Synthetic Cannabinoid Use Research Articles

Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (disc1) Mutant Zebrafish.

Synthetic cannabinoids can cause acute adverse psychological effects, but the potential impact when exposure happens before birth is unknown. Use of synthetic cannabinoids during pregnancy may affect fetal brain development, and such effects could be moderated by the genetic makeup of an individual. Disrupted in schizophrenia 1 (DISC1) is a gene with important roles in neurodevelopment that has been associated with psychiatric disorders in pedigree analyses. Using zebrafish as a model, we investigated (1) the behavioral impact of developmental exposure to 3 μM 1-pentyl-3-(1-naphthoyl)-indole (JWH-018; a common psychoactive synthetic cannabinoid) and (2) whether disc1 moderates the effects of JWH-018. As altered anxiety responses are seen in several psychiatric disorders, we focused on zebrafish anxiety-like behavior. Zebrafish embryos were exposed to JWH-018 from one to six days post-fertilization. Anxiety-like behavior was assessed using forced light/dark and acoustic startle assays in larvae and novel tank diving in adults. Compared to controls, both acutely and developmentally exposed zebrafish larvae had impaired locomotion during the forced light/dark test, but anxiety levels and response to startle stimuli were unaltered. Adult zebrafish developmentally exposed to JWH-018 spent less time on the bottom of the tank, suggesting decreased anxiety. Loss-of-function in disc1 increased anxiety-like behavior in the tank diving assay but did not alter sensitivity to JWH-018. Results suggest developmental exposure to JWH-018 has a long-term behavioral impact in zebrafish, which is not moderated by disc1.

Global and glucocorticoid receptor gene-specific (NR3C1) DNA methylation analysis in patients with cannabinoid or synthetic cannabinoid use disorder

This study investigates the relationship between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and the global methylation, methylation of NR3C1 gene promotor, and NR3C1 BclI polymorphism, considering clinical parameters. Based on the DSM-5 criteria, 172 SCUD patients’ and 44 CUD patients' diagnoses were confirmed with a positive urine test; 88 healthy volunteers were also included in the study. Global DNA methylation was measured using a 5-methylcytosine (5-mC) DNA ELISA Kit. Methylation-specific PCR was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR-RFLP. Our results demonstrated that the mean of 5-mC percentages of SCUD patients differed significantly from those of the control group. When comparing NR3C1 gene methylation and clinical parameters due to NR3C1 genotype distribution in patients, the genotype distribution was significantly different between the groups, due to the former polysubstance abuse. Additionally, there was a significantly positive correlation between the 5-mC percentages of SCUD patients and the reported durations of their disorders. In summary, whereas global DNA methylation may be associated with SCUD, the methylation of the NR3C1 gene and NR3C1 BclI polymorphism were not related to CUD or SCUD.

The severity of non-planning impulsivity and cannabis use problems in distinguishing patients with synthetic cannabinoid use disorder and cannabis use disorder

The severity of non-planning impulsivity and cannabis use problems in distinguishing patients with synthetic cannabinoid use disorder and cannabis use disorder

SYNTHETIC CANNABINOID BONZAI RELATED CREATINE KINASE ENZYME ELEVATION: A TURKISH CENTER STUDY.

SUMMARYSynthetic cannabinoid (locally named ‘Bonzai’ in Turkey) use is increasing worldwide (especially among people with low income). One of its harmful adverse effects is an increase in serum levels of muscle enzymes (i.e., creatine kinase [CK]). The aim of this study was to determine the prevalence of Bonzai use in patients admitted with elevated CK levels and to compare the 1-month survival status of Bonzai users with that of non-Bonzai users. This retrospective study was conducted on a total of 468 patients, median (min-max) age 48±22 (18-93) years. It was found that 10.68% (n=50) of the patients presenting with elevated CK levels were using Bonzai (group 1), while the remaining 418 (89.32%) patients were non-Bonzai users (group 2). Median age was higher in group 2 as compared with group 1 (p=0.001). In group 1, the predominance of male (M) over female (F) patients was interestingly high, yielding a F:M ratio of 1/49 (χ2=110.03, p<0.001). The prevalence of Bonzai use among patients admitted to our center with elevated CK levels was 10.68%. The Bonzai group patients were younger and mostly males, and none of them died at 1 month of admission. These findings may help in the management of such clinical conditions and could be a pathfinder for further studies in this field.

