Charles A. Haertzen

Development of Scales Based on Patterns of Drug Effects, Using the Addiction Research Center Inventory (ARCI):

A series of scales were developed on the basis of the pattern of change of responses on Addiction Research Center Inventory items produced by drugs including morphine, pentobarbital, chlorpromazine, alcohol, LSD, pyrahexyl, and amphetamine in post addicts. The pattern scales were compared with empirically developed scales that measure the effects of each drug as contrasted with placebo. It was found that the empirical scales show a greater sensitivity to general or non-specific drug effects than pattern scales, i.e., all drugs in the series produced significant elevations on empirical scales. Because of this characteristic, less differentiation between drugs is possible with empirical scales. On scales which reflect patterns of drug actions, greater differentiation between drugs was shown. Higher doses produced more specific drug effects than lower doses. This difference was produced probably by a relatively greater contribution of non-specific drug effects for lower doses. Significant reliability coefficients were obtained for all scales. Reliability of scales across conditions was related to the type of scale and similarity of conditions. As indicated by several findings, condition-similarity has implications for relating personality to drug effects.

THE ADDICTION RESEARCH CENTER INVENTORY: STANDARDIZATION OF SCALES WHICH EVALUATE SUBJECTIVE EFFECTS OF MORPHINE, AMPHETAMINE, PENTOBARBITAL, ALCOHOL, LSD-25, PYRAHEXYL AND CHLORPROMAZINE.

SummaryThe ARCI, a 550-item inventory for assessing subjective drug effects and personality characteristics, was standardized using former addict subjects on a number of drug conditions. The inventory was administered under “no-drug” and placebo, and various doses of morphine, pentobarbital, chlorpromazine, LSD-25, amphetamine, pyrahexyl, and alcohol. By means of item analysis, cross-validity and other initial comparisons, items were chosen to comprise each drug scale that discriminated the particular drug from placebo; the (no-drug)-placebo comparison also produced a tentative placebo scale. Since non-significant differences were found when scoring each of the drug scales separately on the nodrug and placebo conditions, these data were combined for standardizing all scales. Validity generalization, dose-effect, and retest studies showed that the drug scales possessed a high degree of validity and reliability. In contrast, the placebo scale lost discrimination entirely in the validity generalization group. Because of the very considerable number of item comprising the scales, only examples were presented. Subjective effects of the various drugs were discussed in terms of specific and general, non-specific actions and patterns of these alterations.

Development of the Addiction Research Center Inventory (ARCI): Selection of items that are sensitive to the effects of various drugs

SummaryA “custom-built” inventory for assessing subjective effects of drugs, the Addiction Research Center Inventory (ARCI), was developed from the use of “sentence completion” and other association techniques on male subjects under drug and no-drug conditions. In addition to demonstrated “drug-sentitive” questions, the final form of the inventory (550 “true-false” items) also contains items which may delineate to some extent schizoid and “psychopathic” characteristics. The format is similar to that of the MMPI and the content has a fairly wide range. Initial use indicates that the inventory is effective in differentiating various subjective effects of drugs and in discriminating some similarities and differences of naturally occurring and experimentally induced behavioral abnormalities. Results also indicate that the effectiveness of specially designed tests, whether in the form of complete sentences or adjective check lists, chiefly depends upon assessment of the “activitysedation” continuum and allied changes in motivation, alterations in mood such as in a “euphoria-dysphoric” continuum, alterations in sensation and perception, and in reportable physiological processes.

Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Center Inventory (ARCI)

The subjective effects of two doses of cyclazocine (0.6 mg and 1.2 mg/70 kg), nalorphine (16 and 32 mg/70 kg), no-drug and placebo were compared with 32 opiate addicts using drug sensitive scales of the Addiction Research Center Inventory (ARCI) items. The effects of these narcotic antagonists were highly similar on ARCI scales and items. Both drugs produced a general drug effect, difficulty in focusing eyes, physical weakness, tiredness, poor motivation, moodiness, misery, anxiety, tension, hallucinations, changes in sensation and perception, and inefficiency of physical, cognitive and social functions. Cyclazocine was 15–26 times more potent than nalorphine. The effects of cyclazocine and nalorphine were differentiated from the effects of other drugs such as morphine, pentobarbital and LSD when the overall pattern of effect was considered.

THE ADDICTION RESEARCH CENTER INVENTORY: APPENDIX. I. ITEMS COMPRISING EMPIRICAL SCALES FOR SEVEN DRUGS. II. ITEMS WHICH DO NOT DIFFERENTIATE PLACEBO FROM ANY DRUG CONDITION.

