Jacob Bell
New Member
VINCENT MARKS, DERRICK TEALE, DENYS FRY
British Medical Journal, 1975, 3, 348-349
Summary
A radioimmunoassay specific for the closed, three-ringed
cannabinoid nucleus was used to detect and measure
cannabis products in urine. Of the 475 urine specimens
examined 82 came from hospital inpatients not suspected
of taking drugs. None of these contained tetrahydrocannabinol
cross-reacting cannabinoids (THC-CRC).
The other 393 specimens were from patients known or
suspected to be taking various drugs. Of these, 51 out of
162 fromn one hospital treatment clinic and 19 out of 50
from another were positive for THC-CRC. Out of 107
urine specimens from an independent drug treatment
clinic 71 were positive for THC-CRC, as were 13 out of 74
specimens from patients in whom drug misuse was
suspected or thought possible.
Introduction
Analysis of urine for drugs of abuse is commonplace in many
clinical laboratories,' the main emphasis in the U.K., as elsewhere,
being on narcotics, amphetamines, and barbiturates.'4
From time to time, however, other drugs, such as methaqualone,5
assume importance. Thin-layer chromatography constitutes the
methodological basis of most drug-detection systems, but latterly
immunoassay techniques have become important.6
Until recently no method of urine analysis was available for
detecting cannabis use. Thus there is a dearth of reliable data
on which to base present and future legislative policy regarding
this drug. The introduction of an exquisitely sensitive, highly
specific radioimmunoassay technique7- 9for measuring cannabis
derivatives in blood and urine has enabled us for the first time
to investigate cannabis use objectively.
Materials and Methods
Urinary tetrahydrocannabinol cross-reacting cannabinoids (THCCRC)
were measured by a radioimmunoassay technique specific for
the closed, three-ringed cannabinoid nucleus. 9 Specimens for analysis
were selected by one of us. All urine samples received for analysis for
drugs at the area laboratory at West Park Hospital between December
1974 and February 1975 were analysed for THC-CRC at regular
intervals in number-coded batches at the University of Surrey.
Included in random order were specimens of control urine. All the
specimens came from patients living in the Greater London or Surrey
areas and were collected between December 1974 and February
1975.
A total of 475 specimens were analysed. Of these, 82 were from
hospital inpatients in whom drug abuse was not (and never had been)
queried but in whom a quantitative measurement of urinary steroids,
catecholamines, or some other endogenous product had beenrequested
for diagnostic purposes; 319 came from two hospital treatment
clinics (A and B) and one independent drug treatment clinic (C), for
all of which the West Park Hospital laboratory provides a routine
service for the analysis of drugs in urine;'0 and 74 came from other
sources, including general medical outpatient departments, psychiatric
clinics, and general practitioners' surgeries, with a request for routine
analysis for drugs. This last, miscellaneous group included 17 specimens
from eight residents of a hostel for former drug addicts. A
condition for entry to and continued residence at the hostel is complete
abstinence from habit-forming drugs, and to ensure compliance with
this rule urine samples are tested regularly for narcotics, amphetamines,
and barbiturates.
For this investigation urine samples containing less than 10 /tg of
THC-CRC per 1 of urine were regarded as negative. More than a third
of the samples from the drug treatment clinics came from patients
who provided two or more specimens.
Results
All 82 urine specimens from the hospital inpatients were negative
for cannabis (see fig.). Of the 162 specimens from clinic A and the 50
from clinic B 51 (31%) and 19 (380%), respectively, were positive for
THC-CRC; 71 (66%') of the 107 specimens from clinic C contained
THC-CRC, as did 13 (18%) of the 74 "miscellaneous" specimens.
Investigation into the origin of the THC-CRC-positive specimens in
the miscellaneous group disclosed that six of them came from the
rehabilitation hostel and were provided by three people.
Altogether 32 patients provided urine specimens on three or more
days. The results of quantitative analysis of the 113 specimens so
provided are shown in the table.
Discussion
The radioimmunoassay used here is specific for the three-ringed
cannabinoid nucleus. 9 It does not distinguish between A 9-THC,
the most pharmacologically active natural cannabinoid, and its
major metabolite 11-hydroxy-THC, which is equally psychoactive.
1' This is of inestimable advantage in the detection of
cannabis use by urine analysis because A9-THC is not itself
excreted in the urine in more than infinitesimal amounts.'2 The
absence of false-positive results in the 82 hospital inpatients
receiving treatment with a wide range of drugs confirms our
earlier conclusions on the assay9 and its suitability for clinical
and epidemiological purposes.
