Hypothesizing that designer drugs containing cathinones (“bath salts”) have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption

Blum, Kenneth; Wang, Kevin; Febo, Marcelo; Borsten, Joan; Giordano, John; Hauser, Mary; Gold, Mark S.

doi:10.1016/j.mehy.2013.06.007

Cited by 24 publications

(21 citation statements)

References 26 publications

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“…As GABAergic neurons modulate cortical synchrony (Fries, 2009) and loss of synchrony can occur in psychosis (Moran and Hong, 2011), GABA-mediated rescue of functional connectivity in the regions reported here (prelimbic cortex, insular cortex, NAc) may be of clinical interest (Bertol et al, 2014;Stoica and Felthous, 2013). Additionally, although not considered here, the reduction in resting state functional connectivity could represent a functional signature associated with neurodegenerative effects that have been reported with other stimulant drugs (Blum et al, 2013;Gold et al, 2009). Finally, future work should consider the combinations of bath salt agents that are typically abused.…”

Section: Discussionmentioning

confidence: 73%

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Colon-Perez

Tran

Thompson

et al. 2016

Neuropsychopharmacol

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The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D 1 /D 2 receptor antagonist cis-flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV.

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Section: Discussionmentioning

confidence: 73%

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Colon-Perez

Tran

Thompson

et al. 2016

Neuropsychopharmacol

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“…Because cathinones are relatively new, research on their acute and long-term neurotoxicity of cathinones is starting to be conducted. A recent report (Blum et al, 2013) stated that cathinones ''have been known to cause intensive cravings for the substances and users have been reported to go on multiday binges that often cause medical problems necessitating medical intervention''.…”

Section: Introductionmentioning

confidence: 99%

Serotonergic impairment and memory deficits in adolescent rats after binge exposure of methylone

et al. 2014

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Methylone is a cathinone derivative that has recently emerged as a designer drug of abuse in Europe and the USA. Studies on the acute and longterm neurotoxicity of cathinones are starting to be conducted. We investigated the neurochemical/enzymatic changes indicative of neurotoxicity after methylone administration (4 x 20 mg/kg, s.c. a day with 3 h intervals) to adolescent rats, to model human recreational use. In addition, we studied the effect of methylone on spatial learning and memory using the Morris water maze (MWM) paradigm. Our experiments were carried out at a high ambient temperature to simulate the hot conditions found in dance clubs where the drug is consumed. We observed a hyperthermic response to methylone that reached a peak 30 min after each dose. We determined a serotonergic impairment in methylone-treated rats, especially in the frontal cortex, where it was accompanied by astrogliosis. Some serotonergic alterations were also present in the hippocampus and striatum. No significant neurotoxic effect on the dopaminergic system was identified. Methylone-treated animals only displayed impairments in the probe trial of the MWM, which concerns reference memory, while the spatial learning process seemed to be preserved.

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“…This may have been coincidental or it is possible that MDPh containing substances induce neurotoxicity and/or inflammation, which may respond to the corticosteroids. 16 However, this has not been described to date with MDMA or MDBP. Further research is warranted to investigate the possibility that high dose steroids may be of benefit in toxicity seen with MDBP and similar compounds.…”

Section: Discussionmentioning

confidence: 93%

Unusually Prolonged Presentation of Designer Drug Encephalopathy Responsive to Steroids

Albadareen¹,

Thornton

Heshmati

et al. 2015

Pediatrics

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The availability and use of novel psychoactive substances has risen dramatically over the last decade. The unpredictability of their toxicity constitutes a real challenge. We report a case of an adolescent who developed prolonged encephalopathy after ingesting "Hot Molly," which was found to contain the novel psychoactive substance, methylenedioxybenzylpiperazine when analyzed by high resolution mass spectrometry assay. This is the first case of human toxicity from methylenedioxybenzylpiperazine ingestion in the medical literature confirmed by body fluid analysis presenting with significant and prolonged encephalopathy. The prolonged course may be due to CYP2D6 inhibition from a combination of the methylenedioxyphenyl moiety and the patient's ultrarapid metabolizer pharmacokinetics. The response to high dose corticosteroids suggests a possible inflammatory effect that warrants further investigation.

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Hypothesizing that designer drugs containing cathinones (“bath salts”) have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption

Cited by 24 publications

References 26 publications

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity

Serotonergic impairment and memory deficits in adolescent rats after binge exposure of methylone

Unusually Prolonged Presentation of Designer Drug Encephalopathy Responsive to Steroids

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