Substance Use & Misuse, 49:793–797, 2014 C 2014 Informa Healthcare USA, Inc. Copyright ISSN: 1082-6084 print / 1532-2491 online DOI: 10.3109/10826084.2014.880178
ORIGINAL ARTICLE
Smoking Crushed Hyoscine/Scopolamine Tablets as Drug Abuse Farzad Jalali1 , Reza Afshari1 and Ali Babaei2 Addiction Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran; 2 Educational and Research Centre, District XI of State Prisons, Mashhad, Iran Subst Use Misuse Downloaded from informahealthcare.com by Texas A & M University on 11/14/14 For personal use only.
1
for opioid abusers (Noori, Narenjiha, Aghabakhshi, Habibi, & Khoshkrood Mansoori, 2012). MMT is used for treatment of prisoners with opioid dependency. Although MMT is useful, co-consumption of other psychoactive drugs, such as methamphetamine in these patients, has been frequently reported (Musshoff, Trafkowski, Lichtermann, & Madea, 2010). Recently, we received a report from prison inmates claiming to smoke crushed Hyoscine N-butyl bromide/scopolamine (H/S) tablets. H/S is an anticholinergic agent. H/S is a well-known antispasmodic drug that has been in use for 60 years (Tytgat, 2008). H/S blocks the action of acetylcholine at parasympathetic sites in smooth muscle and secretary glands by binding muscarinic and nicotinic receptors (Weiser & Just, 2009). H/S decreases the motility of the gastrointestinal genitourinary tracts and is useful in treatment of spasms in these organs, including gastroenteritis, biliary colic, cystitis and primary dysmenorrhea. The inhibitory action on glands in the oral cavity, GI tract, and respiratory tract causes a reduction in secretion (Samuels, 2009). H/S has also been used to treat motion sickness in a transdermal application as well as an anesthetic premedication inducing sedation and reduction of secretions in the oropharynx and the bronchi (Van Sassenbroeck et al., 2005). Anticholinergic agents induce peripheral and central effects (Lieberman, 2004). Central side effects include impaired concentration, confusion, attention deficit, and memory impairment (Kasper & Resinger, 2003). Peripheral symptoms include dry mouth, constipation, urinary retention, bowel obstruction, dilated pupils, blurred vision, increased heart rate and decreased sweating (Talbott, Halesk, & Yudofsky, 1998, McEvoy, 1983). There are reports in which heroin has been adulterated with H/S (Centers for Disease Control and Prevention, 1996; Hamilton et al., 1995). Adding H/S to the abused drug in heroin abusers, who are already often affected by constipation, has led to diminished or absent bowel
Background: Hyoscine N-butyl bromide/scopolamine (H/S) is a type of anticholinergic agent that is commonly used as an antispasmodic drug. We have evaluated the effects of crushed H/S smoking in prisoners who illicitly abused this drug. Methods: All imprisoned cases with at least a 3-month history of HS were evaluated from April 2012 to September 2012. Demographic information, history, and clinical findings were studied. Results: In total, 36 male cases with a mean (SD, min–max) age of 33.3 (3.6, 27–42) years were included. All subjects were cigarette smokers with a history of substance abuse and were under Methadone Maintenance Therapy (MMT). The majority (75%) of participants smoked H/S tablet with pin, and others used aluminum foil. Hallucinations were the most common neurological features. Amnesia (88%), insomnia (83%), palpitation (86%), flushing (86%), irritability (94%), and inability to concentrate (91%) were the most common findings. Among them, auditory (61%), visual (72%), and tactile (72%) hallucinations were reported. Conclusions: This is the first case study of hyoscine smoking abuse. We found that H/S acts similar to other hallucinogens. Concurrent abuse of H/S in cases under MMT could be a future trend of abuse. Clinicians should be aware of abuse potential of H/S in treatment of some patients for drug overdose. Keywords hyoscine N-butyl bromide/scopolamine, abuse, smoking, antimuscarinic agent
INTRODUCTION
Drug abuse is common in Iran (Afshari, Majdzadeh, and Balali-Mood, 2004). The pattern of abuse is changing (Afshari, Shafaeeyan, & Afshari, 2006; Tashakori & Afshari, 2010). In addition, Methadone Maintenance Therapy (MMT) is widely accepted as the treatment of choice
We would like to thank the personnel of Mashhad Central Prison Triangular Clinic for their kind co-operation. Address correspondence to Reza Afshari, Addiction Research Centre, Mashhad University of Medical Sciences, Imam Reza (p) University Hospital, Ibne-Sina-Street, Mashhad, 91735–348, Iran; E-mail: [email protected].