Morbidity and mortality associated with prescription cannabinoid drug use in COPD

IntroductionRespiratory-related morbidity and mortality were evaluated in relation to incident prescription oral synthetic cannabinoid (nabilone, dronabinol) use among older adults with chronic obstructive pulmonary disease (COPD).MethodsThis was a retrospective, population-based,...

Exploring the Relationships between Sexual Orientation and Gender Identity and Youth Synthetic Cannabinoid Use

Purpose: Existing studies have identified sexual minorities as being at enhanced risk for reporting synthetic cannabinoid (SC) use. It is unclear whether this association is the result of those that identify as a minority due to sexual orientation being more likely to use SCs, due to those that identify as transgender using SCs more, or both. Deconstructing this relationship will allow for targeted clinical advice and public health campaigns. Methods: Data from the 2015 and 2017 Youth Risk Behavior Study are utilized. In total, 31,279 youth were asked about their gender identity, sexual orientation, and SC use history. Bivariate analyses and logistic regression models were completed to explore relevant associations. Results: Identifying as lesbian, gay, bisexual, or questioning was linked to SC use and continuing SC use. Similarly, identifying as transgender was linked to SC use and continuing use. Regression analyses showed no significant interactive effect; identifying as both LGBQ and transgender does not have a compounding effect on use likelihood. Conclusions: Both sexual orientation and gender identity contribute to the relationship between sexual minority status and SC use noted in extant literature. This relationship is hypothesized to be tied to increased exposure to discrimination, victimization, and social isolation. Thus, efforts to directly counsel LGBTQ patients about the dangers associated with SC use are warranted as well as social policy reforms to better protect and support members of the LGBTQ community.

The Future of Substance Abuse Now: Relationships among Adolescent Use of Vaping Devices, Marijuana, and Synthetic Cannabinoids

Background: Substances that can be vaped include nicotine, marijuana, cocaine, heroin, and a range of synthetic drugs called new psychoactive substances (NPS). Due to the rising popularity of vaping among adolescents, it is crucial to understand the relationships between vaping and illicit drug use. Objectives: This paper examined the prevalence and trends of using vaping devices, marijuana vaping, marijuana products, synthetic cannabinoids and mist contents among youth. Methods: The study utilized 5 sets of public cross-sectional national data from the “Monitoring the Future” surveys during 2014–2018. It employed logistic regression to analyze the data. Results: There was an increase from 10.5% in 2017 to 20.8% in 2018 for the past 30-day use of vaping devices among 12th graders. Furthermore, there was an increase from 21.6% in 2017 to 34.5% in 2018 for the past 12-month use of marijuana via vaping device among 12th-grade marijuana users. Additionally, there were significant associations between vaping device use and marijuana vaping, between vaping device use and marijuana use, between vaping device use and synthetic cannabinoids use, and between marijuana use and synthetic cannabinoids use from 2016 to 2018. Conclusions: Vaping emerged as another major route of marijuana administration among youth. Adolescent marijuana users had higher odds of using synthetic cannabinoids. This finding highlighted the importance of understanding what adolescent substance consumption pattern would be where marijuana was legalized. It also supported the hypothesis that vaping devices use correlates with, or is associated with, marijuana and synthetic cannabinoids use.

Synthetic cannabinoids enhanced ethanol-induced motor impairments through reduction of central glutamate neurotransmission

Marijuana or synthetic cannabinoids and alcohol are often used together, with these combinations causing motor impairments that can subsequently lead to motor vehicle accidents. This study investigated the combined use of both synthetic cannabinoids and ethanol and their effect on motor coordination in mice in addition to examining the neurochemical changes in the cerebellum. Ethanol (2 g/kg, i.p.) significantly induced motor impairment in the accelerating rotarod test in mice. Furthermore, ethanol-induced motor impairments were further accentuated when combined with the synthetic cannabinoid, JWH-018 or AB-CHMINACA. The enhancement effects of the synthetic cannabinoids were completely antagonized by pretreatment with the selective CB1 receptor antagonist AM251, but not by the selective CB2 receptor antagonist AM630. Neurochemical study results showed that ethanol caused a reduction in the extracellular glutamate levels in the cerebellum during periods of ethanol-induced motor impairment. In addition to the enhanced motor impairment seen when ethanol was combined with JWH-018, these combinations also enhanced the reduction of the extracellular glutamate levels in the cerebellum. We additionally used microelectrode array recordings to examine the effects of ethanol and/or JWH-018 on the spontaneous network activity in primary cultures from mouse cerebellum. Results showed that ethanol combined with JWH-018 significantly reduced spontaneous neuronal network activity in the primary cerebellar culture. Our findings demonstrate that ethanol-induced motor impairments are enhanced by synthetic cannabinoids, with these effects potentially mediated by CB1 receptors. An accentuated reduction of neurotransmissions in the cerebellum may play an important role in motor impairments caused by ethanol combined with synthetic cannabinoids.

