Mephedrone and chemsex: when it stops being a party and becomes a fatal problem

Introduction

Chemsex has become a relevant social problem because of its clinical and epidemiological implications. This sexual practice is based on the voluntary use of psychoactive substances, mainly gamma-hydroxybutyrate (GHB), 4-methylmethcathinone (mephedrone), and methamphetamines, in order to facilitate and/or to enhance the experience of sexual intercourse, principally among men who have sex with men (MSM). It is more common in people living with human immunodeficiency virus (PLWH). ¹ The clinical impact of chemsex is based not only on behavioral problems related to the chronic dependence generated by the drugs used and high-risk sex practices ² but also on the potential toxicity of the drugs. ³ In addition, chemsex increases the risk of contracting sexually transmitted infections associated with unprotected (“condomless”) sexual intercourse and of intravenous drug injection, i.e. “slamming”, by which HIV and hepatitis C virus infections make chemsex a real public health problem. ⁴ We present a clinical case that may reflect the potentially fatal toxicity of these substances.

Clinical case

The patient was a 26-year-old man living with HIV-1 infection since 2012 when he was also diagnosed with lymphogranuloma venereum proctitis. Combination antiretroviral therapy (cART) was started with RPV/FTC/TDF and led to virological suppression, which the patient maintained for six years. In addition, his CD4 cell count recovered to 1229 cells/mm³. In 2016, he was treated for primary syphilis and urethritis caused by Neisseria gonorrhoeae, coinciding with the beginning of sporadic chemsex sessions, during which he used GHB, mephedrone, and occasionally methamphetamines. Over time, the patient became addicted to these substances, with more frequent consumption (almost weekly) and clinical problems, such as psychotic episodes and even admission to hospital in 2017 for coma secondary to consumption of GHB and alcohol. Several harm reduction strategies were proposed, including visits to a psychiatrist, psychologist, and an addiction center, although the patient rejected any kind of help beyond the prescription of olanzapine and zolpidem for psychotic symptoms, as he did not consider himself to have a real problem. In 2018, he was admitted to hospital again with anxiety, tachycardia, high fever, diarrhea (previous 48 h), and signs of dehydration. In the emergency department, he was diagnosed with infectious colitis, which was managed with ciprofloxacin and intravenous fluid replacement. Despite these initial measures, his condition worsened, with hemodynamic instability, hypertonicity, hyperreflexia, and impaired consciousness. He was transferred to the intensive care unit, where he was initially treated for a severe abdominal septic process based on clinical symptoms including fever, colitis, abdominal pain, leukocytosis, and hemodynamic instability. An abdominal computed tomography scan was unremarkable. Despite the use of vasoactive drugs and intensive antibiotic therapy with meropenem, linezolid, and levofloxacin, there was no clinical response. All microbiological tests that included blood and rectal samples were negative. In the following hours, the patient developed myocardial damage and lower and upper limb ischemia and necrosis, followed by multiorgan failure and death. Although the patient had initially denied the use of chemsex drugs, several hours before death he reported voluntary and intensive oral mephedrone use combined with a single dose of oral methamphetamine during the previous days, coinciding with a weekend chemsex session. Basic urinalysis for toxic substances was positive for amphetamines and benzodiazepines. No specific test was performed for GHB or mephedrone.

The cause of death was established in the setting of high mephedrone consumption (recognized by the patient himself), a compatible clinical picture that fulfilled the Hunter Serotonin Toxicity Criteria for serotonin syndrome, ⁵ and once other possibilities were ruled out, particularly infectious disease. Nevertheless, the diagnosis must remain a suspicion, as there is no specific test to confirm serotonin syndrome, and measurement of serotonin levels have not proven to be helpful.

Discussion

Chemsex has become a routine sexual and social practice among MSM, especially those living HIV. This practice may have serious health consequences, as reflected in the present case, not only as a result of the generalization of unprotected sex and therefore a significantly increased risk of sexually transmitted infection^6,7 but also because of the direct toxic effect of the drugs, which could be greater in some patients after combination with antiretrovirals such as ritonavir or cobicistat. ⁸

Deaths resulting from chemsex have been related mainly to depression of the central nervous system induced by GHB, especially when combined with alcohol. ⁹ Fatal outcomes with mephedrone are generally associated with multiple substance abuse. Mephedrone is the most commonly used synthetic cathinone, and is often taken as part of a wider repertoire of substances; typically, it is snorted or swallowed or added to a drink and in some cases used rectally, smoked, or injected. It is taken both for its mood-enhancing properties and as a psychomotor stimulant in social situations. ¹⁰ However, the relatively short duration of its effects is usually associated with repeated dosing during a single session. Its stimulant effects take the form of increasing synaptic concentrations of serotonin, dopamine, and noradrenaline, which also induce its sympathomimetic activity. Cardiac symptoms (hypertension, tachycardia, chest pain, palpitations, diaphoresis, hot flushes, peripheral vasoconstriction), psychiatric symptoms (anxiety, panic, depression, irritability, insomnia, paranoid delusions, short-term psychosis), and neurological symptoms (paresthesia, headache, tinnitus, seizures, nystagmus, mydriasis) are the most commonly reported adverse effects and may require medical care. ¹¹ Serotonin syndrome may occur, especially when the user has been exposed to two or more drugs that increase the effects of serotonin, when taken regularly or as an acute overdose.

In the case we report, repeated use of mephedrone combined with methamphetamine could have led to serotonin syndrome, which is a potentially life-threating adverse reaction to the use of specific drugs (illicit or prescribed) or interactions between drugs,^12,13 and whose initial symptoms fulfilled the Hunter Serotonin Toxicity Criteria. ⁵ Serotonin syndrome has traditionally been described as the triad of mental status changes (anxiety, restlessness, disorientation, agitated delirium), autonomic hyperactivity (diaphoresis, tachycardia, hyperthermia, hypertension, diarrhea), and neuromuscular abnormalities (tremor, muscle rigidity, myoclonus, hyperreflexia). ¹⁴ Toxicity is related to a dose-effect relationship, because high or repeated drug doses can intensify serotonin release, and the simultaneous use of multiple serotonergic substances (e.g. mephedrone and methamphetamine) increases the risk of serotonin syndrome. ¹³

The diagnosis of serotonin syndrome is made solely on clinical grounds. Therefore, a detailed history and thorough physical and neurologic examinations are essential if we are to confirm a syndrome with a spectrum of clinical findings ranging from benign to lethal.

Likewise, the sympathomimetic activity of the drug with peripheral vasoconstriction, together with the use of vasoactive drugs and poor peripheral perfusion, could have worsened the patient’s condition and explain the progressive ischemia and necrosis of the limbs. Cardiotoxicity could be explained both by mephedrone-induced mitochondrial dysfunction in cardiomyocytes ¹⁵ and by myocardial damage resulting from persistent vasoconstriction and hemodynamic instability.

The lack of knowledge about these substances among health professionals in emergency, intensive care and medical departments can delay diagnosis and management of toxicity. As seen in the present case, symptoms can be confused with other clinical disorders, such as infectious and cardiovascular events, and improperly-used treatments can produce interactions or even worsen the patient’s clinical condition. This public health problem has implications for both patients and the community at large. Appropriate training for health professionals and raised awareness of the magnitude of the problem are necessary if we are to develop suitable approaches for modifying behavior and managing toxicity in this group of patients.