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M E R . J. DRUG & ALCOHOL ABUSE, 2(2), pp. 269-275 (1975)
Plasma Testosterone Levels in Healthy Male Marijuana Smokers*
PAUL CUSHMAN, Jr., M.D. Department of Medicine St. Lukes' Hospital Center and Columbia University New York, New York
ABSTRACT Plasma testosterone, FSH, and LH levels were obtained from 25 healthy consecutive heterosexual male marijuana smoking university students. All values were within the range of normal and the means did not differ significantly from those of 13 normal controls. These data suggest that the casual marijuana smoker (at least one time weekly with an average of 5.1 joints per week) may have plasma testosterone levels which are normal for the time of day and the laboratory.
INTRODUCTION Some recent data have suggested that chronic marijuana use may be associated with lower levels of plasma testosterone than in controls [ I ] . An increase in the incidence of oligospermia and reduced libido was also found in this group of 20 chronic marijuana smokers [ 11. On the other hand, another group of investigators recently reported that 27 male marijuana smokers during controlled conditions in a locked psychiatric
*Supported by Grants from the NIMH (DA 00335 and MH 18408).
269
CUSHMAN
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
270
ward showed no change in their normal plasma testosterone levels before, during, and after a period of controlled marijuana smoking [ 2 ] . Because of these inconsistencies, it was elected to study the plasma testosterone levels in a group of young male marijuana smoking university students. It was felt that this population of academically productive, motivated youngsters would be an especially interesting sample of marijuana smokers since they might reflect the sporadic use of marijuana that appears to be very common amongst young persons throughout the country. If low plasma testosterone levels in this population is found then this information should be made readily available to those who are making their decisions whether to use marijuana or not. Furthermore, the possible clinical consequences of reduction in plasma testosterone should be realized.
PATIENTS AND METHODS The marijuana smokers were recruited from a major New York City univeristy. They were 22 years old (1 8-28 mean and range). They gave histories of marijuana use for 2.8 f 0.9 (mean f SD with a range 1-5 years). They averaged 5.1 f 2.3 joints weekly and reported smoking marijuana at least one year weekly with an average of 3.2 1.4 times weekly within the prior three months. All claimed and appeared to be in good health. All denied ever having used morphine, methadone, amphetamines, or barbiturates illegally and all but six denied ever having used LSD, peyote, or mescaline. Within the past two weeks all subjects denied taking any licit or illicit drugs (aside from marijuana) except for three who took aspirin, two who took multivitamins, and one each who took Valium, Librium, Mellaril, Darvon, vitamin E, Dristan, and a proprietary cough medicine of unknown nature. Five reported using 10 or more cigarettes daily. None reported the daily use of alcohol above the equivalent of 2 ounces of whiskey. All gave histories of normal sexual functions while under the influence of marijuana except for three who felt that concomitant marijuana and sexual activity enhanced the cutaneous stimualtory sensations during foreplay and two others who reported their libido to be decreased when “stoned” compared to their response to equivalent sexual opportunities when not
*
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
PLASMA TESTOSTERONE LEVELS
27 1
under the influence of marijuana. All possessed normal secondary sex characteristics, and gynecomastia was not observed. It can never be known exactly what the patients had consumed. Hence, the accuracy of their drug histories is uncertain. From their description of the appearance, styles of use, their subjective reactions t o and conjunctival reactions t o marijuana, they were all very familiar with and presumably had been taking what was being sold as marijuana, at the time. The controls were 13 males attending the same university. They were 25.6 f 4.7 (range 19-40) years of age and all denied marijuana use and that of any other dangerous drug in the past. Twenty-five percent reported smoking at least 10 cigarettes daily and none reported the daily use of 2 ounces of spirits o r more. None reported the use of legal drugs within two weeks of the study except for two who had used aspirin and one who used a multivitamin preparation. None reported any abnormalities in their libido, potency, or secondary sex characteristics. Venous blood was obtained in heparinized tubes between 8-9:30 AM, and the plasma immediately separated. The content of testosterone was estimated by radioimmunoassay.' The luteinizing hormone (LH) and follicle stimulating hormone (FSH) content were measured by double antibody radioimmunoassay in the same plasma sample.2 Three aliquots of the same sample of plasma obtained from a normal subject submitted simultaneously had reported testosterone levels with an interanalysis agreement within 9%. Six other measurements of the same individual's plasma testosterone at various intervals indicated that the day to day measurement fluctuated within a range of 100 ng/100 ml plasma. A spot urine was obtained and its content of dangerous drug determined, with a qualitative screening procedure2 which is said t o detect quinine, morphine, methadone, cocaine, barbiturates, phenthiazines, amphetamines, and codeine. None of the controls tested had any dangerous drug found. All of the marijuana smokers were negative for dangerous drugs except for one in whose urine a phenothiazine was detected and one who refused to give a urine specimen. 'Performed at the Bio Science Laboratories, Van Nuys, California. 'Performed at the Center for Laboratory Medicine, Metuchen, New Jersey.