Clinical features and cognitive profiles of psychotic disorders due to synthetic cannabinoid use: controlled first attack follow-up

Amaç: Bu çalışmanın amacı, sentetik kannabinoidler (SK) kullanıma bağlı psikotik bozuklukların klinik görünümünü araştırmaktır. Gereç ve Yöntem: Çalışma, kapalı serviste yatarak tedavi gören hastalarla yürütüldü. Klinik değişkenleri değerlendirmek amacıyla Pozitif ve Negatif Belirti Ölçeği (PNBÖ), Kısa Psikiyatrik Değerlendirme Ölçeği (KPDÖ) ve İşlevselliğin Genel Değerlendirmesi Ölçeği (İGD) uygulanırken bilişsel işlevleri değerlendirmek için de; Standartize Mini Mental Test (MM), Sürekli Performans Testi (SPT), Frontal Değerlendirme Bataryası (FDB) ve Renk İzleme Testi (RİT) uygulandı ve yanı sıra vital ölçümleriyle biyokimya değerleri alındı.Bulgular: Çalışmamızda SK kullanımına bağlı ilk atak psikotik bozukluk grubu hastalarının %73’ünün ergenlik döneminde de kannabinoid türevlerini (esrar ve SK’ler birlikteliğinde; %93,6) kullandığı görüldü. PANSS pozitif belirtiler alt ölçeği ile bilişsel işlev açıdan ise MM, RİT-2, FDB ve SPT’de istatistiksel olarak anlamlı düzeyde daha fazla bozulma olduğu bulundu. Takip süresi boyunca her iki grupta da (SK’da belirginlik göstermekte) değişkenlerdeki başlangıçta görülen etkilenmenin devam ettiği gözlendi.Sonuç: SK kullanımına bağlı ilk atak psikotik bozukluğunun uzun süreli kullananlar arasında sık görüldüğü, klinik görünümde vital ve biyokimyasal etkilenme, pozitif belirtiler ve bilişsel bozulmanın daha fazla olduğu görüldü. Bu etkilenmenin zaman içindeki seyri değerlendirildiğinde, SK kullanımı olan grupta klinik ve bilişsel bozulmanın devam ettiği saptandı. Bu sonuçlar, SK kullanımına bağlı psikotik bozukluğun kötü bir klinik seyre sahip olduğunu göstermektedir.

Predicting Daily Sheltering Arrangements among Youth Experiencing Homelessness Using Diary Measurements Collected by Ecological Momentary Assessment.

Youths experiencing homelessness (YEH) often cycle between various sheltering locations including spending nights on the streets, in shelters and with others. Few studies have explored the patterns of daily sheltering over time. A total of 66 participants completed 724 ecological momentary assessments that assessed daily sleeping arrangements. Analyses applied a hypothesis-generating machine learning algorithm (component-wise gradient boosting) to build interpretable models that would select only the best predictors of daily sheltering from a large set of 92 variables while accounting for the correlated nature of the data. Sheltering was examined as a three-category outcome comparing nights spent literally homeless, unstably housed or at a shelter. The final model retained 15 predictors. These predictors included (among others) specific stressors (e.g., not having a place to stay, parenting and hunger), discrimination (by a friend or nonspecified other; due to race or homelessness), being arrested and synthetic cannabinoids use (a.k.a., “kush”). The final model demonstrated success in classifying the categorical outcome. These results have implications for developing just-in-time adaptive interventions for improving the lives of YEH.

The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations.

