Future studies should examine the impact that within-individual changes in psychiatric problems have on substance use in the current context. Our study shows that when adolescent boys experience an increase in conduct disorder problems, they subsequently experience an increase in the quantity and frequency of substance use, while an increase in alcohol use can also subsequently result in increased anxiety problems in adolescence. Reducing fluctuations in conduct disorder problems and substance use at sensitive developmental turning points such as early and late adolescence may have lasting effects in preventing psychiatric and substance use problems by young adulthood. Synthetic cannabinoids are a class of drugs that are becoming increasingly popular throughout the United States and Europe. Also known as “K2,” “spice,” spike,” or “legal marijuana,” SC are causing intoxication requiring emergency department visits in epidemic and unparalleled numbers.1 Patients present with a wide array of symptoms, ranging from nausea and vomiting to confusion, agitation, short-term memory loss, cognitive impairment, psychosis, seizures, arrhythmias, strokes and even death.SC have often been associated with sympathomimetic effects such as mydriasis, hypertension and tachycardia.We present a case series of patients with SC intoxication who presented atypically with central nervous system and cardiovascular depression over a five-month period; in addition, we present an analysis of blood, urine and SC samples using mass spectrometry. Intoxication with SC products should be considered for patients with undifferentiated psychomotor depression and bradycardia in addition to the excitatory effects previously described.Samples were extracted with organic solvent and concentrated to isolate any drugs present on the plant material. Briefly, 5 mg aliquots of an unknown plant material, or 100 μL of submitted blood/urine,vertical grow rack systems were transferred to screwtop centrifuge tubes. Two mL of ethyl acetate were added and the samples were thoroughly mixed. Samples were extracted for 10 minutes on a nutating mixer at 24 revolutions per minute. The solvent was transferred to clean test tubes and the extracts were evaporated to dryness under nitrogen at 45°C.
Samples were reconstituted in 50 μL methanol and 50 μL 0.1% formic acid in water and transferred to conical autosampler vials for analysis by liquid chromatography time-of-flight mass spectrometry. Similarly, samples were reconstituted in 50 μL ethyl acetate for GC/MS confirmation analysis. Biological samples underwent a 20-minute room temperature hydrolysis period prior to liquid-liquid extraction. Hundreds of distinct SC compounds have been identified.SCs are responsible for a rapidly growing number of presentations to EDs throughout the U.S. in the past several years.SC use causes intense highs and has become popularized due to accessibility, affordability and limited detectability in common drug screens.Intoxications often present in clusters due to local distribution of a single product and great variability in the herbal mixtures.In 2011, SCs were the second most commonly used drug in the 10th grade and the third most common in eighth grade following marijuana and inhalants.Despite the federal ban on SCs that year, there was no decline in frequency of use in high school students the following year. However, use declined in each of the next three years.Users of SCs vary greatly in both demographics and motivation, but are typically males aged 13-59, most with polydrug use and are found in larger, urban populations.SCs are known to interact with the cannabinoid receptors, CB1 and CB2 , leading to changes in levels of multiple neurotransmitters including acetylcholine, dopamine, noradrenaline, glutamine and GABA.Genetic polymorphisms in enzymes responsible for metabolism of SCs can lead to increased blood levels of the parent compound and prolonged duration of action, and therefore a potential increased risk of adverse events.In addition, many SC metabolites retain biological activity.Combination of these metabolites with accumulation of the parent drug creates complex pharmacodynamics, especially when the multitude of other compounds typically found within herbal mixtures is considered. SCs have been reported to exhibit a wide array of effects. CNS effects include psychosis, anxiety, agitation, irritability, memory changes, sedation, confusion and hallucinations,in addition to lowering the seizure threshold in susceptible individuals.Reported cardiovascular effects include tachycardia, chest pain, dysrhythmias, myocardial ischemia and cerebrovascular accident caused by embolisms due to cardiac arrhythmias or reversible cerebral vasoconstriction syndrome.By the end of 2012, JWH-018 was not detected in samples, and XLR-11 became the most common SC detected,as exhibited in our sample analysis.
In our case series, CID and alkyl SC derivatives, such as INACA compounds and XLR-11,were the most commonly detected with no opiates, imidazoline receptor agonists, benzodiazepines or other sedative-hypnotics detected that might explain the atypical presentations.Seventy-five percent of blood samples and 77% of urine samples tested positive for SC. Unlike their predecessors, novel SC appear to be associated with significant CNS depression and bradycardia. The compounds detected in our case series tended to be full agonists at the cannabinoid receptor and are more potent than Δ9-THC.The lack of other CNS and cardiovascular depressants suggests that the clinical findings are due to the combination of these compounds and not coingestants or adulterants. It is important to note that many substances detected in the plant samples were not detected in the blood or urine samples. Some examples include 5-Fluoro-NNEI 2’-naphthyl isomer, 5-fluoropentylindole, NM-2201 and NPB-22. There are multiple explanations for these findings. The patient may have used SC products that were not included in our plant samples and therefore would not be associated with the urine and blood samples. It is also possible that the metabolites of the compound were not in the database or that the level was below the LC TOF detection limits. Furthermore, the metabolite may have been metabolized to a common XLR metabolite that was detected, or the drug had already been eliminated from the body. More than one-quarter of a million women in the United States are currently living with HIV , and many women living with HIV fare poorly on the HIV Care Continuum . In 2015, only 50% of WLHIV were retained in care and 48% achieved HIV viral suppression . Despite the broad availability of effective antiretroviral medications, WLHIV also experience high rates of morbidity and mortality compared to the general population . Trauma is increasingly recognized as a near-universal experience among WLHIV and as a key contributor to HIV acquisition, morbidity, and mortality. Defined as “an event, series of events, or set of circumstances that is experienced by an individual as physically or emotionally harmful or threatening and that has lasting adverse effects” , trauma can include childhood and/or adult physical, sexual, or emotional abuse or neglect,vertical grow racks cost as well as sociostructural violence such as racism, sexism, homophobia, transphobia, xenophobia, or living in a community where violence is common. People living with HIV experience disproportionately high rates of trauma , including rates of childhood sexual abuse that are more than twice the rates among the general population .