Hitherto, attempts to detect and measure cannabis derivatives
in blood and urine have been either unsuccessful or so tedious,
expensive, and technically demanding'3 14 as to be quite impracticable
except for small-scale research investigations. A
radioimmunoassay for THC-CRC of different sensitivity and
specificity to our own has been described in preliminary form by
Gross et al."5 Estimates of the frequency of cannabis use among known
narcotics users in the U.K. made by several groups1 6-19 on the
basis of personal histories, which are notoriously unreliable in
such patients, without objective assessment have ranged from
86% to 100%. These estimates are much higher than were
actually observed and may represent the difference between
sporadic and more or less constant use. The rate of cannabis use
in our study was similar in patients attending the two hospital
treatment clinics but was substantially higher in patients attending
the independent clinic, at which treatment with narcotics,
especially heroin and methadone, is specifically avoided.
The rate of cannabis use as shown by urine analysis in patients
suspected of but not necessarily admitting to misusing drugs was
10%. The relatively high rate-3 out of 8 patients, and 6 out of
17 urine specimens-of cannabis use by "rehabilitated" narcotics
users living in a hostel was unsuspected. The concentration of a
drug in the urine is at best a poor guide to the amount actually
taken, since a low concentration can be the result of either a large
dose taken a long time previously or a small dose taken a short
time previously. Nevertheless, the wide range of values for
urinary THC-CRC concentrations observed (nil to over 1500
jig/l) lends credence to the suggestion by Fairbairn et al.20 that
the daily cannabis intake may vary by more than a hundredfold
among persons admitting to using the drug.
The quantitative urine analysis data appeared (fig.) to reveal
two populations among the patients attending the drug dependence
clinics-those who use a lot of cannabis and thus excrete
large amounts of THC-CRC in their urine, and those who
abstain from cannabis completely. This concept gained support
when the data on the 32 individual patients from whom multiple
samples were obtained and examined. There was an unmistakable
tendency (admittedly not absolute) for the specimens from one
patient to be either all negative or all positive, though the actual
concentration of THC-CRC might vary considerably. Clearly
more extensive investigation is necessary before firm conclusions
concerning the prevalence ofcannabis useamong drug-dependent
persons and others can be drawn. Nevertheless, it seems reasonable
to suppose that radioimmunoassay could provide the
objective basis for such study.
This work was made possible through the generosity of the M.R.C.
References
Marks, V., Br-itish Journal of Addiction, 1966, 61, 291.
2 Dole, V. P., Kim, W. K., and Eglitis, I., J'ournal of the American Medical
Association, 1966, 198, 349.
3 Davidow, B., Petri, N. L., and Quame, B., American Journal of Clinical
Pathology, 1968, 50, 714.
4 Marks, V., and Fry, D., Proceedings of the Association of Clinical Biochemists,
1968, 5, 95.
5Allen, J. T., Fry, D., and Marks, V., Lancet, 1970, 1, 951.
6 Mule, S. J., et al., Radioimmunoassay for Drugs Subject to Abuse. Cleveland,
CRC Press, 1974.
7 Teale, J. D., et al., Nature, 1974, 249, 154.
8 Teale, J. D., et al., Lancet, 1974, 2, 553.
9 Teale, J. D., et al., Journal of Pharmacy and Pharmacology, 1975, 27,
465.
10 Marks, V., et al., British Medical Journal, 1969, 2, 153.
1 Hollister, L. E., in Research Advances in Alcohol and Drug Problems, ed.
R. J. Gibbins, et al., Vol. 1, p. 243. New York, Wiley, 1974.
12 Hollister, L. E., et al., Research Communications in Chemical Pathology and
Pharmacology, 1974, 8, 579.
13 Agurell, S., et al., J7ournal of Pharmacy and Pharmacology, 1973, 25, 554.
14 Rosenfeld, J. J., et al., Analytical Chemistry, 1974, 46, 2232.
15 Gross, S. J., et al., Nature, 1974, 252, 581.
16 Kosviner, A., et al., Lancet, 1968, 1, 1189.
17 Anumoyne, A., and McClure, J. L., British Journal of Addiction, 1970,
65, 25.
18 Mitcheson, M., et al., Lancet, 1970, 1, 606.
19 Stimson, G. V., and Ogbome, A. C., Lancet, 1970, 1, 1163.
20 Fairbairn, J. W., et al., Nature, 1974, 249, 276.
Source: Detection of cannabis products in urine by radioimmunoassay.
