Catatonia Induced by First-Time Use of Synthetic Cannabinoids: A Case Report.

We present the case of a 32-year-old woman who developed life-threatening catatonia in the setting of synthetic cannabis use. She was treated with high doses of lorazepam (up to 26 mg) and eventually transferred to receive electroconvulsive therapy (ECT). Synthetic cannabis poses a unique risk as it is widely available, difficult to regulate, and with adverse effects that are not well understood due to the presence of ever-changing chemical compounds. In this case report, we present one of the first cases of catatonia induced by first-time synthetic cannabinoids with no previous history of cannabis use disorder.

New-Onset Prolonged Psychosis Following Synthetic Cannabinoid Use in an Older Patient: A Case Report.

Synthetic cannabinoids (SCs), a class of new psychoactive substances (NPS) commonly known as "spice," has rapidly gained popularity and become the most ubiquitous NPS on the illegitimate drug market. SCs, unlike natural cannabis (NC), are not controlled by international drug conventions, posing a significant risk to public health. These substances are easily accessible, relatively inexpensive, and challenging to detect in routine drug screenings. The existing literature provides strong evidence of an association between NC use and psychosis, but there is significantly less data on SC psychosis. We present a clinical case report of a 51-year-old African American female with no known psychiatric history who was admitted to the inpatient psychiatric unit after reported paranoia and altered mental status for the preceding six days. During hospitalization, she exhibited disorganization, persecutory delusions, extreme agitation, and bizarre behaviors that included the concealment of a set of stolen keys in her vagina, necessitating an ethics consult. After consideration of differentials, the patient was diagnosed with substance-induced psychotic disorder secondary to SC. The patient was stabilized on 3 mg Risperidone at bedtime. After 16-day hospitalization, she reached her baseline and later revealed that she had recently smoked SC for the first time. The primary goal of this case is to highlight the sequelae of SC-associated psychosis. A SC-associated psychosis could drastically vary from NC and is often undetectable on a typical UDS, which may result in a lifelong primary psychotic disorder misdiagnosis.

From Euphoria to Emergency: Exploring the Role of K2/Spice in Diffuse Alveolar Hemorrhage.

Marijuana or cannabis has been one of the most widely used recreational drugs, in the United States. However, a sinister counterpart has emerged in recent times: K2/Spice, a synthetic rendition of tetrahydrocannabinol (THC), capturing increasing popularity. Alarming reports have linked this synthetic compound to a multitude of life-threatening complications, ranging from acute kidney injury (AKI) from direct nephrotoxicity to cardiac arrest. Here we present the case of a 34-year-old man who presented with hemoptysis, later found to have diffuse alveolar hemorrhage (DAH) on the investigation after smoking K2/Spice successfully treated with a course of intravenous steroids. The case presented underscores the urgent need for increased awareness about the potential complications associated with synthetic compounds like K2/Spice, such as diffuse alveolar hemorrhage, and the importance of developing effective treatment strategies.

A Case of Near-Fatal Bradycardia Caused by Accidental Cannabis Intoxication.

The recreational and medicinal uses of cannabis are increasing worldwide. Given the recent legalization of marijuana in some regions of the United States, the use of edible formulations has become increasingly popular, especially among the elderly. These new formulations can be up to 10 times more potent than previously available preparations and have been associated with a variety of cardiovascular adverse effects. Here, we present a case of an elderly male who presented with dizziness and altered mental status. He was found to be severely bradycardic and emergently required atropine. Further investigation revealed that he accidentally ingested large amounts of oral cannabis. An extensive cardiac workup revealed no other etiology for his arrhythmia. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the most commonly studied cannabis compounds. With the increased access to and popularity of edible cannabis formulations, this case demonstrates the need for further research regarding the safety of oral cannabis.

Synthetic cannabinoid poisonings and access to the legal cannabis market: findings from US national poison centre data 2016-2019.