Recreational use of synthetic cannabinoids (SCs) before and during pregnancy poses a major public health risk, due to the potential onset of neurodevelopmental disorders in the offspring. Herein, we report the assessment of the neurotoxic potential of two commonly abused SCs, THJ-2201 and 5F-PB22, particularly focusing on how they affect neuronal differentiation in vitro. Differentiation ratios, total neurite length, and neuronal marker expression were assessed in NG108-15 neuroblastoma x glioma cells exposed to the SCs at non-toxic, biologically relevant concentrations (≤1 μM), either in acute or repeated exposure settings. Both SCs enhanced differentiation ratios and total neurite length of NG108-15 cells near two-fold compared to vehicle-treated cells, in a CB1R activation-dependent way, as the CB1R blockade with a specific antagonist (SR141718) abrogated SC-induced effects. Interestingly, repeated 5F-PB22 exposure was required to reach effects similar to a single THJ-2201 dose. Cell viability and proliferation, mitochondrial membrane potential, and intracellular ATP levels were also determined. The tested SCs increased mitochondrial tetramethyl rhodamine ethyl ester (TMRE) accumulation after 24 h at biologically relevant concentrations but did not affect any of the other toxicological parameters. Overall, we report firsthand the CB1R-mediated enhancement of neurodifferentiation by 5F-PB22 and THJ-2201 at biologically relevant concentrations.

An investigation of the COMT gene Val158Met polymorphism in patients admitted to the emergency department because of synthetic cannabinoid use

Catechol-O-methyl transferase (COMT) enzyme has a role in the inactivation of catecholamine neurotransmitters. Functional polymorphism in the COMT gene has been reported to play an important role in schizophrenia, bipolar affective disorder, aggressive and antisocial behavior, suicide attempts and the pathogenesis of Parkinson’s disease. In this study, we aimed to investigate the effect of the Vall58Met polymorphism of the COMT gene on substance use, and treatment history in patients with synthetic cannabinoid (SC) intoxication. The COMT enzyme Val158Met polymorphisms from DNA of 49 patients who were evaluated in the Emergency Department after SC use and 50 healthy control groups aged 18-45 years, were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses as reported in the literature. Information regarding recurrent intake or hospitalization due to substance use was obtained from hospital records. Wild-type (WT) genotypes in 14 (28.6%) patients, heterozygous genotypes in 25 (51.0%) and homozygous genotypes in 10 (20.4%) patients were detected. Wild-type genotypes The homozygous genotype was found to be significantly higher in patients hospitalized due to drug addiction and substance use (p 0.008). The Vall58 Met polymorphism of the COMT gene was not found to be significant in the first use after substance intake, while a significant relationship was found in terms of this polymorphism in patients with substance addiction diagnosis and treatment history.

A 4-Year Retrospective Analysis of Patients Presenting at the Emergency Department With Synthetic Cannabinoid Intoxication in Turkey

The number of patients with acute synthetic cannabinoid intoxication (SCI) has increased in recent years although the prohibition of its legal sale and use in Turkey despite other countries allowing to some extent sale and use. The reported clinical findings of acute SCI are similar to the symptoms of several diseases. The first case of acute SCI seen in our hospital was in 2014. The aim of this study was to share the data of synthetic cannabinoid use in a research hospital in Turkey and to contribute the epidemiologic data globally betwen 2014 and 2017. A retrospective evaluation was made of patients who presented at emergency department (ED) because of SCI between January 2014 and December 2017. The initial diagnosis of the patients was done either via their self-report or clinician's clinical observation (family history with hallucination, lethargy, convulsions, dizziness, etc.). Totally, 352 patients were included to the study whose cannabioid use was proven with their urine drug analysis. Men were predominantly high (93.8%). Nearly all patients (93.5%) were followed up and discharged in 24 hours. Among them, 21 (5.9%) patients were admitted for hospitalization, and mortality was seen in 2 (0.6%). The mean number of previous presentations at ED with a similar diagnosis was 8.6 ± 10.31. Great care must be taken in respect of complications related to SCI, which can even result in death. Patients have a tendency to not disclose the substance they have taken because it is illegal. Patients presenting at ED with recurrent symptoms must be referred to relevant legal authorities. For patients presenting with different clinical effects, SCI must be considered.

Neurological Manifestations Associated with Synthetic Cannabinoid Use- A Case Series

Background: Synthetic Cannabinoid (SC) use has emerged as a growing public health threat in the United States. Several unexpected cases, presenting with a constellation of unrelated symptoms, but all having toxicity linked to SC use, have been reported in the last decade (2010-2019). Methods: We report a cluster of several independent cases where patients were admitted having different neurological manifestations. Extensive and expensive work-ups were performed. Upon further inspection, extended toxicology screens were found to be positive for SC metabolites. Results: It is alarming to observe that several reports highlight an increase in the varied and significant morbidity associated after SC use. Various SC compositions have been synthesized and distributed, with new molecules being generated at a staggering rate leading to unexpected manifestations. Conclusion: Young people are the most frequent users owing to its recreational effects, its easy accessibility, lower cost and difficulty in being detected in the urine by routine drug screens. From a hospital quality improvement perspective, efforts to characterize the presence of newly generated SC molecules and establish more accessible in-house screening methods will be a starting step in reducing the associated cost-burden. This will also minimize the unnecessary invasive procedures performed on a specific patient. From a socioeconomic viewpoint, solid and systematic crosstalk with increased recognition and reporting mechanism between the healthcare staff and public health personnel is strongly warranted to support state and federal regulatory efforts in combating this ongoing SC epidemic.

