Is tetrodotoxin intoxication the cause of "zombi voice" in Haiti?

OBJECTIVE: Zombification, a magical and religious process in Haiti, has been scientifically studied and remains relevant. Originating from the convergence of African, Caribbean, and Christian rites, it involves a comatose trance, transforming individuals into living dead through Voodoo practices. Haitian zombies consistently exhibit a preserved expression marked by a nasal voice, a result of nasalization-using nasal cavities as resonators during phonation. The aim of this study was to ascertain the mechanisms through which zombification could impact the voices of the subjects. METHODS: A comprehensive investigation was conducted using both primary and secondary sources. Primary sources involved direct or reported testimonies of individuals undergoing zombification, with audio or video recordings available from the collections of the Laboratory of Anthropology, Archaeology, and Biology (UVSQ/Paris-Saclay University), as well as on the internet. Secondary sources encompassed the entirety of existing literature regarding zombification in Haiti on one hand, alterations in the voices of subjects when mentioned on the other hand, and toxicological hypotheses or evidence available on PubMed/Medline and Google Scholar. RESULTS: Few post-zombification observations exist, but 20th-century studies clarified the physio pathological process, confirming its reality. Wade Davis demonstrated in 1983 that zombification results from poisoning, with effects ranging from reversible to fatal, implicating substances like tetrodotoxin and datura. Nasalization can be natural or pathological, affecting various phonemes. No mutilating acts or surgery have been reported related to Haitian zombification. CONCLUSION: The pharmacological characteristics of tetrodotoxin, coupled with testimonials, present a medical hypothesis elucidating the biological mechanism underlying nasalization in this context. Given that tetrodotoxin induces flaccid paralysis as a neurotropic poison, its neurological impact could account for soft palate paralysis or spasms. Additionally, the severe hypotension induced by tetrodotoxin may elucidate oral and pharyngeal necrosis.

Impulsivity and self-harm behavior in patients with synthetic cannabinoids dependence.

BACKGROUND: Synthetic cannabinoids (SCs) dependence is increasingly prevalent among young individuals globally, with limited understanding of their potential detrimental effects. Therefore, we conducted this comparative study to assess impulsivity and non-suicidal self-harm behavior in patients with SCs dependence. SUBJECTS AND METHOD: We conducted this comparative, case-control study in the outpatient clinics of (Beni-suef University Hospital). We recruited 30 patients with SCs dependence and the 30 healthy subjects as a control group. Psychometric scales, including Addiction Severity Index (ASI), Barratt Impulsivity Scale-11 (BIS-11), Deliberate Self-harm Inventory-Short Version (DSHI), SCID I, SCID II, and drug urine screen, were applied to compare the two study arms. RESULTS: DSHI-s scores were significantly higher between the two study arms (3.23 ± 4.97 vs. 0.0 ± 0.0, p < 0.001, for cases and controls, respectively). Similarly, the mean ± SD score of the BIS scale was significantly higher in cases 68.13 ± 9.75 compared to the control group (45.67 ± 5.12) with a statistically significant difference (p < 0.001). Using the regression analysis, we observed a significant positive linkage between age, duration of substance use, DSHI-s, and the Barratt scale. CONCLUSION: Patients with synthetic cannabis addiction exhibited more impulsivity and self-harm behaviors compared to healthy controls. The adverse effects of substance use disorder escalated, notably in individuals classified as having severe addiction based on the Addiction Severity Index. Age and length of substance use were found to be potential factors influencing the level of impulsivity and self-harm actions.

Discrepancies between the stated contents and analytical findings for electronic cigarette liquid products: Identification of the new cannabinoid, Δ9-tetrahydrocannabihexol acetate.