CUSHMAN
272
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Liver function tests were analyzed in simultaneously obtained sera by the 12 channel Auto Analyzer procedure. Statistical treatments of the data include the students t test.
RESULTS The plasma testosterone levels fell over a very broad range in both the normal and the marijuana smoker populations. All the 25 marijuana smokers had plasma testosterone values within the range of normal and their mean values were not different from those of the controls (Table 1). The plasma LH and FSH levels in the marijuana smokers were within the normal range and no individual value was below the lower limit of normal range. The marijuana smokers had normal calcium, cholesterol, total proteins, albumins, uric acid, SGOT, alkaline phosphatase values as did the controls. The possibility that the interval since the initiation of the last marijuana episode might be a significant variable in the plasma testosterone determinations was considered. The subjects reported smoking marijuana from 5-72 hours before study (mean 19-16 hours) and no relation with plasma testosterone and the time since last reported use was found.
DISCUSSION Plasma testosterone levels in normal males fluctuate throughout a very wide range [ 3 ] . They can be influenced by the rates of testosterone Table 1
~
~~~
~~
Marijuana smokers Nonsmoking controls
No. 25 13
Age
Testosterone (ngl100ml)
(mIu/ ml)
LH (mIu/ml)
21.2 k2.9
639 *270
14.3 4.6
11.1 3.1
22.6 k3.0
633 *295
14.4 2.1
11.9 3.3
NS
NS
NS
FSH
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
PLASMA TESTOSTERONE LEVELS
273
secretion, the concentration and binding affinities of the sex hormone transport protein, and the rate of removal from the plasma. In addition, there may be diurnal fluctuations [4-61, which are relatively small in relation to other circulating hormones, as cortisol [7] and ACTH [ 8 ] . Other factors that affect plasma testosterone levels are LH, the physiological stimulator of testosterone secretion, estrogen [ 91 , liver disease [ 101 , possibly ACTH [ l 11 although there are some data to the contrary [6, 121 ; mental [ 131 and surgical stress [ 141 ; epinephrine [ 151 and exogenous testosterone [ 161. Some drugs are reported to affect plasma testosterone levels: opioids and narcotics [ 17-19], and possibly alcohol [20, 21 1, although there are data to the contrary [22]. Since male subjects with hypogonadism and andorgen insufficiency have low plasma testosterone levels, the concentration of plasma testosterone can be considered a reflection of the degree of andogenicity. However, it is far from clear what is the clinical or biochemical significance of a lower plasma concentration rather than a higher one if both are within the range of the normal. The present data indicate that all of a randomly selected group of healthy functioning university students have plasma testosterone levels within the limits of normal. This contrasts with the previous study of plasma testosterone levels in which marijuana smokers reporting an average use of 10 or more joints per week had lower mean testosterone levels than those reporting the use of 5-9 joints weekly and both groups of smokers were below that of the age matched controls. Some of the subjects, particularly those reporting an average use of 10 or more joints per week had testosterone levels below the lower limit of normal for that laboratory [ 231. The differences between the St. Louis data and the present series may be related to the greater frequency with which marijuana was consumed, and/or to the larger number of weekly marijuana joints used in the St. Louis group. Other reasons for the difference in the findings may be other drugs, which could not be controlled in any of the patients studied, sample differences, or possibly differences in the analytic methods used. Another laboratory studied plasma testosterone serially in 27 marijuana smoking males sequestral in an isolated controlled in-patient setting. There was no difference between those patients who reported heavy use (42 times monthly) in baseline studies before the onset of daily