UHPLC-HRMS and GC-MS Screening of a Selection of Synthetic Cannabinoids and Metabolites in Urine of Consumers.

Background and Objectives: The use of synthetic cannabinoids has increased around the world. As a result, the implementation of accurate analysis in human biological matrices is relevant and fundamental. Two different analytical technologies, ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and high-sensitivity gas chromatography-mass spectrometry (GC-MS) were used for the determination of three synthetic cannabinoids JWH-122, JWH 210, UR-144 and their metabolites in urine of consumers. Materials and Methods: Sample preparation included an initial hydrolysis with β-glucuronidase and liquid-liquid extraction. The UHPLC-HRMS method included a Kinetex 2.6 u Biphenyl 100A (100 × 2.1 mm, 2.6 μm) (Phenomenex, Italy) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode was used (mass range 100–1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m × 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40–550 m/z). Results: Both methods have been successfully used for screening of parent synthetic cannabinoids and their metabolites in urine samples of consumers. Conclusions: The screening method applied JWH-122, JWH-210, UR-144 and their metabolites in urine of consumers can be applied to other compounds of the JWH family.

The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice

BackgroundRecent years have seen a rise in the diversity and use of synthetic cannabinoids. The present study evaluated the behavioral effects of the third-generation indazole-3-carboxamide-type synthetic cannabinoid, AB-FUBINACA. MethodsAdult male and female C57BL/6J mice were treated with AB-FUBINACA (0−3 mg/kg, i.p.) and tested repeatedly in the tetrad battery measuring catalepsy, antinociception, hypothermia, and locomotor activity. Mice treated with AB-FUBINACA (≥2 mg/kg, i.p.) displayed classic cannabinoid effects in the tetrad that were blocked by the CB1 receptor selective antagonist rimonabant. To address tolerance and withdrawal effects, a second group of mice was injected with AB-FUBINACA (3 mg/kg, s.c.) or vehicle consisting of 5% ethanol, 5% Kolliphor EL, and 90 % saline every 12 h and tested daily in modified tetrad over the course of 5 days. On the 6th day, withdrawal was precipitated using rimonabant (3 mg/kg, s.c.), and somatic signs of withdrawal (i.e., head twitches and paw tremors) were quantified. ResultsAlthough mice did not develop tolerance to AB-FUBINACA or cross-tolerance to Δ9-tetrahydrocannabinol (THC; 50 mg/kg, i.p.), somatic precipitated withdrawal signs were observed. Repeated tetrad testing up to 48 h post injection indicated that AB-FUBINACA effects are relatively short-lived, as compared with THC. Brain levels of AB-FUBINACA, as quantified by UHPLC-MS/MS, were undetectable 4 h post injection. ConclusionsThese data indicate that the cannabinoid effects of AB-FUBINACA are relatively short-lived, yet sufficient to induce dependence in mice.

Evaluation of COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in synthetic cannabinoid use disorder patients

Synthetic cannabinoids (SC) are psychoactive drugs that generally produce more severe clinical outcomes compared to Δ9-tetrahydrocannabinol. This study aimed to evaluate the relationship between clinical features of synthetic cannabinoid use disorder (SCUD) and COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in SCUD patients by comparing the genotype distributions of gene variants between patients and healthy controls. Based on the DSM-5 criteria, 94 patients with SCUD, confirmed with a positive urine test, and 95 healthy volunteers were included in the study. Self-mutilation, suicidal behavior, psychotic symptoms, drug-induced psychosis, tobacco use disorder (TUD) or alcohol use disorder (AUD) comorbidity, and family history of TUD or AUD were evaluated in all patients. PCR-RFLP was used to identify gene variants from DNA material. The distributions of CNR2 (rs2229579) and UCP2 (rs659366) variants were significantly different in patients diagnosed with SCUD compared to the control group. SC-related psychotic symptoms were associated with the IL-17 (rs763780) variant in SCUD patients who had an onset of SC usage under 18 years of age. While the COMT Val108Met gene variant was related to self-mutilation, the COMT Val158Met variant was associated with attempted suicide. In addition, in SCUD patients, the UCP2 (rs659366) variant was associated with a family history of AUD or TUD. In summary, CNR2 (rs2229579) and UCP2 (rs659366) variants were associated with SCUD. While SC-related psychotic symptoms were related to the IL-17 (rs763780) variant, the COMT variants were associated with self-mutilation or attempted suicide in SCUD patients.