AIM: To investigate trends in synthetic cannabinoid exposures reported to United States (US) poison control centres, and their association with status of state cannabis legalisation. METHODS: A retrospective study of National Poison Data System (NPDS) data from 2016 to 2019 identified and associated synthetic poisoning reports with annual state cannabis law and market status. State status was categorised as restrictive (cannabis illegal or limited medical legalisation), medical (allowing THC-containing medical cannabis use) and permissive (allowing non-medical use of THC-containing cannabis by adults). We categorised a subset of states with permissive policies by their implementation of legal adult possession/use and opening retail markets, on a quarterly basis. Mixed-effects Poisson regression models assessed synthetic exposures associated with legal status, first among all states using annual counts, and then among states that implemented permissive law alone using quarterly counts. RESULTS: A total of 7600 exposures were reported during the study period. Overall, reported synthetic exposures declined over time. Most reported exposures (64.8%) required medical attention, and 61 deaths were documented. State implementation of medical cannabis law was associated with 13% fewer reported annual exposures. Adoption of permissive state cannabis policy was independently and significantly associated with 37% lower reported annual synthetic exposures, relative to restrictive policies (IRR: 0.63, 95% CI: 0.50-0.79). Among states with permissive law during the period, implementation of legal adult possession/use was associated with 22% fewer reported quarterly exposures. Opening of retail markets was associated with 36% fewer reported exposures, relative to states with medical cannabis only. CONCLUSIONS: Adoption of permissive cannabis law was associated with significant reductions in reported synthetic cannabinoid exposures. More permissive cannabis law may have the unintended benefit of reducing both motivation and harms associated with use of synthetic cannabis products.

'Synthetic cannabis': A dangerous misnomer.

The term 'synthetic cannabis' has been widely used in public discourse to refer to a group of cannabinoid receptor agonists. In this paper we detail the characteristics of these drugs, and present the case that the term is a misnomer. We describe the pharmacodynamics of these drugs, their epidemiology, mechanisms of action, physiological effects and how these differ substantially from delta-9-tetrahydrocannabinol (THC). We argue that not only is the term a misnomer, but it is one with negative clinical and public health implications. Rather, the substances referred to as 'synthetic cannabis' in public discourse should instead be referred to consistently as synthetic cannabinoid receptor agonists (SCRAs), a drug class distinct from plant-derived cannabinoids. SCRAs have greater potency and efficacy, and psychostimulant-like properties. While such terminology may be used in the scientific community, it is not widely used amongst the media, general public, people who use these drugs or may potentially do so. A new terminology has the potential to reduce the confusion and harms that result from the misnomer 'synthetic cannabis'. The constant evolution of this distinct drug class necessitates a range of distinct policy responses relating to terminology, harm reduction, epidemiology, treatment, and legal status.

Cannabis health knowledge and risk perceptions among Canadian youth and young adults.

BACKGROUND: Although recreational cannabis is now legal in Canada, little empirical evidence exists regarding young Canadians' cannabis literacy, cannabis-related risk perceptions, and risk of different forms of cannabis or the effect that public health education may have on these perceptions. The present study sought to address these knowledge gaps to examine health knowledge and risk perceptions associated with cannabis use. METHODS: An online survey was conducted with a national sample (N = 870) of Canadians aged 16 to 30 years in October 2017 using a commercial panel. The study examined young Canadians' awareness of negative health effects related to cannabis, evaluation of known risks, and risk perceptions of different forms of administration. RESULTS: Most respondents were aware of a cannabis-related physical health effect (78.0%). Approximately one-third reported having been exposed to public health messaging about cannabis; digital media was reported most frequently. Compared to never users, ever users were less likely to report general likelihood of addiction (p < 0.001) and harm to mental health (p < 0.001). Approximately one-quarter of past 3-month cannabis users reported they were at least "a little" addicted. Respondents who reported using a particular form of cannabis self-administration (e.g., edibles, smokables) were less likely to perceive harm than those who did not use each form (p < 0.001). CONCLUSIONS: The current study is among the first to measure the knowledge and perceptions of risks of Canadian youth about cannabis. The study, conducted in the time immediately preceding legalization, may serve as a reference point for future studies examining changes in cannabis knowledge and risk perceptions. This will be important in addressing the need for monitoring and enhancing public awareness of the impact and potential harms of this newly legalized substance.

Cannabis-Induced Catatonia: A Case Series.

Catatonia is a psychomotor condition characterized by physical presentations ranging from severe immobility to excessive psychomotor agitation with an array of accompanying emotional aspects. Though initially thought to be a subform of schizophrenia, it is now recognized to be associated with many different psychiatric, neurological, and medical diagnoses. The emergence of catatonia is becoming more prevalent with its changing pattern and extensive use of recreational and illegal drugs. With the legalization of marijuana, its use is on the rise leading to several mental health conditions, including catatonia. If left untreated, catatonia has a significant morbidity and mortality rate; hence, prompt evaluation and diagnosis are critical for the prevention of adverse events. Benzodiazepines (BZDs) and electroconvulsive therapy (ECT) have been found to be most effective and remained as the preferred treatment options. In this paper, we present the case of two patients who presented with catatonia after cannabis consumption and discuss their treatment course and management.