British Medical Journal, 1975, 3, 348-349
Summary
A radioimmunoassay specific for the closed, three-ringed
cannabinoid nucleus was used to detect and measure
cannabis products in urine. Of the 475 urine specimens
examined 82 came from hospital inpatients not suspected
of taking drugs. None of these contained tetrahydrocannabinol
cross-reacting cannabinoids (THC-CRC).
The other 393 specimens were from patients known or
suspected to be taking various drugs. Of these, 51 out of
162 fromn one hospital treatment clinic and 19 out of 50
from another were positive for THC-CRC. Out of 107
urine specimens from an independent drug treatment
clinic 71 were positive for THC-CRC, as were 13 out of 74
specimens from patients in whom drug misuse was
suspected or thought possible.
Introduction
Analysis of urine for drugs of abuse is commonplace in many
clinical laboratories,' the main emphasis in the U.K., as elsewhere,
being on narcotics, amphetamines, and barbiturates.'4
From time to time, however, other drugs, such as methaqualone,5
assume importance. Thin-layer chromatography constitutes the
methodological basis of most drug-detection systems, but latterly
immunoassay techniques have become important.6
Until recently no method of urine analysis was available for
detecting cannabis use. Thus there is a dearth of reliable data
on which to base present and future legislative policy regarding
this drug. The introduction of an exquisitely sensitive, highly
specific radioimmunoassay technique7- 9for measuring cannabis
derivatives in blood and urine has enabled us for the first time
to investigate cannabis use objectively.
Materials and Methods
Urinary tetrahydrocannabinol cross-reacting cannabinoids (THCCRC)
were measured by a radioimmunoassay technique specific for
the closed, three-ringed cannabinoid nucleus. 9 Specimens for analysis
were selected by one of us. All urine samples received for analysis for
drugs at the area laboratory at West Park Hospital between December
1974 and February 1975 were analysed for THC-CRC at regular
intervals in number-coded batches at the University of Surrey.
Included in random order were specimens of control urine. All the
specimens came from patients living in the Greater London or Surrey
areas and were collected between December 1974 and February
1975.
A total of 475 specimens were analysed. Of these, 82 were from
hospital inpatients in whom drug abuse was not (and never had been)
queried but in whom a quantitative measurement of urinary steroids,
catecholamines, or some other endogenous product had beenrequested
for diagnostic purposes; 319 came from two hospital treatment
clinics (A and B) and one independent drug treatment clinic (C), for
all of which the West Park Hospital laboratory provides a routine
service for the analysis of drugs in urine;'0 and 74 came from other
sources, including general medical outpatient departments, psychiatric
clinics, and general practitioners' surgeries, with a request for routine
analysis for drugs. This last, miscellaneous group included 17 specimens
from eight residents of a hostel for former drug addicts. A
condition for entry to and continued residence at the hostel is complete
abstinence from habit-forming drugs, and to ensure compliance with
this rule urine samples are tested regularly for narcotics, amphetamines,
and barbiturates.
For this investigation urine samples containing less than 10 /tg of
THC-CRC per 1 of urine were regarded as negative. More than a third
of the samples from the drug treatment clinics came from patients
who provided two or more specimens.
Results
All 82 urine specimens from the hospital inpatients were negative
for cannabis (see fig.). Of the 162 specimens from clinic A and the 50
from clinic B 51 (31%) and 19 (380%), respectively, were positive for
THC-CRC; 71 (66%') of the 107 specimens from clinic C contained
THC-CRC, as did 13 (18%) of the 74 "miscellaneous" specimens.
Investigation into the origin of the THC-CRC-positive specimens in
the miscellaneous group disclosed that six of them came from the
rehabilitation hostel and were provided by three people.
Altogether 32 patients provided urine specimens on three or more
days. The results of quantitative analysis of the 113 specimens so
provided are shown in the table.
Discussion
The radioimmunoassay used here is specific for the three-ringed
cannabinoid nucleus. 9 It does not distinguish between A 9-THC,
the most pharmacologically active natural cannabinoid, and its
major metabolite 11-hydroxy-THC, which is equally psychoactive.
1' This is of inestimable advantage in the detection of
cannabis use by urine analysis because A9-THC is not itself
excreted in the urine in more than infinitesimal amounts.'2 The
absence of false-positive results in the 82 hospital inpatients
receiving treatment with a wide range of drugs confirms our
earlier conclusions on the assay9 and its suitability for clinical
and epidemiological purposes.
