A cluster of lysergic acid diethylamide (LSD) poisonings following insufflation of a white powder sold as cocaine.

OBJECTIVE: Adulteration, substitution or contamination of illicit substances can have clinically significant implications when other illicit substances are included. Such circumstances can present as clusters of poisonings, including severe toxicity and death following exposure to unexpected illicit substances. We report a cluster of laboratory-confirmed lysergic acid diethylamide (LSD) in a powder that was sold as cocaine and used recreationally. METHODS: The Prescription, Recreational and Illicit Substance Evaluation (PRISE) program established by the New South Wales Ministry of Health includes State-based hospital toxicology services, Poisons Information Centre, Forensic & Analytical Science Service and emergency services to identify clusters of severe and unusual toxicity associated with substance use. PRISE criteria include a known cluster (geographically or situationally related) of people with acute severe toxicity, especially when accompanied by a toxidrome that is inconsistent with the history of exposure. A timely comprehensive drug screen and quantification is performed in eligible cases and the results are related to the clinical features. The need for a public health response is then considered. Four individuals inhaled a white powder that was sold as cocaine and developed severe toxicity that was not consistent with cocaine which prompted transfer to hospital for further management. RESULTS: LSD was confirmed in four subjects, and the concentrations in 3 of the individuals were 0.04-0.06 mg/L which are among the highest reported in the literature. Common clinical features were hallucinations, agitation, vomiting, sedation, hypertension, and mydriasis. One subject required intubation and admission to the intensive care unit, two required overnight admission, and the fourth was discharged following oral diazepam after observation. No subject suffered persistent injury. CONCLUSIONS: A close working relationship between pre-hospital emergency services, hospital-based clinical services, public health authorities, and analytical laboratories appears to be advantageous. Favourable clinical outcomes are observed from LSD poisoning despite high exposures with good supportive care.

Death due to consumption of ibogaine: case report.

Ibogaine is a psychotropic indole alkaloid extracted from the roots of the Tabernanthe iboga shrub from the Apocynaceae family. Depending on the taken dose, it can lead to stimulant effects, euphoria, visual and auditory hallucinations, along with auditory, olfactory, and gustatory synesthesia. In addition to its historical usage in spiritual rituals of African tribes, these days iboga extract presents a prohibited, alternative drug widely used as a part of addiction treatment. Ibogaine used in opioid withdrawal is associated with serious side effects and sudden deaths. Besides its main use as an anti-addiction medication in alternative medicine, in moderate doses (from 100mg to 1g) ibogaine most commonly causes a "trance-like state".In this paper, we report the case of a heroin addict who died suddenly 5-12 hours after oral ingestion of powder labeled Tabernanthe iboga which had been bought online and used in the process of detoxification during an addiction treatment. The man was found dead in a rented apartment, where he was undergoing the addiction treatment.External examination revealed no lesions other than nonspecific injuries on the legs. The autopsy showed congestion of internal organs and pulmonary edema. Histopathological analysis of the heart showed neither macroscopic nor microscopic abnormalities. The concentration of ibogaine was 3.26mg/L. Moreover, systematic toxicological analyses of biological samples showed the presence of morphine and codeine. These data suggest that death, which occurred unnaturally after initiation of the "treatment", was probably the result of the cardiovascular effects caused by the ibogaine powder.The presented case highlights the worldwide problem of various products being widely available over the internet and the danger associated with consumption thereof.

Management of overdoses of salvia, kratom, and psilocybin mushrooms: a literature review.

INTRODUCTION: Despite the relative reduction in opioid and other illicit substance overdoses in the past few years, clinicians must remain vigilant in keeping up to date on emerging trends with regard to potential substances of abuse. As overdoses of traditional drugs of abuse decrease in light of legislative and de-prescribing initiatives, it stands to reason that alternative agents, including natural products, have increased. Toxicities associated with these agents have been contributing to emergency department visits across the globe. AREAS COVERED: This evaluation covers salvia, kratom, and psilocybin mushrooms, and was accomplished through a comprehensive review of PubMed, SCOPUS, ProQuest Central, ProQuest Dissertations, and CINAHL. Thirty-one pieces of literature are included in this evaluation. The objective of this review is to provide clinicians with the information necessary to provide bedside care for overdoses of salvia, kratom, and psilocybin mushrooms. EXPERT OPINION: Salvia, kratom, and psilocybin mushrooms may not be an initial consideration when healthcare practitioners are triaging an overdose scenario; however, data from around the world demonstrate an increased use of these agents. While not typically fatal, clinicians must be prepared to assess these as a potential etiology of overdoses and provide appropriate supportive care.