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
274
CUSHMAN
smoking of government supplied marijuana of known content. During the course of smoking marijuana for 21 days there was no change in the mean of either the heavy or casual smokers’ testosterone levels [ 21. Since all the values reported were within the limits of normal, it appears unlikely that exposure to known, and often large amounts of marijuana influence plasma testosterone levels as determined in their laboratory by a commercial double antibody radioimmunoassay procedure. The St. Louis group has recently reported the results of serial plasma testosterone levels in a small group of in-patient marijuana users who had been withdrawn from all drugs for 11 days. Compared to a control day on which no marijuana was smoked, they reported significantly lower mean plasma testosterone levels 120 and 180 minutes after smoking one marijuana cigarette [ 241. However, the preponderance of their values, i.e., all but one or two individual values, were within the normal range for that time of day. These findings were interpreted to reflect a marijuana induced reduction in plasma testosterone, and may be best considered to reflect an acute effect after a single dose. It is possible that small changes in plasma testosterone levels may occur acutely after marijuana exposure as suggested by the St. Louis data. It is not possible t o reconcile all these data at present. It appears that many casual marijuana smokers have normal plasma testosterone values although there may be some especially heavy smokers whose plasma testosterone levels are low in absolute terms. The clinical significance of somewhat lower plasma testosterone levels in heavy marijuana smokers, especially of the levels that remain within the range of normal regards such androgen mediated functions as libido, secondary sex characteristics, prostate size, is not immediately evident.
REFERENCES
[ 11 Kolodny, R. C., et ul., Depression of plasma testosterone levels after chronic intensive marijuana use, New Eng. J. Med. 290:872 (1974). [2] Mendelson, J. H., et ul., Plasma testosterone levels before, during and after marijuana smoking, New Eng. J. Med. 291: 105 1 (1974). [3] Naftolin, F., Judd, H. L., and Yen, S. S. C., Pulsatile patterns of gonadotropins and testosterone in man: The effects of clomiphene with and without testosterone, J. Clin. Endocrinol. Metub. 36:285 (1973). [4] Lacerda, L., et ul., Integrated concentration and circadian variation of plasma testosterone in normal men, J. Clin. Endocrinol. Metub. 37:366 (1973).
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
PLASMA TESTOSTERONE LEVELS
275
[5] Resko, J. A., and Eik-Nes, K. B., Diurnal variation of testosterone in peripheral plasma of male subjects, J. Clin. Endocrinol. Metab. 26:573 (1966). [6] Kirschner, M. A., Lipsett, M. B., and Collins, D. R., Plasma ketosteroids and testosterone in man: A study of the pituitary-testicular axis, J. Clin. Invest. 44:657 (1965). [7] Orth, D. N., Island, D., and Liddle, G. W., Experimental alteration of the circadian rhythm in plasma cortisol concentration in man, J. Clin. Endocrinol. Metab. 27: 549 (1 967). [8] Liddle, G. W., Island, D., and Meador, C. K., Normal and abnormal regulation of corticotropin secretion in man, Recent h o p . Hormone Res. 18: 125 (1962). [9] Ettinger, B., et al., Plasma testosterone stimulation-suppression dynamics in hirsute women, Amer. J. Med. 54: 195 (1973). [lo] Chopra, I. J. Tulchinsky, D., and Greenway, F. L., Estrogen-androgen imbalance in hepatic cirrhosis: Studies in 13 male patients, Ann. Intern. Med. 7 9 :198 (1973). [ l l ] Rivarola, M., et al., Metabolic clearance rate and blood production rate of testosterone and androgen under basal conditions, J. Clin. Endocrinol. Metab. 