Acosta-Armas Te sting for LSD

Psychiatric Bulletin (2003), 27,17^19 A. J. ACOSTA-ARMAS original Problems encountered when testing for LSD in a regional papers medium secure unit

AIMS AND METHOD same day, to two different labora- without adequate confirmatory Between1998 and 2000, a surpris- tories. At the first laboratory, only analysis, many psychiatric and non- ingly high number of positive results one test method was used and at the psychiatric prescribed drugs can give was noticed in our regional medium second one test plus two confirma- false positives. secure unit when testing for D- tory tests were carried out. lysergic acid diethylamide (LSD).This CLINICAL IMPLICATIONS led to an investigation of possible RESULTS Positive LSD results should be con- factorsinvolved.Itwasfeltthatthe Outofatotalof23patientstestedon firmed by at least one, preferably testing protocol, particularly the use two separate occasions, the first chromatographic, alternative of a single, non-isotopic homoge- laboratory gave three positive results method. A protocol for testing and neous immunoassay without routine the first time and three positive reporting LSD in psychiatric patients further confirmatory testing, was results the second, while the second should be considered in order to largely to blame for what seemed to laboratory gave only one positive minimise the risk of obtaining false- be a high incidence of false positives. result on the second occasion that positive results which have negative On two different occasions, samples samples were sent and none on the clinical, legal and psychological from each patient were sent, on the first.This reinforces the belief that, repercussions.

Introduction immunoassays (enzyme-linked immunosorbent assay (ELISA) and enzyme-multiplied immunoassay technique The use of D-lysergic acid diethylamide (LSD), a strong (EMIT)), high performance thin-layer chromatography and hallucinogenic drug, continues to cause concern within gas or liquid chromatography linked to mass spectro- the medical profession and particularly in the field of metry. Recently, homogeneous immunoassays have mental health, because of its association with different become more popular because they are easier to perform psychiatric conditions, especially panic reactions, and they produce results more quickly. Unfortunately, prolonged schizoaffective psychoses and post-halluci- they are associated with lack of sensitivity and, in nogen perceptual disorder (Abraham & Aldridge, 1993). particular, lack of specificity (Liu, 1995). There is evidence to suggest that its use has increased in A very high incidence of positive LSD results past years, particularly by young people (Sankar, 1997; (between 4.5% and 9%) were being found in our patient Schwartz, 1995). The use of illicit drugs, including LSD, has population, sometimes in cases where it was very unlikely a particular relevance in forensic psychiatry because that any illicit drugs had been taken. The interference of substance misuse has been shown consistently to be a other prescribed and non-prescribed drugs in testing for significant risk factor for violence and disturbed beha- LSD has been documented (Ritter et al, 1997; Rohrich et viour (Soyka, 2000). LSD was the first synthetic halluci- al, 1998), although little research has been done and the nogenic compound, accidentally discovered by a Swiss information available is sparse. chemist, Albert Hoffman, in 1943. The first systematic This small piece of research is important because study of the clinical effects of LSD was carried out in 1947 there seems to be little understanding and knowledge of at the University Psychiatric Clinic in Zurich. Its medical drug-testing, particularly about possible interference by use became popular in the USA in the 1950s, when it was drugs commonly prescribed in psychiatry, and our work used to assist psychotherapy sessions by releasing shows how easy it can be to give a false-positive result forgotten memories from childhood. Its abuse first unless these potential problems are taken into consid- appeared in the 1960s when it became an essential part eration. The repercussions of a false-positive result on any of the drug scene. In the UK, LSD was proscribed under patient, particularly within our type of service, could be the 1971 Misuse of Drugs Act. The LSD that is used on the quite detrimental for future decision-making and, hence, streets appears in different forms, usually adsorbed onto their future clinical management, so it is even more microdots or paper with colourful designs. important to ensure that the risks of false-positive results The detection of LSD use is a challenge for toxi- are minimised. cology laboratories because of the very low concentra- tions of LSD and its metabolites found in body fluids. LSD is also relatively unstable and sensitive to ultraviolet light Background and heat. Several methods have been developed for detection of LSD in body fluids, particularly in urine. Such Around February 1998, there was increasing concern in methods include: radioimmunoassays, non-isotopic our regional medium-secure psychiatric unit about the