Syrian rue seeds interacted with acacia tree bark in an herbal stew resulted in N,N-dimethyltryptamine poisoning.

Introduction: Illicit substance use is an increasing problem all over the world, especially in adolescents and young adults. It is a challenge to make a definitive diagnosis of a specific substance in a poisoning case without toxicology laboratory confirmation. We confirmed the presence of N,N-dimethyltryptamine (DMT) by liquid chromatograph tandem mass spectrometer (LC/MS/MS) in biologic samples from two patients who presented with signs and symptoms consistent with sympathomimetic toxicity following the consumption of an herbal stew. Case: Two patients consumed an herbal stew together developed DMT poisoning from the interaction between Syrian rue seeds containing alkaloids with monoamine oxidase inhibitor (MAOI) activity and Acacia tree bark containing DMT. Patients' blood and spot urine was analyzed by LC/MS/MS which revealed the presence of DMT (case 1 urine: 1206 ng/mL, serum: 25 ng/mL; case 2 urine: 478 ng/mL, serum: undetectable) and harmaline (case 1 urine: 1564 ng/mL, serum: 3.3 ng/mL; case 2 urine: 1230 ng/mL, serum: undetectable). Discussion: The diagnosis of DMT poisoning is confirmed by the presence of DMT and harmaline in patients' serum and urine. Case 1 exhibited more severe signs and symptoms (e.g., altered consciousness, rhabdomyolysis, and elevated liver enzyme) than case 2. This may be explained by the presence of psychoactive DMT levels in the blood of case 1 whereas DMT was undetected in the blood of case 2. Conclusions: Consumption of an herbal stew composed of Syrian rue seeds and Acacia tree bark may be equivalent to taking a combination of DMT and MAOI, which may precipitate a sympathomimetic syndrome. Physicians should be aware that unusual clinical presentations may be the result of drug-drug interactions from a mixed herbal preparation.

Clinical and Toxicological Profile of NBOMes: A Systematic Review.

BACKGROUND: NBOMes are a new class of potent hallucinogens widely present in illicit drugs. Little is known about this class of drugs, regarding its detection and clinical manifestations of intoxication. OBJECTIVE: This study aims to enhance care involving NBOMes by reviewing the literature on their clinical manifestations and laboratorydetection. METHODS: A systematic review was performed on the clinical manifestations and laboratory tests of NBOMEs ingestion. Embase, Pubmed, PsycINFO, and Cochrane databases were employed in this analysis. RESULTS: Forty-five articles met the inclusion criteria out of the 2814 nonduplicated studies on the theme. Seventy case reports of intoxication were found in the analyzed articles (64.3% were men and 11.4% were women, mean age of 22.5). The technique most employed for NBOMes identification was chromatography of blood, urine, and oral fluids. Moreover, the studies identified 13 chemical structures differentfrom the NBOMes on their toxicological analyses.According to these studies, most of these drugs were ingested orally-nasal use was the second preferred administration route, followed by intravenous administration. CONCLUSION: Better identification of the clinicalmanifestations and laboratory profile of NBOMes is crucial to the recognition of intoxication as well as to its effective treatment.

Does getting high hurt? Characterization of cases of LSD and psilocybin-containing mushroom exposures to national poison centers between 2000 and 2016.

BACKGROUND: Lysergic acid diethylamide (LSD) and psilocybin are serotonergic hallucinogens that are used primarily for recreational abuse. Small studies evaluated the efficacy of LSD and psilocybin for several psychiatric conditions. There are limited safety or toxicity data for either of these substances, especially in large populations. METHODS: This was a retrospective analysis of single-substance exposures of LSD or psilocybin-containing mushrooms (PcMs) reported to United States poison centers from 1 January 2000 to 31 December 2016. The study describes the most frequent toxicities, management sites, and medical outcomes. RESULTS: A total of 5883 PcM and 3554 LSD exposures were included. Most patients were between 13 and 29 years of age (83.9% PcM, 88.9% LSD) and primarily male (77.9% PcM, 74.1% LSD). Most common clinical effects were hallucinations (45.8% PcM, 37.4% LSD), agitation (24.1% PcM, 42.4% LSD), and tachycardia (18.0% PcM, 38.6% LSD). Serious clinical effects were infrequent, but included hyperthermia, seizures, coma, increased serum creatinine, and cardiac arrest. Most patients were treated and released from the emergency department. More LSD patients were admitted to critical care and non-critical care units than PcM patients. Moderate effect was the most frequent outcome for both substances (61.0% PcM, 62.3% LSD). CONCLUSION: These data find that LSD and PcM use occurs primarily in adolescents and young adults, who experience mild to moderate adverse effects. Serious effects are infrequent but can occur. While most LSD and PcM users require only emergency department management, LSD use is more likely to require medical admission.

