time of arrest, and, if so, what category of drug(s). The goal of this project was to investigate the relative importance of face-to-face interactions with the suspect, physical evidence (drugs or paraphernalia found), and confessions/statements made by the suspect (or others) in making these determinations. Seventy records of DRE evaluations were selected from a database containing information from all evaluations conducted in Oregon between 1996 and 1998. Each of the 70 records represented a suspect who had either taken a drug from one of four categories (CNS depressant, CNS stimulant, narcotic analgesic, or cannabis) or who had not taken a drug. To be included, the original DRE evaluation and the subsequent toxicology analysis had to agree that the suspect was under the influence of a drug from one of the four categories or not under the influence of a drug. Records from the 70 cases were submitted in written form to 18 Oregon DREs with statements made by suspects or arresting officers, confessions, toxicology results, and descriptions of drugs or paraphernalia found on the suspect omitted. Based only on the written reports of direct observations, and with physiological and psychophysical test results, the DREs attempted to determine whether each of the 70 suspects was under the influence of a drug or drugs, and, if so, what category of drug(s). If the officers determined that a suspect was under the influence of a drug, their accuracy in specifying the drug category was 81% for cannabis, 94% for narcotic analgesics, 78% for CNS stimulants, and 69% for CNS depressants. Overall accuracy in recognizing drug intoxication was 95%. These percentages indicate that although face-to-face interactions, physical evidence, and confessions/statements can be useful adjuncts to DRE decision-making, the majority of drug category decisions can be made solely on the basis of recorded suspect observations and DRE evaluation results.

[Opioid overdose]. / Opioidu perdozavimas.

The dangers of opioid overdose have been recognized for as long as the use of opium itself. When used correctly for medical purposes, opioids are remarkably safe and effective agents. However, excessive dosing, whether with therapeutic, suicidal, or euphoric intent, may results in significant toxicity. In a number of countries the use of heroin and other opioids in nonmedical contexts in associated with on increasing rate of overdose and often of fatal opioid overdose. This review article discusses opioid-receptor pharmacology, which is necessary for understanding of the signs and symptoms of opioid ingestion and management principles, clinical and toxic effects mediated with the opioids, the diagnosis and management guidelines in opioid intoxication, a clinical prediction rule to identify patients who can be safely discharge from hospital, the problems of the significant morbidity and mortality associated with opioid overdose.

Schedules of controlled substances: rescheduling of buprenorphine from schedule V to schedule III. Final rule.

This final rule is issued by the Deputy Administrator of the Drug Enforcement Administration (DEA) to reschedule buprenorphine from a Schedule V narcotic to a Schedule III narcotic under the Controlled Substances Act (CSA). This action is based on a rescheduling recommendation by the Department of Health and Human Services (DHHS) and a DEA review indicating that buprenorphine meets the criteria of a Schedule III narcotic. The DEA published a proposed rule to reschedule buprenorphine on March 21, 2002 (67 FR 13114). The comment period was extended for an additional 30 days until May 22, 2002 (67 FR 20072). The DEA received ten comments but no requests for hearings. This final action will impose the regulatory controls and criminal sanctions of a Schedule III narcotic on those persons who handle buprenorphine or products containing buprenorphine

Estupefacientes: normativa actual / Estupefacients: current legislation

La entrada en vigor de la Orden Ministerial de 25 de abril de 1994, supuso grandes cambios en la tramitación administrativa de los estupefacientes que hasta entonces había que realizar y agilizó la adquisición de los mismos por parte de los pacientes. A fecha de hoy esta Orden Ministerial, ha quedado atrasada por diferentes motivos: I) el movimiento de estupefacientes en las farmacias ha aumentado mucho, 2) las Administraciones Sanitarias actualmente depositarias de las recetas de estupefacientes que se venden en las farmacias comunitarias han quedado colapsadas y 3) las existencias mínimas de las farmacias no se corresponden con las necesidades de los pacientes (AU)

The appearance of the Ministry Order of Aril 25th 1994, supposed great changes in the administrative procedures of stupefacients, which until then was done and quicken their acquisition by patients. Up to date, this Ministry Order is old fashioned by different causes: 1) stupefacients movement in community pharmacies has substantially increased, 2) Health Administrations, keepers of the prescription forms dispensed in pharmacies have become collapsed and 3) minimum stocks in community pharmacies do nor correspond with patients' needs (AU)