A New Source of Opioid and Lead Toxicity on the Block—Kamini: An Emerging Health Hazard—A Case Series

Abstract

Introduction:

Illicit drug abuse with opioids can inadvertently lead to refractory anemia and lead poisoning. ¹ The absence of adequate regulations for Ayurvedic herbal products has led to the adulteration of opioid-containing drugs with lead. ² As a result, lead toxicity has become a concern within this seldom-addressed population of opioid users. In this report, we present a collection of cases where individuals developed lead toxicity while being dependent on opioids due to their use of a little-known herbal product called Kamini, which contains Papaver somniferum. This retrospective case series aims to raise awareness about and foster broader recognition of opioid dependence linked to herbal products like Kamini, along with the associated risks associated with its usage.

Methods:

We retrospectively analyzed the records of three patients who were opioid abusers and presented with symptoms and signs of lead poisoning.

Results:

All three patients were male and presented with complaints of abdominal pain and generalized weakness. Laboratory examinations showed high lead levels and low hemoglobin as well as basophilic stippling. Urine porphyrins were falsely positive in two patients. All three patients showed symptomatic improvement with a decrease in lead levels after chelation therapy.

Discussion and Conclusion:

This case series highlights the need for awareness regarding opioid dependence syndrome and potential lead toxicity stemming from the use of Ayurvedic preparations over the counter, such as Kamini. A low threshold should be kept for testing for lead poisoning in patients who present with anemia and/or abdominal pain with a history of opioid dependence.

The rising popularity of traditional remedies can be attributed to their widespread accessibility and individuals’ reliance on these age-old treatments. Other factors that contribute to their usage include erroneous beliefs, claims about their potent effects, dissatisfaction, and negative experiences with modern drugs. However, significant concern has arisen due to the lack of scientific research and unqualified individuals’ improper use of these remedies. This has raised serious safety issues.^1–6 Non-allopathic healthcare systems face several challenges and obstacles, including regulatory oversight, misuse, the purity of remedies, the adoption of new manufacturing methods, the unrestricted availability of these treatments, and issues related to their quality.^7,8 Kamini is a herbal medicine containing opioids packed in the form of small pellets that can be easily swallowed and has been purported to improve overall health, vitality, and sexual functioning. ⁹

Lead is added as an adulterant in opioid-containing products due to its high molecular weight, easy availability, and similar color. This is known as “stepping up or blowing up,” where weight is increased and purity is decreased, making it profitable.^10-12 Historically, opioids have been adulterated with harmful substances such as thallium, lead, paracetamol, and strychnine. ¹³

Here, we report a case series highlighting lead intoxication from the use of an herbal medicine called Kamini.

Case 1

A 47-year-old married male patient, a businessman by occupation, presented to psychiatry OPD with complaints of difficulty concentrating, abdominal pain, and generalized weakness for one month. He was diagnosed with bipolar disorder eight years ago and was in remission and managing well with mood stabilizers and antipsychotics (divalproex sodium 750 mg/daily, quetiapine 50 mg/daily, and clonazepam 1 mg at night). He had a history of consuming opioid-containing herbal medicinal products sold under the name of “Kamini.” He has been taking six pellets of the said medication daily for the past 20 years, along with a history of smoking 10–15 cigarettes a day for 25 years. He had pallor and right iliac and hypochondrial tenderness on palpation. He was admitted for one day for abdominal pain and treated symptomatically before he left against medical advice with no obvious diagnosis. During follow-up next week, his laboratory reports revealed a hemoglobin of 7.6 g/dL with normal leukocyte and platelet counts.

Upper GI endoscopy and colonoscopy were normal. Ultrasonography of the whole abdomen and pelvis showed hepatomegaly with fatty infiltrates. There was no renal dysfunction based on renal function tests. Laboratory tests revealed basophilic stippling, and subsequently, a urine porphyrin report came positive, and high lead blood levels of 111 mcg/dL were detected using atomic absorption spectrometry. His history revealed no occupational exposure to lead, and his vitamin D levels were not evaluated. The patient was initiated on chelation therapy with intramuscular injections of British Anti-Lewisite (BAL) (50 mg/m² every four hours) for seven days in conjugation with calcium EDTA (calcium disodium senate 1,500 mg/m²/day as an intravenous infusion) for five days. The patient also received one unit of packed blood cells for his low hemoglobin levels and anemia. He was also started on oral tapentadol, pregabalin, and clonidine, given that he was developing withdrawal symptoms from opioids. The patient was also given nicotine replacement therapy. Blood lead levels gradually decreased to 54 mcg/dl after one week of initiation of chelation, along with concurrent improvement in symptoms. Blood lead levels decreased to less than 1 mcg/dL on subsequent monthly follow-ups.

Case 2

A 27-year-old single male, a post-graduate professor of history by occupation, was referred with chief complaints of generalized weakness for one month and nausea, vomiting, abdominal cramps, and body aches for the last three days. He had a history of consuming alcohol for six years but was abstinent for four months. He also had a history of raw opium use for six years, which was substituted with an herbal opioid derivative (Kamini) twice daily for six months. The patient mentioned that he started consuming the herbal opioid to ease the pain he would have when not taking raw opium. He had pallor on examination. Laboratory investigations revealed Hb of 5.6 mg/dl with a peripheral smear suggestive of microcytosis, hypochromia, and mild transaminitis. Bone marrow aspiration and biopsy were suggestive of sideroblastic anemia. Urine porphyrin was positive, and he had elevated blood lead levels of 79.25 mcg/dL on atomic absorption spectrometry. A diagnosis of sideroblastic anemia secondary to lead poisoning was made. The patient was started on chelation therapy with oral D-penicillamine 250 mg thrice daily and oral pyridoxine 50 mg twice daily. Opioid withdrawal symptoms were managed with intravenous tramadol and subsequently also required fentanyl infusion and ketamine for abdominal pain. The patient showed symptomatic improvement in a week and was discharged on oral pregabalin 75 mg twice daily for pain and anxiety. He was continued on chelation therapy for three months, and blood lead level one week after discharge was 49.9 mcg/dL, along with marked improvement in abdominal pain.

