Recent statistics in England have reported an increased number of hospital admissions with a primary diagnosis of drug-related mental health/behavioural disorders and poisoning by illicit drugs, respectively of 12 and 40% compared to statistics released in 2006/07 [1]. Over the last five years deaths involving Novel Psychoactive Substances (NPS) have sadly increased, with a further 8% increase in 2016 [2]. NPS represent an emerging and concerning global phenomenon [3,4,5] mainly due to: (1) the difficulties posed in the clinical management, of both mental and physical health; and (2) the absence of a clear and formal/structured description of the clinical presentation of patients using NPS, with obvious repercussions on clinical management.

NPS are a heterogeneous class of typically synthetic molecules including: synthetic cannabinoid receptor agonists (SCRAs), synthetic cathinones, amphetamine-derivatives, psychedelic phenethylamines, ketamine derivatives, novel tryptamines, synthetic opioids and sedatives (GABA-A/B agonists) [3,6,7]. Trends in illicit drug use over the last decade clearly show that adolescents and young adults give preference to NPS instead of traditional psychoactive substances (TPS) (e.g., cannabis, cocaine, heroin, amphetamines, LSD, ecstasy, ketamine, etc), because NPS are cheap and easily available either on the street or from websites [6,7,8]. They are difficult to identify in blood or urine drug screening (UDS) [9]. Lifetime NPS consumption was reported by 8% of young individuals in 2015 [10] up from 5% in 2011 [6]. Young adults (aged 16 to 24) are around twice as likely to have used an NPS in their lifetime compared to older adults (aged 16 to 59) [11]. It has recently been reported that the three psychiatric diagnoses most frequently associated with NPS use are bipolar disorder (23.1%), personality disorders (11.8%), and schizophrenia and related disorders (11.6%) [12].

In comparison to TPS users, poly NPS users are more likely to be young males [11], with daily use of traditional cannabis, weekly or more use of ecstasy, recent LSD use, higher levels of poly drug use, and a history of overdose on any drug in the past year [13]. Young adults attending nightlife events in pubs and discos are also more prone to poly-substance use, mainly combining NPS with alcohol and cocaine [14]. NPS users also tend to have a forensic history and a history of promiscuous sexual activity (e.g., chem-sex) [13].

Few studies have attempted to provide a psychopathological description of the clinical presentation of NPS users in acute settings. For example, in an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London, the most common clinical features identified were seizures and agitation [15]. In a recent study looking into the impact of NPS misuse on admissions to an acute psychiatric facility in London, increased levels of violence in the group of NPS users were identified ([16]. Data collected in the Accident and Emergency departments (A&Es) of ten European countries have shown that the association between NPS use and the occurrence of psychosis varied considerably, depending on the type of drug used [17]. In particular, psychotic symptoms were noted in 6.3% of a large sample (5529 consecutive cases), with psychosis being more common amongst NPS users that had used tryptamines, methylenedioxypyrovalerone (MDPV), methylphenidate, SCRAs and amphetamine-type compounds [17]. A mounting range of evidence suggests that SCRAs can trigger the onset of acute psychosis in vulnerable individuals and/or exacerbate psychotic episodes in those patients with a previous psychiatric history. The literature reports a wide range of psychopathological issues such as paranoid thoughts, increases in aggressive and combative behavior, together with confusion, agitation and suicidal thoughts [18]. It has been suggested that SCRAs may have a higher psychosis-inducing potential compared to natural cannabis [19] because of the lack of cannabidiol—a substance associated with the medicinal effects of cannabis. For a review on existing studies and models of cannabis induced psychosis see a review from Murray et al [20].

Professionals usually report feeling less confident about managing NPS compared to TPS users, specifically because of the lack of clear guidance regarding the clinical management and the increased risk of toxicity [10,11,12,13,14,15,16,17,18,21]. For example, with the ingestion of NPS with high serotonergic activity (e.g.: psychedelic phenethylamines), misusers may present with hyperthermia, seizures, and hyponatraemia. Conversely, NPS with high dopaminergic activity (e.g., methylphenidate-like drugs such as some synthetic cathinones) are highly addictive and associated with prolonged stimulation, insomnia, agitation, and psychosis [22,23]. Furthermore, most SCRAs are at times associated with medical emergencies such as hypertension, myocardial infarction, renal failure [24], elevated heart rate, hyperglycaemia, nausea, vomiting, hypokalaemia, and seizures [18]. Moreover, in view of the increased use of latest generation of sedatives or ultra-high potency fentanyl derivatives, the assessment of vital parameters is of paramount importance when NPS users are presenting to an emergency or acute facility [3,4,5,6].

The implementation of an appropriate and safe clinical management plan is commonly based on patients’ accounts on which kind of NPS have been used. Acute mental health and emergency services are not routinely equipped with urine drug screening tests (UDS) for NPS in order to identify and provide an appropriate toxicological confirmation [15]. This causes considerable limitations when offering a targeted treatment strategy that can address patients’ presentations and potentially life-threatening intoxications [9,13,25].

At present, there is a dearth of detailed information relating to the clinical presentation of NPS users in acute mental health settings, especially in terms of: (1) descriptions of behavioural and psychopathological features using structured assessment and psychometric scales; (2) analytical toxicology and identification of the index NPS used; and (3) appropriate and evidence-based clinical management plans. This results in a range of difficulties in formulating targeted/individually tailored treatment plans.

The aims of this case series are: (1) to offer a standardized description of NPS users’ clinical presentations to provide clinicians with objective and measurable clinical pictures aimed at shaping protocols and standard operating procedures when NPS use is suspected and/or detected; (2) to provide best practice advice in the management of mental state alterations and medical complications, with the goal of reducing the number of serious adverse outcomes associated with NPS use.