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Cognitive deficits and neurotoxicity induced by synthetic cathinones: is there a role for neuroinflammation?

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Abstract

Rationale

The number of synthetic derivatives of cathinone, the primary psychoactive alkaloid found in Catha edulis (khat), has risen exponentially in the past decade. Synthetic cathinones (frequently referred to as “bath salts”) produce adverse cognitive and behavioral sequelae, share similar pharmacological mechanisms of action with traditional psychostimulants, and may therefore trigger similar cellular events that give rise to neuroinflammation and neurotoxicity.

Objectives

In this review, we provide a brief overview of synthetic cathinones, followed by a summary of cognitive deficits in animals and humans that have been documented following acute or repeated exposure. We also summarize growing evidence from in vitro and in vivo studies for synthetic cathinone-induced neurotoxicity, and provide a working hypothetic model of potential cellular mechanisms.

Results

Synthetic cathinones produce varying effects on markers of monoaminergic terminal function and can increase the formation of reactive oxygen and nitrogen species, induce apoptotic signaling, and cause neurodegeneration and cytotoxicity. We hypothesize that these effects result from biochemical events similar to those induced by traditional psychostimulants. However, empirical evidence for the ability of synthetic cathinones to induce neuroinflammatory processes is currently lacking.

Conclusions

Like their traditional psychostimulant counterparts, synthetic cathinones appear to induce neurocognitive dysfunction and cytotoxicity, which are dependent on drug type, dose, frequency, and time following exposure. However, additional studies on synthetic cathinone-induced neuroinflammation are clearly needed, as are investigations into the neurochemical and neuroimmune mechanisms underlying their neurotoxic effects. Such endeavors may lead to novel therapeutic avenues to promote recovery in habitual synthetic cathinone users.

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Funding

This work was supported by Public Health Service grant DA042172 from the National Institute on Drug Abuse.

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  1. Department of Psychology, Arizona State University, 950 S. McAllister Ave., Tempe, AZ, 85287, USA

    Jonna M. Leyrer-Jackson, Erin K. Nagy & M. Foster Olive

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  1. Jonna M. Leyrer-Jackson
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  2. Erin K. Nagy
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  3. M. Foster Olive
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Correspondence to M. Foster Olive.

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Leyrer-Jackson, J.M., Nagy, E.K. & Olive, M.F. Cognitive deficits and neurotoxicity induced by synthetic cathinones: is there a role for neuroinflammation?. Psychopharmacology 236, 1079–1095 (2019). https://doi.org/10.1007/s00213-018-5067-5

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