A number of synthetic cannabinoids have been appearing in the recreational drug market for more than a decade. Recent additions are so-called semi-synthetic cannabinoids, and they structurally closely resemble the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol. Knowledge of new (semi-)synthetic cannabinoids is essential to help identify them in authentic forensic case samples. Therefore, the aim of the study was to examine two commercially available electronic cigarette liquid products claiming to contain cannabinoids and characterize the structures of the main compounds. The liquid products were analyzed by gas chromatography-mass spectrometry (GC-MS), GC-quadrupole time-of-flight mass spectrometry (GC-QTOF-MS), and liquid chromatography-high-resolution mass spectrometry (LC-HRMS). In product A, typical cannabinoids (cannabidiol, cannabigerol, and cannabinol) and terpenes (α-caryophyllene and ß-caryophyllene) were identified by comparison with reference materials. An unknown peak was isolated by semi-preparative high-performance LC, analyzed by nuclear magnetic resonance (NMR) spectroscopy, and identified to be Δ9-tetrahydrocannabihexol acetate (Δ9-THCH-O). To the authors' knowledge, this is the first report of the identification of Δ9-THCH-O in commercially available products. Another compound estimated as cannabihexol acetate was also detected. In product B, cannabidiol, cannabinol, α-caryophyllene, and ß-caryophyllene were identified, while two unknown peaks were estimated as tetrahydrocannabidiol isomers. Despite products A and B being labeled to contain "60% HHCPM" and "80% 10-OH-HHC," respectively, no such compounds were detected. The findings of this study could help detect Δ9-THCH-O in case samples and highlight the need to keep monitoring commercial products to identify new drugs, while warning that the package labels cannot be trusted.

Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?

Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC-MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.

JWH-182: a safe and effective synthetic cannabinoid for chemotherapy-induced neuropathic pain in preclinical models.

Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation.

Synthetic Cannabinoid Identification in Cases Associated with Blue Lotus and Valerian Root.

Synthetic cannabinoids emerged in the early 21st century and have continued to evolve and flourish to present day. Like other novel psychoactive substances (NPS), synthetic cannabinoids have been sold under the guise of legitimate products. Some examples include "potpourri," "incense," and herbal material. Between May 2020 and December 2023, Drug Chemistry Lab (Chem Lab) received 29 seized drug cases mentioning "blue lotus" or "valerian root." In 90% of these cases, at least one exhibit contained one or more synthetic cannabinoids. During the same timeframe, Toxicology Lab (Tox Lab) received 65 toxicology cases that contained synthetic cannabinoids and/or their corresponding hydrolyzed metabolites where case history mentioned "blue lotus." The most frequently observed compounds between laboratories were 5F-MDMB-PICA, ADB-BUTINACA, and MDMB-4en-PINACA. Innocuous branding and marketing may deceive law enforcement, investigators, and healthcare providers into believing that the adverse effects of erratic behavior, sedation, slurred speech, and hallucinations are a result of toxicity from botanical extracts (e.g., apomorphine and nuciferine in blue lotus). Due to the dangerous nature of these NPS, it is recommended that synthetic cannabinoid screening is performed on all cases where there is suspected use of vaping products suggested to contain "blue lotus" or "valerian root" as drug vendors continue to conceal the presence of these compounds.

In vitro activation of the CB1 receptor by the semi-synthetic cannabinoids hexahydrocannabinol (HHC), hexahydrocannabinol acetate (HHC-O) and hexahydrocannabiphorol (HHC-P).

Semi-synthetic cannabinoids (SSCs) including hexahydrocannabinol (HHC) are emerging on the drug market and sold openly as purportedly legal replacements for cannabis and Δ9-THC. By the beginning of 2024, 24 European countries had identified HHC, often sold openly in edibles (foods/candy), vapes and low-THC cannabis flowers and resins. The SSC market is developing rapidly, with HHC acetate (HHC-O), hexahydrocannabiphorol (HHC-P) and others recently identified. These developments may mark the first major change in the market for 'legal' replacements to cannabis since 'Spice' containing synthetic cannabinoids, such as JWH-018, emerged in 2008. Currently, there are some data available on the pharmacology of SSCs, which is crucial for understanding their effects, evaluating health risks and informing public health responses. This study focused on characterizing the in vitro activation of the human CB1 receptor by the (R)- and (S)-epimers of HHC, HHC-P and HHC-O. Using recombinant CHO-K1 cells expressing the human CB1 receptor, the potency (EC50) and efficacy were determined. It was established that (9R)-HHC and (9R)-HHC-P activated the CB1 receptor as partial agonists and with five and two times lower potency compared to JWH-018, respectively, while the (S)-epimers exhibited even lower potency. The (R)-epimer of HHC-O activate the CB1 receptor to even lesser extent and the (S)-epimer showed no activation. For HHC and HHC-P, all epimers exhibited similar level of efficacy. This available evidence suggests cannabimimetic effects of the tested SSC with the exception for the acetates that likely function as pro-drugs in vivo.