Self-reported Use of K2/Spice for Appetite Stimulation: A Case Report.

This case report explores the use of K2/Spice (synthetic cannabinoids) in a patient as an appetite stimulant. The effects of synthetic cannabinoids range widely but are more commonly known to suppress appetite in the cannabinoid-naive. Our patient was not cannabinoid- naive and had used cannabis before. Rat models have demonstrated results similar to those in this patient, who had prior tetrahydrocannabinol (THC) exposure resulting in appetite stimulation rather than suppression when exposed to a synthetic cannabinoid. This is likely explained by other rat models that have shown long-term use of cannabis resulting in receptor downregulation of cannabinoid receptor type 1 (CB-1).

Psychopathological symptoms associated with synthetic cannabinoid use: a comparison with natural cannabis.

BACKGROUND: Synthetic cannabinoids (SCs) are a class of new psychoactive substances that have been rapidly evolving around the world throughout recent years. Many different synthetic cannabinoid analogues are on the consumer market and sold under misleading names, like "spice" or "incense." A limited number of studies have reported serious health effects associated with SC use. In this study, we compared clinical and subclinical psychopathological symptoms associated with SC use and natural cannabis (NC) use. METHODS: A convenience sample of 367 NC and SC users was recruited online, including four validated psychometric questionnaires: The Drug Use Disorders Identification Test (DUDIT), Insomnia Severity Index (ISI), Altman Mania Scale (Altman), and Brief Symptom Inventory (BSI). The two groups were compared with analysis of variance (ANOVA) and covariance (ANCOVA), chi2 tests, and logistic regression when appropriate. RESULTS: The SC user group did not differ in age from the NC user group (27.7 years), but contained less females (21% and 30%, respectively). SC users scored higher than NC users on all used psychometric measures, indicating a higher likelihood of drug abuse, sleep problems, (hypo)manic symptoms, and the nine dimensions comprising the BSI, somatization, obsessive-compulsive behavior, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. Odds ratios (95% CI) for the SC user group vs NC user group were, respectively, drug dependence 3.56 (1.77-7.16), (severe) insomnia 5.01 (2.10-11.92), (hypo-)mania 5.18 (2.04-13.14), and BSI psychopathology 5.21 (2.96-9.17). DISCUSSION: This study shows that SC use is associated with increased mental health symptomatology compared to NC use.

Review of the many faces of synthetic cannabinoid toxicities.

INTRODUCTION: Synthetic cannabinoids (SCs) are psychoactive substances that are gaining popularity for their availability and lack of detection by standardized drug tests. Although some users may perceive SCs as safer alternatives to marijuana, some SCs are more potent and result in more severe toxicities. METHODS: A search of the literature was conducted in the PubMed and SciFinder databases. Results in PubMed were limited to human studies, and only articles in English were included. RESULTS: Review of the literature illustrates the hazards associated with SC use. A range of severe toxicities affecting numerous systems has been identified, such as arrhythmias, myocardial infarction, sudden cardiac death, psychosis, suicidal ideation, seizures, acute tubular necrosis, and intracranial hemorrhage. Additionally, a recent outbreak of coagulopathies and at least 4 associated deaths due to SCs tainted with brodifacoum have been reported. DISCUSSION: Synthetic cannabinoids may be perceived as a safer alternative to marijuana; however, SCs can be more potent at the cannabinoid receptors and in turn have greater toxicities. Limited information is available on the metabolism of SCs; however, cytochrome P450 pathways may be involved, which could result in drug interactions and unpredicted adverse effects. Toxicity with SC use is not just related to its effects, but also to additives that may taint these products and enhance their effects. Health care providers should be aware of the range of toxicities related to SC use, and tainted products such as these agents are not detected on routine drug screens.

What are the psychological effects of using synthetic cannabinoids? A systematic review.

