The present study described the presentations related to acute recreational drug toxicity at a large urban ED in Bern, Switzerland. Over a period of four years (May 2012 - April 2016), most presentations due to acute recreational drug toxicity were associated with cocaine and cannabis use. Those were also the substances most commonly analytically detected. Only 2 presentations were related to acute toxicity of NPSs. The typical patient was young and male, and alcohol had been co-ingested in the majority of the cases. There were two fatalities and further severe complications, such as myocardial infarction and intracranial haemorrhage, while approximately one fifth of the cases were unconscious at presentation or prior to hospital admission. However, most intoxications were of moderate severity and most patients were discharged home directly from the ED.

Comparing our findings with the similar studies from Basel [6, 7], another city in Switzerland with an University Hospital and a large urban ED, in both centres cannabis and cocaine seem to be the leading substances resulting in ED presentations due to acute toxicity, possibly indicating a general trend across the country. In the European data, cocaine and cannabis were also among the most commonly reported substances (number 2 and 3, respectively), but the most commonly reported drug was heroin [5]. Possible reasons for such differences could be local trends, the well-established heroin substitution programs in Switzerland, and price differences of substances among countries. In all studies, the typical patient presenting to the ED due to acute toxicity of recreational substances was male, in his early thirties, and was usually brought to the ED by ambulance overnight after using a classical recreational substance, often in combination with alcohol [5–7].

Another interesting similarity among the studies mentioned is that - despite the dramatic increase in the number of NPSs detected in recent years - presentations related to NPSs were much less common than those related to classical recreational drugs. This may indicate that NPSs possess less acute toxicity than classical recreational substances, that NPSs are consumed to a lesser extent or may be due to the fact that they escape detection with the normal immunoassay in many cases, especially if the patient does not report or is unaware of their use (e.g., if they are sold under other names, or in combination with other substances). One such example in the present study was the 2C-P case (detected by using liquid chromatography-mass spectrometry, usual doses 6–10 mg), which was mistaken for the better-known, less potent and shorter-acting 2C-B (usual doses 10–20 mg), and thus led to more severe and prolonged intoxication after intake of approximately 25 mg [12]. The 2C drugs are a subgroup of phenethylamines with primarily hallucinogenic properties [13]. Different ligands at position 4 on the phenyl ring within this family (e.g., bromine in 2C-B or propyl in 2C-P) can lead to great differences in receptor affinity [14]. The second NPS reported in our study was the synthetic cathinone 3,4-methylenedioxymethylcathinone (methylone or βk- MDMA) [15]. In this case, the patient reported buying the substance from Beijing, where it was still legal. The immunoassay drug screening was negative, as this test cannot detect most NPSs, so no NPS would have been registered without self-report. Methylone is a first generation synthetic substance from the group of the cathinones [16], which are derivatives of the naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant [17]. Methylone, the beta-ketone analogue of MDMA, emerged in the recreational drug market in the mid-2000’s under the brand name “Explosion” and was the first of these substances to be marketed via the Internet and at smart shops [16]. Desired effects range from amphetamine-like stimulation (e.g., increased energy, alertness) to entactogenic effects similar to those produced by MDMA (e.g., empathy, openness) [15]. In accordance with the symptoms reported by the patient in our study, the most common adverse effects include palpitations, vomiting, anxiety, sweating, unsteadiness of the hands, but also seizures, hyperthermia, psychosis, hallucinations and suicidal ideation [15]. Fatalities have also been reported [18–20]. Common oral doses (the most popular route of administration) are 100–300 mg, and doses higher than 250 mg are considered as “heavy” consumption [16]. The total dose reported by our patient (1–1.5 g) is thus very high. However, it is possible that the patient used a larger dose as “boosting” first, followed by smaller doses (“bumps”) to maintain the desired effects [15].