Low-triggering-potential electrochemiluminescence based on mental-organic frameworks encapsulation of ruthenium for synthetic cathinone detection by coupling photonic crystal light-scattering signal amplification of covalent-organic frameworks.

Developing effective electrochemiluminescence (ECL) platforms is always an essential concern in highly sensitive bioanalysis. In this work, a low-triggering-potential ECL sensor was designed for detecting synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) based on a dual-signal amplification strategy. Initially, a probe was created by integrating Ruthenium into the hollow porphyrin-based MOF (PCN-222) structure to decrease the excitation potential and enhance ECL performance without external co-reaction accelerators. Additionally, for the first time, photonic crystals (PCs) assembled from covalent organic frameworks (COFs) were employed to amplify the ECL signal, thereby increasing the photon flux and the loading capacity of the ECL emitter to enhance sensitivity of the sensor. In the presence of the target MDPV, the aptamer labeled with Ferrocene (Fc) experienced conformational changes, causing Fc to approach the luminophore and resulting in ECL quenching. This effect was attributed to aptamer's conformational changes induced by the target, directly correlating with the target concentration. The constructed sensor showed good linearity with the target MDPV concentration, covering a dynamic range from 1.0 × 10-14 to 1.0 × 10-6 g/L and achieved an ultra-low detection limit of 4.79 × 10-15 g/L. This work employed dual amplification strategies to enhance ECL signals effectively, providing a novel method for developing highly responsive and bioactive sensors.

An Internet Snapshot Survey Assessing the sale of Synthetic Cannabinoid Receptor Agonists for use with Electronic Vaping Devices.

INTRODUCTION: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web. METHODS: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.com' using the search terms "buy c-liquid vape", "buy herbal incense vape liquid", "buy cannabis vape liquid", "buy hashish vape liquid", "buy K2 vape liquid". RESULTS: 62 websites selling 128 SCRA vaping brands were identified. Most were purportedly based in the USA (41 websites, 66%) and most sold other controlled substances. Purchase incentives offered included discreet packaging (38, 61%), discounts for bulk purchase (34, 55%) and tracked delivery (30, 48%). Many websites stated SCRA products were: not for human consumption (41, 66%), for research purposes only (15, 24%), or legal (28, 45%). Websites sold a median (IQR) of 16 (7-25) SCRA vaping brands. Almost all were bottles of vaping liquid (1220/1225, 99.6%). The most common bottle size was 5mL (60%), the median (IQR) total volume of SCRA liquid per sale was 50mL (10-200mL). Median (IQR) price was £3.39/mL (£2.01/mL- £5.29/mL). Price decreased with increasing volume purchased (£6.58/mL for ≤ 5mL, £1.60/mL for > 200mL). CONCLUSION: SCRA vaping products are easily obtainable online, in both small and bulk quantities. Information provided to purchasers on safety and legality is lacking or misleading. Further studies are needed to confirm the chemistry of these products. Policymakers should consider steps to limit the potential harm caused by the purchase and use of these products.

Delineating the molecular mechanisms of hippocampal neurotoxicity induced by chronic administration of synthetic cannabinoid AB-FUBINACA in mice.