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sounds (Centers for Disease Control and Prevention, 1996 July 10). This study has been designed to evaluate this new type of drug abuse outbreak. To our knowledge, no literature is available in smoking crushed H/S tablets although in few reports, snorting H/S contamination of heroin that had clinical manifestations of anticholinergic toxicity have been reported (Centers for Disease Control and Prevention, 1996 July 10; Hamilton et al., 1995). H/S is an antimuscarinic drug, which is primarily used in the prophylaxis and treatment of motion sickness and as a premedication to dry bronchial and salivary secretions (Carmela & Corallo Ann, 2009). Clinical applications of hyoscine N-butyl bromide include abdominal pain (nonspecific colic) and Irritable Bowel Syndrome (IBS) (Am´erico, Miranda, Cor´a, & Romeiro, 2009; MuellerLissner et al., 2006), renal colic (Holdgate & Oh, 2005), dysmenorrhea (Hern´andez Bueno, de la JaraD´ıaz, Sede˜no Cruz, & Llorens Torres, 1998), labor pain (Sirohiwal, Dahiya, & De, 2005), esophageal obstruction (Thomas, Webb, Duvvi, Jones, & Reddy, 2005), and adjunctive relief in cancer pain. (Barcia, Mart´ın, Azuara, S´anchez, & Negro, 2007).
morphine every 2 weeks. Liver function tests and ECG are performed at the beginning of MMT program, and being repeated on the request of physicians and at least every six months to screen for potential side effects. In emergency ward of prison, doctors discovered confused hyperthermic agitated patient who had hallucinations. In some cases, they received unnecessary medical testing such as CT scans or LP’s. In a prison, meningitis must have been a big concern once they discovered confused hyperthermic agitated patients. Some of the patients received intravenous physostigmine and their symptoms were resolved. Most of these patients declared that they were hyoscine abusers. Among all self-declared hyoscine abusers, 36 cases were selected with simple random sampling. All subjects with at least 3-month history of smoking hyoscine were included. Number of hyoscine tablets, co-addiction, age, gender, length of stay in prison, history of addiction, and clinical findings were recorded in a predesigned questionnaire. We adjusted the questionnaire within the first 10 cases. This questionnaire was completed by a trained physician. Statistical analysis was performed using SPSS 13.5 (Chicago, Illinois, USA). The descriptive results are reported in Tables 1 and 2.
METHODS
This study was a cross-sectional case series. Ethics approval was obtained from District 6 of State Prisons, Educational and Research Centre. The process of data gathering and clinical evaluation were anonymous and did not influence the patients’ rights or any other treatments. On the first visit, subjects were reassured that their information would remain confidential, and a trust-based relationship was developed with the result being that verbal consent was obtained. The data was collected in the presence of an employee of the prison MMT Clinic. The study was conducted between April 2012 and September 2012 in Mashhad Central Prison in collaboration with Addiction Research Centre, Mashhad University of Medical Sciences. Patients are receiving a daily dose of methadone syrup, under close monitoring within prison MMT clinic. Resident physicians visit patients every week. Prisoners take part in counselling sessions and being tested for urinary
RESULTS Setting
The study was conducted in Mashhad Central Prison, which is one of the most populated prisons in Iran. Prison authorities do not allow number of prisoners to be revealed. Demographic
In total, 36 hyoscine smoke abusers were included. All subjects were male with a mean (SD, min–max) age of 33.3 (3.6, 27–42) years. Almost half (47%) of patients were married. The majority of cases did not finish secondary education (72%). The duration of imprisonment was 16.3 (10.5, 5–58) months. The majority of cases were repeat offenders (81%). Mean systolic and diastolic blood pressures were 122 (1.73) and 78 (2.3) mmHg. Heart rate
TABLE 1. Demographic data of participants in study (n = 36) Variables
Frequency (Percentage%)
Marital status Single Married Divorced Widowed
3 (8) 17 (47) 16 (45) 0 (0)
Detention First-time offender Repeated offender
7 (20) 29 (81)
Variables Education Illiterate Primary school Junior high school Senior high school University Cigarette smoking and drug status Cigarette smokers History of substance abuse Methadone maintenance therapy
Frequency (Percentage%) 0 (0) 14 (39) 12(33) 10 (28) 0 (0) 36 (100) 36 (100) 35 (94%)
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HYOSCINE TABLETS ABUSE
TABLE 2. Hyoscine smoking induced clinical findings (n = 36)
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Variables
Frequency (Percentage%)
Neurological Insomnia Irritability Inability to concentrate Incoherent speech Slurredspeech Amnesia Agitation Illogical thinking Cessation of sweating
30 (83) 34 (94) 33 (91) 32 (89) 32 (89) 32 (89) 31 (86) 30 (83) 30 (83)
Apprehension Visual hallucination Tactile hallucination Auditory hallucination Pressured speech
28 (77) 26 (72) 26 (72) 22 (61) 2 (6)
was 112 (10.7) bpm. Demographic data are presented in Table 1. Cigarette Smoking and Drug Status
All subjects were current cigarette smokers with a history of substance abuse. Majority of participants (94%) were under MMT. Mean daily dose of methadone in these prisoners were 57.4 mg (13.2, 35–90). At the time of completing the questionnaire, morphine urine tests were negative in all cases. None of them reported previous H/S abuse prior to imprisonment. Hyoscine Smoking Status
All cases have smoked Hyoscine N-butyl bromide/ scopolamine (H/S) crushed tablets. They obtained this drug illegally. The mean duration of hyoscine smoking was 6.5 (2.1, 3–16) months. On an average, they were smoking 2.0 (0.84, 1–4) tablets per day. Among them, 75% smoked hyoscine N-butyl bromide tablet with pin (they put a piece of crushed hyoscine tablets on a pin and light on fire and inhaled smoke). The rest, used aluminum foil to smoke. Subjects reported a white smoke released from crushed hyoscine when exposed to heat, as well as a bitter taste in their mouth during smoking. Most of them drank sweet juices after smoking to decrease the bitter taste. Clinical Findings
Subjects reported that a time elapsed of 15.4 (7.4, 5–60) minutes between smoking and receiving effects. On an average, 2.0 (0.66, 1–3) hr after smoking, all symptoms had worn off. Hallucination was the most common neurological findings. All cases reported to have at least one of the visual 26 (72%), Tactile 26 (72%) or auditory 22 (61%) hallucinations. Amnesia, which lasted for at least 1 hr reported in 32 cases (89%). Majority (89%) reported slurred speech.