Case 3

A 25-year-old unemployed single male presented with a history of occasional episodes of reddish-brown urine for four months, easy fatigability, and abdominal pain for 20 days. He had been abusing opioids for the last four years (2–4 pellets of oral herbal opioid derivative (Kamini) 2–3 times a day). On examination, he was icteric. Laboratory reports showed anemia, hyponatremia, transaminitis, and mild direct hyperbilirubinemia. The hepatotropic viral panel was negative. Peripheral blood film showed anisopoikilocytosis and basophilic stippling. During the ward course, he had GTCS along with neuropathy and salt- losing nephropathy. A muscle biopsy of the right quadriceps muscle showed mild atrophy with minimal inflammation.

Subsequent evaluation found elevated blood lead levels of 111.9 mcg/dL. A diagnosis of lead poisoning with multisystem toxicity was made, and chelation was started with dimercaprol and EDTA. Repeat blood lead levels after one week were 52.0 mcg/dL, and chelation therapy was stopped.

Drug analysis of the herbal opioid derivative consumed in all three cases was suggestive of significant adulteration with lead; 53,654 mcg of lead per gram dry weight of the herbal product was detected in the said derivative after testing at a specialized laboratory affiliated with the hospital.

Discussion

Lead toxicity often presents with anemia and abdominal pain and, therefore, should be considered as a differential diagnosis in patients presenting with these symptoms to avoid unnecessary investigations and medications. ¹⁴ Patients with lead toxicity can also present with neurological manifestations, having both central and peripheral nervous system manifestations, such as restriction of upper and lower limb movements, lower back pain, myalgia, tremors, trismus, and weakness. At times, they also exhibit sleeplessness, irritability, seizures, and coma. The most common gastrointestinal symptoms exhibited are jaundice, cholestasis, abdominal cramps, and constipation. Chronic use or dependence on contaminated products is a risk factor for developing lead poisoning.^15,16 A distinctive symptom is a blue line across the gums, also known as Burton’s line. ¹⁷ Radio-opaque particles in the bowel can be appreciated in some cases.^15,16 Increased free erythrocyte protoporphyrin levels and low delta-aminolevulinic acid dehydratase levels are also helpful diagnostically. ¹⁸ Hemolytic anemia and basophilic stippling of erythrocytes are some of the common findings of lead poisoning. ¹⁸ Patients also show false positive results on urine porphyrin, leading physicians to mistake lead poisoning for acute porphyria. ¹⁹

The first step toward the treatment of lead intoxication is the removal of exposure. Patients are categorized as mild, moderate, and severe, depending on the severity of their symptoms. Mild toxicity (10–44 mcg/dl) does not require chelation; moderate levels amounting to a BLL of 45–69 with no symptoms and signs might be considered for chelation with oral and parenteral agents. Severe poisoning that has a BLL of >70 or the presence of encephalopathy needs parenteral chelation and is considered a medical emergency. Chelators are administered to symptomatic patients whose blood lead levels are between 40 and 80 mcg/dl. Chelation therapy is not advised for levels <45 mg/dl if the patient is at risk of re-mobilization.^20,21 Chelation therapy is usually the primary treatment for lead intoxication.^22,23 However, it comes with limitations, which include low efficacy, organ toxicity, risk for lead re-mobilization, and low intracellular penetration. The patient’s age, severity of the illness, presence of encephalopathy, and blood lead levels are the most important factors to commence treatment. Chelating formulations are used in the form of injections as the GI motility is compromised in lead poisoning. The most common chelating agents used for treatment are DMSA, dimercaptopropane sulfonate (DMPS), dimercaprol (British Anti-Lewisite), penicillamine, and calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA). DMSA is the first choice among oral agents as it has a wide therapeutic window and is FDA approved for blood lead levels of more than 45 mcg/dl. Penicillamine is the second-line oral agent for the treatment of lead poisoning. It does not have FDA approval as GI contents reduce its absorption, which can lead to transient leukopenia, rashes, shortness of breath, and increased liver transaminase. Parenteral treatment is required when oral administration is not sufficient. Dimercaprol and CaNa2 EDTA are the most common chelating agents used in patients whose blood lead levels are on the higher side. Intravenous formulations of DMSA or DMPS can be considered in cases of severe toxicity.^24-27

Management of simple lead poisoning is very different from opioid-related lead toxicity due to demographic, pathophysiologic, and epidemiologic factors. Opioid dependence and its withdrawal symptoms can aggravate or camouflage the presentation of lead poisoning. Patients tend to consume more opioids to control the pain caused by lead poisoning, which results in further absorption of lead, resulting in a vicious cycle. ²⁸ Opioids decrease gastric motility, causing further lead absorption by prolonged intestinal exposure, resulting in increased lead levels in the bloodstream.

The reports of lead intoxication identified and presented here are likely to be only the “tip of the iceberg” for several reasons. Thus, a detailed history of supplements and herbal medications should be taken as part of the protocol. Patients who have a history of herbal medicine intake should be thoroughly screened for lead exposure and should be reinforced to stop the further use of these medications. The provision of standard pharmaceutical opioid preparations and safer long-acting preparations as opioid substitutes may be effective for hazard control. Clinicians should be aware of the prospect of abuse of certain categories of herbal medicines, which contain addictive substances such as opium and cannabis. Over-the-counter and online sales of these drugs need to be banned, and they need to be strictly regulated by the DGCI.