Kavita M. Babu

Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines.

Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called “bath salts,” have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as “legal ketamine.” Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as “legal Ecstasy.” These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.

Opioid receptors and legal highs: Salvia divinorum and Kratom

Salvia divinorum and Mitragyna speciosa (“Kratom”), two unscheduled dietary supplements whose active agents are opioid receptor agonists, have discrete psychoactive effects that have contributed to their increasing popularity. Salvia divinorum contains the highly selective kappa- opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia. Mitragynine, the major alkaloid identified from Kratom, has been reported as a partial opioid agonist producing similar effects to morphine. An interesting minor alkaloid of Kratom, 7-hydroxymitragynine, has been reported to be more potent than morphine. Both Kratom alkaloids are reported to activate supraspinal mu- and delta- opioid receptors, explaining their use by chronic narcotics users to ameliorate opioid withdrawal symptoms. Despite their widespread Internet availability, use of Salvia divinorum and Kratom represents an emerging trend that escapes traditional methods of toxicologic monitoring. The purpose of this article is to familiarize toxicologists and poison control specialists with these emerging psychoactive dietary supplements.

Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth)

BACKGROUND Kratom (Mitragynia speciosa korth) is recognized increasingly as a remedy for opioid withdrawal by individuals who self-treat chronic pain. CASE DESCRIPTION A patient who had abruptly ceased injection hydromorphone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb with modafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administration stopped. We confirmed the identity of the plant matter he ingested as kratom and identified no contaminants or adulterants. We also conducted high-throughput molecular screening and the binding affinity at mu, delta and kappa receptors of mitragynine. CONCLUSION We report the self-treatment of chronic pain and opioid withdrawal with kratom. The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additional receptor affinities that might augment its effectiveness at mitigating opioid withdrawal. The natural history of kratom use, including its clinical pharmacology and toxicology, are poorly understood.

Toxicity of energy drinks.

Purpose of review ‘Energy drinks’, ‘energy shots’ and other energy products have exploded in popularity in the past several years; however, their use is not without risk. Caffeine is the main active ingredient in energy drinks, and excessive consumption may acutely cause caffeine intoxication, resulting in tachycardia, vomiting, cardiac arrhythmias, seizures, and death. The effects of chronic high-dose caffeine intake in children and adolescents are unknown. Caffeine may raise blood pressure, disrupt adolescent sleep patterns, exacerbate psychiatric disease, cause physiologic dependence, and increase the risk of subsequent addiction. Recent findings Coingestion of caffeine and ethanol has been associated with increased risk-taking behaviors, harm to adolescent users, impaired driving, and increased use of other illicit substances. The toxicity of ingredients often present in energy drinks, such as taurine, niacin, and pyridoxine, is less well defined. Recent and significant literature describing adverse events associated with energy drink use are reviewed. Summary Although prior studies have examined the effects of caffeine in adolescents, energy drinks should be considered a novel exposure. The high doses of caffeine, often in combination with ingredients with unknown safety profiles, mandates urgent research on the safety of energy drink use in children and adolescents. Regulation of pediatric energy drink use may be a necessary step once the health effects are further characterized.

Dabigatran: Review of Pharmacology and Management of Bleeding Complications of This Novel Oral Anticoagulant

Dabigatran (Pradaxa) is a competitive direct thrombin inhibitor approved by the US FDA for prevention of embolic stroke in patients with nonvalvular atrial fibrillation. Dabigatran has a pharmacokinetic profile that produces predictable anticoagulation responses, does not undergo CYP 450 metabolism, has few drug–drug and drug–food interactions, and does not require frequent laboratory monitoring of clotting parameters. Clinicians are rapidly prescribing this agent as a replacement for warfarin therapy. However, no therapeutic agent has been accepted to reliably reverse the hemorrhagic complications of dabigatran. As of yet, there is no solid evidence to guide management of bleeding complications; management should start with local control of bleeding when possible and transfusion of pRBCs if needed. Transfusion of FFP would not be expected to help control bleeding. Limited and mixed data exist for transfusion of factor VIIa and prothrombin complex concentrates; these therapies should be considered as well as dialysis, which will increase elimination in patients with life-threatening or closed-space bleeding due to dabigatran. We present an article that reviews the pharmacokinetics, clinical trial literature, and consensus guidelines regarding this novel oral anticoagulant.