Variables Gastrointestinal Dry mouth Dry throat Diminished bowel movement
Frequency (Percentage%) 36(100) 36(100) 14(39)
Cardiovascular Palpitation Flushing
31(86) 31(86)
Ocular Blurred vision Photophobia (Sensitivity to light)
26(72) 21(58)
Agitation (86%), palpitation (86%), flushing (86%), and insomnia (83%) were also common. The energy level was reported to remain mostly unchanged (83%). In most cases, appetite decreased (78%). Only two cases experienced pressured speech. Clinical findings are summarized in Table 2. DISCUSSION
The first case study of 36 smoke crushed H/S tablets in prison inmates is reported. This study revealed that smoking H/S leads to visual, tactile, or auditory hallucinations as well as amnesia, slurred speech, agitation, palpitation, flushing, insomnia, and decreased appetite. These effects are consistent with anticholinergic overdose induced effects (Carmela and Corallo, 2009). It has been previously shown that H/S ingestion overdose leads to increased heart rate and shortness of breath (Gregory, Mersfelder & Jamieson, 2010), decreased ability to concentrate, memory disturbances, tremor, and photoand phonophobia (Van Sassenbroeck et al., 2005), and acute onset of confusion and visual hallucinations (Ayub, Donaldson, Bedford, Alloway, & Ryalls, 1997). It was reported in 1995 that eight subjects were treated in the emergency department in New York for acute onset of agitation and hallucinations approximately 1 hr after “snorting” heroin (Centers for Disease Control and Prevention, 1996). All patients presented with clinical manifestations of anticholinergic toxicity including tachycardia, mild hypertension, dilated pupils, dry skin and mucous membranes, and diminished or absent bowel sounds. Five cases observed with urinary retention. Heroin was analyzed by gas chromatography-mass spectrophotometry and showed contained heroin and hyoscine. They received intravenous physostigmine. After 5 to 10 min, their paranoia, hallucinations, and agitation resolved (Hamilton et al., 1995). Another study of an epidemic of poisoning caused by heroin adulterated with hyoscine/scopolamine was described before (Hamilton et al., 2000).
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While some reports of H/S ingestion overdose has been reported, smoking crushed H/S has just been reported in one prison inmate in Luxemburg (Frascht, Schneider, Lemmer, Schuman, & Wennig, 2007). To our knowledge, this is the first case study of H/S abuse to get high. This study gives light to clinical manifestation of crushed H/S, which was very similar to ingested H/S. It was previously shown that if hyoscine N-butylbromide is heated, hyoscine will be released (Frascht, Schneider, Lemmer, Schuman, & Wennig, 2007). Prisoners were abusing H/S in addition of methadone, as even though their opioid dependence was being treated, they were seeking a psychotropic effect to achieve extra hallucinogenic effects, being high and because of boredom in prison. It is reported during the initial clusters of anticholinergic toxicity in heroin abusers, medical staff, and clinicians did not recognize the manifestations suggesting hyoscine/scopolamine poisoning and treated some patients for drug overdose with the opioid antagonist naloxone, which was associated with increased severity of agitation, hallucinations, and other manifestations of anticholinergic toxicity (Hamilton et al., 1995). Our finding may be useful for educating clinicians encountering adulterated heroin. Another application of these findings is that hyoscine was abused in cases under MMT. It is noticeable that in cases whose withdrawal symptoms are covered with methadone, concurrent use of hyoscine could lead to being high. As a practical result of this study, hyoscine tablet prescription is extremely limited in this prison. And it appears that hyoscine should be prescribed under close monitoring in all other prisons.