BACKGROUND: Synthetic cannabinoids are, typically, full agonists at the cannabinoid CB1 receptor, and therefore considerably more potent than natural cannabis and may have correspondingly more serious psychological effects. Despite government sanctions against their production they continue to be available in ever-increasing varieties over the Internet. The psychological consequences of synthetic cannabinoid use are relatively unknown. AIM: The purpose of this study was to synthesise the available research on the psychological consequences of synthetic cannabinoid use. METHOD: A literature search of three databases was conducted in February 2018, including the following keywords: Spice, synthetic cannabis, cognition, affect, behaviour, psychosis, depression and anxiety. RESULTS: Seventeen studies involving a variety of participants were eligible for inclusion: one controlled administration study, seven cross-sectional studies, five Internet surveys and four qualitative studies. The controlled administration study showed that, compared to placebo, synthetic cannabinoids acutely affected some aspects of cognitive functioning and subjective psychological ratings. Non-controlled, cross-sectional studies generally showed that synthetic cannabinoid users had lower performance on cognitive tasks and showed elevated symptomatology (e.g. paranoia) compared to both natural cannabis and non-cannabis users. Methodological limitations were noted across different study designs. There is limited research on how doses, frequency or type of synthetic cannabinoid influence outcomes. CONCLUSIONS: Acute synthetic cannabinoid use can result in a range of psychological outcomes and, when non-intoxicated, synthetic cannabinoid users appear to differ from natural cannabis and non-users on various affective and cognitive domains. As synthetic cannabinoid use is increasing in at-risk populations there is an urgent need for more and better research to inform users, professionals and policymakers.

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

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

Clinical and financial implications of emergency department visits for synthetic marijuana.

BACKGROUND: Many users believe that synthetic cannabinoids offer a safe and legal means of getting high. However, spikes in emergency department visits have been associated with use of synthetic cannabinoids. The purpose of the current study was to document emergency department visits from three large hospitals in one metropolitan area over a two month period. METHOD: This was a retrospective chart review examining 218 patients presenting to three inner city emergency departments between March and April 2014. Data collected included demographic information, information regarding ED diagnosis and treatment, signs and symptoms, ancillary testing, ED disposition, and cost of the medical treatment. RESULTS: The majority of patients (75.7%) were discharged after ED workup, but 12.4% were admitted for medical treatment and 11.5% were admitted for psychiatric treatment. Ten patients (4.6%) were admitted to the ICU. Symptoms experienced most frequently include: hypertension, tachycardia, agitation, drowsiness, nausea, and confusion. Cluster analysis revealed four symptom clusters of individuals presenting after using synthetic cannabinoids: 1) confusion, hostility, agitation, 2) nausea, vomiting, abdominal pain, 3) drowsiness, and 4) the absence of these symptoms. CONCLUSION: This study has three important findings. First, significant ED resources are being used to treat individuals presenting due to effects of synthetic cannabis. Second, synthetic cannabis is not a benign substance. Third, while the hostile and agitated user is generally presented in the media, this study finds significant heterogeneity in presentation. Further research is needed to fully understand the implications of synthetic cannabinoid use.

Signs and symptoms associated with synthetic cannabinoid toxicity: systematic review.

AIMS: Use of synthetic cannabinoids is associated with significant physical and psychological harms. This research quantified reported toxicities from published reports and assessed the influence of size of the reported study population on rates of symptom reporting. METHODS: Systematic review of published case reports and case series of toxicity associated with use of synthetic cannabinoids. RESULTS: Symptoms associated with synthetic cannabinoid toxicity were reported for 3695 individuals, predominantly young males. Symptoms included physiological (e.g. tachycardia, hypertension, nausea/vomiting), emotional (e.g. agitation, irritability, paranoia), behavioural (e.g. drowsiness, aggression) and perceptual (e.g. hallucinations) domains. Most common symptoms were tachycardia (30.2% of cases), agitation (13.5%), drowsiness (12.3%), nausea/vomiting (8.2%) and hallucinations (7.6%). Death or serious medical complications were uncommon (e.g. death 0.2%, stroke 0.1%, myocardial infarction 0.09%). Case reports/smaller case series (n<10) reported statistically significantly higher rates for 29/34 symptoms than larger case series (n≥10), which could represent selection bias. CONCLUSIONS: Symptoms of synthetic cannabinoid toxicity are variable and cover a number of physical and psychological domains. Symptom reporting varies by study population size. Due to the variable presenting symptoms of synthetic cannabinoid toxicity, clinicians in emergency services should consider synthetic cannabinoid toxicity when evaluating young adult male patients presenting with unexplained agitation or cardiovascular symptoms.

Teenage cardiac arrest following abuse of synthetic cannabis.

