7:45 – 9 am Presenter Disclosure Information

The following relationships exist related to this presentation: Emerging Drugs of Abuse: From Ecstasy to Bath Salts, Synthetic ►Petros Levounis, MD, MA: No financial relationships to disclose. Cannabinoids, and Beyond Off-Label/Investigational Discussion SPEAKER ►In accordance with pmiCME policy, faculty have been Petros Levounis, MD, MA asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations.

Outline Learning Objectives

• List the four major classes of emerging drugs of abuse. 1. Stimulants • Identify the pleasurable effects of methylene-dioxy- methamphetamine (MDMA), bath salts, synthetic 2. Cannabinoids cannabinoids, salvia divinorum, dextromethorphan, and kratom. 3. Hallucinogens • Identify major detrimental effects of methylene-dioxy- methamphetamine (MDMA), bath salts, synthetic cannabinoids, salvia divinorum, dextromethorphan, and 4. Opioids kratom. 5. Management • Describe the mechanism of action of street stimulants. 6. Summary

1 Ecstasy The Stimulants Methylene-Dioxy-Meth-Amphetamine (MDMA) Effects

• Essentially partly a stimulant and partly a hallucinogen: . An attenuated form of cocaine, plus “Freshmen love it, . An attenuated form of LSD. Sophomores like it, • Empathy (more than ecstasy). Juniors are ambivalent, and • Profound feelings of relatedness to the Seniors are afraid.” rest of the world. • In the 1970s, it was used in psychotherapy (unsuccessfully).

Neurobiology Intoxication

• Acutely increases serotonin levels by: • “Disco dump” and bruxism. . Blocking reuptake, and • Stimulant effects: . Directly releasing the neurotransmitter. . Wakefulness, endurance, energy. • Chronically decreases serotonin . Trismus, anorexia, diaphoresis, hot flashes. levels by: • Serotonin Syndrome: . Depleting serotonin stores . Treat with hydration, cooling, and sedation. . Inhibiting the synthesis of new serotonin. . Do not use beta-blockers, which may • Neurotoxicity. worsen vasospasm and hypertension.

Withdrawal Long-term Effects

• Anhedonia and depressed mood. • Associated with: • Lethargy and fatigue for several days. . Depression . Anxiety • Frank suicidality in the absence of co- . Panic Disorder occurring depressive disorder is rare. . Increased impulsivity • No indication for treatment. . Sleep disturbances . Cognitive dysfunction • No FDA approved medications. • MET and CBT are the major treatment modalities. Effects

• Euphoria Bath Salts • Heightened alertness • Elevated energy • Increased sexual arousal

Levounis P and Herron A. The Addiction Casebook. 2014.

“Hey, I just met you, 2 and this is crazy, but I’m on bath salts, and your face looks tasty.” The Cannabinoids

Names

• Spice, Spice Gold, Spice Diamond • K2, K2 Blonde • Aroma • Yucatan Fire Synthetic • XXX • Black Box Cannabinoids • Zombie • Skunk • Moon Rocks • Bizarro Effects

• Mild euphoria and relaxation • The giggles “Why drink and drive, • Increased sensitivity to external stimuli: when you can smoke and fly.” . Colors seem brighter . Smells are more pungent “If we all had a bong, • Distortion of time perception we’d all get along.” • Frank, vivid hallucinations

Neurobiology SC Neurobiology

• Cannabinoids activate the CB1 and CB2 • Synthetic Cannabinoids (SCs) are full and cannabinoid receptors: potent agonist of the CB1 receptor.

. CB1 has high density in cerebellum, basal ganglia, hippocampus, cerebral cortex. • 4- to 5-fold higher affinity to CB1 receptor. . CB has low density in the brainstem, hence low risk 1 • 10-fold higher affinity to CB receptor. of respiratory depression. 2

. CB2 is found in spleen, hematopoietic cell lines, mast • 2 to 3 times more likely to be associated cells. with sympathomimetic effects. . CB2 activation may be the primary cause of addiction to cannabis. • Approximately 5 times more likely to be associated with hallucinations. • Anandamide is the endogenous ligand.

Forrester MB, Kleinschmidt K, Schwarz E, Young A. Hum Exp Toxicol 2012; 31:1006–11.

Synthetic Drug Abuse Prevention Act of 2012 • Cannabimimetic Agents are Schedule I. • “Unless specifically exempted or unless listed 3 in another schedule, any material, compound, mixture, or preparation which contains any quantity of cannabimimetic agents, or which contains their salts, The Hallucinogens isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation.” Names

• Diviners Sage • Magic Mint • Maria Pastora • Purple Sticky Salvia • Sally D Salvia Divinorum • Salvia Zone

Effects

• Highly selective kappa opioid receptor agonist Dextromethorphan • Intense hallucinations DXM • Heightened sensations • Synesthesia

DXM Effects DXM Plateaus

o Great for conversation 1st 100 – 250 mg o Great insights to everything • Low dose – Opioid o “Good for a party or concert!” o More euphoria • Higher dose – Hallucinogen 2nd 250 – 450 mg o Decreased sense of time o Decreased sense of surroundings o Visual hallucinations, mostly spirals and fluids 3rd 450 – 800 mg o Popping up of thoughts and feelings of one's own life o “This is definitely not a party plateau.” o Alien encounters o Out of body experiences th 800 – 1,800 mg 4 o “Not for beginners—not be done without close access to a hospital and a smart trip-sitter.” o Very few reports of a 5th plateau o Profuse sweating, extreme nausea, blackouts th Over 1,800 mg 5 o “Point of no return. Unless you want to go through physical and mental hell, don't try and hit this point.”

DXM.darkridge.com The 2C Family 4 e.g., 2,5-dimethoxy-4-iodophenethylamine The Opioids

Names

• Ithang • Kakuam • Ketum • Krypton Kratom • Thom Mitragyna Speciosa

Effects

• Low dose – Stimulant • Higher dose – Opioid • 13 times more potent than morphine Krokodil 4,5-α-epoxy-17-methylmorphinan-3-ol Urine Toxicology Examination

• “Current immunoassay-based screening methods are not ideal for presumptively 5 identifying most designer drugs.” • In general: Management Opioids give False Negatives, Amphetamines give False Positives, and Cocaine is Cocaine.

ForensicMag.com, 2014.

Intoxication and Withdrawal Bottom Line

• Make a “best guess” about the class of • Opioids: Use Naloxone. the suspected substance based on: • Sedatives: Use Benzodiazepines. Presenting Symptoms • Everything else: Use Supportive Care. History Physical Examination Urine Toxicology Examination • Treat the patient as if she or he had used the prototype of that class.

ForensicMag.com, 2014.

Addiction Resources • No FDA-approved medications and none recommended. • NIDA.gov (Reliable but less current) • Coordination of care with addiction counselors, clinics, and psychiatrists. • Wikipedia.org JUST PERFECT • Psychosocial Approaches: Erowid.org (Current but less reliable) 12-Step Facilitation • Cognitive Behavioral Therapy Motivational Interviewing GOOD BAD X Empathy Panic Bath Salts Happiness Addiction 6 SC Euphoria Psychosis Salvia Visions Flashbacks Summary DXM Insights Hell Kratom Pain Relief Death Krokodil Not Here Zombie

Thank you

NJMS.Rutgers.edu/Psychiatry