Reza Afshari, MD, MPH, MSc, PHD, is an associate professor and consultant toxicologist, Mashhad University of Medical Sciences, Iran. His areas of interest are medical toxicology, substance abuse, and toxicoepidemiology. Currently, Reza Afshari holds the various positions, such as:
• Founding member and Director; Addiction Research Centre (ADRC)• President; Asia Pacific Association of Medical Toxicology (APAMT) • Editor in Chief; Future of Medical Education Journal (FMEJ) • Editor in Chief; Asia Pacific Journal of Medical Toxicology (APJMT) • Co-Founder; Medical Toxicology Research Centre (MTRC) • Director; Medical Toxicology Centre (MTC) (Sept, 2012) • Director; Education development Centre (EDC), (May, 2012 • Board Member; Iranian Society of Toxicology (IRANTOX) • Member of Reference Group; World Health Organization (WHO) • Young Affiliate of Academy of Sciences for the Developing World (TWAS) • Founding member and Director; Imam Reza (p) Rehabilitation Centre • Member of European Association of Poison Centers and Clinical Toxicologists (EAPCCT) Ali Babaei, MD, is manager of Educational and Research Centre, District XI of State Prisons, Mashhad, Iran, Islamic Republic of Iran. His areas of interest are harm reduction, prisoner’s health, health policy, and health promotion.
Limitation
This is a retrospective study on a sensitive issue (addiction). The results could be subjected to recall bias and under reporting. Declaration of Interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. THE AUTHORS Farzad Jalali, MD, MPH, is a researcher at Mashhad University of Medical Sciences, Iran. His areas of interest are substance abuse, addiction, prisoner’s health, and smoking cessation. Currently, he holds the various positions, such as:
GLOSSARY
Hyoscine/Scopolamine (H/S): Scopolamine is an anticholinergic medicine. Hyoscine/Scopolamine abuse: Smoked crushed Hyoscine/Scopolamine tablets with pin and aluminum foil. Methadone Maintenance Therapy (MMT): A comprehensive treatment program that involves the long-term prescribing of methadone as an alternative to the opioid on which the client was dependent. Prison: A prison or jail is a facility in which individuals are forcibly confined and denied a variety of freedoms under the authority of the state as a form of punishment. REFERENCES
• Member of Mashhad Addiction Research Centre (ADRC) • Manager of Mashhad Central Prison Triangular Clinic
Afshari, R., Majdzadeh, R., & Balali-Mood M. (2004). Pattern of acute poisonings in Mashhad, Iran 1993–2000.
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HYOSCINE TABLETS ABUSE
Journal of Toxicology—Clinical Toxicology (JournalSeek), 42(7), 965–975. Afshari, R., Shafaeeyan, H., & Afshari, R. (2006).An epidemiologic study of opioid dependent subjects who were volunteered for opioid detoxification in Iran in 2005. Journal of Toxicology—Clinical Toxicology (JournalSeek), 44,4; 581–582. Am´erico, M. F., Miranda, J. R., Cor´a, L. A., & Romeiro, F. G. (2009). Electrical and mechanicaleffects of hyoscine butylbromide on the human stomach: A non-invasiveapproach. Physiological Measurement, 30(4), 363–370. Ayub, N., Donaldson, D., Bedford, D., Alloway, R., & Ryalls, M. (1997). Lessons to be learned: A case study approach. Hyperactivity and confusion in the presentation of hyoscine overdose. Journal of the Royal Society of Health, 117(4), 242–244. Barcia, E., Mart´ın, A., Azuara, M. L., S´anchez, Y., & Negro, S. (2007). Tramadol and hyoscine N-butylbromide combined in infusion solutions: Compatibility and stability. Support Care Cancer, 15(1), 57–62. Carmela, E., & Corallo Ann. (2009). Anticholinergic syndrome following an unintentional overdose of scopolamine. Therapeutics and Clinical Risk Management, 5, 719–723. Centers for Disease Control and Prevention. (1996). Scopolamine poisoning among heroin users–New York City, Newark, Philadelphia, and Baltimore, 1995 and 1996. The Journal of the American Medical Association, 276(2), 92–93. Frascht, M., Schneider, S., Lemmer, P., Schuman, M., & Wennig, R. (2007). Getting High by Smoking Hyoscine Butylbromide?! The annual meetings of International Council on Alcohol, Drugs, and Traffic Safety (ICADTS) (pp. 26–30). Seattle, Washington. Gregory, M. D., Mersfelder, T. L., & Jamieson, T. (2010). Accidental overdose of tiotropium in a patient with atrial fibrillation. Annals of Pharmacotherapy, 44(2), 391–393. Hamilton, R. J., Perrone, J., Hoffman, R., Henretig, F. M., Karkevandian, E. H., Marcus, S., et al. (2000). A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine. Journal of Toxicology - Clinical Toxicology, 38(6), 597–608. Hamilton, R., Perrone, J., Meggs, W., Jolian, A., Trachtenberg, J., Zhang, Y., et al. (1995). Epidemic anticholinergic poisoning from scopolaminetainted heroin. Journal of Toxicology - Clinical Toxicology, 33, 502. Hern´andez Bueno, J. A., de la Jara D´ıaz, J., Sede˜no Cruz, F., & Llorens Torres, F. (1998). Analgesic-antispasmodic effect and safety of lysine clonixinate and L-hyoscinbutylbromide in the treatment of dysmenorrhea. Ginecolog´ıa y Obstetricia de M´exico, 66, 35–39. Holdgate, A., & Oh, C. M. (2005). Is there a role for antimuscarinics in renal colic? A randomized controlled trial. Journal of Urology, 174(2), 572–575.