Chronic Use of Synthetic Cannabinoids Is Associated With Impairment in Working Memory and Mental Flexibility.

BackgroundWe have recently shown that chronic use of Synthetic Cannabinoids (SCs) has been associated with mood disorders and impairments in executive functions. There is also evidence indicating that chronic SC users have higher rates of comorbidity with depression and psychotic symptoms. Here, we investigate performance on executive function and emotional processing tasks in regular SC users and a measure of schizotypal traits.MethodThirty chronic SC users, 32 recreational cannabis users, and 32 non-using control participants, without history of mental disorder, or current substance abuse diagnosis (mean age 26 ± 4.27 years; 85 males, 9 females), were tested in addiction treatment centers in Israel. Computerized neurocognitive function tests; the N-back task, Go/No-Go task, Wisconsin Sorting Card-like Task (WSCT), and emotional face recognition task and questionnaires of depression, anxiety and schizotypal traits and symptoms were used.ResultsSC users have performed worse than recreational cannabis users and non-cannabis users on the N-back working-memory task (lower accuracy) and the WSCT cognitive flexibility task. SC users showed greater schizotypal traits and symptoms compared with recreational cannabis users and non-user control participants. A positive association was found in cannabinoid-user groups between schizotypal traits and symptoms and cognitive and emotional processing measures. Finally, SC users have scored higher on depression and state-trait anxiety measures than recreational cannabis users or healthy control participants.ConclusionsRepeated use of SCs is associated with impairment in executive functions and emotional processing. These alterations are associated with depression and schizotypal traits and symptoms. This adds to existing evidence on the long-term consequences of SC drugs and their risks for mental health.

Mechanisms for the Risk of Acute Coronary Syndrome and Arrhythmia Associated With Phytogenic and Synthetic Cannabinoid Use.

Phytogenic cannabinoids from Cannabis sativa and synthetic cannabinoids are commonly used substances for their recreational and medicinal properties. There are increasing reports of cardiotoxicity in close temporal association with cannabinoid use in patients with structurally normal hearts and absence of coronary arterial disease. Associated adverse events include myocardial ischemia, conduction abnormalities, arrhythmias, and sudden death. This review details the effects of phytogenic and synthetic cannabinoids on diverse receptors based on evidence from in vitro, human, and animal studies to establish a molecular basis for these deleterious clinical effects. The synergism between endocannabinoid dysregulation, cannabinoid receptor, and noncannabinoid receptor binding, and impact on cellular ion flux and coronary microvascular circulation is delineated. Pharmacogenetic factors placing certain patients at higher risk for cardiotoxicity are also correlated with the diverse effects of cannabinoids.

Investigation of DNA damage, oxidative stress, and inflammation in synthetic cannabinoid users.

The widespread use of synthetic cannabinoids (SCs) among youth has become an important public health problem. Several life-threatening side effects of SC have been reported, including cardiovascular, gastrointestinal, neurological, renal, metabolic, ophthalmologic, and pulmonary effects, besides skin toxicity and hepatotoxicity. Given that high levels of SC can lead to oxidative stress, DNA damage, and inflammation, it has been aimed in this study to investigate the effects of SC in aspects of primary DNA damage, plasma total oxidant status (TOS)/total antioxidant status (TAS), thiol-disulfide homeostasis, myeloperoxidase (MPO) level, and cytokine levels (interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α)) of 40 SC users (SCUs) in Turkey. Mean plasma TOS levels were significantly higher in the SCUs group than in the healthy group (HG). Similarly, mononuclear leukocyte DNA damage, plasma TOS, MPO activity, disulfide, oxidative stress index levels, IL-1β, IL-6, and TNF-α levels were significantly higher in the SCU group than in the HG, whereas plasma TAS, total, and native thiol levels were significantly lower in the SCU group than in the HG. It is concluded that SC can cause increase in oxidative stress and in inflammatory processes in addition to its potential for DNA damage. Additional studies with larger sample sizes and longer durations should be held to understand more specific outcomes of SC use.