Abstract
Hyperthermia is a well-known, potentially life-threatening, side effect of stimulant psychoactive substances that worsens the neurological outcome of hospitalized patients. However, current in vitro methods to assess the hazard of psychoactive substances do not account for hyperthermia. Therefore, this study determined the potency of five psychoactive substances (cocaine, MDMA (3,4-methylenedioxymethamphetamine), methamphetamine, 3-MMC (3-methylmethcathinone) and TFMPP (3-trifluoromethylphenylpiperazine)) to affect neuronal activity at physiological and hyperthermic conditions.Neuronal activity of rat cortical cultures grown on microelectrode arrays (MEAs) was recorded at 37 °C before exposure. Following 30 min and 4.5 h drug exposure (1-1000 μM) at 37 °C or 41 °C, neuronal activity was measured at either 37 °C or 41 °C.Without drug exposure, hyperthermia induced a modest decrease in neuronal activity. Following acute (30 min) exposure at 37 °C, all drugs concentration-dependently inhibited neuronal activity. Increasing the temperature to 41 °C significantly exacerbated the reduction of neuronal activity ~ 2-fold for all drugs compared to 37 °C. Prolonged (4.5 h) exposure at 41 °C decreased neuronal activity comparable to 37 °C. Neuronal activity (partly) recovered following drug exposure at both temperatures, although recovery from exposure at 41 °C was less pronounced for most drugs. None of the exposure conditions affected viability.Since acute exposure at hyperthermic conditions exacerbates the decrease in neuronal activity induced by psychoactive substances, effects of hyperthermia should be included in future hazard assessment of illicit drugs and new psychoactive substances (NPS).
Highlights
One in twenty people between 15 and 64 years are estimated to have used at least one drug in the last year (UNODC, 2019b)
The baseline neuronal activity of the cultures, i.e. before assessing effects of changes in temperature, did not differ subsequently between cultures measured at 37 °C and at 41 °C (p = .84)
When temperature increased from 37 °C to 41 °C during acute (30 min) recordings, neuronal activity (weighted mean spike rate, weighted mean burst rate, and weighted mean network burst rate) was reduced with 23–29% (Fig. 2)
Summary
One in twenty people between 15 and 64 years are estimated to have used at least one drug in the last year (UNODC, 2019b). The drug-induced increases in extracellular monoamines can result in intended effects (Capela et al, 2009; Glennon, 2014), and in adverse psychiatric and cardiovascular effects (Tyrkko et al, 2016; UNODC, 2019a). Hyperthermia is amongst the most often reported adverse effects following exposure to classic stimulants and NPS (Greene et al, 2008; UNODC, 2019a). This is at least partly due to drug-induced activation of cell metabolism (increasing heat production) and peripheral vasoconstriction (reducing heat dissipation)(Greene et al, 2008). As drugs are often used in warm and humid dance clubs, fatal body temperatures up to 43 °C have been reported (Greene et al, 2003)
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