26: 1208 (1 966). [12] Smals, A. G. H., Kloppenborg, P. W. C., and Benraad, T. J., Diurnal plasma rhythm and the effect of short-term ACTH administration on plasma testosterone in man, J. Clin. Endocrinol. Metab. 38:608 (1974). [13] Kreuz, L. E., Rose, R. M., and Jennings, J. R., Suppression of plasma testosterone levels and psychological stress, Arch. Gen. Psych. 26:479 (1972). [I41 Aono, T., et aZ., Influence of major surgical stress on plasma levels of testosterone, luteinizing hormone and follicle stimulating hormone in male patients, J. Clin. Endocrinol. Metab. 35:535 (1972). [15] Levin, J., et aZ.. The effect of epinephrine on testosterone production, Acta Endocrin. 5 5 : 184 (1 967). [16] Morse, H. C., et al., Testosterone concentrations in testes of normal men: Effects of testosterone proprionate administration, J. Clin. Endocrinol. Metab. 37:88 1 (1973). [17] Cushman, P., Plasma testosterone in narcotic addiction, Amer. J. Med. 55:452 (1 973). [18] Mendelson, J. F., Mendelson, J. E., and Patch, V. D., Plasma testosterone levels in heroin addiction and during methadone maintenance, J. Pharmacol. Exp. Ther. 17:529 (1975). [ 191 Azzizi, F., et al., Decreased serum testosterone concentration in male heroin and methadone addicts, Steroids 22:467 (1973). [20] Mendelson, J. H., and Mello, N. K., Alcohol, aggression, and androgens, in Aggression (S. Frazier, Ed.), Williams & Wilkins, Baltimore, Md., pp. 225-247, 1974. [21] Liegel, J., Fabre, L. F., and Howard, P. Y.,Plasma testosterone and sex hormone binding globulin in alcoholic subjects, Physiologist 15:198 (1 972). [22] Toro, G., et al., Failure of alcohol to alter pituitary and target organ hormone levels, Clin. Res. 21:505 (1973). [23] Kolodny, R. C., personal communication. [24] Kolodny, R. C., et al., Depression of plasma testosterone with acute marijuana administration, presented at the Int. Conf. on the Pharmacology of Cannabis, Dec. 4, 1974.
M E R . J. DRUG & ALCOHOL ABUSE, 2(2), pp. 269-275 (1975)
Plasma Testosterone Levels in Healthy Male Marijuana Smokers*
PAUL CUSHMAN, Jr., M.D. Department of Medicine St. Lukes' Hospital Center and Columbia University New York, New York
ABSTRACT Plasma testosterone, FSH, and LH levels were obtained from 25 healthy consecutive heterosexual male marijuana smoking university students. All values were within the range of normal and the means did not differ significantly from those of 13 normal controls. These data suggest that the casual marijuana smoker (at least one time weekly with an average of 5.1 joints per week) may have plasma testosterone levels which are normal for the time of day and the laboratory.
INTRODUCTION Some recent data have suggested that chronic marijuana use may be associated with lower levels of plasma testosterone than in controls [ I ] . An increase in the incidence of oligospermia and reduced libido was also found in this group of 20 chronic marijuana smokers [ 11. On the other hand, another group of investigators recently reported that 27 male marijuana smokers during controlled conditions in a locked psychiatric
*Supported by Grants from the NIMH (DA 00335 and MH 18408).
269
CUSHMAN
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
270
ward showed no change in their normal plasma testosterone levels before, during, and after a period of controlled marijuana smoking [ 2 ] . Because of these inconsistencies, it was elected to study the plasma testosterone levels in a group of young male marijuana smoking university students. It was felt that this population of academically productive, motivated youngsters would be an especially interesting sample of marijuana smokers since they might reflect the sporadic use of marijuana that appears to be very common amongst young persons throughout the country. If low plasma testosterone levels in this population is found then this information should be made readily available to those who are making their decisions whether to use marijuana or not. Furthermore, the possible clinical consequences of reduction in plasma testosterone should be realized.