SummaryThe present listing of items of the Addiction Research Center Inventory (ARCI) is presented as an appendix to papers that describe the development and initial use of this instrument which was devised for assessing subjective effects of drugs. All items are classified according to their effectiveness in discriminating various drug effects from the placebo condition. The drugs used were morphine, amphetamine, pentobarbital, alcohol, LSD-25, pyrahexyl and chlorpromazine. Two types of scales, developed for each of these conditions separately are presented for each drug under the following headings: 1. Significant scales, composed of items that maintained discrimination at the 0.05 level in two groups of 50 subjects each; 2. Marginally significant scales, composed of additional items for whichP=0.05 or less in the total sample of 100 Ss; 3. Nondifferentiating items that did not discriminate between placebo and any of the drugs reported upon here. Inspection of these items, answers to which were not changed by drugs, shows a rather striking difference from the “scale-items.” When the former are classified for content (Table 2, p. 164,Haertzen et al. 1963) it is seen that questions concerning attitudes toward individuals and institutions, and questions on philosophy of life including hostilities of various sorts are not generally in the significantly altered category. In contrast, items that are sensitive to drug effects are very frequently questions on sensations, perception, bodily symptoms, moods, drives, attitudes toward taking the test and motivations. With regard to future work, some anticipated analyses were mentioned in the previous paper which will involve the study of “pattern effects” and other procedures for isolating specificity as well as generality of drug actions.

Simulation of gambling responses on the Addiction Research Center Inventory.

Abstract The present study investigated possible commonalities between compulsive gambling and abuse of psychoactive drugs. Nineteen volunteers with histories of compulsive gambling were tested twice using the Addiction Research Center Inventory (ARCI): Once answering items as they felt at the time of the test, the other simulating how they felt while winning at gambling. The main findings were that, as measured on the ARCI, “simulated winning at gambling” produced a euphoria similar to the euphoria induced by the psychoactive drugs of abuse, particularly psychomotor stimulants; secondly, that as a group, the pathological gamblers, demonstrated elevated psychopathy scale scores similar to psychopathy scores found among persons with histories of drug dependence.

REVIEW OF THE EFFECTS IN MAN OF MARIJUANA AND TETRAHYDROCANNABINOLS ON SUBJECTIVE STATE AND PHYSIOLOGIC FUNCTIONING

A number of tetrahydrocannabinols and related compounds have been studied in man for activity at the Addiction Research Center. Three of these cannabinoids have been shown to produce effects in man, and one aspect of these studies has been the delineation of those pharmacologic effects that relate to the abuse potential of tetrahydrocannabinols and Cannabis. This presentation will review these studies and will focus principally on the subjective states induced by these tetrahydrocannabinols as they relate to the abuse potential of Cannabis and tetrahydrocannabinols. Two compounds that are active in man are homologs originally derived by Adams and his coworkers from d,l-synthetic tetrahydrocannabinol (THC) .14 These two homologs are the n-hexyl derivative known as synhexyl or pyrahexyl, and the dimethylheptyl derivative (DMHP), also known as CA-101 or SKF-5350 (FIGURE 1). These two homologs differ in potency both in animals and man. Loewe4 found that pyrahexyl in the dog ataxia test was approximately 1%-2 times as potent, and DMHP about 500 times as potent as d,l-synthetic THC. Although the dhynthetic THC was utilized as the reference standard by Loewe4 in his dog ataxia test, d,l-synthetic THC was only 1/13th as potent as the best natural preparations of THC. Utilizing total dosages of 1 .O-5.0 mg administered orally (approximately 10-70 pg/kg), Isbel15 found that DMHP elicited marijuana-like identifications and symptoms in experienced marijuana users in the lower dose ranges. Larger doses of DMPH produced psychotic reactions. Outstanding characteristics of the effects of DMHP in man, in addition to its potency, are relatively long duration of action, marked sedative effects, and postural hypotension associated with tachycardia. Himmelsbach and collaboratorss studied the abuse potentiality of pyrahexyl and found that 60-240 mg intramuscularly (i.m.) or 60 mg orally of pyrahexyl did not suppress the morphine abstinence syndrome in subjects undergoing morphine withdrawal, although affect was flattened and restlessness was reduced. Himmelsbach also found that 60 mg of pyrahexyl administered orally produced significant Cannabis-like effects, whereas the same dose of i.m. pyrahexyl produced little or no effect. Williams and his collaborators7 studied the effects. of chronically administered pyrahexyl to determine if marijuana-like compounds produced physical dependence. Pyrahexyl was administered orally for 26-31 days with doses and intervals between doses chosen by the subjects. Total daily doses ranged from 60-2,400 mg. Briefly, they reported that subjects were initially euphoric, had increased appetites, swollen eyelids, and spontaneous laughter, but demonstrated no gross ataxia. After several days, a general lassitude and carelessness in personal appearance and untidiness of the subjects were observed. Subjects reported that the drug was similar to but stronger than marijuana, and stated they preferred marijuana cigarettes to pyrahexyl. Tolerance

