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July 1974, Vol 31, No. 1 >
Article | July 1974

Repeat Administration of Marihuana Smoke to Humans

Pierre F. Renault, MD; Charles R. Schuster, PhD; Daniel X. Freedman, MD; Branimar Sikic, MD; Dorothy Nebel de Mello; Angelos Halaris, MD
[+] Author Affiliations

Accepted for publication March 8, 1974.

Reprint requests to the Department of Psychiatry, University of Chicago, 950 E 59th St, Chicago, IL 60637 (Dr. Freedman).


Arch Gen Psychiatry. 1974;31(1):95-102. doi:10.1001/archpsyc.1974.01760130071012
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Tolerance to marihuana was investigated in two experiments. Four men were given smoke from 435 mg of marihuana (1.5 Δ-9-tetrahydrocannabinol [THC]) twice a day for ten days preceded and followed by three days of a placebo twice a day; three additional men were given a higher dose (2.8% THC).

Time estimation was disrupted on the higher dose and gradually improved. Heart rate increase did not show tolerance. Enhancement of postural cradiovascular responses, when present, decreased in duration in three subjects. One developed a brief toxic psychosis, another pneumonitis of uncertain etiology. Dysphoric and psychotoxic effects were evident as a cumulative effect of the high dose.

Three additional men were given the low dosage once a week for six to eight weeks, and time estimation and heart rate changes were similar to those seen with frequent administration at that dose. Tolerance, recently reported in man, probably requires more frequent administration or a different dosage than the schedules employed here.

REFERENCES

1 +
Carlini EA:  Tolerance to chronic administration on Cannabis sativa (Marihuana) in rats . Pharmacology 1:135-142, 1968;.
2 +
McMillan DE, Dewey WL, Harris LS:  Characteristics of tetrahydrocannabinol tolerance . Ann NY Acad Sci 191:83-96, 1971;.
3 +
Melges FT, et al:  Marihuana and temporal disintegration . Science 168:1118-1120, 1970;.
4 +
Melges FT, et al:  Temporal disintegration and depersonalization during marihuana intoxication . Arch Gen Psychiatry 23:204-210, 1970;.
5 +
Melges FT, et al:  Marihuana and the temporal span of awareness . Arch Gen Psychiatry 24:564-567, 1971;.
6 +
Clark LD, Hughes R, Nakashima EN:  Behavioral effects of marihuana . Arch Gen Psychiatry 23:193-198, 1970;.
7 +
Conrad DG, Elsmor TF, Sodetz FJ:  Delta-9-tetrahydrocannabinol: Dose related effects on timed behavior in chimpanzee . Science 175:547-550, 1972;.
8 +
Hollister LE, Richards RK, Gillespie HK:  Comparison of tetrahydrocannabinol and synhexyl in man . Clin Pharmacol Ther 9:783-791, 1968;.
9 +
Waskow IE, et al:  Psychological effects of tetrahydrocannabinol . Arch Gen Psychiatry 22:97-107, 1970;.
10 +
Renault PF, et al:  Marihuana: Standardized smoke administration and dose effect curves on heart rate in humans . Science 174:589-591, 1971;.
11 +
Kiplinger GF, et al:  Dose-response analysis of tetrahydrocannabinol in man . Clin Pharmacol Ther 12:650-657, 1971;.
12 +
Uhlenhuth KR, et al:  Drug, doctor's verbal attitude and clinic setting in the symptomatic response to pharmacotherapy . Psychopharmacologia 9:392-418, 1966;.
13 +
Clyde DJ: Clyde Mood Scale Manual . Coral Gables, Fla, University of Miami, Biometrics Laboratory, 1963;.
14 +
McNair DM, Lorr M:  An analysis of mood in neurotics . J Abnorm Soc Psychol 69:620-627, 1964;.
15 +
Nowlis V:  Research with the mood adjective checklist , in Tompkins SS, Izard CE (eds): Affect, Cognition and Personality . New York, Springer Publishing Co, 1965;, pp 352-389.
16 +
Matingly D:  A simple fluorometric method for estimating 11-hydrocorticoids in human plasma . J Clin Pathol 15:374-379, 1962;.
17 +
Rosalki SB:  An improved procedure for serum creatine phosphokinase determination . J Lab Clin Med 69:696-705, 1967;.
18 +
Lemberger L, et al:  Delta 9-tetrahydrocannabinol metabolism and disposition in long term smokers . Science 173:72-73, 1971;.
19 +
Freedman DX, et al:  Tolerance to the behavioral effects of LSD-25 in rat . J Pharmacol Exp Ther 143:309, 1964;.
20 +
Weil AT:  Clinical and psychological effects of marihuana in man . Science 162:1234-1242, 1968;.
21 +
Schuster CR, Dockens WS, Wooks JH:  Behavioral variables affecting the development of amphetamine tolerance . Psychopharmacologia 9:170-182, 1966;.
22 +
Marihuana: A signal of misunderstanding, in the First Report of the National Commission on Marihuana and Drug Abuse, Appendix 1. Government Printing Office, Superintendent of Documents, 1972.

