Drug Impairment Reviews: Opiates and Minor Tranquilizers


STUDY: Gordon, N.B. Reaction Times of Methadone-Treated Heroin Addicts. Psychopharmacologia, 16:337-344. 1970.

Site: Rockefeller University and Yeshiva University, New York City, New York.

Subjects: The subjects were divided into six groups. Groups 1 and 3 both had been maintained for at least 1 year on methadone for the treatment of heroin addiction. Group 1 had 18 males whose average age was 32.5 years; group 3 had 9 females whose average age was 33.5 years. Group 2 consisted of 20 unpaid male volunteers who did not use drugs; they averaged 32.5 years. The participants in groups 4 and 5 had recently withdrawn from narcotic drugs. The 20 males in group 4 averaged 31.5 years and had withdrawn 14 days earlier. The 19 males in group 5 averaged 30 years and had withdrawn 4 days earlier. Group 6 consisted of 9 females whose average age was 23 years. They were paid volunteers from the nonprofessional hospital staff, and did not use drugs.

Method: Measurements were taken under controlled laboratory conditions; urines were tested (details were not given) for drugs to assure conformity to group. Variations of reaction time were tested in a button-pressing situation: (a) simple reaction time (one of six stimuli); (b) multiple discrimination/multiple response (one of six stimuli for one of six responses); (c) multiple discrimination/single response (one of six discrimination presented in random spatial and temporal order, with single response). A diagram of the instrument used was provided. The digit 1 readout was sequestered from the subject and a noise level was introduced to obscure instrumental sounds which might be used by the subject to his advantage.

Dosage: Subject group 1 (males) received 100 mg of methadone per subject per day for a year or more. Subject group 5 was composed of females, who also received 100 mg of methadone per subject per day for a year or more. The other subject groups received no drugs: group 2 had males who were not drug users; group 3 had persons withdrawn from drugs for 14 days; group 4 had males withdrawn from drugs 4 days prior to testing; and group 6 had females who were not drug users – paid volunteers from nonprofessional hospital staff.

Results: The subjects receiving methadone had shorter reaction times an did the others to the tests administered. The results were statistically significant except in the cases of the 4-day and 14-day detoxified groups.

Comment: The findings would be much more significant if, following the original observations, closed- and/or open-course driving tests had been made along with simulator tests such as tracking, tests involving divided attention, etc.

STUDY: Kiplinger, G.F., G. Sokol, and B.E. Rodda. Effect of Combined Alcohol and Propoxyphene on Human Performance. Arch. Int. Pharmacodyn., 212:175-180. 1974.

Site: Lilly Laboratory for Clinical Research, Marion County General Hospital and Indiana University School of Medicine, Indianapolis, Indiana.

Subjects: Eight medical and graduate students and others participated and were paid for their services. Essentially no information was provided regarding sex, age, size, driving history, and their general state of health and lifestyle was self-assessed.

Method: Subjects were asked to refrain from taking CNS-affectant drugs (except for tobacco) for 24 hours prior to testing. The purpose of the tests was explained to them and they fasted for 6 hours prior to drug administration. Combinations of alcohol, propoxyphene, and control placebos were administered in four treatment sequences that followed a randomized block design; each subject received all treatments in the course of the experiments. Testers used double-blind technique under controlled laboratory conditions. Parameters of measurement included: (a) four pursuit meter patterns (); (b) four conditions of standing stability (); and nine verbal tests ().

Dosage: Mixed in an iced pineapple-grapefruit beverage, alcohol was given at 15 ml ethanol per 50 lb body weight, a dose designed to produce a concentration of about 0.05% v/v in 60 minutes when 30 minutes was taken for ingestion. The alcohol placebo was iced beverage alone. Subjects received propoxyphene as a 65-mg capsule, its placebo being starch and talc. The capsule was swallowed at the start of each experiment so that the peak plasma concentration could be expected to occur during the experimental period.

Results: The data were statistically evaluated. Very little difference was found between the modest impairing effects of ethanol and those of propoxyphene at the doses given. Dosage with both drugs produced moderate additive impairments. There was no evidence for interaction.

Comment: It would have helped to have studied doses considered “abuse” quantities. Also, closed-course driving might have yielded more evidence of significant impairments.

STUDY: Linnoila, M., and M.J. Mattila: Drug Interaction on Psychomotor Skills Related to Driving: Diazepam and Alcohol Europ. J. Clin. Pharmacol., 5:186-194. 1973.

STUDY: Landauer, A.A., G. Milner, and J. Patman. Alcohol and Amitriptyline Effects on Skills Belated to Driving Behavior, Science, 163:1467-1468. 1969.

STUDY: Clayton, A.B., T.A. Betts, and G.M. Mackay. A Study of the Effects of Certain Tranquilizers and Small Amounts of Alcohol on Driving Performance European J. Toxicol., 5:254-257. 1972.

STUDY: Betts, T.A., A.B. Clayton, and G.M. Mackay. Effects of Four Commonly Used Tranquilizers on Low Speed Driving Performance Tests Brit. Med. J., 4:580-584. 1972.

STUDY: Patman, J., A.A. Landauer, and G. Milner. The Combined Effect of Alcohol and Amitriptyline on Skills Similar to Motor Car Driving. Medical J. of Australia, 2:946-949. 1969.

Site: Department of Psychology, University of Western Australia and Claremont Hospital, Nedlands, Western Australia.