Self-Treatment of Opioid Withdrawal with a Dietary Supplement, Kratom

We examined the use of Kratom (Mitragyna sp.), a dietary supplement with mu-opioid agonist activity, by members of a cybercommunity who self-treat chronic pain with opioid analgesics from Internet pharmacies. Within one year, an increase in the number of mentions on Drugbuyers.com, a Web site that facilitates the online purchase of opioid analgesics, suggested that members began managing opioid withdrawal with Kratom. This study demonstrates the rapidity with which information on psychoactive substances disseminates through online communities and suggests that online surveillance may be important to the generation of effective opioid analgesic abuse prevention strategies.

Adverse Effects in Children After Unintentional Buprenorphine Exposure

Buprenorphine in sublingual formulation was recently introduced to the American market for treatment of opioid dependence. We report a series of 5 toddlers with respiratory and mental-status depression after unintentional buprenorphine exposure. Despite buprenorphine’s partial agonist activity and ceiling effect on respiratory depression, all children required hospital admission and either opioid-antagonist therapy or mechanical ventilation. Results of routine urine toxicology screening for opioids were negative in all cases. Confirmatory testing was sent for 1 child and returned with a positive result. The increasing use of buprenorphine as a home-based therapy for opioid addiction in the United States raises public health concerns for the pediatric population.

Energy drink and other substance use among adolescent and young adult emergency department patients.

Objective This study aimed to understand current patterns of energy drink use and compare the extent of usage of energy drinks and other commonly used and misused substances between adolescent (13–17-years-old) and young adult (18–25-years-old) emergency department (ED) patients. Methods During a 6-week period between June and August 2010, all patients presenting to an adult or pediatric ED were asked to complete a computer-based, anonymous questionnaire regarding use of energy drinks and other substances. Wilcoxon rank-sum, 2-sample tests of binomial proportions, Pearson &khgr;2 testing, and regression models were used to compare energy drink and substance use by age groups. Results Past 30-day energy drink use was greater for young adults (57.9%) than adolescents (34.9%) (P < 0.03). Adolescents typically consumed a mean of 1.5 and young adults a mean of 2.6 energy drinks per day when using energy drinks and drank at most a mean of 2.4 and 2.6 drinks per day, respectively. Among adolescents, energy drink usage was more common than alcohol, “street” or illicit drugs, and tobacco usage, but less common than caffeine product usage. For young adults, energy drink usage was more common than “street” or illicit drugs, but less common than caffeine use, and similar to tobacco and alcohol usage. Young adult energy drink users were more likely than young adult non–energy drink users also to use tobacco and caffeine. Conclusions Energy drink use is common among ED patients. Given the high prevalence of energy drink use observed, emergency physicians should consider the involvement of energy drinks in the presentations of young people.

ANCA-positive necrotizing vasculitis and thrombotic vasculopathy induced by levamisole-adulterated cocaine: A distinctive clinicopathologic presentation

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Serotonin syndrome in dextromethorphan ingestion responsive to propofol therapy.

An 18-year-old male developed a severe serotonin syndrome after recreational ingestion of Coricidin HBP (chlorpheniramine 4 mg and dextromethorphan hydrobromide 30 mg). Propofol infusion rapidly normalized his agitation, neuromuscular hyperactivity, and autonomic instability. Confirmatory analysis demonstrated a dextromethorphan serum concentration of 930 ng/mL. Dextromethorphan can produce serotonin syndrome in the absence of another serotonergic drug.