Chronic use of synthetic cannabinoids (SCs) has been associated with cognitive and behavioural deficits and an increased risk of neuropsychiatric disorders. The underlying molecular and cellular mechanisms of the neurotoxic effects of long-term use of SCs have not been well investigated in the literature. Herein, we evaluated the in vivo effects of chronic administration of AB-FUBINACA on the hippocampus in mice. Our results revealed that the administration of AB-FUBINACA induced a significant impairment in recognition memory associated with histopathological changes in the hippocampus. These findings were found to be correlated with increased level of oxidative stress, neuroinflammation, and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating synaptic plasticity integral for promoting learning and memory in the hippocampus. Additionally, we showed that AB-FUBINACA significantly decreased the expression of NR1, an important functional subunit of glutamate/NMDA receptors and closely implicated in the development of toxic psychosis. These findings shed light on the long-term neurotoxic effects of SCs on hippocampus and the underlying mechanisms of these effects. This study provided new targets for possible medical interventions to improve the treatment guidelines for SCs addiction.

[Toxicology of synthetic cannabinoids]. / Toxicologie des cannabinoïdes de synthèse.

Synthetic cannabinoids (CS), or synthetic endocannabinoid receptor agonists, were initially synthesized for basic research into exocannabinoid signaling pathways, as well as in clinical research for their analgesic properties. The use of CS for recreational purposes is a recent phenomenon, but one that has grown very quickly in recent years, since these molecules now represent the main category of new synthetic products (NPS). This literature review aims to bring together current data regarding the use and effects caused by CS in humans. The relationship between the structure and activity of these CSs, the pharmacology and adverse effects of these CSs and finally the different methods of analyzing CSs. A better understanding of this phenomenon is essential to raise awareness among stakeholders in the health field.

A systematic review of novel cannabinoids and their targets: Insights into the significance of structure in activity.

To provide a comprehensive framework of the current information on the potency and efficacy of interaction between phyto- and synthetic cannabinoids and their respective receptors, an electronic search of the PubMed, Scopus, and EMBASE literature was performed. Experimental studies included reports of mechanistic data providing affinity, efficacy, and half-maximal effective concentration (EC50). Among the 108 included studies, 174 structures, and 16 targets were extracted. The most frequent ligands belonged to the miscellaneous category with 40.2% followed by phytocannabinoid-similar, indole-similar, and pyrrole-similar structures with an abundance of 17.8%, 16.6%, and 12% respectively. 64.8% of structures acted as agonists, 17.1 % appeared as inverse agonists, 10.8% as antagonists, and 7.2% of structures were reported with antagonist/inverse agonist properties. Our outcomes identify the affinity, EC50, and efficacy of the interactions between cannabinoids and their corresponding receptors and the subsequent response, evaluated in the available evidence. Considering structures' significance and very important effects of on the activities, the obtained results also provide clues to drug repurposing.

Identification of ADB-5'Br-BINACA in plant material and analytical characterization using GC-MS, LC-QTOF-MS, NMR and ATR-FTIR.

Synthetic cannabinoids are a class of novel psychoactive substances that emerged in the drug market in the early 2010s. Since then, a wide range of different synthetic cannabinoids has been detected in drug materials and in biological specimens collected from intoxication cases. In general, synthetic cannabinoids are reported first in seized materials. In this study, the identification of the novel synthetic cannabinoid, ADB-5'Br-BINACA is reported. A plant material suspected to contain a synthetic cannabinoid was extracted and analyzed. Analyses were performed using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and one dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. An aliquot of the sample was extracted using methanol and deuterated chloroform, and analyzed via GC-MS and NMR, respectively. Further dilution of the methanolic extract was analyzed via LC-QTOF-MS. For ATR-FTIR analyses, a few drops of the extract in deuterated chloroform were analyzed. GC-MS, LC-QTOF-MS, and 1H NMRwere successfully used to elucidate and confirm the structure of ADB-5'Br-BINACA in the drug sample. ATR-FTIR and 13C NMR analyses of the extracts did not result in significant information for the confirmation of ADB-5'Br-BINACA in the plant material likely due to low amount of drug material and high background noise. The chemical characterization of ADB-5'Br-BINACA in an authentic sample is reported herein, and chromatographic, mass spectrometric and spectroscopic data are provided for use in future analysis of this drug in suspected samples.