Fatality Following Ingestion of Tetrahydrofuranylfentanyl, U-49900 and Methoxy-Phencyclidine.

Novel psychoactive substances (NPS), and specifically novel opioids, continue to cause adverse events, including death, within drug-using populations. As the number of opioid-related overdoses continues to increase, laboratories have identified the emergence of new fentanyl analogues and other synthetic opioid-related drugs. Tetrahydrofuranylfentanyl (THFF) has been identified in Europe and the United States as an emerging novel opioid, causing death in at least 15 drug-using individuals to date. THFF is structurally similar to furanylfentanyl, a previously characterized novel opioid responsible for numerous adverse events, including death. In this case report, THFF, U-49900 and methoxy-phencyclidine were identified in postmortem blood and urine specimens collected after a suspected overdose. As part of the death investigation, an unknown substance was collected from the scene and analytically confirmed as THFF and U-49900. To further assist laboratories in identifying THFF ingestion, metabolic profiling was conducted using pooled human liver microsomes. Characterized metabolites were then confirmed in the specimens collected during this investigation. In total, seven metabolites were identified for THFF, most notably THF-norfentanyl and hydroxyl-THFF. THF-norfentanyl provides utility as a biomarker because it is a unique metabolite of THFF. 4-Anilino-N-phenethylpiperidine (4-ANPP) and its metabolite, hydroxyl-4-ANPP, were identified in microsomal incubations and collected specimens, but usefulness as biomarkers is limited due to commonality between other fentanyl analogues and co-ingestion as a synthesis precursor. To our knowledge, this case report is the first to document a fatality after ingestion of THFF and U-49900 in the United States.

Retrospective Demonstration of 25I-NBOMe Acute Poisoning Using Hair Analysis.

BACKGROUND: The abuse of new psychoactive substances or NPS has been dramatically increasing all around the world since the last half of the year 2000 and has become a serious public health problem. NPS are a challenge for the worldwide forensic community due to the difficulties to accurately document the cases. The N-benzylmethoxy (NBOMe) group is a new class of hallucinogenic designer drugs and has gained importance in recent years. 25I-NBOMe (2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)- methyl]ethanamine) is an analog of the 2C series of psychedelic phenethylamine drugs that contain an N-methoxybenzyl substituent, which significantly affects their pharmacological activities. It is a potent agonist of 5-HTA receptors and a severe hallucinogenic drug, with numerous irreversible psychedelic effects which can last from 5 to 10 hours. It is consumed most often in the form of drops or blotters by the transmucosal, sublingual or intranasal routes. The active dosage is very low, supposed to be less than 100 µg. The literature is poor in reporting cases where 25I-NBOMe was identified. Only very few clinical cases of over dosages were published, suggesting a low prevalence of this compound. METHODS: We present a retrospective demonstration of 25I-NBOMe acute poisoning with dramatic outcome, using hair analysis. Two hair strands, measuring 9.5 cm, were collected 6.5 months after drug consumption during a forensic clinical evaluation of brain dysfunctions after cardiorespiratory arrest and were analyzed by ultra-high performance liquid chromatography system coupled to a tandem mass spectrometry (UPLC-MS/MS) and using two specific transitions: m/z 428.1 > 121.2 (quantification) and 428.1 > 90.6 (confirmation). Hair strands were segmented to determine the historic pattern of drug use and differentiate a single exposure from a chronic exposure. The hair test result for 25I-NBOMe was the following: not detected (0-2 cm), not detected (2-4 cm), 1.0 pg/mg (4-6 cm), 4.9 pg/mg (6-8 cm) and not detected (8-9.5 cm). RESULT: The result of the segment 6-8 cm coincides with the date of consumption (calculated with a hair growth rate at 1 cm/month) and the low concentration detected in the segment 4-6 cm probably corresponds to the contribution of dormant hair. The toxicological significance of the measured concentrations is difficult to determine because this is the first case dealing with hair analysis for 25I-NBOMe. CONCLUSION: The use of hair analysis for NPS is still at the initial stages. In particular, little is known about the incorporation into the keratin matrix after intake and the correlation between dosage frequency of use, and hair concentrations. Under these circumstances, NPS hair analysis should be cautiously interpreted by experienced forensic toxicologist.

NBOMe hallucinogenic drug exposures reported to the Danish Poison Information Centre.