Beside the use of classical recreational drugs and NPSs, a further issue of increasing concern is the recreational use of prescription drugs. Among the ten cases of reported recreational methadone use in our study, seven were in a methadone substitution program, and in one of the fatal cases the patient used the methadone of her partner who was under maintenance therapy. Such cases demonstrate some of the risks related to long-term opioid maintenance treatment and the importance of the adjunctive psychosocial care of these patients. Sedatives and hypnotics are after opioids the most commonly misused prescription drugs in Europe [21]. Accordingly, benzodiazepines were the more commonly self-reported substances after cocaine, cannabis and heroin in our study. According to surveys, the main reasons for their use were to help sleep, to cope with stress, and/or to “get high” and almost 15% of the participants misusing them reported doing so at least once weekly [22]. Although the abuse and misuse potential of many of the other self-reported recreationally used prescription drugs in our study is known and plausible on the basis of their mechanism of action (e.g., psychostimulant effect of methylphenidate and modafinil, dissociative effect of N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine and dextromethorphan, sedative effect of antihistamines), this is not always the case for other substance groups, e.g., antidepressants. Antidepressants include a variety of substances with different pharmacological properties (e.g., sedation, stimulation), some of which make abuse attractive [23]. For example, bupropion, the most commonly misused antidepressant of the last decade [23], acts by inhibiting norepinephrine and dopamine reuptake [24], similarly to other indirect sympathomimetics (e.g., cocaine). In our study, recreational bupropion was administered intravenously in one case (approximately 1500 mg i.v.) and was intended to cause an amphetamine-like effect. Intravenous abuse of bupropion is also found in case reports and the drug can be acquired relative easily by expressing the wish to quit smoking [25]. Another category of antidepressants commonly misused are MAO inhibitors, which prevent the breakdown of monoamine neurotransmitters by MAO-A and/or MAO-B [23]. In our study, MAO inhibitor use was reported in six cases by the same patient, who presented a total of 16 times to the ED due to acute recreational substance use toxicity. The patient used the MAO inhibitor in combination with phenethylamine in five of the cases, most probably as an attempt to decrease its breakdown and thus potentiate its effects. Phenethylamine, also known as β-phenylethylamine, enhances catecholamine release, and can be obtained legally as dietary supplement. Unlike its derivatives (e.g., amphetamine), it is rapidly metabolised primarily by MAO-B, thus normally preventing significant concentrations from reaching the brain [26, 27]. Recreational use of methylphenidate was reported in 15 cases in our study by 12 different patients (one patient presented four times). An increase in reports of non-medical use of methylphenidate in recent years has been shown in a retrospective analysis from the Swiss Toxicological Information Centre [28]. In that study, the most common route of application was oral, but nasal and intravenous administration route was used in a substantial proportion of the cases, and 40% of the abusers reportedly used methylphenidate as a prescription drug for ADHD. Similar to those findings, half of the patients in our study (6 out of 12) received methylphenidate as treatment for their ADHD, but used it differently than prescribed (higher doses and/or other route of administration), and one patient took the drug from his girlfriend who had an ADHD diagnosis. In our study, the reported administration route was oral in the majority of the cases (9/15), i.v. and nasal administration were reported in 2 and 1 case(s), respectively, while in 3 cases the route of administration was not specified. Methylphenidate was also the most commonly reported prescription drug used for neuroenhancement (e.g., nonmedical use of a substance to improve cognitive function) in surveys among Swiss university students [29] and Swiss secondary school students [30].

As main limitations of the study, there were some missing data (the initial patient data were not recorded in a standardised manner), some symptoms described could have been related to substance withdrawal and not acute toxicity (e.g., seizures associated with benzodiazepine or alcohol withdrawal) or to aetiologies other than the acute toxicity of the psychoactive substances studied (e.g., vomiting because of alcohol co-ingestion or gastroenteritis, pre-existing psychiatric pathologies not recognised or documented as such). Because of the co-use of alcohol leading to impaired consciousness in many cases, severe intoxications may have been overrepresented. Furthermore, substances taken as medication (e.g., benzodiazepines, methadone, antidepressants) or given by the paramedics (e.g., benzodiazepines) could have been overrepresented in the analytical results; this also applies to substances that can be detected in urine samples beyond the time period of acute intoxication (e.g., cannabis). On the other hand, substances which can be detected only during a very short time period (e.g., GHB) or cannot be detected with the immunoassay test used in the study (e.g., LSD, NPSs) may have gone undetected if their use was not reported. Additionally, some patients with psychiatric symptoms were transferred to a psychiatric ward shortly after arrival at the ED, thus not allowing full documentation of treatment and outcome. Moreover, data from only one ED may reflect local trends and may not be representative.

The strengths of our study include the sensitive search algorithm used and the detailed documentation, in contrast to studies based on coded diagnoses only, which would have led to missing relevant cases with substance use not mentioned as a diagnosis, or studies based on laboratory data only, which would have caused the inclusion of not clinically relevant cases (e.g., cannabis detection long after acute intoxication). Further strengths include the drug screening performed in most cases, the relatively long time period studied, and the collection and analysis of data in a systematic manner, which allowed a comparison with the similar data from other cities in Switzerland (i.e., Basel) and elsewhere in Europe.