Trauma exposure in PLHIV is associated with nonAIDS related deaths , and is predictive of experiencing later violence . It is also closely associated with mental health disorders including depression, PTSD, and anxiety , as well as with increased HIV-risk behavior, including substance use disorders . HIV diagnosis is itself often highly traumatic . Among PLHIV, trauma and substance use often function syndemically, as “epidemics interacting synergistically and contributing, as a result of their interaction, to excess burden of disease in a population” . The syndemic of violence/trauma, substance use, and HIV has been identified as one of the main drivers of HIV infection and of poor health outcomes among women living with HIV . Research has consistently shown high rates of substance use among people living with HIV, and rates that are higher than among the general population . Substance use has also been shown to have a negative impact on HIV treatment adherence and virologic suppression .The link between trauma and health outcomes has led to calls for increased attention to trauma in health care by advocates and government leaders, including the U.S. Preventive Services Health Task Force, the Institute of Medicine, and the Agency for Healthcare Research and Quality . While an emerging literature describes interventions to address trauma and PTSD among PLHIV , no prospective study has evaluated the impact of a comprehensive model of trauma-informed health care delivery on health outcomes. To address this gap, we initiated implementation of a model of traumainformed health care in one clinic serving WLHIV in the San Francisco Bay Area. As part of this effort, we are conducting a broad evaluation of the impact of TIHC on patient health outcomes. Here we report results of baseline data analyses, examining the association of trauma with physical, behavioral, and social health indicators, with particular attention to quality of life and undetectable viral load. We then consider how the results of the investigation serve to inform efforts within health care settings to improve outcomes. Women were recruited from the waiting room during regular clinic hours on two half-days each week. Researchers approached patients in the waiting room, briefly explained the purpose of the study and, if a patient was interested, met with her in a private room. At that time, the researchers reviewed consent documents, explained the study procedures including data abstraction from the electronic health record , and answered any questions. Individuals were eligible to participate if they self-identified as cisgender or transgender women who were 18 years of age or older, were currently receiving primary HIV care at the clinic, and were English-speaking and cognitively able to complete the interview. If the patient was eligible and willing, she signed a general consent form and an EHR data abstraction consent form. Following consent, the researcher conducted the interview by reading each question aloud and marking responses in a survey booklet. At the end of the interview, the participant received a $25 gift card inappreciation of her time. Most interviews took 30-45 minutes to complete. After the interview, researchers abstracted relevant data from the participant’s EHR. Anxiety symptoms were assessed using the Generalized Anxiety Disorder scale , a 7-item self-report scale to measure symptom severity. A score of 10 or above indicates at least moderate anxiety. Substance use was measured in three ways. Alcohol use was assessed using the short Alcohol Use Disorders Identification Test , a 3-item screen to identify individuals who may be hazardous drinkers or who have alcohol use disorders . The instrument provides a raw numerical score ; an indicator of binge drinking; and a diagnostic of AUD . Drug use was measured using one question from the Alcohol, Smoking and Substance Involvement Screening Test asking about substance use in the past three months. We dichotomized this into any non-prescribed drug use in the past 3 months, and a similar variable of “hard” drug use that excludes marijuana. Drug abuse was measured using the Drug Abuse Screening Test 10 , which yields a score range of 0-10. A score of 3 or greater indicates at least a moderate level of drug abuse. Quality of Life was measured using the five-item WHO-Five, developed crossculturally by the World Health Organization . The instrument measures self-reported quality of life over the past two weeks in the areas of mood, physical vitality, and interest in life. A score below 13 indicates poor quality of life . Mental well-being was measured using the seven-item Short WarwickEdinburgh Mental Well being Scale, which focuses on emotions and mental functioning , and yields a score of 7-35. Undetectable viral load. For participants who consented to having data abstracted from their electronic health record , we abstracted HIV viral load and CD4 counts. Data were abstracted only if the person had had a test within the past year, and the most recent test result was used. Viral load was dichotomized as detectable or undetectable . For the analysis, we focused on undetectable viral load as the outcome of interest. Patient-Provider relationship was measured using the Engagement with Health Care Provider scale , a 13-item instrument in which clients rate their interactions with their providers on a scale of 1 “always” to 4 “never”. Responses are summed to get a total score of 1-52, with lower scores indicated greater engagement. Appointment Adherence. We abstracted EHR data to examine appointment adherence as a proxy for engagement in care.