INTRODUCTION: N-benzylmethoxy (NBOMe) is a new class of hallucinogenic designer drugs sold on cheap blotter papers. They are potent 5-hydroxytryptamine-2A-receptor agonists, and since their recent entry into the drug market there have been worldwide reports of severe intoxications and even fatalities. This study reviews suspected NBOMe drug exposures reported to the Danish Poison Information Centre (DPIC). METHODS: Data from the DPIC database were extracted, including all enquiries with NBOMe exposures reported from 1 January 2013 to 30 June 2016. The following data were extracted: age, sex, date of exposure, risk assessment, co-exposures, geography and reported symptoms. RESULTS: A total of 43 cases were identified: one in 2013, five in 2014, 32 in 2015 and five in the first six months of 2016. The mean patient age was 21 years (range: 15-34 years) with 32 (74%) male and 11 (26%) female patients. The patients most frequently presented with hallucinations/psychosis (n = 18), tachycardia (n = 18) and agitation (n = 15). A total of 16 patients were admitted with co-exposures to other drugs such as alcohol (n = 9), cannabis (n = 7), amphetamine (n = 5) cocaine (n = 3), benzodiazepines (n = 1) and 3,4-methylenedioxymethamphetamine (n = 1). The cases were distributed evenly across the entire country with only ten cases having a postal address in one of the three major cities of Denmark. CONCLUSIONS: This study has shown a steep and sudden rise in reported NBOMe exposures in Denmark within 3-4 years. Geographical data demonstrate an even distribution throughout the country. However, our results also suggest that the use has started to decline. FUNDING: none. TRIAL REGISTRATION: This study was approved by the Danish Data Protection Agency. (BFH-2016-070/04985).

A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP.

INTRODUCTION: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016. CASE DESCRIPTIONS: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse. METHODS: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry. RESULTS: In the clinical case, the concentration of 3-MeO-PCP was 0.14µg/g at admission, 0.08µg/g 2.5h after admission, 0.06µg/g 5h after admission and 0.04µg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05µg/g to 0.38µg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well. CONCLUSION: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.

Ecstasy-Intoxikation mit disseminierter intravasaler Gerinnung und Multiorganversagen.

This case presents the clinical treatment of a patient with severe MDMA intoxication. The history of stimulating psychotropic substances is presented as well as the modes of action of current party drugs. Data from the Austrian Drug Report indicate a tendency away from "hard drugs" towards the consumption of cannabis and amphetamine derivates. The lethal outcome in our case demonstrates the risk potential of these substances and underlines the necessity of aggressive resuscitation efforts.

Mistaking 2C-P for 2C-B: What a Difference a Letter Makes.

2,5-Dimethoxy-4(n)-propylphenethylamine (2C-P) is a synthetic phenethylamine derivative belonging to the large family of the so-called 2C drugs. These compounds can differ significantly in receptor affinity, potency and duration of action, and an important structural difference is the ligand in the 4 position of the phenyl ring, such as propyl in 2C-P or bromine in 2,5-dimethoxy-4-bromophenethylamine (2C-B). The 2C drugs are known for their hallucinogenic properties. We present a case of a 19-year-old male admitted to the emergency department with severe hallucinations, mydriasis, tachycardia, agitation and confusion following the use of a substance sold as 2C-B. By using liquid chromatography-mass spectrometry, the more potent substance 2C-P was detected and quantified. On the basis of two blood sample concentrations, the estimated elimination half-life was 19 h. This case report illustrates and discusses the differences in potency and duration of action of 2C drugs.

Ayahuasca Exposure: Descriptive Analysis of Calls to US Poison Control Centers from 2005 to 2015.