Perioperative Cannabinoids Significantly Reduce Postoperative Opioid Requirements in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.

Synthesis of novel indol-3-acetamido analogues as potent anticancer agents, biological evaluation and molecular modeling studies.

Cannabinoids bind to cannabinoid receptors CB1 and CB2 and their antitumoral activity has been reported against some various cancer cell lines. Some synthetic cannabinoids possessing indole rings such as JWH-015 and JWH-133 particularly bind to the cannabinoid CB2 receptor and it was reported that they inhibit the proliferation and growth of various cancer cells without their psychoactive effects. However, the pharmacological action mechanisms of the cannabinoids are completely unknown. In this study, we report the synthesis of some new cannabinoidic novel indoles and evaluate their anticancer activity on various cancerous and normal cell lines (U87, RPMI 8226, HL60 and L929) using several cellular and molecular assays including MTT assay, real-time q-PCR, scratch assay, DAPI assay, Annexin V-PE/7AAD staining, caspase3/7 activity tests. Our findings indicated that compounds 7, 10, 13, 16, and 17 could reduce cell viability effectively. Compound 17 markedly increased proapoptotic genes (BAX, BAD, and BIM), tumor suppressor gene (p53) expression levels as well as the BAX/BCL-2 ratio in U87 cells. In addition, 17 inhibited cell migration. Based on these results, 17 was chosen for determining the mechanism of cell death in U87 cells. DAPI and Annexin V-7AAD staining results showed that 17 induced apoptosis, moreover activated caspase 3/7 significantly. Hence, compound 17, was selected as a lead compound for further pharmacomodulation. To rationalize the observed biological activities of 17, our study also included a comprehensive analysis using molecular docking and MD simulations. This integrative approach revealed that 17 fits tightly into the active site of the CB2 receptor and is involved in key interactions that may be responsible for its anti-proliferative effects.

An emerging trend in Novel Psychoactive Substances (NPSs): designer THC.

Since its discovery as one of the main components of cannabis and its affinity towards the cannabinoid receptor CB1, serving as a means to exert its psychoactivity, Δ9-tetrahydrocannabinol (Δ9-THC) has inspired medicinal chemists throughout history to create more potent derivatives. Initially, the goal was to synthesize chemical probes for investigating the molecular mechanisms behind the pharmacology of Δ9-THC and finding potential medical applications. The unintended consequence of this noble intent has been the proliferation of these compounds for recreational use. This review comprehensively covers the most exhaustive number of THC-like cannabinoids circulating on the recreational market. It provides information on the chemistry, synthesis, pharmacology, analytical assessment, and experiences related to the psychoactive effects reported by recreational users on online forums. Some of these compounds can be found in natural cannabis, albeit in trace amounts, while others are entirely artificial. Moreover, to circumvent legal issues, many manufacturers resort to semi-synthetic processes starting from legal products extracted from hemp, such as cannabidiol (CBD). Despite the aim to encompass all known THC-like molecules, new species emerge on the drug users' pipeline each month. Beyond posing a significantly high public health risk due to unpredictable and unknown side effects, scientific research consistently lags behind the rapidly evolving recreational market.

Acute Liver Ischemia Caused by Vasculitis Due to the Use of Synthetic Cannabinoids.

Teaching Point: Synthetic cannabinoids are drugs whose use has increased significantly in recent years and whose toxicological effects cannot be ignored. Chronic inflammatory processes such as vasculitis that may be caused by these substances pose serious health problems at all ages.

Brodifacoum contamination of synthetic cannabinoid causing unexplained coagulopathy in multiple trauma: A case report.