Hitherto, attempts to detect and measure cannabis derivatives
in blood and urine have been either unsuccessful or so tedious,
expensive, and technically demanding'3 14 as to be quite impracticable
except for small-scale research investigations. A
radioimmunoassay for THC-CRC of different sensitivity and
specificity to our own has been described in preliminary form by
Gross et al."5 Estimates of the frequency of cannabis use among known
narcotics users in the U.K. made by several groups1 6-19 on the
basis of personal histories, which are notoriously unreliable in
such patients, without objective assessment have ranged from
86% to 100%. These estimates are much higher than were
actually observed and may represent the difference between
sporadic and more or less constant use. The rate of cannabis use
in our study was similar in patients attending the two hospital
treatment clinics but was substantially higher in patients attending
the independent clinic, at which treatment with narcotics,
especially heroin and methadone, is specifically avoided.
The rate of cannabis use as shown by urine analysis in patients
suspected of but not necessarily admitting to misusing drugs was
10%. The relatively high rate-3 out of 8 patients, and 6 out of
17 urine specimens-of cannabis use by "rehabilitated" narcotics
users living in a hostel was unsuspected. The concentration of a
drug in the urine is at best a poor guide to the amount actually
taken, since a low concentration can be the result of either a large
dose taken a long time previously or a small dose taken a short
time previously. Nevertheless, the wide range of values for
urinary THC-CRC concentrations observed (nil to over 1500
jig/l) lends credence to the suggestion by Fairbairn et al.20 that
the daily cannabis intake may vary by more than a hundredfold
among persons admitting to using the drug.
The quantitative urine analysis data appeared (fig.) to reveal
two populations among the patients attending the drug dependence
clinics-those who use a lot of cannabis and thus excrete
large amounts of THC-CRC in their urine, and those who
abstain from cannabis completely. This concept gained support
when the data on the 32 individual patients from whom multiple
samples were obtained and examined. There was an unmistakable
tendency (admittedly not absolute) for the specimens from one
patient to be either all negative or all positive, though the actual
concentration of THC-CRC might vary considerably. Clearly
more extensive investigation is necessary before firm conclusions
concerning the prevalence ofcannabis useamong drug-dependent
persons and others can be drawn. Nevertheless, it seems reasonable
to suppose that radioimmunoassay could provide the
objective basis for such study.
This work was made possible through the generosity of the M.R.C.
References
Marks, V., Br-itish Journal of Addiction, 1966, 61, 291.
2 Dole, V. P., Kim, W. K., and Eglitis, I., J'ournal of the American Medical
Association, 1966, 198, 349.
3 Davidow, B., Petri, N. L., and Quame, B., American Journal of Clinical
Pathology, 1968, 50, 714.
4 Marks, V., and Fry, D., Proceedings of the Association of Clinical Biochemists,
1968, 5, 95.
5Allen, J. T., Fry, D., and Marks, V., Lancet, 1970, 1, 951.
6 Mule, S. J., et al., Radioimmunoassay for Drugs Subject to Abuse. Cleveland,
CRC Press, 1974.
7 Teale, J. D., et al., Nature, 1974, 249, 154.
8 Teale, J. D., et al., Lancet, 1974, 2, 553.
9 Teale, J. D., et al., Journal of Pharmacy and Pharmacology, 1975, 27,
465.
10 Marks, V., et al., British Medical Journal, 1969, 2, 153.
1 Hollister, L. E., in Research Advances in Alcohol and Drug Problems, ed.
R. J. Gibbins, et al., Vol. 1, p. 243. New York, Wiley, 1974.
12 Hollister, L. E., et al., Research Communications in Chemical Pathology and
Pharmacology, 1974, 8, 579.
13 Agurell, S., et al., J7ournal of Pharmacy and Pharmacology, 1973, 25, 554.
14 Rosenfeld, J. J., et al., Analytical Chemistry, 1974, 46, 2232.
15 Gross, S. J., et al., Nature, 1974, 252, 581.
16 Kosviner, A., et al., Lancet, 1968, 1, 1189.
17 Anumoyne, A., and McClure, J. L., British Journal of Addiction, 1970,
65, 25.
18 Mitcheson, M., et al., Lancet, 1970, 1, 606.
19 Stimson, G. V., and Ogbome, A. C., Lancet, 1970, 1, 1163.
20 Fairbairn, J. W., et al., Nature, 1974, 249, 276.
Source: Detection of cannabis products in urine by radioimmunoassay.