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1 +
Carlini EA:  Tolerance to chronic administration on Cannabis sativa (Marihuana) in rats . Pharmacology 1:135-142, 1968;.
2 +
McMillan DE, Dewey WL, Harris LS:  Characteristics of tetrahydrocannabinol tolerance . Ann NY Acad Sci 191:83-96, 1971;.
3 +
Melges FT, et al:  Marihuana and temporal disintegration . Science 168:1118-1120, 1970;.
4 +
Melges FT, et al:  Temporal disintegration and depersonalization during marihuana intoxication . Arch Gen Psychiatry 23:204-210, 1970;.
5 +
Melges FT, et al:  Marihuana and the temporal span of awareness . Arch Gen Psychiatry 24:564-567, 1971;.
6 +
Clark LD, Hughes R, Nakashima EN:  Behavioral effects of marihuana . Arch Gen Psychiatry 23:193-198, 1970;.
7 +
Conrad DG, Elsmor TF, Sodetz FJ:  Delta-9-tetrahydrocannabinol: Dose related effects on timed behavior in chimpanzee . Science 175:547-550, 1972;.
8 +
Hollister LE, Richards RK, Gillespie HK:  Comparison of tetrahydrocannabinol and synhexyl in man . Clin Pharmacol Ther 9:783-791, 1968;.
9 +
Waskow IE, et al:  Psychological effects of tetrahydrocannabinol . Arch Gen Psychiatry 22:97-107, 1970;.
10 +
Renault PF, et al:  Marihuana: Standardized smoke administration and dose effect curves on heart rate in humans . Science 174:589-591, 1971;.
11 +
Kiplinger GF, et al:  Dose-response analysis of tetrahydrocannabinol in man . Clin Pharmacol Ther 12:650-657, 1971;.
12 +
Uhlenhuth KR, et al:  Drug, doctor's verbal attitude and clinic setting in the symptomatic response to pharmacotherapy . Psychopharmacologia 9:392-418, 1966;.
13 +
Clyde DJ: Clyde Mood Scale Manual . Coral Gables, Fla, University of Miami, Biometrics Laboratory, 1963;.
14 +
McNair DM, Lorr M:  An analysis of mood in neurotics . J Abnorm Soc Psychol 69:620-627, 1964;.
15 +
Nowlis V:  Research with the mood adjective checklist , in Tompkins SS, Izard CE (eds): Affect, Cognition and Personality . New York, Springer Publishing Co, 1965;, pp 352-389.
16 +
Matingly D:  A simple fluorometric method for estimating 11-hydrocorticoids in human plasma . J Clin Pathol 15:374-379, 1962;.
17 +
Rosalki SB:  An improved procedure for serum creatine phosphokinase determination . J Lab Clin Med 69:696-705, 1967;.
18 +
Lemberger L, et al:  Delta 9-tetrahydrocannabinol metabolism and disposition in long term smokers . Science 173:72-73, 1971;.
19 +
Freedman DX, et al:  Tolerance to the behavioral effects of LSD-25 in rat . J Pharmacol Exp Ther 143:309, 1964;.
20 +
Weil AT:  Clinical and psychological effects of marihuana in man . Science 162:1234-1242, 1968;.
21 +
Schuster CR, Dockens WS, Wooks JH:  Behavioral variables affecting the development of amphetamine tolerance . Psychopharmacologia 9:170-182, 1966;.
22 +
Marihuana: A signal of misunderstanding, in the First Report of the National Commission on Marihuana and Drug Abuse, Appendix 1. Government Printing Office, Superintendent of Documents, 1972.

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