17 Acosta-Armas Te s ting for LSD

use of LSD by in-patients and its effect on their mental toxicologists on LSD testing. Discussions with a senior state, particularly when a positive result was obtained toxicologist at the toxicology department of another UK original after a significant deterioration in a patient’s condition. hospital (Laboratory B), which is experienced in LSD papers Towards the end of that year, over a period of almost 2 testing, confirmed our initial suspicion that certain drugs months, there were six positive results involving five which are commonly prescribed in psychiatry can inter- patients from a total population of approximately 22, fere with LSD testing. It appeared that confirmatory tests although not everybody on the wards was tested at the are essential to rule out the high incidence of false posi- same time. During the following 3 months, 10 more tives that occur in such cases, particularly when immu- positive results were obtained, involving 7 patients in the noassay is the only test used. We also contacted the unit. This led to great concern among members of the manufacturers of the EMIT test and they provided a list of medical, nursing and managerial staff who decided to commonly prescribed drugs that were known by them to introduce random blanket-testing for all patients in the cause interference in LSD testing using EMIT. unit from April 1999. Five blanket-testing sessions were The initial literature search identified numerous conducted between April and May 1999 with two posi- papers on different methods of LSD testing, but only two tive results out of a total of 22 patients (9%) in the first on interference with testing for LSD. One paper, by Ritter session, and one positive result (4.5%) in the second. The et al (1997), was particularly useful. The other paper, by three following blanket-testing sessions gave only nega- Rohrich et al (1998), was also useful although their work tive results in all the patients tested. Following these was done with intensive care patients only. No systematic negative findings, systematic testing was suspended in reviews had been conducted on this matter, possibly June 1999. In February 2000, there was another signifi- because of the paucity of previous research work. cant change in a patient’s mental state and the use of Because of the surprisingly high rate of positive illicit drugs was suspected. One urine sample was sent for results, we decided to collect two urine samples from testing and it showed a positive result for LSD. The each patient in the unit on two separate occasions and concerns from the previous year returned and random send one sample to the original reference laboratory blanket-testing was reintroduced in the unit in February, (Laboratory A) and the other to Laboratory B in order to producing two positive results out of a total of 22 compare the results from each. Each sample was split, patients (9%). with one aliquot going to Laboratory A and one to By this time, there was a strong suspicion that the Laboratory B. We knew that Laboratory A would only incidence of positive results was too high and that there perform a simple immunoassay (EMIT II LSD) and that had to be an explanation for those findings. We consid- Laboratory B would perform two initial screening tests (a ered various explanations, including the possibility of radioimmunoassay, manufactured by Cozart Biosciences, false-positives because of interference from other and an enzyme-immunoassay, produced by Diagnostic substances or prescribed drugs in the test method used. We also questioned the methodology used by the Products Corporation) plus a confirmatory test (high laboratory when carrying out the tests. performance liquid chromatographic method using The samples taken from our patients were tested in fluorometric detection). On two separate occasions, 46 a designated laboratory (Laboratory A) in another city urine samples were taken from 23 patients. because there are few laboratories around the country which perform LSD tests. The original samples were collected in specific containers and kept refrigerated as Results and discussion required. They were then sent to our local hospital and On the first occasion, three positive results were given by from there to Laboratory A where the tests were carried Laboratory A and no positive results by Laboratory B. On out using EMIT, a non-isotopic immunoassay from Dade the second occasion, there were three positive results Behring Diagnostics (2000). The laboratory does not again from the samples sent to Laboratory A and only one normally perform confirmatory tests when it has a posi- positive result in those sent to Laboratory B. tive result unless this is specifically requested and results Two patients tested positive in the samples sent to are considered to be positive when they are above a cut- Laboratory A on both occasions. The other two positive off point of drug concentration. During a telephone results were from two different patients. The patient who discussion, it became clear that they were partly aware gave a positive result when the samples were tested by of certain drugs, particularly , giving false- Laboratory B was one of those testing positive twice at positive results, but they claimed to have never previously Laboratory A. Table 1 shows the prescribed drugs being been told that they had produced false-positive results. taken by patients when they tested positive for LSD. According to the list provided by Dade Behring Diagnostics, the manufacturer of the EMIT test, sertra- Method line, chlorpromazine and , but not diazepam, We began with a literature search, using Medline, the can cause cross-reactivity at certain concentration levels Cochrane Library and the National Library of Medicine when using the EMIT II LSD Assay (Dade Behring Diag- databases, for previous work done on LSD testing and nostics, 2000). Folic acid, procyclidine, multivitamins, interference with other drugs. We also contacted another omeprazole, lithium, ispaghula and risperidone were not laboratory in the UK to determine the views of other listed.

