Effect of new legislation in Germany on prevalence and harm of synthetic cannabinoids.

CONTEXT: New psychoactive substances (NPS) have become an ongoing threat to public health. To prevent the emergence and spread of NPS, a new German law, the 'NpSG' took effect in November 2016. This study presents an overview of analytically confirmed synthetic cannabinoid (SC) intoxications from January 2015 to December 2018. In order to demonstrate effects of the NpSG, the results of 23 month before and 25 month after the introduction of the law were compared. METHODS: Within the scope of a prospective observational study blood and urine samples were collected from emergency patients with suspected NPS intoxication. Comprehensive drug analyses were performed by LC-MS/MS analysis. RESULTS: In the period considered, 138 patients were included. Within these, SC intake was verified in 65 patients (73%) in the period before the law change, and in 30 patients (61%) after. The median age increased significantly from 19.5 to 26 years. Seizures and admission to the ICU were reported significantly less frequently (seizures 29% versus 6.7%, p = 0.0283; ICU admission 42% versus 13%, p = 0.0089). 34 different SCs were detected, including four SCs (Cumyl-PEGACLONE, 5 F-MDMB-P7AICA, EG-018, 5 F-Cumyl-P7AICA) not covered by the NpSG at the time of detection. In the first period the most prevalent SC was MDMB-CHMICA (n = 24). 5 F-ADB was the most prevalent SC overall, detected in 7 patients (11%) in the first, and in 24 patients (80%) in the second period. CONCLUSION: The number of SC intoxications decreased overall after the implementation of the NpSG. The shift in the detected SCs can be considered a direct effect of the NpSG but unfortunately the market supply does not appear to have been reduced. Although changes in the age distribution and in the severity of intoxications may be seen as secondary effects of the law, the main objectives of the new law to prevent the emergence and spread of further chemical variations of known scheduled drugs, have apparently not been achieved from the perspective of this study.

[Illicit Drug Exposures Reported to the Poisons Information Centre Erfurt (2011 to 2020)]. / Illegale Drogenexpositionsfälle im Einzugsbereich des Giftnotrufs Erfurt (2011 bis 2020).

AIM OF THE STUDY: Because of significant changes in recent years, cases of illicit drug exposure reported to the Poisons Information Centre (PIC) Erfurt during the last 10 years were investigated. METHODS: Retrospective analysis of above-mentioned cases from 2011 to 2020 according to substance classes, symptom severity, age groups, and gender. RESULTS: Cases of illicit drug exposure (4,963, 2.8% of all exposures) increased from 316 in 2011 to 614 in 2015, decreased to 514 in 2017, and rose again to 578 in 2019. In 2020, a drop to 549 cases was observed. The ratio of multiple to single drug exposure cases, however, increased from 1.0 to 1.7 in 2020. Cases of exposure to psychostimulants almost doubled from 168 in 2011 to 319 in 2020. Cases of exposure to new psychoactive substances (NPS) rose from 21 in 2011 to 126 in 2015 and fell to 16 in 2020. 320 cases (6.5%) of illicit drug exposures resulted in severe, 1902 cases (38.3%) in moderate and 2139 cases (43.1%) in minor or no symptoms. Age groups mainly involved were adults of middle age (72.7%) and unknown age (12.7%) as well as adolescents (12.1%). Men (69.9%) were more often involved than women (26.9%). CONCLUSIONS: Illicit drug exposures reported to the Poisons Information Centre (PIC) Erfurt discontinuously increased from 2011 to 2020 mainly by increase in mixed consumption. The intermittent decrease in 2016 and 2017 was caused by the fall of NPS exposures. Data of substance abuse from PICs could supplement official annual drug reports in aspects of Clinical Toxicology.

[Substance Abuse Poisoning Reported to the Poisons Information Centre Erfurt from 2002 to 2016]. / Substanzmissbrauch ­ Entwicklung des Vergiftungsgeschehens im Einzugsbereich des Giftnotrufes Erfurt 2002­2016.