PATIENTS AND METHODS The marijuana smokers were recruited from a major New York City univeristy. They were 22 years old (1 8-28 mean and range). They gave histories of marijuana use for 2.8 f 0.9 (mean f SD with a range 1-5 years). They averaged 5.1 f 2.3 joints weekly and reported smoking marijuana at least one year weekly with an average of 3.2 1.4 times weekly within the prior three months. All claimed and appeared to be in good health. All denied ever having used morphine, methadone, amphetamines, or barbiturates illegally and all but six denied ever having used LSD, peyote, or mescaline. Within the past two weeks all subjects denied taking any licit or illicit drugs (aside from marijuana) except for three who took aspirin, two who took multivitamins, and one each who took Valium, Librium, Mellaril, Darvon, vitamin E, Dristan, and a proprietary cough medicine of unknown nature. Five reported using 10 or more cigarettes daily. None reported the daily use of alcohol above the equivalent of 2 ounces of whiskey. All gave histories of normal sexual functions while under the influence of marijuana except for three who felt that concomitant marijuana and sexual activity enhanced the cutaneous stimualtory sensations during foreplay and two others who reported their libido to be decreased when “stoned” compared to their response to equivalent sexual opportunities when not
*
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
PLASMA TESTOSTERONE LEVELS
27 1
under the influence of marijuana. All possessed normal secondary sex characteristics, and gynecomastia was not observed. It can never be known exactly what the patients had consumed. Hence, the accuracy of their drug histories is uncertain. From their description of the appearance, styles of use, their subjective reactions t o and conjunctival reactions t o marijuana, they were all very familiar with and presumably had been taking what was being sold as marijuana, at the time. The controls were 13 males attending the same university. They were 25.6 f 4.7 (range 19-40) years of age and all denied marijuana use and that of any other dangerous drug in the past. Twenty-five percent reported smoking at least 10 cigarettes daily and none reported the daily use of 2 ounces of spirits o r more. None reported the use of legal drugs within two weeks of the study except for two who had used aspirin and one who used a multivitamin preparation. None reported any abnormalities in their libido, potency, or secondary sex characteristics. Venous blood was obtained in heparinized tubes between 8-9:30 AM, and the plasma immediately separated. The content of testosterone was estimated by radioimmunoassay.' The luteinizing hormone (LH) and follicle stimulating hormone (FSH) content were measured by double antibody radioimmunoassay in the same plasma sample.2 Three aliquots of the same sample of plasma obtained from a normal subject submitted simultaneously had reported testosterone levels with an interanalysis agreement within 9%. Six other measurements of the same individual's plasma testosterone at various intervals indicated that the day to day measurement fluctuated within a range of 100 ng/100 ml plasma. A spot urine was obtained and its content of dangerous drug determined, with a qualitative screening procedure2 which is said t o detect quinine, morphine, methadone, cocaine, barbiturates, phenthiazines, amphetamines, and codeine. None of the controls tested had any dangerous drug found. All of the marijuana smokers were negative for dangerous drugs except for one in whose urine a phenothiazine was detected and one who refused to give a urine specimen. 'Performed at the Bio Science Laboratories, Van Nuys, California. 'Performed at the Center for Laboratory Medicine, Metuchen, New Jersey.
CUSHMAN
272
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Liver function tests were analyzed in simultaneously obtained sera by the 12 channel Auto Analyzer procedure. Statistical treatments of the data include the students t test.
RESULTS The plasma testosterone levels fell over a very broad range in both the normal and the marijuana smoker populations. All the 25 marijuana smokers had plasma testosterone values within the range of normal and their mean values were not different from those of the controls (Table 1). The plasma LH and FSH levels in the marijuana smokers were within the normal range and no individual value was below the lower limit of normal range. The marijuana smokers had normal calcium, cholesterol, total proteins, albumins, uric acid, SGOT, alkaline phosphatase values as did the controls. The possibility that the interval since the initiation of the last marijuana episode might be a significant variable in the plasma testosterone determinations was considered. The subjects reported smoking marijuana from 5-72 hours before study (mean 19-16 hours) and no relation with plasma testosterone and the time since last reported use was found.