Subjects: Subjects were healthy volunteers over 21 years of age – 12 men and 12 women whose mean age was 26.0 (S.D. about 6.0). They did not show histories of illnesses and were not on medication.

Method: Measurements were taken under controlled laboratory conditions, using double-blind techniques; results were evaluated by statistical analysis of variance. The subjects were divided into four equal groups and the individuals completed a battery of psycho-motor tests on three consecutive mornings. Groups 1 and 2 were given the active drug and groups 3 and 4 received a placebo. The effects of alcohol were tested by giving groups 1 and 3 alcohol at the second testing session (fourth day of drug administration) and placebo alcohol at the third session (fifth day of drug administration). Groups 2 and 4 received their placebo alcohol at the second testing session and alcohol at the third testing session. The testing sessions for each subject were on the third, fourth, and fifth days of medication. Testing sessions involving alcohol were given to half the subjects on the fourth day and the other half on the fifth day.

The tasks consisted of a short clerical test (ACER, 1967); a dot tracking test; a pursuit rotor test; and a simulated driving test. The latter three are described in the other Landauer et al. study reviewed earlier in this report.

Dosage: Each subject received tablets every day for five days. The tablets for groups 1 and 2 were amitriptyline; those for groups 3 and 4 were placebo. On day 1, the dosage was two tablets. Subjects each received four tablets, spaced, on days 2, 3, and 4. On day 5, the dosage was again two tablets. In addition, each group was given both alcohol and placebo: group 1 – alcohol on day 4, placebo on day 5; group 2 – placebo on day 4, alcohol on day 5; group 3 – alcohol on day 4, placebo on day 5; and group 4 -placebo on day 4, alcohol on day 5.

Results: Amitriptyline caused no effects on performance. Some decrement of performance was found due to alcohol in the pursuit rotor and simulated driving tests. No evidence for interaction with amitriptyline was found.

Comment: The findings support earlier ones that impairment from Interaction of alcohol with amitriptyline is more apt to be observed during the first 2 days of administration, and that the impairment decreases with time. It would have been worthwhile to have had data in which the alcohol and drug doses were increased to “abuse” quantities, to see if their interaction persisted.

STUDY: Huffman, W.J., A.E. Florio, J.L. Payne, and F.E. Bays. The Influence of Two Selected Tranquilizers on Driving Skills. Amer. J. Psychiatry, 119:885-886. 1963.

Site: Department of Health and Safety Education, University of nois, Urbana, Illinois.

Subjects: Twenty-five young adults participated – 15 men, with a mean age of 22.5 years, and 10 women, whose mean age was 20.5 years. They had normal health histories, possessed valid drivers licenses, and were familiarized with the test procedures.

Method: This study consisted of a controlled laboratory experiment and three driving tests, all double blind and counterbalanced in design. Each subject served as his own control. Hydroxyphenamate (“Listica”) and meprobamate were compared with a placebo. For Phase I, subjects were tested after “normal” doses of the two drugs vs. placebos. Phase II occurred when, after about a month, the subjects were again tested, this time with double the dosage of drugs.

Sixteen measurements were made on each subject on six separate occasions: the first two after placebo; the third after hydroxyphenamate, 200 mg; the fourth after hydroxyphenamate, 400 mg; the fifth after meprobamate, 400 mg; and the sixth after meprobamate, 800 mg.

Subjects were tested for (1) reaction time; (2) hand steadiness; (3) visual acuity (both eyes); (4) acuity, right eye; (5) acuity, left eye; (6) stereo (depth) perception; (7) color perception; (8) vertical deviation; (9) lateral deviation; (10) near visual acuity, both eyes; (11) near acuity, right eye; (12) near acuity, left eye; (13) near lateral deviation; (14) reaction time distance; (15) braking distance; and (16) total stopping distance. The last three tests involved use of an automobile. Data significance was assessed by means of t tests.

Dosage: The Phase I dosage was 200 mg of hydroxyphenamate and 400 mg of meprobamate; for Phase II, dosages doubled. The tablets were administered 1 hour before testing and tests were completed by 2 hours. (No interaction with alcohol was studied.)

Results: The 96 tests showed five significant effects. In Phase I, visual acuity of the right eye improved after hydroxyphenamate compared to placebo; visual acuity in the left eye improved after hydroxyphenamate compared to meprobamate. In Phase II, reaction time increased after meprobamate compared to placebo. Acuity (both eyes) diminished after hydroxyphenamate compared to placebo, and near acuity (both eyes) diminished after meprobamate compared with placebo.

Comment: The data seem clear-cut and are very simply presented, as compared to many other reports. The relevance of the 16 measurements to real-world driving, however, is questionable. In any event, one would surmise that in other tests of the effects of these two drugs at the two dosages given, there would not be much impairment.

STUDY: Landauer, A.A., and G. Milner. Desipramine and Imipramine Alone and Together with Alcohol in Relation to Driving Safety Pharmacopsychiatric Neuropsychopharmakologia, 4:265-275. 1971.

STUDY: Linnoila, M., I. Saario, and M. Maki. Effect of Treatment With Diazenam or Lithium and Alcohol on Psychomotor Skills Related to Driving European J. of Clinical Pharm., 7:337-342. 1974.


Selections from the book: “Drugs and Driving”. Robert Willette, Ph.D., editor. State-of-the art review of current research on the effects of different drugs on performance impairment, particularly on driving. National Institute on Drug Abuse Research Monograph 11. March 1977.