Abuse of Prescription Drugs in the Context of Novel Psychoactive Substances (NPS): A Systematic Review

Abstract

Recently, a range of prescription and over-the-counter drugs have been reportedly used as Novel Psychoactive Substances (NPS), due to their potential for abuse resulting from their high dosage/idiosyncratic methods of self-administration. This paper provides a systematic review of the topic, focusing on a range of medications which have emerged as being used recreationally, either on their own or in combination with NPS. Among gabapentinoids, pregabalin may present with higher addictive liability levels than gabapentin, with pregabalin being mostly identified in the context of opioid, polydrug intake. For antidepressants, their dopaminergic, stimulant-like, bupropion activities may explain their recreational value and diversion from the therapeutic intended use. In some vulnerable clients, a high dosage of venlafaxine (‘baby ecstasy’) is ingested for recreational purposes, whilst the occurrence of a clinically-relevant withdrawal syndrome may be a significant issue for all venlafaxine-treated patients. Considering second generation antipsychotics, olanzapine appears to be ingested at very large dosages as an ‘ideal trip terminator’, whilst the immediate-release quetiapine formulation may possess proper abuse liability levels. Within the image- and performance- enhancing drugs (IPEDs) group, the beta-2 agonist clenbuterol (‘size zero pill’) is reported to be self-administered for aggressive slimming purposes. Finally, high/very high dosage ingestion of the antidiarrhoeal loperamide has shown recent increasing levels of popularity due to its central recreational, anti-withdrawal, opiatergic effects. The emerging abuse of prescription drugs within the context of a rapidly modifying drug scenario represents a challenge for psychiatry, public health and drug-control policies.

New/emerging psychoactive substances and associated psychopathological consequences

“…Over the past decade the recreational use of several psychoactive pharmaceuticals has emerged in the NPS scene, including: antidepressants; antipsychotics; gabapentinoids; Z-drugs and designer benzodiazepines; and OTC drugs (Schifano et al, 2015;Schifano et al, 2018).…”

“…A range of experiences may be associated with gabapentinoid highdosage abuse, including euphoria, improved sociability, opiate-like sedation, entactogenic feelings/dissociation, and psychedelic effects (Schifano et al, 2015). Gabapentinoids may be ingested to cope with opiate/opioid withdrawal symptoms (Schifano et al, 2018). Unconventional routes of administration have been reported, e.g.…”

Pregabalin: A range of misuse‐related unanswered questions

“…4 Accordingly, patients reported pleasant stimulation and euphoria when using supratherapeutic/mega (eg 1500-12 000 mg) pregabalin dosages. 5,6 Hence, one could wonder if there may be a different/unclear range of neurotransmitter involvement, and receptors' activation intensity, in high/very high pregabalin dosage ingestion. Overall, similar to what was observed with a range of further medications (eg, venlafaxine, bupropion, quetiapine, and loperamide), 6 it has been suggested that gabapentinoids may induce a "liking" (euphoric high) subjective feeling, due to their gamma-aminobutyric acid (GABA)-mimetic action, but more limited levels of "wanting"/behavioral dependence.…”

Novel opioid detoxification using loperamide and P‐glycoprotein inhibitor

“…Current literature confirms that only excessively high doses can cause serious cardiac side-effects and potential death. [24][25][26][27][28][29][30][31] This study addressed the safety of loperamide over a short period of time and during the study development no serious adverse events were reported. Despite differences in study design, this finding is comparable with other treatment approaches used for opioid detoxification 17,18,32,33 and, when considered together with the finding that no instances were reported of additional requests for either medication, suggests that this protocol is not only safe, but also well-tolerated.…”