DISCUSSION Plasma testosterone levels in normal males fluctuate throughout a very wide range [ 3 ] . They can be influenced by the rates of testosterone Table 1
~
~~~
~~
Marijuana smokers Nonsmoking controls
No. 25 13
Age
Testosterone (ngl100ml)
(mIu/ ml)
LH (mIu/ml)
21.2 k2.9
639 *270
14.3 4.6
11.1 3.1
22.6 k3.0
633 *295
14.4 2.1
11.9 3.3
NS
NS
NS
FSH
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
PLASMA TESTOSTERONE LEVELS
273
secretion, the concentration and binding affinities of the sex hormone transport protein, and the rate of removal from the plasma. In addition, there may be diurnal fluctuations [4-61, which are relatively small in relation to other circulating hormones, as cortisol [7] and ACTH [ 8 ] . Other factors that affect plasma testosterone levels are LH, the physiological stimulator of testosterone secretion, estrogen [ 91 , liver disease [ 101 , possibly ACTH [ l 11 although there are some data to the contrary [6, 121 ; mental [ 131 and surgical stress [ 141 ; epinephrine [ 151 and exogenous testosterone [ 161. Some drugs are reported to affect plasma testosterone levels: opioids and narcotics [ 17-19], and possibly alcohol [20, 21 1, although there are data to the contrary [22]. Since male subjects with hypogonadism and andorgen insufficiency have low plasma testosterone levels, the concentration of plasma testosterone can be considered a reflection of the degree of andogenicity. However, it is far from clear what is the clinical or biochemical significance of a lower plasma concentration rather than a higher one if both are within the range of the normal. The present data indicate that all of a randomly selected group of healthy functioning university students have plasma testosterone levels within the limits of normal. This contrasts with the previous study of plasma testosterone levels in which marijuana smokers reporting an average use of 10 or more joints per week had lower mean testosterone levels than those reporting the use of 5-9 joints weekly and both groups of smokers were below that of the age matched controls. Some of the subjects, particularly those reporting an average use of 10 or more joints per week had testosterone levels below the lower limit of normal for that laboratory [ 231. The differences between the St. Louis data and the present series may be related to the greater frequency with which marijuana was consumed, and/or to the larger number of weekly marijuana joints used in the St. Louis group. Other reasons for the difference in the findings may be other drugs, which could not be controlled in any of the patients studied, sample differences, or possibly differences in the analytic methods used. Another laboratory studied plasma testosterone serially in 27 marijuana smoking males sequestral in an isolated controlled in-patient setting. There was no difference between those patients who reported heavy use (42 times monthly) in baseline studies before the onset of daily
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
274
CUSHMAN
smoking of government supplied marijuana of known content. During the course of smoking marijuana for 21 days there was no change in the mean of either the heavy or casual smokers’ testosterone levels [ 21. Since all the values reported were within the limits of normal, it appears unlikely that exposure to known, and often large amounts of marijuana influence plasma testosterone levels as determined in their laboratory by a commercial double antibody radioimmunoassay procedure. The St. Louis group has recently reported the results of serial plasma testosterone levels in a small group of in-patient marijuana users who had been withdrawn from all drugs for 11 days. Compared to a control day on which no marijuana was smoked, they reported significantly lower mean plasma testosterone levels 120 and 180 minutes after smoking one marijuana cigarette [ 241. However, the preponderance of their values, i.e., all but one or two individual values, were within the normal range for that time of day. These findings were interpreted to reflect a marijuana induced reduction in plasma testosterone, and may be best considered to reflect an acute effect after a single dose. It is possible that small changes in plasma testosterone levels may occur acutely after marijuana exposure as suggested by the St. Louis data. It is not possible t o reconcile all these data at present. It appears that many casual marijuana smokers have normal plasma testosterone values although there may be some especially heavy smokers whose plasma testosterone levels are low in absolute terms. The clinical significance of somewhat lower plasma testosterone levels in heavy marijuana smokers, especially of the levels that remain within the range of normal regards such androgen mediated functions as libido, secondary sex characteristics, prostate size, is not immediately evident.
REFERENCES
[ 11 Kolodny, R. C., et ul., Depression of plasma testosterone levels after chronic intensive marijuana use, New Eng. J. Med. 290:872 (1974). [2] Mendelson, J. H., et ul., Plasma testosterone levels before, during and after marijuana smoking, New Eng. J. Med. 291: 105 1 (1974). [3] Naftolin, F., Judd, H. L., and Yen, S. S. C., Pulsatile patterns of gonadotropins and testosterone in man: The effects of clomiphene with and without testosterone, J. Clin. Endocrinol. Metub. 36:285 (1973). [4] Lacerda, L., et ul., Integrated concentration and circadian variation of plasma testosterone in normal men, J. Clin. Endocrinol. Metub. 37:366 (1973).