BACKGROUND: Ayahuasca is a hallucinogenic plant preparation which usually contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea originates from the Amazon Basin where it is used in religious ceremonies. Because interest in these religious groups spreading as well as awareness of use of ayahuasca for therapeutic and recreational purposes, its use is increasing. Banisteriopsis caapi is rich in ß-carbolines, especially harmine, tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI) activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include hallucination, dissociation, mood alteration and perception change. Undesired findings previously reported are nausea, vomiting, hypertension, and tachycardia. METHODS: All human exposure calls reported to the American Association of Poison Controls Centers' (AAPCC) National Poison Data System (NPDS) between September 1, 2005 and September 1, 2015 were reviewed. Cases were filtered for specific plant derived ayahuasca-related product codes. Abstracted data included the following: case age and gender, exposure reason, exposure route, clinical manifestations, treatments given, medical outcomes and fatality. RESULTS: Five hundred and thirty-eight exposures to ayahuasca botanical products were reported. The majority of the calls to poison control centers came from healthcare facilities (83%). The most common route of exposure was ingestion. Most cases were men (437, 81%, 95% CI 77.7% - 84.3%). The median age was 21 (IQR 18-29). Most exposures were acute. Three hundred thirty-seven (63%) were reported to have a major or moderate clinical effect. The most common clinical manifestations reported were hallucinations (35%), tachycardia (34%), agitation (34%), hypertension (16%), mydriasis (13%) and vomiting (6%). Benzodiazepines were commonly given (30%). There were 28 cases in the series who required endotracheal intubation (5%). Four cases were reported to have had a cardiac arrest and 7 a respiratory arrest. Twelve cases had a seizure. Reports of exposures called to poison centers appeared to increase during this period based on annual estimates. Three fatalities were reported. CONCLUSIONS: Ayahuasca use appears to be rising in the United States based on calls to poison control centers. While most use is reported to be safe and well tolerated, with possible beneficial effects, serious and life threatening adverse manifestations are possible. Most of the exposures reported to poison control centers were young people, more likely to be men and already in a healthcare facility. Further research, which includes comprehensive drug testing, will be needed to better identify the risks and effects of ayahuasca use.

Medicolegal aspects of PMA-related deaths.

Unlike amphetamine, amphetamine-like substances accessible on the drug market are less expensive and more easily available; they also produce hallucinogenic effects expected by the users. Such properties render them more attractive as compared to amphetamine. On the other hand, the knowledge of the toxicity of these compounds is very limited, what in consequence generates problems that create ever-expanding research areas, including analytical, clinical and medicolegal issues, thus leading to development of systemic databases. An example here is paramethoxyamphetamine (PMA), which appeared on the drug market in recent years as a result of creative inventiveness of producers of psychoactive substances, who aimed at PMA replacing the popular ecstasy (MDMA) as a less expensive and more available product. It is more potent than MDMA, but has a slower onset of action, which encourages users to take more. The problem is illustrated in the present paper by three fatal cases involving PMA, which were comprehensively investigated taking into consideration case histories, pathological and toxicological findings obtained with the use of LC-MS-MS method. In blood samples taken from all the three victims, very high concentrations of PMA were found (in the range of 10-27mg/L) and thus the cause of deaths was determined as overdoses of PMA with the underlying mechanism of acute cardiorespiratory failure.

A fatal case of paramethoxyamphetamine poisoning and its detection in hair.

Paramethoxyamphetamine (PMA) is a phenethylamine derivative that is structurally related to 3,4-methylenedioxymethamphetamine (MDMA), but has higher toxicity than MDMA. Here, we report a fatal intoxication case involving PMA. A 36-year-old man was found dead in a hotel room. Toxicological analysis revealed that PMA concentrations were 0.57 and 0.59mg/L in peripheral and heart blood, respectively. Ketamine and diazepam were also detected in his blood. Based on toxicological results and autopsy findings, the cause of death was determined to be acute fatal intoxication with PMA. Hair analysis using gas chromatography/mass spectrometry was performed and PMA was detected at a concentration of 20.1ng/mg after methanol extraction for 20h. This is the first report of the determination of PMA concentration in the hair from a drug abuser.

Hallucinogen Use Disorders.

Use of hallucinogenic substances as a public health concern has increased over the past decade. Among adolescents, there are increasing emergency department presentations for intoxication with these drugs, contrary to decreasing reported use of classical hallucinogens such as LSD. Academic and governmental groups have monitored use of hallucinogens, highlighting a notable change in perceptions about use among adolescents thought to contribute to these trends. Special populations and religious groups, though, have been granted governmental permission to use hallucinogens for their cultural practices. Novel designer hallucinogens have gained popularity and may have serious medical and psychological side effects from use.

"Herbal seizures"--atypical symptoms after ibogaine intoxication: a case report.

INTRODUCTION: Misuse of various new psychotropic substances such as ibogaine is increasing rapidly. Knowledge of their negative side effects is sparse. CASE PRESENTATION: We present a case of intoxication with the herbal substance ibogaine in a 22-year-old white man. After taking a cumulative dose of 38 g (taken in two doses), he developed visual memories, nausea and vomiting. He developed a generalized tonic-clonic seizure with additional grand mal seizures. He was treated with midazolam and levetiracetam. Extended drug screenings and computed tomography and magnetic resonance imaging findings were all negative. CONCLUSIONS: Knowledge of the side effects of ibogaine has mainly come from reports of cardiovascular complications; seizures are rarely mentioned and experimental findings are inconsistent. It seems that ibogaine acts like a proconvulsive drug at high doses.