18 Acosta-Armas Te sting for LSD

Table 1. Prescribed drugs being taken by patients that tested drugs, as is commonly the case for psychiatric patients. positive for LSD in LaboratoryA1 This is particularly important in forensic psychiatric patients, where such findings could have considerable Patient testing original positive Prescribed drug Dose implications in future management decisions and where papers the legal aspects of their care are much more complex. 11 Risperidone 8 mg daily For that reason, a clear protocol for LSD testing should Sertraline 150 mg daily be considered as a way of minimising the probability of Folic acid 5 mg daily such problems arising in clinical practice. There are Multivitamins one capsule per day considerable clinical, legal and psychological repercus- 2 Chlorpromazine 800 mg daily sions of falsely giving a positive result for LSD to a Diazepam 20 mg daily patient. Paroxetine 20 mg daily Further research in this area would be very valuable Procyclidine 5 mg daily and clear guidelines are necessary for laboratories and Omeprazole 20 mg daily services dealing with psychiatric patients that need to be Ispaghula husk one sachet twice daily 3 Lithium citrate 32.4 mmol Li+ daily tested for LSD and other illicit drugs. This would be Omeprazole 20 mg daily particularly important within the forensic psychiatric Risperidone 14 mg daily services. 4 Risperidone 14 mg daily Procyclidine 10 mg daily Acknowledgements 1. Patient 1 tested positive in both laboratories, i.e. by four different analytical methods. I would like to thank Mr Frank Tames for his valuable information and advice and Dr A. R. Tomison for his support and comments.

We could confirm that the LSD EMIT assay was associated with a high rate of false-positive results, References particularly when used in patients from psychiatric ABRAHAM, H. D. & ALDRIDGE, A. M. ROHRICH, J., ZORNTLEIN, S., LOTZ, J., et settings. It became evident that in situations where a (1993) Adverse consequences of al (1998) False-positive LSD testing in lysergic acid diethylamide. Addiction, urine samples from intensive care single type of LSD test is carried out, particularly only the 88,1327-1324. patients. Journal of Analytical EMIT test, there is a likelihood of more positive results. Toxicology, 23,393-395. DADE BEHRING DIAGNOSTICS (2000) Since it has been clearly documented that certain Cross-Reactivity List for the Emit II LSD SANKAR, D.V. S. (1997) Psychoactive prescribed drugs can cause drug interference when Assay (data on file). substances LSD - aresurrection. Research Communications in testing for LSD, particularly with homogeneous immuno- LIU, R. H. (1995) Evaluation of common and Substances of Abuse, 18,1-18. assays, we considered that this was the most likely cause immunoassay kits for effective of the high number of positive results given by the first workplace drug testing. In Handbook of SCHWARTZ, R. H. (1995) LSD: its rise, laboratory, i.e. that the patients’ prescribed drugs, or Workplace DrugTesting, first edition fall, and renewed popularity among (eds R. H. Liu & B. A. Goldberger), high school students. Pediatric Clinics their metabolites, may have been responsible for most of pp.67^129.Washington D.C.: AACC of North America, 42,403-413. Press. the false-positive results by the EMIT test. SOYKA, M. (2000) Substance misuse, We concluded that positive LSD test results should RITTER, D., CORTESE, C. M., EDWARDS, psychiatric disorder and violent and be confirmed by at least one alternative method. We also L. C., et al (1997) Interference with disturbed behaviour. BritishJournal of concluded that any positive result using a single immuno- testing for lysergic acid diethylamide. Psychiatry, 176,345-350. Clinical Chemistry, 43,635-637. assay method such as the EMIT test, should not be accepted as valid without confirmation, particularly in A. J. Acosta-Armas Specialist Registrar in Forensic Psychiatry, Devon situations where the subjects are taking other prescribed Partnership NHS Trust, Langdon Hospital, Exeter Road, Dawlish, Devon EX7 0NR

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