INTRODUCTION: The cardiac effects of many illegal substances (cocaine, methadone) have previously been well described [1,2]. However the association between synthetic cannabis and cardiac arrest is less well documented. Here we describe an out-of-hospital cardiac arrest in a previously healthy 16-year-old female associated with the use of inhaled synthetic cannabis. METHODS: An electronic systematic search of online databases PubMed and Embase was performed using keywords, "synthetic cannabis death" and "cardiac arrest". RESULTS: In this case study a previously healthy 16-year-old had a cardiac arrest after synthetic cannabis use. Despite extensive investigations no other cause for her arrest was found. To the best of our knowledge there has been one previous case report of cardiac arrest following synthetic cannabis use in a 56-year-old man [3]. CONCLUSIONS: This case report augments the relationship between synthetic cannabis and cardiac arrest in the medical community. More awareness surrounding the risk of synthetic cannabinoids is warranted.

Quantitation of Synthetic Cannabinoids in Plant Materials Using High Performance Liquid Chromatography with UV Detection (Validated Method).

Plant based products laced with synthetic cannabinoids have become popular substances of abuse over the last decade. Quantitative analysis for synthetic cannabinoid content in the laced materials is necessary for health hazard assessments addressing overall exposure and toxicity when the products are smoked. A validated, broadly applicable HPLC-UV method for the determination of synthetic cannabinoids in plant materials is presented, using acetonitrile extraction and separation on a commercial phenylhexyl stationary phase. UV detection provides excellent sensitivity with limits of quantitation (LOQs) less than 10 µg/g for many cannabinoids. The method was validated for several structural classes (dibenzopyrans, cyclohexylphenols, naphthoylindoles, benzoylindoles, phenylacetylindoles, tetramethylcyclopropylindoles) based on spike recovery experiments in multiple plant materials over a wide cannabinoid contents range (0.1-81 mg/g). Average recovery across 32 cannabinoids was 94% for marshmallow leaf, 95% for damiana leaf, and 92% for mullein leaf. The method was applied to a series of case-related products with determined amounts ranging from 0.2 to >100 mg/g.

Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample.

BACKGROUND: Synthetic cannabinoids (SCs) have become increasingly popular in recent years. Diverse in chemical structure, many have been subjected to legislative regulation, but their availability and use persists. Often marketed to reflect their similar effects to cannabis, their use has been associated with a range of negative health effects. We sought to determine the relative risk of seeking emergency medical treatment (EMT) following use of SCs and natural cannabis. METHODS: We utilized an anonymous online survey of drug use, obtaining data from 22,289 respondents. We calculated the relative risk of seeking EMT between the two substances using an estimate for days used in the past year. RESULTS: Thirty-seven cannabis users (0.2%) and 21 SC users (1.0%) had sought EMT during the past year following use. The relative risk associated with the use of SCs was 30 (95% CI 17.5-51.2) times higher than that associated with cannabis. Significantly more symptoms (p=0.03) were reported by respondents seeking treatment for SCs than for cannabis. CONCLUSIONS: Whilst these findings must be treated with caution, SCs potentially pose a greater risk to users' health than natural forms of cannabis. Regulation is unlikely to remove SCs from the market, so well-informed user-focused health promotion messages need to be crafted to discourage their use.

Spicing up the military: Use and effects of synthetic cannabis in substance abusing army personnel.

Synthetic cannabis (SC) use has been increasing within the United States. Due to difficulties with its detection through standard testing, it may be an attractive substance of abuse for military personnel. However, few studies have examined the consequences of its use in this population, including evidence for its potential for abuse and dependence. Participants included 368 active-duty Army personnel who expressed interest in participating in a "check-up" around their alcohol or substance use, of whom 294 (80%) met DSM-IV criteria for substance abuse or dependence (including alcohol, illicit drugs, and prescription medications) and were not engaged in substance abuse treatment. Forty-one participants (11%) reported using SC in the last 90 days. Of those, 27 listed SC as their drug of choice. There were no significant differences in race, ethnicity, deployment history, or religion between SC users and others. Users of SC were generally younger and had less education and income than those who used only alcohol. Among SC users, 12% met criteria for drug abuse and 68% for dependence. Participants perceived SC use to be significantly more prevalent among military personnel than among civilians. Results suggest that SC is prevalent among substance-using soldiers and that DSM-IV criteria for abuse and dependence apply to SC. In addition, results highlight the importance of assessing and treating SC use among active-duty military personnel.