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New ‘legal’ highs: Kratom and

Julianna D. Troy, MD, MPH

Dr. Troy is a Psychiatrist with he demand for “legal highs”— times more potent than , and Counseling and Psychological intoxicating natural or synthetic 7-hydroxymitragynine is 4 times more Services, Purdue University, West Lafayette, IN. substances that are not prohibited potent than .2 T Disclosure by law—continues to increase. Young Kratom is available as , pow- Dr. Troy reports no financial adults may use these substances, which dered leaves, or gum. It can be smoked, relationship with any company are widely available on the internet, at brewed into tea, or mixed with liquid whose products are mentioned in this article or with manufacturers of “head shops,” and at gas stations. Such and ingested. Effects are dose-dependent; competing products. substances frequently cause adverse med- lower doses tend to produce a ical and psychiatric effects, exemplified by effect and higher doses produce an opi- recent reports concerning the dangers of oid effect. A typical dose is 1 to 8 g.3 Users using (eg, “Spice,” may take Kratom to experience “K2”) and synthetic cathinones (“bath or analgesia, or to self-treat with- salts”). Although these 2 substances now drawal symptoms.3 Kratom withdrawal are illegal in many jurisdictions, other syndrome shares many features of clas- novel substances of misuse remain legal sic —diarrhea, rhinor- and widely available, including Kratom rhea, cravings, , tremor, myalgia, and methoxetamine. sweating, and irritability—but has been Because these substances usually are reported to be less severe and shorter- not detectable on standard urine toxicol- lasting.1 Kratom withdrawal, like opioid ogy screens, clinicians need to be aware withdrawal, may respond to supportive of them to be able to take an accurate care in combination with opioid-replace- substance use history, consider possible ment therapy. Airway management and dangerous interactions with prescribed treatment may be needed on an psychotropics, and address medical and emergent basis if a user develops respi- psychiatric complications. ratory .2 There have been case reports of occurring following Kratom is an herbal product derived Kratom use.2 from speciosa, a native to . Traditionally used as a Methoxetamine is a analog medicinal herb, it increasingly is being originally developed as an alternative to used for recreational purposes and re- ketamine. It isn’t classified as a controlled mains legal and widely available in the substance in the United States and is avail- United States. Kratom’s leaves contain able on the internet.2 Methoxetamine is a Discuss this article at multiple , including mitragynine white powder typically snorted or taken www.facebook.com/ CurrentPsychiatry and 7-hydroxymitragynine, which are be- sublingually, although it can be injected lieved to act as agonists at the μ-opioid intramuscularly. Because methoxetamine’s receptor. Mitragynine also may have ago- structure is similar to ketamine, its mecha- nist activity at post-synaptic α2-adrenergic nism of action is assumed to involve gluta- receptors, as well as antagonist activity mate N-methyl-d-aspartate receptor antag- Current Psychiatry at 5-HT2A receptors.1 Mitragynine is 13 onism and dopamine reuptake inhibition. Vol. 12, No. 4 E1 continued Pearls

Doses range from 20 to 100 mg orally and Staying current is key 10 to 50 mg when injected. Effects may not A paucity of clinical research on these be apparent for 30 to 90 minutes after the substances means their effects are poorly is snorted, which may cause users understood, which creates a dangerous to take another dose or ingest a different situation for users and physicians. In addi- substance, possibly leading to synergistic tion, many users assume these substances adverse effects. Effects may emerge within are safer than illegal substances. New and 5 minutes when injected. The duration of potentially dangerous substances are be- effect generally is 5 to 7 hours—notably ing produced so quickly distributors are longer than ketamine—but as little as 1 able to stay ahead of regulatory efforts. hour when injected. When one substance is declared illegal, an- No clinical human or animal studies other related substance quickly is available have been conducted on methoxetamine, to take its place. To provide the best care Kratom and which makes it difficult to ascertain the for our patients, it is essential for psychia- drug’s true clinical and toxic effects; in- trists to stay up-to-date about these novel methoxetamine stead, these effects must be surmised from substances. usually are user reports and case studies. Desired ef- undetectable on fects described by users are similar to References 1. McWhirter L, Morris S. A case report of inpatient toxicology screens those of ketamine: dissociation, short-term detoxification after kratom (Mitragyna speciosa) dependence. mood elevation, visual , Eur Addict Res. 2010;16(4):229-231. 2. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone and alteration of sensory experiences. tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (), Reported adverse effects include catato- Kratom, , methoxetamine, and piperazines. nia, , agitation, and depression.4 J Med Toxicol. 2012;8(1):15-32. 3. Boyer EW, Babu KM, Macalino GE. Self-treatment of opioid In addition, methoxetamine may induce withdrawal with a , Kratom. Am J sympathomimetic toxicity as evidenced by Addict. 2007;16(5):352-356. 4. Corazza O, Schifano F, Simonato P, et al. Phenomenon of and hypertension. Researchers new on the Internet: the case of ketamine derivative have suggested that patients who experi- methoxetamine. Hum Psychopharmacol. 2012;27(2): 145-149. ence methoxetamine toxicity and require 5. Wood DM, Davies S, Puchnarewicz M, et al. Acute toxicity emergency treatment be managed with associated with the recreational use of the ketamine derivative methoxetamine. Eur J Clin Pharmacol. 2012; supportive care and .5 68(5):853-856.

Current Psychiatry E2 April 2013