Caffeine and MDMA (ecstasy) exacerbate ER stress triggered by hyperthermia

Drugs of abuse can cause local and systemic hyperthermia, a known trigger of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Another trigger of ER stress and UPR is ER calcium depletion which causes ER exodosis, the secretion of ER resident proteins. Club drugs such as 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) can create hyperthermic conditions in the brain and cause toxicity that is affected by the environmental temperature and the presence of other drugs, such as caffeine. Here we examine the secretion of ER resident proteins and activation of the UPR under combined exposure to MDMA and caffeine in a cellular model of hyperthermia. We show that hyperthermia triggers the secretion of normally ER resident proteins and that this aberrant protein secretion is potentiated by the presence of MDMA, caffeine, or a combination of the two drugs. Hyperthermia activates the UPR but the addition of MDMA or caffeine does not alter canonical UPR gene expression despite the drug effects on ER exodosis of UPR-related proteins. One exception was increased BiP/Grp78 mRNA levels in MDMA-treated cells exposed to hyperthermia. These findings suggest that club drug use under hyperthermic conditions exacerbates disruption of ER proteostasis contributing to cellular toxicity.

Club Drugs and Psychiatric Sequelae: An Issue of Vulnerability and Previous Psychiatric History

The pursuit of pleasure among clubbers and disco-goers often involves drug use. However, whether substance use may represent a relevant risk factor contributing to the development of psychiatric symptoms and of mental illness remains debated. The purposes of this study were to evaluate the percentage of subjects who developed long-lasting psychiatric symptoms in a sample of subjects reporting use of substances in nightclubs, and to evaluate the role of a previous psychiatric diagnosis in these subjects. Data were collected during three consecutive years in dedicated nursing units inside all the nightclubs of Ibiza, in emergency hospital rooms at the Can Misses Hospital and inside the psychiatric ward. A total of 10,163 subjects required medical assistance inside discos in the medical-nursing units, of which 223 required transfers to hospital emergency rooms. Of these, 110 required subsequent psychiatric hospitalization. Ninety-one (82.7 %) of these patients had a positive psychiatric history, which was also found in thirty-one of the 113 subjects (27.4%) not requiring psychiatric hospitalization. Negative psychiatric history was negatively associated with hospitalization (Coefficient = −2.574; p = 0.000) and for subjects with a negative psychiatric history the odds to be hospitalized changed by a factor of 0.076. Gender, age, civil status and nationality were not significant predictors of hospitalization. Overall, the number of subjects who developed major psychiatric disorders appeared to be limited. However, the presence of a psychiatric history here played a crucial role. Club drugs are therefore able to induce psychiatric sequelae requiring hospitalization mainly in subjects who are already vulnerable from a psychopathological point of view.

Uso de club drugs entre estudantes de graduação: prevalência, características associadas e a influência dos pares

RESUMO Objetivo Medir a prevalência do uso na vida, no último ano e no último mês de duas club drugs – o ecstasy e o LSD –, bem como as características associadas ao uso dessas substâncias, no último mês, entre estudantes de graduação de uma universidade no Sul do Brasil. Métodos Trata-se de um estudo transversal conduzido no ano de 2015 com amostragem aleatória sistemática por conglomerados. Participaram 1.423 estudantes de graduação. Foi utilizado um modelo de análise multivariável em três níveis hierárquicos por meio da regressão de Poisson com ajuste robusto da variância. Resultados As prevalências de uso na vida, no último ano e no último mês de club drugs foram de 12,7%, 7,8% e 3,8%, respectivamente. Indivíduos do sexo masculino, com orientação sexual homossexual ou bissexual, mais jovens, que moravam com seus pares, solteiros, e que relataram uso no último mês de tabaco e maconha apresentaram maior probabilidade de ter feito uso no último mês de alguma club drug. Entretanto, a variável mais fortemente associada a esse desfecho foi ter algum amigo que já fez uso de alguma droga ilícita na vida (RP = 19,54). Conclusões O ambiente universitário parece ser um terreno fértil para a difusão do uso de club drugs. O fortalecimento de uma rede de apoio institucional da universidade, capaz de propor atividades de prevenção, bem como de identificar, acolher e encaminhar casos em que haja abuso e dependência dessas substâncias, pode ser uma estratégia importante para lidar com essa problemática.

Suicidal Behavior and Club Drugs in Young Adults

Psychoactive drugs play a significant role in suicidality when used for intentional overdose or, more frequently, when the intoxication leads to disinhibition and alterations in judgment, thereby making suicide more likely. In this study, we investigated suicidality prevalence among drug users and evaluated the differences in suicide ideation, taking into account the substance categories and the association of suicide ideation intensity with other psychiatric symptoms. Subjects admitted to the Can Misses Hospital’s psychiatry ward in Ibiza were recruited during summer openings of local nightclubs for four consecutive years starting in 2015. The main inclusion criterium was an intake of psychoactive substances during the previous 24 h. The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess the suicide risk. Suicidality was present in 39% of the study cohort. Suicide Ideation Intensity overall and in the previous month was higher in users of opioids and in general of psychodepressors compared to psychostimulants or psychodysleptics. Suicidality was not correlated with alterations in any of the major psychopathological scales employed to assess the psychiatric background of the study subjects. The presence of high levels of suicidality did not specifically correlate with any major symptom indicative of previous or ongoing psychopathological alterations. These findings suggest that impulsivity and loss of self-control may be determinants of the increased suicidality irrespectively of any major ongoing psychiatric background.

“Hot” and “Cold” Cognition in Users of Club Drugs/Novel Psychoactive Substances

Novel psychoactive substances (NPS) are popular “club/party” drugs that first attracted attention in the UK in 2009 and remained legal until the 2016 Psychoactive Substances Act criminalized their distribution. Unlike “traditional” illicit drugs, very little is known about the influence of their analogs on neuropsychological functioning. We characterized the cognitive and emotional profile of NPS/polydrug users using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and EMOTICOM test battery in adult male (aged 20–49 years) recreational users without psychiatric comorbidities (n = 27; “psychonauts”), service users attending a UK specialist “Club Drug” Clinic for problematic use (n = 20) and healthy control volunteers without significant drug-taking histories (n = 35). Tasks were selected to distinguish “hot” cognitive processes that are highly influenced by emotion from “cold” cognitive processes that are largely independent of emotional influence. Both user groups reported significantly higher sensation-seeking traits compared with non-users. Recreational NPS users demonstrated more risk-taking behavior compared with controls and treatment-seeking NPS users showed poorer learning, episodic memory and response inhibition compared with the other two groups. These effects persisted, when controlling for age, intelligence, alcohol and cannabis use severity, nicotine dependence, trait anxiety, depression, childhood adversity, impulsivity, and sensation seeking. Overall, recreational NPS users showed elevated “hot” (emotion-laden) cognition in the absence of “cold” (non-emotional) cognitive deficits, whereas “cold” cognitive dysfunction was pronounced in individuals seeking treatment for problematic NPS use. High trait impulsivity and poor self-control may confer additional risk to NPS/polydrug use severity and separate those seeking treatment from those using NPS recreationally.