Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents.

Four novel synthetic hallucinogens (25B-NBOMe, 25C-NBOMe, 25I-NBOMe, and 5-MeO-DALT) were tested in rats and mice for their behavioral effects. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe reduced locomotor activity in mice, while 5-MeO-DALT increased activity at 10 mg/kg but suppressed it at 25 mg/kg. In rats trained to discriminate the hallucinogen DOM or the entactogen MDMA, 25B-NBOMe fully substituted for both drugs at 0.5 mg/kg, but higher doses reduced drug-appropriate responding. 25C-NBOMe fully substituted for DOM but only partially for MDMA. 5-MeO-DALT fully substituted for DOM but not MDMA. 25I-NBOMe failed to fully substitute for either, likely due to its strong rate-depressant effects. The compounds appear attractive for hallucinogenic use but less so as MDMA substitutes, and their abuse potential matches that of scheduled compounds.

Study at a glance

Abstract

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74-78% drug-appropriate responding in DOM-trained and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25I-NBOMe, fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.