AIM OF THE STUDY: Poisoning due to substance abuse has changed significantly during the last few years. Therefore, developments of substance abuse reported to the Poisons Information Centre Erfurt were investigated and compared to other circumstances of human exposures during the last 15 years. METHODS: Retrospective analysis of all cases of human exposures (intentional abuse, accidental and unknown circumstances, and suicide attempts) for the period 2002-2016 according to substance classes, reasons of exposures, symptom severity, age groups, and gender. RESULTS: Cases of substance abuse (n=7,237, 3.5% of all exposures) continuously increased from 250 (159 with one and 91 with multiple substances) in 2002 to 830 in 2016 (398 with one and 432 with multiple substances). Cases of exposure to metamphetamine strongly increased from 10 in 2003 to 100 in 2012 and dropped to 52 in 2016. Cases of exposure to new psychoactive substances (NPS) rose from 1 in 2008 to 130 in 2015 and fell to 90 in 2016. Substance abuse significantly (p<0.001) more often caused moderate (29.1%) and severe symptoms (5.8%) than suicide attempts (11.6%; 4.9%). NPS and their subgroup synthetic cannabinoids led significantly (p<0.001 and 0.025) more frequently to moderate and severe symptoms (46.9% and 43.6%; 7.9% and 6.0%) than cannabis exposure (19.7%; 2.1%). CONCLUSIONS: Clinical significance of substance abuse is shown by the fact that it resulted more often in moderate and severe symptoms than suicide attempts. Data of substance abuse from PICs could supplement those on clinical toxicology in official annual drug reports.

Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.

INTRODUCTION: In 2014, the "European Monitoring Centre for Drugs and Drug Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among these were indole- and indazole-based valine derivatives with a cyclohexylmethyl side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of SCs. METHODS: A prospective observational study of patients treated in emergency departments (EDs) after the intake of SCs was conducted. Clinical and laboratory data were combined and reported to a poison control centre. Serum and/or urine samples of ED patients were analyzed using LC-MS/MS. RESULTS: Forty four patients (39 male, five female, 12-48 years) were included. AB-CHMINACA (MDMB-CHMICA) was identified in 20 (19) serum samples, and in 21 (25) urine samples, respectively. In 19 of the cases, more than one SC was present. Other psychoactive substances (mainly amfetamines) were identified in seven cases, but in five out of these in urine samples only. Based on the Poison Severity Score, severity of poisoning was minor (4), moderate (31) or severe (9). Most frequently reported neuropsychiatric symptoms were CNS-depression (n = 21, 61%), disorientation (n = 20, 45%), generalized seizures (n = 12, 27%), combativeness (n = 8, 18%) and extreme agitation (n = 7, 16%). Duration of symptoms lasting 24 hours or longer occurred in 15 cases (34%). DISCUSSION: The prevalence of certain neuropsychiatric symptoms was higher in our study than in former reports after the intake of SCs of the aminoalkylindole-type (first generation) SCs. In addition, severe poisoning and duration of symptoms were also higher. CONCLUSIONS: In this study, the valine derivative AB-CHMINACA and the tert-leucine derivative MDMB-CHMICA ("third generation of SCs") seem to be associated with more severe clinical toxicity than was previously reported in patients exposed to earlier generation SCs such as JWH-018. However, this observation needs to be confirmed with a larger cohort of patients with analytically confirmed abuse of third generation SCs. The rapid turnover of SCs on the drug market together with the occurrence of SCs such as AB-CHMINACA and MDMB-CHMICA is alarming, especially because of the unexpectedly high frequency of neuropsychiatric symptoms.

[Desoxypipradrol - a new (already well known) designer drug]. / Desoxypipradrol - eine neue (alte) Designerdroge.

Novel psychoactive substances (NPS) are easily accessible and the consumption has increased in recent years. New compounds as well as compounds derived from pharmaceutical research or the patent literature are provided, mostly without any declaration. As a consequence, severe adverse reactions may occur after consumption of unknown doses of these drugs, in particular after mixed intake of different psychoactive substances or co-medication. The toxic effects in such cases are not predictable. We report cases of rhabdomyolysis in patients after consumption of desoxipipradrol in combination with other NPS. Particularly in case of synergistic serotonergic effects a distinct stimulation of 5-HT2A-receptors (or 5-HT1A-receptors) should be considered which may lead to serotonergic syndrome.