Synthetic Drugs of Abuse: ‘Spice,’ ‘K2’ and ‘Bath Salts’ Erik Gunderson, MD Assistant Professor Department of Psychiatry and Neurobehavioral Sciences and Department of Medicine Director, Clinical Pharmacological Research Unit University of Virginia April 14, 2011

Synthetic Cannabinoids (SCs) Spice/K2 brands marketed as natural herbal incense “Not for human consumption” Available convenience stores, gas stations, Internet Cannabis substitute Psychonaut Web Mapping Research Group (2009.) Spice Report. Institute of Psychiatry, King’s College London: London UK.

Spice and K2 Cost: $30-45 per 3gm Route: pipes, water pipes or rolled cigarettes Contents: inert plant material sprayed with SCs JWH-018, JWH-073, JWH- 250, CP-47,497, HU ory/news/

Pharmacology delta-9 tetrahydro- cannabinol (∆ 9 -THC) agonism of cannabinoid receptor type 1 (CB1) SCs more potent Typical doses are often less than 1mg Not readily detectable JWH-018 ∆ 9 -THC

Psychoactive Effects Marketed as similar to cannabis: Euphoria Sociability Anxiolytic Relaxation Stimulant Cross tolerance with THC?

Side Effects of SC Products Anxiety Paranoia Headache Vomiting Psychosis Diaphoresis HR/BP increase Seizures

Legal Timeline for SCs 2009: Restricted in the UK, EU 11/2010: DEA Notice of Intent to temporarily ban 5 SCs 3/1/2011: Five SCs Designated Schedule I JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol Effective for one year

Current and Future Epidemiology? No data on prevalence of use American Association of Poison Control Centers: Synthetic cannabinoids: 2009: 13 calls 2010: 2304 calls (Nov), a projected 200x increase Marijuana: 2008: 4009 calls, with 1020 for marijuana alone

Synthetic Stimulants Methylenedioxypyrovalerone (MDPV) and Mephedrone Sold as “bath salts” or “plant fertilizer” Currently legal in the United States Available online and in convenience stores

MDPV and Mephedrone CNS stimulants Related to cathinone, an active alkaloid found in the khat plant (N. Africa) Previously abused primarily in Europe and Australia

Product Marketing Mtv MDPK Magic Super Coke Peevee Energy-1 (NRG1) Charge Plus White Lightning Scarface Cloud 9 Ocean Ivory Wave

MDPV Route: Intranasal most common Also: oral, smoking, rectal, and IV White to light brown crumbly powder Degrades if exposed to air for significant periods of time MDMA

Pharmacology of MDPV CNS stimulant similar to methamphetamine, MDMA, or cocaine Norepinephrine-dopamine reuptake inhibitor (NDRI) Increased alertness, arousal, anxiety, agitation, diminished requirement for food and sleep, sexual arousal Tachycardia, hypertension, vasoconstriction, diaphoresis

Effects of MDPV “High” lasts 3-4 hours Physical effects may last 6-8 hours May cause seizures, panic attacks, or psychosis with high doses or increased frequency of use Avg dose: 5 to 20mg hina-Mdpv-by-pevukka.html

Other Sequelae of MDPV Trismus (inability to open mouth) or bruxism Panic attacks Psychosis with sleep deprivation Hallucinations, delusions, suicidal ideation Abstinence syndrome: depression, lethargy, anxiety, postural hypotension Leads to frequent re-dosing

MDPV’s Legal Status UK: MDPV regulated under the Misuse of Drugs Act 1971 US: Not scheduled but banned in some states DEA: controlled by the Federal Analogue Act? temporary-ban-on-spice-and.html

Mephedrone 4-methylmethcathinone (4-MMC) Meow Meow MCAT Miaow Drone Plant Feeder Bubbles

Pharmacology NE-DA reuptake inhibitor Similar to MA/MDMA Reportedly less potent, shorter duration Oral dose: 20-50mg “Come up”: min Peak: min “Comedown”: min Re-dosing: common Mephedrone Amphetamine

Routes of Administration Oral ingestion Swallowing capsules Bombing (swallowing powder wrapped in cigarette paper) Insufflation (snorting) Rectally (either plugging or enema) IV (use 1/2 to 1/3 dose)

Effects of Mephedrone Euphoria Sociability Stimulation Sexual Arousal Music Appreciation Hallucinations

Mephedrone Side Effects Loss of appetite Increase in body temperature, sweating, hot flushes Tense jaw, bruxism, stiff neck, muscle clenching HR/BP elevation, chest pains Dehydration Mydriasis, nystagmus Painful nasal drip/ulcers in mouth (after insufflation) Insomnia, paranoia, anxiety, dysphoria, psychosis

Mephedrone’s Legal Status : Banned in many European counties December 2010: Illegal throughout the EU Mephedrone is not specifically banned in the United States However, some states have banned mephedrone DEA: may be controlled by the Federal Analogue Act as an analogue of methcathinone

Current and Future Epidemiology? No data on prevalence of use American Association of Poison Control Centers: Bath Salts: 2010: 292 calls 2011: 469 calls (2/14/11), a projected14-fold increase

Questions?

References Brunt, T.; Poortman, A.; Niesink, R.; Van Den Brink, W. (2010). "Instability of the ecstasy market and a new kid on the block: mephedrone". Journal of psychopharmacology. Drug Enforcement Administration: Office of Diversion Control; Drug and Chemical Evaluation Section. Methylenedioxypyrovalerone [(MDPV) (1-(1,3-Benzodioxol-5-yl)-2-(1-pyrrolidinyl)-1-pentanone]. Available at: Accessed February 7, EMCDDA (2009). Action on new drugs briefing paper: Understanding the ‘spice’ phenomenon. A report from an EMCDDA expert meeting, 6 March, 2009, Lisbon. "Europol - MCDDA Joint Report on a new psychoactive substance: 4-methylmethcathinone (mephedrone)". European Monitoring Centre for Drugs and Drug Addiction. 27 May Psychonaut WebMapping Research Group (2009). MDPV report. Institute of Psychiatry, King’s College London: London UK. Available at: Accessed February 23, Psychonaut WebMapping Research Group (March 2010). "Mephedrone Report." Institute of Psychiatry, King's College: London UK. Psychonaut Web Mapping Research Group (2009.) Spice Report. Institute of Psychiatry, King’s College London: London UK. United States Drug Enforcement Agency. Office of Diversion Control. Drugs and Chemical of Concern: 4- methylmethcathinone [Mephedrone, 4-MMC, meow meow, m-CAT, bounce, bubbles, mad cow]. July United States Drug Enforcement Agency. Office of Diversion Control. Rules 2011:Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into Schedule I. Federal Register Volume 76, Number 40 (Tuesday, March 1, 2011). Wehrman J. U.S. Poison Centers Raise Alarm about Toxic Substance Marketed as Bath Salts; States Begin Taking Action. AAPCC. February 14, Available at: Winstock, A.; Mitcheson, L.; Deluca, P.; Davey, Z.; Corazza, O.; Schifano, F. (2010). "Mephedrone, new kid for the chop?". Addiction 106 (1).

Acknowledgement Laura Willing, BS Contact Information Erik Gunderson, MD office