Am J Drug Alcohol Abuse Downloaded from informahealthcare.com by Nyu Medical Center on 01/06/15 For personal use only.
PLASMA TESTOSTERONE LEVELS
275
[5] Resko, J. A., and Eik-Nes, K. B., Diurnal variation of testosterone in peripheral plasma of male subjects, J. Clin. Endocrinol. Metab. 26:573 (1966). [6] Kirschner, M. A., Lipsett, M. B., and Collins, D. R., Plasma ketosteroids and testosterone in man: A study of the pituitary-testicular axis, J. Clin. Invest. 44:657 (1965). [7] Orth, D. N., Island, D., and Liddle, G. W., Experimental alteration of the circadian rhythm in plasma cortisol concentration in man, J. Clin. Endocrinol. Metab. 27: 549 (1 967). [8] Liddle, G. W., Island, D., and Meador, C. K., Normal and abnormal regulation of corticotropin secretion in man, Recent h o p . Hormone Res. 18: 125 (1962). [9] Ettinger, B., et al., Plasma testosterone stimulation-suppression dynamics in hirsute women, Amer. J. Med. 54: 195 (1973). [lo] Chopra, I. J. Tulchinsky, D., and Greenway, F. L., Estrogen-androgen imbalance in hepatic cirrhosis: Studies in 13 male patients, Ann. Intern. Med. 7 9 :198 (1973). [ l l ] Rivarola, M., et al., Metabolic clearance rate and blood production rate of testosterone and androgen under basal conditions, J. Clin. Endocrinol. Metab. 26: 1208 (1 966). [12] Smals, A. G. H., Kloppenborg, P. W. C., and Benraad, T. J., Diurnal plasma rhythm and the effect of short-term ACTH administration on plasma testosterone in man, J. Clin. Endocrinol. Metab. 38:608 (1974). [13] Kreuz, L. E., Rose, R. M., and Jennings, J. R., Suppression of plasma testosterone levels and psychological stress, Arch. Gen. Psych. 26:479 (1972). [I41 Aono, T., et aZ., Influence of major surgical stress on plasma levels of testosterone, luteinizing hormone and follicle stimulating hormone in male patients, J. Clin. Endocrinol. Metab. 35:535 (1972). [15] Levin, J., et aZ.. The effect of epinephrine on testosterone production, Acta Endocrin. 5 5 : 184 (1 967). [16] Morse, H. C., et al., Testosterone concentrations in testes of normal men: Effects of testosterone proprionate administration, J. Clin. Endocrinol. Metab. 37:88 1 (1973). [17] Cushman, P., Plasma testosterone in narcotic addiction, Amer. J. Med. 55:452 (1 973). [18] Mendelson, J. F., Mendelson, J. E., and Patch, V. D., Plasma testosterone levels in heroin addiction and during methadone maintenance, J. Pharmacol. Exp. Ther. 17:529 (1975). [ 191 Azzizi, F., et al., Decreased serum testosterone concentration in male heroin and methadone addicts, Steroids 22:467 (1973). [20] Mendelson, J. H., and Mello, N. K., Alcohol, aggression, and androgens, in Aggression (S. Frazier, Ed.), Williams & Wilkins, Baltimore, Md., pp. 225-247, 1974. [21] Liegel, J., Fabre, L. F., and Howard, P. Y.,Plasma testosterone and sex hormone binding globulin in alcoholic subjects, Physiologist 15:198 (1 972). [22] Toro, G., et al., Failure of alcohol to alter pituitary and target organ hormone levels, Clin. Res. 21:505 (1973). [23] Kolodny, R. C., personal communication. [24] Kolodny, R. C., et al., Depression of plasma testosterone with acute marijuana administration, presented at the Int. Conf. on the Pharmacology of Cannabis, Dec. 4, 1974.