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Kasper, S., & Resinger, E. (2003). Cognitive effects and antipsychotic treatment. Psychoneuro-Endocrinology, 28, 27–38. Lieberman, J. A. (2004). Managing anticholinergic side effects, Prim Care Companion. Journal of Clinical Psychiatry, 6(Suppl 2), 20–23. McEvoy, J. (1983). The clinical use of anticholinergic drugs as treatment for extrapyramidal side effects of neuroleptic drugs. Journal of Clinical Psychopharmacology, 3, 288–302. Mueller-Lissner, S., Tytgat, G. N., Paulo, L. G., Quigley, E. M., Bubeck, J., Peil, H., et al. (2006). Placebo- and paracetamolcontrolled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain. Alimentary Pharmacology & Therapeutics, 23(12), 1741–1748. Musshoff, F., Trafkowski, J., Lichtermann, D., & Madea, B. (2010). Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs. International Journal of Legal Medicine, 124(5), 499–503. Noori, R., Narenjiha, H., Aghabakhshi, H., Habibi, G., & Khoshkrood Mansoori, B. (2012). Methadone maintenance therapy outcomes in Iran. Substance Use & Misuse, 47(7), 767– 773. Samuels, L. A. (2009). Pharmacotherapy Update: Hyoscine Butylbromide in the treatment of abdominal spasms clinical medicine. Citation: Clinical Medicine: Therapeutics, 1, 647–655 Sirohiwal, D., Dahiya, K., & De, M. (2005). Efficacy of hyoscineN-butylbromide (Buscopan) suppositories as a cervical spasmolytic agent in labor. Australian and New Zealand Journal of Obstetrics and Gynaecology, 45(2), 128–129. Talbott, J. A., Halesk, E., & Yudofsky, S. C. (1998). The American Psychiatric Press Textbook. Washington, DC: American Psychiatric Press, Inc; . Tashakori, A., & Afshari, R. (2010). Tramadol Overdose as a cause of Serotonin Syndrome: A case series. Clinical Toxicology (Phila), 48(4), 337–341. Thomas, L., Webb, C., Duvvi, S., Jones, T., & Reddy, K. T. (2005). Is buscopan effective in meat bolus obstruction? Clinical Otolaryngology 30(2), 183–185. Tytgat, G. N. (2008). Hyoscine butylbromide—a review on its parenteral use in acute abdominal spasm and as an aid in abdominal diagnostic and therapeutic procedures. Current Medical Research and Opinion, 24, 3159–3173. Van Sassenbroeck, D. K., Hemelsoet, D. M., Vanwalleghem, P., Verstraete, A. G., Santens, P., Monsieurs, K. G., et al. (2005). Three cases of substitution errors leading to hyoscine hydrobromide overdose. Clinical Toxicology (Phila), 43(7), 861–865. Weiser, T., & Just, S. (2009). Hyoscine butylbromide potently blocks human nicotinic acetylcholine receptors in SH-SY5Y cells. Neuroscience Letters, 450(3), 258–261.
ORIGINAL ARTICLE
Smoking Crushed Hyoscine/Scopolamine Tablets as Drug Abuse Farzad Jalali1 , Reza Afshari1 and Ali Babaei2 Addiction Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran; 2 Educational and Research Centre, District XI of State Prisons, Mashhad, Iran Subst Use Misuse Downloaded from informahealthcare.com by Texas A & M University on 11/14/14 For personal use only.
1
for opioid abusers (Noori, Narenjiha, Aghabakhshi, Habibi, & Khoshkrood Mansoori, 2012). MMT is used for treatment of prisoners with opioid dependency. Although MMT is useful, co-consumption of other psychoactive drugs, such as methamphetamine in these patients, has been frequently reported (Musshoff, Trafkowski, Lichtermann, & Madea, 2010). Recently, we received a report from prison inmates claiming to smoke crushed Hyoscine N-butyl bromide/scopolamine (H/S) tablets. H/S is an anticholinergic agent. H/S is a well-known antispasmodic drug that has been in use for 60 years (Tytgat, 2008). H/S blocks the action of acetylcholine at parasympathetic sites in smooth muscle and secretary glands by binding muscarinic and nicotinic receptors (Weiser & Just, 2009). H/S decreases the motility of the gastrointestinal genitourinary tracts and is useful in treatment of spasms in these organs, including gastroenteritis, biliary colic, cystitis and primary dysmenorrhea. The inhibitory action on glands in the oral cavity, GI tract, and respiratory tract causes a reduction in secretion (Samuels, 2009). H/S has also been used to treat motion sickness in a transdermal application as well as an anesthetic premedication inducing sedation and reduction of secretions in the oropharynx and the bronchi (Van Sassenbroeck et al., 2005). Anticholinergic agents induce peripheral and central effects (Lieberman, 2004). Central side effects include impaired concentration, confusion, attention deficit, and memory impairment (Kasper & Resinger, 2003). Peripheral symptoms include dry mouth, constipation, urinary retention, bowel obstruction, dilated pupils, blurred vision, increased heart rate and decreased sweating (Talbott, Halesk, & Yudofsky, 1998, McEvoy, 1983). There are reports in which heroin has been adulterated with H/S (Centers for Disease Control and Prevention, 1996; Hamilton et al., 1995). Adding H/S to the abused drug in heroin abusers, who are already often affected by constipation, has led to diminished or absent bowel