An 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated partial thromboplastin time. Thromboelastography demonstrated a flatline tracing. The patient denied use of anticoagulation but admitted to synthetic cannabinoid use. It was believed the patient had taken synthetic cannabinoid contaminated by brodifacoum. She was therefore given prothrombin complex concentrate and vitamin K with blood products. The patient underwent sequential embolization, laparotomy, thoracotomy, and repair of the vena cava with a shunt. Thirty minutes postoperatively, her coagulation tests and thromboelastography were much improved. Two and a half hours postoperatively, it was determined she had sustained non-survivable injuries. The patient experienced brain death due to prolonged hypotension as a result of hemorrhagic shock with bleeding exacerbated by brodifacoum. To our knowledge, this is the first case reported of a trauma-induced coagulopathy exacerbated by brodifacoum-contaminated synthetic cannabinoid. Her coagulopathy was clearly not due to trauma alone and contributed greatly to the difficulty in controlling hemorrhage. The synthetic cannabinoid-associated coagulopathy rendered her otherwise potentially survivable injuries fatal. Given the frequency of multiple trauma and the recent increase in the prevalence of synthetic cannabinoid, it can be expected that the incidence of trauma complicated by synthetic cannabinoid-associated coagulopathy will increase in the near future. For patients that present with prolonged prothrombin time and/or activated partial thromboplastin time, it is important to inquire about recent synthetic cannabinoid use.

'Spice' Use Motivations, Experiences, and Repercussions among Veterans of the United States Armed Forces.

BACKGROUND AND OBJECTIVES: The potential for synthetic cannabinoids (SCs) to function as an alternative to marijuana without the same risk of a positive urinalyses led to claims of pervasive military SC use. Case studies confirm use among veterans, but no study has adequately explored SC use in the military using detailed interview data. METHODS: Interviews (1-2 h) were conducted with 318 justice-involved veterans. Recruitment was attempted with all participants in eight veterans treatment courts in three U.S. states (54.9% of 579 eligible veterans). Interviews were transcribed and thematic analyses completed. RESULTS: SC use was reported by 65 participants (21.3%). Major emergent themes indicated SCs were perceived as unpleasant, overly powerful, and a poor substitute for marijuana. Further, habitual use was rare as many chose not to reuse after initial negative experiences. Few indicated that the perception that SCs would not appear on routine military urinalyses enabled their use. Veterans were aware of the changing drug composition and feared "bad batches." CONCLUSIONS: SCs were explicitly disliked both independently and relative to marijuana. Nine discussed avoiding positive military drug screens as a consideration, but negative initial experiences generally prevented progression to habitual use. Veterans did not view SCs as a suitable marijuana replacement. Fears that SCs are being used as a marijuana alternative among veterans subject to frequent drug testing appear unfounded. These interviews suggest that routine military drug testing did not motivate individuals to use SCs habitually as a marijuana replacement; however, veterans' negative interpretation of SC effects contributed to this outcome.

5-HT2A receptors are involved in the pharmaco-toxicological effects of the synthetic cannabinoids JWH-018 and 5F-PB22: In vivo studies in mice.

Over the last years, Synthetic Cannabinoids (SCs) have been among the largest and most frequently seized groups of Novel Psychoactive Substances (NPS). These substances have been frequently detected in biological samples from patients involved in several intoxication and death cases. Their serious adverse effects have been related to their action as potent agonist of cannabinoid CB1 receptors. However, evidence concerning the potential interaction between SCs and serotoninergic mechanisms has emerged. Therefore, this study aims to evaluate the involvement of 5-HT2A receptors in the effects induced by acute systemic administration of 1-pentyl-3-(1-naphthoyl)indole (JWH-018; 1 mg/kg) and quinolin-8-yl 1-pentyfluoro-1H-indole-3-8-carboxylate (5F-PB22; 1 mg/kg). Sensorimotor (visual, acoustic, and tactile) responses, pain threshold (acute mechanical and thermal nociception), core temperature, breath rate and motor performance (stepping activity) have been assessed in CD-1 male mice. The present results pointed out that both substances deeply alter sensorimotor responses, nociceptive threshold, core temperature, breath rate and motor activity in mice. Noteworthy, pretreatment with the selective 5-HT2A receptors antagonist MDL100907 (0.1 mg/kg) at least partially prevented sensorimotor disruption, antinociception and hypothermic effects. Conversely, the respiratory and motor impairment was not prevented. Thus, it states the relevance of serotoninergic 5-HT2A mechanisms on pharmaco-toxicological effects induced by SCs.