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Synthetic Cathinones: Clinical Manifestations, Diagnosis, and Treatment David A. Gorelick, M. D. , Ph. D. , DLFAPA Professor of Psychiatry

Euphoria Clinical Manifestations of Synthetic Cathinones Heightened sensory awareness Increased sexual drive Decreased appetite Alertness Increased sociability Empathy Karila, L. , J. Billieux, et al. (2016). "The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences. " Brain Res Bull 126(Pt 1): 61 -67. Energy

Effects start 10 - 20 mins after dosing Effects last 6 - 12 hours Users seek medical attention due to: • Greater potency compared to cocaine/ amphetamines • Uncertainty of dosing Karila, L. , J. Billieux, et al. (2016). "The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences. " Brain Res Bull 126(Pt 1): 61 -67.

Medical Effects of Synthetic Cathinones Syncope Seizures Bruxism Lightheadedness Blurred vision Mydriasis Chest pain ST-segment changes Tachycardia Arrhythmias Myocarditis Hypertension Rhabdomyolysis Acute renal failure Diaphoresis Myoclonus Karila, L. , J. Billieux, et al. (2016). "The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences. " Brain Res Bull 126(Pt 1): 61 -67.

Confusion Agitation Combative behavior Neuropsychiatric Effects Paranoid delusions Hallucinations May persist up to 4 weeks Long-term hospitalization Karila, L. , J. Billieux, et al. (2016). "The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences. " Brain Res Bull 126(Pt 1): 61 -67. Suicidal ideation

Clinical Laboratory Abnormalities + K CPK Mephedrone Na + Sweating Secretion of ADH Karila, L. , J. Billieux, et al. (2016). "The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences. " Brain Res Bull 126(Pt 1): 61 -67.

Diagnosis of Intoxication History Drug samples Stimulant intoxication syndrome Packaging Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8. Collateral informants Paraphernalia

Synthetic Cathinones Legitimate bath products Tablet or capsule Colorful fragrant crystals Small colorful packets White-yellow or brown, odorless, fine-grain powder Prominent warning label, such as “not for human consumption” Small warning labels that do not detract from the advertising messages Image: https: //i 2. wp. com/ppaccentral. org/wp-content/uploads/2016/12/bath-salts-packaging. jpg? resize=310%2 C 187&ssl=1 Image: https: //sattvicfoods. in/wp-content/uploads/2017/02/Himalayan-Bath-Salt-crystals. jpg

Synthetic Cathinone Street Names Vanilla Sky Pixie Dust Zoom Ivory Wave Purple Rain Hurricane Charlie Cloud 9 Sextacy

Useful Resources drugfree. org/drug/bath-salts US Drug Enforcement Administration (DEA) www. dea. gov US National Institute on Drug Abuse (NIDA) www. drugabuse. gov Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Review of systems Clinical laboratory testing • Complete blood count • Electrolytes • Blood chemistry Medical Evaluation 12 -lead electrocardiogram Imaging Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8. Physical and neurological examination

Diagnosis is often made by exclusion. Confirmed by sophisticated and expensive assay methods Results are delayed several days. False negative results possible due to novel chemical structures Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Clinical Manifestations Warranting a High Index of Suspicion (1) Sudden onset of otherwise unexplained psychosis (2) Sudden onset of otherwise unexplained cognitive impairment, such as disorientation or disorganized speech Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Clinical Manifestations Warranting a High Index of Suspicion (3) Sudden onset of otherwise unexplained kidney, neurological (e. g. , seizures), or cardiovascular problems (e. g. , chest pain, tachycardia, arrhythmia, or hypertension) (4) Signs and symptoms consistent with stimulant intoxication, such as jaw clenching, bruxism, muscle spasms, or diaphoresis, in the absence of a drug test positive for cocaine/amphetamines. Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Observation and monitoring Supportive and symptomatic measures • Short-acting benzodiazepine for agitation, anxiety, or muscle spasm • Antipsychotic for severe or persistent psychosis Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Observation and monitoring Supportive and symptomatic measures Psychiatric symptoms > 1 week: • Close evaluation for a comorbid psychiatric disorder Transient suicidal ideation rarely requires antidepressant treatment unless: • It persists. • It reflects a comorbid mood disorder. Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Anxiety Synthetic Cathinone Withdrawal Syndrome Irritability Depression Suicidal ideation Insomnia Increased drug craving Headache Decreased appetite Increased muscle tone Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8. Twitchin g Chills and sweating

• No approved pharmacological treatments for synthetic cathinone withdrawal • No consensus clinical practice guidelines for its treatment Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Clinical Management of Withdrawal Observation and monitoring Supportive and symptomatic measures Antidepressants if: • Intravenous fluids for dehydration • Depression persisted more than several days • Short-acting benzodiazepine for agitation or anxiety • Known, independent, comorbid mood disorder • Acetaminophen for pain or headache Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Substance Use Disorder Continued use of the substance despite suffering adverse consequences from such use 15%30% Regular, conventional stimulant users ? Synthetic cathinone users Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8. Develop stimulant use disorder Intranasally (snorting) Intravenously Smoking

No formal diagnosis in DSM-5 or ICD-10 Diagnosis could be made by generalizing from the criteria provided for stimulant and other substance use disorders. Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

*No specific treatment protocol General principles for any substance use disorder CBT Group Individual ü Understand the adverse consequences ü Learn better coping strategies Weaver, M. F. , Hopper, J. A. , & Gunderson, E. W. (2015). Designer drugs 2015: assessment and management. Addiction science & clinical practice, 10(1), 8.

Key Points • Synthetic cathinones have stimulant-like clinical manifestations similar to, but often more intense and longer lasting than, those of conventional stimulants, such as cocaine and amphetamines. • Treatment of intoxication and withdrawal is supportive and symptomatic.

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