Background: Hyoscine N-butyl bromide/scopolamine (H/S) is a type of anticholinergic agent that is commonly used as an antispasmodic drug. We have evaluated the effects of crushed H/S smoking in prisoners who illicitly abused this drug. Methods: All imprisoned cases with at least a 3-month history of HS were evaluated from April 2012 to September 2012. Demographic information, history, and clinical findings were studied. Results: In total, 36 male cases with a mean (SD, min–max) age of 33.3 (3.6, 27–42) years were included. All subjects were cigarette smokers with a history of substance abuse and were under Methadone Maintenance Therapy (MMT). The majority (75%) of participants smoked H/S tablet with pin, and others used aluminum foil. Hallucinations were the most common neurological features. Amnesia (88%), insomnia (83%), palpitation (86%), flushing (86%), irritability (94%), and inability to concentrate (91%) were the most common findings. Among them, auditory (61%), visual (72%), and tactile (72%) hallucinations were reported. Conclusions: This is the first case study of hyoscine smoking abuse. We found that H/S acts similar to other hallucinogens. Concurrent abuse of H/S in cases under MMT could be a future trend of abuse. Clinicians should be aware of abuse potential of H/S in treatment of some patients for drug overdose. Keywords hyoscine N-butyl bromide/scopolamine, abuse, smoking, antimuscarinic agent
INTRODUCTION
Drug abuse is common in Iran (Afshari, Majdzadeh, and Balali-Mood, 2004). The pattern of abuse is changing (Afshari, Shafaeeyan, & Afshari, 2006; Tashakori & Afshari, 2010). In addition, Methadone Maintenance Therapy (MMT) is widely accepted as the treatment of choice
We would like to thank the personnel of Mashhad Central Prison Triangular Clinic for their kind co-operation. Address correspondence to Reza Afshari, Addiction Research Centre, Mashhad University of Medical Sciences, Imam Reza (p) University Hospital, Ibne-Sina-Street, Mashhad, 91735–348, Iran; E-mail: [email protected].
793
Subst Use Misuse Downloaded from informahealthcare.com by Texas A & M University on 11/14/14 For personal use only.
794
F. JALALI ET AL.
sounds (Centers for Disease Control and Prevention, 1996 July 10). This study has been designed to evaluate this new type of drug abuse outbreak. To our knowledge, no literature is available in smoking crushed H/S tablets although in few reports, snorting H/S contamination of heroin that had clinical manifestations of anticholinergic toxicity have been reported (Centers for Disease Control and Prevention, 1996 July 10; Hamilton et al., 1995). H/S is an antimuscarinic drug, which is primarily used in the prophylaxis and treatment of motion sickness and as a premedication to dry bronchial and salivary secretions (Carmela & Corallo Ann, 2009). Clinical applications of hyoscine N-butyl bromide include abdominal pain (nonspecific colic) and Irritable Bowel Syndrome (IBS) (Am´erico, Miranda, Cor´a, & Romeiro, 2009; MuellerLissner et al., 2006), renal colic (Holdgate & Oh, 2005), dysmenorrhea (Hern´andez Bueno, de la JaraD´ıaz, Sede˜no Cruz, & Llorens Torres, 1998), labor pain (Sirohiwal, Dahiya, & De, 2005), esophageal obstruction (Thomas, Webb, Duvvi, Jones, & Reddy, 2005), and adjunctive relief in cancer pain. (Barcia, Mart´ın, Azuara, S´anchez, & Negro, 2007).
morphine every 2 weeks. Liver function tests and ECG are performed at the beginning of MMT program, and being repeated on the request of physicians and at least every six months to screen for potential side effects. In emergency ward of prison, doctors discovered confused hyperthermic agitated patient who had hallucinations. In some cases, they received unnecessary medical testing such as CT scans or LP’s. In a prison, meningitis must have been a big concern once they discovered confused hyperthermic agitated patients. Some of the patients received intravenous physostigmine and their symptoms were resolved. Most of these patients declared that they were hyoscine abusers. Among all self-declared hyoscine abusers, 36 cases were selected with simple random sampling. All subjects with at least 3-month history of smoking hyoscine were included. Number of hyoscine tablets, co-addiction, age, gender, length of stay in prison, history of addiction, and clinical findings were recorded in a predesigned questionnaire. We adjusted the questionnaire within the first 10 cases. This questionnaire was completed by a trained physician. Statistical analysis was performed using SPSS 13.5 (Chicago, Illinois, USA). The descriptive results are reported in Tables 1 and 2.
