Conference Agenda

The introduction of numerous new psychoactive substances (NPS) in the drug market as legal alternatives to common drugs of abuse led to a new “drug scenario” characterized by an increased number of intoxicated people presenting with emergencies after consumption of drugs with unknown effects or safety profiles. Indeed, the acute effects of NPS and their long-term side effects are not always known, and safety data regarding their toxicity are often unavailable. This talk will provide preclinical evidence of how arylcyclohexylamine derivatives, like methoxetamine (MXE), phenethylamines like 2-Cl-4,5-MDMA, and cathinones like 3,4-MDPHP can have on brain and behavior. MEX is a dissociative drug structurally similar to ketamine and phencyclidine that (i) possesses ketamine-like discriminative and positive rewarding effects in rats, (ii) affects brain processing involved in cognition and emotional responses, (iii) causes long-lasting behavioral abnormalities and neurotoxicity in rats and (iv) induces neurological, sensorimotor and cardiorespiratory alterations in mice. Serotonin 5-HT₂ receptors seem to play a crucial role in the expression of the sensorimotor altering effects of MXE, although NMDA and GABA receptors may be other important targets of action. Contrary to MXE, 2-Cl-4,5-MDMA and 3,4-MDPHP do not sustain self-administration behavior in rats, at least under the experimental conditions used in our study, suggesting that they are devoid of strong abuse potential and, hence, are unlikely to induce dependence in sporadic, occasional users. Yet, these two emerging NPSs can induce other effects at both central and peripheral levels that may significantly differ between males and females. Indeed, 3,4-MDPHP, but not 2-Cl-4,5-MDMA, alters plasma corticosterone levels in female (but not male) rats, while both drugs can stimulate VTA dopaminergic signaling in males, but not females.

Several new psychoactive substances (NPS) are responsible for intoxication involving the cardiovascular and respiratory systems. Among NPS, synthetic cannabinoids (SCs) provoked side effects in humans characterized by tachycardia, arrhythmias, hypertension, breathing difficulty, apnoea, myocardial infarction, and cardiac arrest. Therefore, we investigated the cardio-respiratory and vascular effects induced by JWH-018 (0.3-6 mg/kg) and Δ⁹-THC (0.3–6 mg/kg), administered in awake CD-1 male mice. The results showed that higher doses of JWH-018 (3–6 mg/kg) induced deep and long-lasting bradycardia, alternated with bradyarrhythmia, spaced out by sudden episodes of tachyarrhythmias (6 mg/kg), and characterized by ECG electrical parameters changes, sustained bradypnea, and systolic and transient diastolic hypertension. Otherwise, Δ⁹-THC provoked delayed bradycardia (minor intensity tachyarrhythmias episodes) and bradypnea, also causing a transient and mild hypertensive effect. These effects were prevented by both selective CB₁ (AM 251, 6 mg/kg) and CB₂ (AM 630, 6 mg/kg) receptor antagonists and their combination, even if in a different manner. This suggests that cardio-respiratory and vascular symptoms could be induced by peripheral and central CB₁ and CB₂ receptors stimulation. Moreover, we investigate how cardio-respiratory and -vascular JWH-018 (6 mg/kg) responses can be modulated by antidotes already in clinical use. The tested antidotes are amiodarone (5 mg/kg), atropine (5 mg/kg), nifedipine (1 mg/kg) and propranolol (2 mg/kg). Results show that only atropine completely revert the reduction of heart rate and pulse distension; all tested antidotes reduce tachycardia and tachyarrhythmias and improve breathing functions. These data may suggest that cardiorespiratory mechanisms JWH-018-induced involve sympathetic, cholinergic and ion channel modulation. Current findings would also provide valuable indication to identify potential antidotal intervention to support physicians in the treatment of intoxicated patient in emergency clinical settings. These findings may represent a starting point for necessary future studies aimed at exploring the proper antidotal therapy to be used in SCs-intoxicated patient management

Several lines of evidence have highlighted that the consumption of novel psychoactive substances (NPS) and the misuse of prescription drugs, especially by attendees of dance parties and nightclubs, is significantly correlated to the onset and progression of psychiatric conditions, thus representing a major worldwide health issue. Furthermore, those psychoactive compounds are significantly involved in suicidality, not only in the case of intentional overdose, but also when the intoxication results in behavioural disinhibition and altered judgment.

Here, in a sample of 110 disco goers and clubbers admitted from 2015 to 2018 to a psychiatric ward in Ibiza, Spain with a diagnosis of substance abuse or acute intoxication, we evaluated the most implicated drugs, psychopathological features, the use of unprescribed pharmaceuticals, and suicidality prevalence.

The use of depressors was found in 15% of the recruited subjects, while stimulants and psychodysleptics were used by 40% and 45% of the sample, respectively. Multiple substance use was found in 70% of the study cohort and, clinically, this was positively associated to bipolar disorder. Furthermore, 40% of the inpatients misused prescription drugs, such as benzodiazepines, antiepileptics, antidepressants, opioids, antipsychotics, stimulants, and non-steroidal anti-inflammatory drugs, and this was negatively correlated with psychodysleptic consumption. Suicidality was detected in 39% of the subjects, with suicide ideation intensity being higher in psychodepressor users. However, this was not associated with any alterations in the major psychopathological scales.

In conclusions, our results highlight that NPS use/poly-use by clubbers and disco goers leads to severe psychopathological consequences and that prescription drugs are frequently intaken by those subjects as an alternative to traditional psychoactive compounds. Thus, health programs and preventive strategies should provide adequate information about the possible risks of NPS use, both alone and in combination with prescription drugs, in order to prevent the development of severe medical and psychiatric disorders.