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Correspondence to Dr Matthew G K Benesch, [email protected]
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
Table 1
Sample list of common new/novel psychoactive substances*2
| 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 | 2 F-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 µ-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.