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Background
'Legal highs' or 'new/novel psychoactive substances' sold as research chemicals have a grey legal status in most countries, particularly in North America. Disguised with the label 'Not for human consumption', they are able to evade the regulatory processes in most countries. 1 These synthetic compounds have increasing popularity due to their accessibility, low cost, psychoactive effects and inability to be detected by screening drug tests like immunoassays ( table 1 ). 1 2 Up to 200 of these substances are designed every year, with the majority first making appearances in Europe. 3 Given attempts by chemists to circumvent drug enforcement laws through slight alteration of parent compounds which are already illegal, in 2016 the UK banned all novel psychoactive substances. 4 Nevertheless worldwide, these drugs are easily obtainable over the internet and present significant challenges to patient management in emergency and critical care settings. 5
| Group | Common examples | General usage reactions |
| Aminoindanes | 2-A1, 5-IAI, MDAI, MMAI. | Analogues of amphetamines with euphoric effects. |
| Amphetamine-type compounds | 3-FPM, 2-FA, 2-FMA, 3-FA, 3-FEA, 4-FA, 4-FMA, BZP, ethylphenidate, MDAI, mephedrone, MPDV, NRG-1. | Primarily stimulants, with possible psychedelic effects through dopaminergic, serotonergic and adrenergic pathways. |
| Arylcyclohexylamines | 2F-K, 2'-Oxo-PCE (O-PCE), 3-MeO-PCE, 4-MeO-PCP, PCE, methoxetamine. | PCP-like drugs, with dissociation, anaesthesia and hallucinogenic effects primarily through N-methyl-D-aspartate receptor antagonism. |
| Benzodiazepine/sedative-type compounds | Diclazepam, etizolam, flubromazepam, nifoxipam, pyrazolam. | Sedative, hypnotic, anxiolytic, anticonvulsant and muscle relaxant properties through enhancement of gamma-aminobutyric acid signalling. |
| Cannabinoids (synthetic) | APICA, BB-22, JWH-018, STS-135. THJ-018, THJ-2201 (may be sold as any of these names: Clockwork Orange, Black Mamba, Spice, Exodus Damnation, K2, Kronic, Northern Lights, Kaos). | Analogues of tetrahydrocannabinol, act on cannabinoid receptors. |
| Cathinone-like compounds | Alpha-PVP (Flakka), mephedrone (4-MMC, Meow Meow, M-CAT), methylone (bk-MDMA), MDPV (Ivory Wave), NRG-1 (Naphyrone). | Monoamine alkaloids with stimulant properties. |
| Phenethylamines | 25i-NBOMe, 5-APB, benzodifurans (Bromo-Dragonfly), PMMA. | Psychedelic effects via serotonergic agonism. |
| Synthetic opioids/fentanyl analogues | Carfentanil, cyclopropyl fentanyl, furanylfentanyl, methoxyacetylfentanyl, U-47700. | Activates [micro]-opioid receptors, strong euphoria effects, high risk of respiratory depression. |
| Tryptamines | 4-AcO-DMT, 4-AcO-Met, AMT, DMT, 5-Meo-DMT, 5-Meo-DPT. | Psychedelic and entheogenic effects, largely acting on serotonergic receptors. |
*This list is only a representation of common new/novel psychoactive substances. The names listed are presented as they are commonly sold online.
3-FPM, 3-fluorophenmetrazine; PCE, eticyclidine; PCP, phencyclidine.
Typically, most patients who overdose on these substances appear in the emergency...