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Toxicology

Designer Drugs

By Jonathan Schimmel, with Jason Hack
Division of Medical Toxicology, Brown University

Excerpts from the Toxic Matter Newsletter

“Designer drugs” refers to psychoactive compounds often created by chemically modifying existing drugs. The term encompasses a broad range of drugs that are widely available, constantly changing, and unfamiliar to most clinicians. They can be obtained online or in stores, and may range from powder or crystals, to liquids, tablets, or herbal plants that have been chemically coated. They are often labeled “not for human consumption” and claim to be intended for other uses to avoid legal liability. Their novel and ever-changing nature has made them difficult both to regulate and to test for in a clinical laboratory.

When managing these patients, given the breadth of designer drugs with scarce data on each specific compound, the rational approach is often to consider each drug as class, and to use clinical judgement to extrapolate to specific compounds in the context of general state of health and potential co-ingestions. There is not a widely recognized time point when patients are considered safe for discharge given lack of data, so they should be observed until mental status and vital signs normalize. After ensuring airway, breathing, and circulation, always consider whether decontamination, specific antidotes, or enhanced elimination techniques would be beneficial. Treatment for these patients is typically supportive, with emphasis on managing hyperthermia, hypo/hypertension, emesis, dehydration, seizures, dysrhythmias, and acute psychiatric abnormalities. Antipsychotics should be used very judiciously, since their anticholinergic properties can worsen hyperthermia and lower seizure threshold. Benzodiazepines are a mainstay of treatment. Below is a narrow review of designer drugs:

Tryptamines
Examples: Natural substances include psilocybin from psychoactive mushrooms. Synthetic derivatives include DMT (dimethyltriptamine), AMT (alpha methylated tryptamines), and 5-MeO-DiPT (aka Foxy Methoxy). Lysergamides such as LSD (lysergic acid diethylamide) and LSA (lysergamide, found in Woodrose seeds) are also tryptamines.
Mechanism: Agonists for serotonin (5-HT, aka 5-hyroxytryptamine).
Presentation: Primarily hallucinogenic, but may also have sympathomimetic symptoms, in some cases severe.

Phenethylamines
Background: Synthetic derivatives were popularized in a 1991 book titled PiHKAL (Phenethylamines i Have Known And Loved). Includes amphetamines.

2C
Examples: 2C-I (often sold as mescaline), 2C-E (Europa), 25I-NBOMe (N bomb)
Background: Their structures include two carbons in a consistent location, thus they’re called 2C drugs.
Presentation: Primarily hallucinogenic and sympathomimetic, potential for serotonin syndrome.

Benzodifurans
Examples: Bromo-DragonFLY
Background: First cases of recreational use in 2001, effects can last up to 3 days. Can act as a potent vasoconstrictor, with a case report requiring amputations.
Presentation: Primarily hallucinogenic, and may have agitation, seizures, kidney injury, and sequelae of marked vasoconstriction.

MDxx (aka substituted methylenedioxyphenethylamine) includes MDMA and its analogs.

Synthetic cathinones (aka bath salts)
Examples: mephedrone, MDPV, methcathinone, methylone, α-PVP (flakka)
Background: Cathinone is derived from the Khat plant, and can be modified into synthetic cathinones which are structurally similar to amphetamines. Abuse may occur in binge sessions lasting hours to days, with development of physical dependence and withdrawal.
Presentation: Primarily sympathomimetic.

Synthetic cannabinoids (aka Spice, K2)
Examples: JWH-018, JWH-073, JWH-250, CP 47-497, HU-210.
Mechanism: Cannabinoid receptor agonists, with potencies up to 800 times that of Δ9-THC.
Background: Initially developed in the 1960’s, they are divided into 7 categories based on structure. One theory for the severe psychosis seen is the lack of cannabidiol, a natural flavinoid present in marijuana with anxiolytic and antipsychotic effects.
Presentation: Acute psychosis, and may also have hyperthermia, seizures, kidney injury, and even rhabdomyolysis.

Piperazines (aka party pills, legal ecstasy)

Examples: BZP (benzylpiperazine), TFMPP (trifluoromethylphenylpiperazine)
Background: These are fully synthetic, unrelated to the other common classes and without natural examples. They were initially developed as anti-helminthics then studied as antidepressants. Piperazines considered psychoactive designer drugs are divided into the benzylpiperazines and phenylpiperazines.
Presentation: Primarily sympathomimetic, and the phenylpiperazines can potentially cause serotonin syndrome.

Synthetic opioids
Examples: acetylfentanyl, α-methylfentanyl (China white), MPPP
Background: Mainly derivatives of fentanyl or meperidine.
Presentation: Mimics that of opioid overdose.

References

  1. Dean, Be Vang, et al. "2C or not 2C: phenethylamine designer drug review." Journal of Medical Toxicology 9.2 (2013): 172-178.
  2. Hill, Simon L., and Simon HL Thomas. "Clinical toxicology of newer recreational drugs." Clinical toxicology 49.8 (2011): 705-719.
  3. Madras, Bertha K. "Designer drugs: An escalating public health challenge." Journal of Global Drug Policy and Practice 206.1 (2012).
  4. Musselman, Megan E., and Jeremy P. Hampton. "“Not for human consumption”: a review of emerging designer drugs." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 34.7 (2014): 745-757.
  5. Nelson, Michael E., Sean M. Bryant, and Steven E. Aks. "Emerging drugs of abuse." Emergency medicine clinics of North America 32.1 (2014): 1-28.

 

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