METHODS
This study was a cross-sectional case series. Ethics approval was obtained from District 6 of State Prisons, Educational and Research Centre. The process of data gathering and clinical evaluation were anonymous and did not influence the patients’ rights or any other treatments. On the first visit, subjects were reassured that their information would remain confidential, and a trust-based relationship was developed with the result being that verbal consent was obtained. The data was collected in the presence of an employee of the prison MMT Clinic. The study was conducted between April 2012 and September 2012 in Mashhad Central Prison in collaboration with Addiction Research Centre, Mashhad University of Medical Sciences. Patients are receiving a daily dose of methadone syrup, under close monitoring within prison MMT clinic. Resident physicians visit patients every week. Prisoners take part in counselling sessions and being tested for urinary
RESULTS Setting
The study was conducted in Mashhad Central Prison, which is one of the most populated prisons in Iran. Prison authorities do not allow number of prisoners to be revealed. Demographic
In total, 36 hyoscine smoke abusers were included. All subjects were male with a mean (SD, min–max) age of 33.3 (3.6, 27–42) years. Almost half (47%) of patients were married. The majority of cases did not finish secondary education (72%). The duration of imprisonment was 16.3 (10.5, 5–58) months. The majority of cases were repeat offenders (81%). Mean systolic and diastolic blood pressures were 122 (1.73) and 78 (2.3) mmHg. Heart rate
TABLE 1. Demographic data of participants in study (n = 36) Variables
Frequency (Percentage%)
Marital status Single Married Divorced Widowed
3 (8) 17 (47) 16 (45) 0 (0)
Detention First-time offender Repeated offender
7 (20) 29 (81)
Variables Education Illiterate Primary school Junior high school Senior high school University Cigarette smoking and drug status Cigarette smokers History of substance abuse Methadone maintenance therapy
Frequency (Percentage%) 0 (0) 14 (39) 12(33) 10 (28) 0 (0) 36 (100) 36 (100) 35 (94%)
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TABLE 2. Hyoscine smoking induced clinical findings (n = 36)
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Variables
Frequency (Percentage%)
Neurological Insomnia Irritability Inability to concentrate Incoherent speech Slurredspeech Amnesia Agitation Illogical thinking Cessation of sweating
30 (83) 34 (94) 33 (91) 32 (89) 32 (89) 32 (89) 31 (86) 30 (83) 30 (83)
Apprehension Visual hallucination Tactile hallucination Auditory hallucination Pressured speech
28 (77) 26 (72) 26 (72) 22 (61) 2 (6)
was 112 (10.7) bpm. Demographic data are presented in Table 1. Cigarette Smoking and Drug Status
All subjects were current cigarette smokers with a history of substance abuse. Majority of participants (94%) were under MMT. Mean daily dose of methadone in these prisoners were 57.4 mg (13.2, 35–90). At the time of completing the questionnaire, morphine urine tests were negative in all cases. None of them reported previous H/S abuse prior to imprisonment. Hyoscine Smoking Status
All cases have smoked Hyoscine N-butyl bromide/ scopolamine (H/S) crushed tablets. They obtained this drug illegally. The mean duration of hyoscine smoking was 6.5 (2.1, 3–16) months. On an average, they were smoking 2.0 (0.84, 1–4) tablets per day. Among them, 75% smoked hyoscine N-butyl bromide tablet with pin (they put a piece of crushed hyoscine tablets on a pin and light on fire and inhaled smoke). The rest, used aluminum foil to smoke. Subjects reported a white smoke released from crushed hyoscine when exposed to heat, as well as a bitter taste in their mouth during smoking. Most of them drank sweet juices after smoking to decrease the bitter taste. Clinical Findings
Subjects reported that a time elapsed of 15.4 (7.4, 5–60) minutes between smoking and receiving effects. On an average, 2.0 (0.66, 1–3) hr after smoking, all symptoms had worn off. Hallucination was the most common neurological findings. All cases reported to have at least one of the visual 26 (72%), Tactile 26 (72%) or auditory 22 (61%) hallucinations. Amnesia, which lasted for at least 1 hr reported in 32 cases (89%). Majority (89%) reported slurred speech.
Variables Gastrointestinal Dry mouth Dry throat Diminished bowel movement
Frequency (Percentage%) 36(100) 36(100) 14(39)
Cardiovascular Palpitation Flushing
31(86) 31(86)
Ocular Blurred vision Photophobia (Sensitivity to light)
26(72) 21(58)
Agitation (86%), palpitation (86%), flushing (86%), and insomnia (83%) were also common. The energy level was reported to remain mostly unchanged (83%). In most cases, appetite decreased (78%). Only two cases experienced pressured speech. Clinical findings are summarized in Table 2. DISCUSSION
The first case study of 36 smoke crushed H/S tablets in prison inmates is reported. This study revealed that smoking H/S leads to visual, tactile, or auditory hallucinations as well as amnesia, slurred speech, agitation, palpitation, flushing, insomnia, and decreased appetite. These effects are consistent with anticholinergic overdose induced effects (Carmela and Corallo, 2009). It has been previously shown that H/S ingestion overdose leads to increased heart rate and shortness of breath (Gregory, Mersfelder & Jamieson, 2010), decreased ability to concentrate, memory disturbances, tremor, and photoand phonophobia (Van Sassenbroeck et al., 2005), and acute onset of confusion and visual hallucinations (Ayub, Donaldson, Bedford, Alloway, & Ryalls, 1997). It was reported in 1995 that eight subjects were treated in the emergency department in New York for acute onset of agitation and hallucinations approximately 1 hr after “snorting” heroin (Centers for Disease Control and Prevention, 1996). All patients presented with clinical manifestations of anticholinergic toxicity including tachycardia, mild hypertension, dilated pupils, dry skin and mucous membranes, and diminished or absent bowel sounds. Five cases observed with urinary retention. Heroin was analyzed by gas chromatography-mass spectrophotometry and showed contained heroin and hyoscine. They received intravenous physostigmine. After 5 to 10 min, their paranoia, hallucinations, and agitation resolved (Hamilton et al., 1995). Another study of an epidemic of poisoning caused by heroin adulterated with hyoscine/scopolamine was described before (Hamilton et al., 2000).
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While some reports of H/S ingestion overdose has been reported, smoking crushed H/S has just been reported in one prison inmate in Luxemburg (Frascht, Schneider, Lemmer, Schuman, & Wennig, 2007). To our knowledge, this is the first case study of H/S abuse to get high. This study gives light to clinical manifestation of crushed H/S, which was very similar to ingested H/S. It was previously shown that if hyoscine N-butylbromide is heated, hyoscine will be released (Frascht, Schneider, Lemmer, Schuman, & Wennig, 2007). Prisoners were abusing H/S in addition of methadone, as even though their opioid dependence was being treated, they were seeking a psychotropic effect to achieve extra hallucinogenic effects, being high and because of boredom in prison. It is reported during the initial clusters of anticholinergic toxicity in heroin abusers, medical staff, and clinicians did not recognize the manifestations suggesting hyoscine/scopolamine poisoning and treated some patients for drug overdose with the opioid antagonist naloxone, which was associated with increased severity of agitation, hallucinations, and other manifestations of anticholinergic toxicity (Hamilton et al., 1995). Our finding may be useful for educating clinicians encountering adulterated heroin. Another application of these findings is that hyoscine was abused in cases under MMT. It is noticeable that in cases whose withdrawal symptoms are covered with methadone, concurrent use of hyoscine could lead to being high. As a practical result of this study, hyoscine tablet prescription is extremely limited in this prison. And it appears that hyoscine should be prescribed under close monitoring in all other prisons.
Reza Afshari, MD, MPH, MSc, PHD, is an associate professor and consultant toxicologist, Mashhad University of Medical Sciences, Iran. His areas of interest are medical toxicology, substance abuse, and toxicoepidemiology. Currently, Reza Afshari holds the various positions, such as:
• Founding member and Director; Addiction Research Centre (ADRC)• President; Asia Pacific Association of Medical Toxicology (APAMT) • Editor in Chief; Future of Medical Education Journal (FMEJ) • Editor in Chief; Asia Pacific Journal of Medical Toxicology (APJMT) • Co-Founder; Medical Toxicology Research Centre (MTRC) • Director; Medical Toxicology Centre (MTC) (Sept, 2012) • Director; Education development Centre (EDC), (May, 2012 • Board Member; Iranian Society of Toxicology (IRANTOX) • Member of Reference Group; World Health Organization (WHO) • Young Affiliate of Academy of Sciences for the Developing World (TWAS) • Founding member and Director; Imam Reza (p) Rehabilitation Centre • Member of European Association of Poison Centers and Clinical Toxicologists (EAPCCT) Ali Babaei, MD, is manager of Educational and Research Centre, District XI of State Prisons, Mashhad, Iran, Islamic Republic of Iran. His areas of interest are harm reduction, prisoner’s health, health policy, and health promotion.
Limitation
This is a retrospective study on a sensitive issue (addiction). The results could be subjected to recall bias and under reporting. Declaration of Interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. THE AUTHORS Farzad Jalali, MD, MPH, is a researcher at Mashhad University of Medical Sciences, Iran. His areas of interest are substance abuse, addiction, prisoner’s health, and smoking cessation. Currently, he holds the various positions, such as:
GLOSSARY
Hyoscine/Scopolamine (H/S): Scopolamine is an anticholinergic medicine. Hyoscine/Scopolamine abuse: Smoked crushed Hyoscine/Scopolamine tablets with pin and aluminum foil. Methadone Maintenance Therapy (MMT): A comprehensive treatment program that involves the long-term prescribing of methadone as an alternative to the opioid on which the client was dependent. Prison: A prison or jail is a facility in which individuals are forcibly confined and denied a variety of freedoms under the authority of the state as a form of punishment. REFERENCES
• Member of Mashhad Addiction Research Centre (ADRC) • Manager of Mashhad Central Prison Triangular Clinic
Afshari, R., Majdzadeh, R., & Balali-Mood M. (2004). Pattern of acute poisonings in Mashhad, Iran 1993–2000.
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