Development of a “Psychopathic“ Scale for the Addiction Research Center Inventory (ARCI)

An empirical psychopathic deviate scale (Pyp) for the Addiction Research Center Inventory (ARCI) was developed with 785 subjects by selecting items which differentiated presumed psychopathic (criminals, opiate addicts and alcoholics) and nonpsychopathic groups (mentally ill and normal). The scale, consisting of 74 items, highly distinguished the psychopathic and nonpsychopathic groups and was significantly correlated with three independent measures of social deviation. Criminals and addicts were most socially deviant, alcoholics were intermediate, and normal subjects were the least deviant. Better overall differentiation of pertinent groups is obtained with the Pyp scale than with other commonly used standard tests such as the MMPI, CPI, 16 P. F., and GZTS. It is thought that the psychopathic factor is a minor personality factor which accounts for only a small proportion of variability of responses to inventory questions which have negative social implications.

Manual for Alcoholic Scales of the Inventory of Habits and Attitudes (IHA)

Scales designed to show individual differences in alcoholics and differences between alcoholics and other groups were developed by factor analytic and empirical methods using personaliry, demographic, and alcohol experience items from the Inventory of Habits and Attitudes (IHA). IHA was constructed by Monroe and Hill as a matched form of their Personal Inventory (PI). PI was designed to measure characteristics of opiate addicts, especially Acceptability for Psychotherapy (AP). Several studies have indicated the utility of AP. A Language of Addiction and General Alcoholic Scale differentiated alcoholics from opiate addicts, mentally ill, and normal Ss by 3 SDs. The factor strucrure of scales was similar in boch alcoholics and nonalcoholics.

Reaction time (“mental set”) in control and chronic schizophrenic subjects and in postaddicts under placebo, LSD-25, morphine, pentobarbital and amphetamine

Summary1.Auditory-manual reaction times, 2, 3.5, 5, 10 and 20 sec after flashing of a “warning” light, both on “irregular” and “regular” schedules of preparatory intervals, were measured under “no medication” conditions in 10 personnel control and 13 chronic schizophrenic subjects, as well as in “postaddicts” after administration of placebo, LSD-25, morphine, pentobarbital or amphetamine.2.Each subject was tested twice under each condition (no medication, placebo or drug) on different days, once with the “irregular” procedure preceding the “regular,” and again in the reverse order. Comparisons of the effects of treatment (placebo or drugs) on mean reaction times of “postaddicts” with mean reaction times of personnel controls and schizophrenic subjects were based on the “combined order” data (average of the two “irregular” and the two “regular” data under each condition).3.Compared with personnel controls, mean reaction times of chronic schizophrenic subjects were significantly longer, variance due to difference in procedure (“irregular” or “regular”) was significantly smaller, and shortest reaction times tended to occur at the 3.5 sec interval (rather than at the 2 sec interval).4.In the “postaddict” group under the placebo condition, mean reaction times on the “irregular” procedure were shorter than in the personnel control group, with consequent reduction of variance due to difference in procedure. At a dose level of 1.0 mcg/kg, LSD-25 prolonged reaction times on the “irregular” procedure, thereby “normalizing” the relationships between the “irregular” and “regular” curves.5.LSD-25 at the dose level of 2.0–3.0 mcg/kg, morphine (15 and 30 mg), and pentobarbital (250 mg) all prolonged reaction times significantly and produced a trend for occurrence of shortest reaction times at the 3.5 sec interval on the “regular” procedure. While these treatments did not affect reaction times on the “irregular” and “regular” procedures differentially, indirect evidence suggests that they did impair the ability of “postaddicts” to profit from regularization of the presentation of preparatory intervals. Amphetamine had no effect except to shorten reaction times to some extent.6.It is concluded that LSD-25 (2.0–3.0 mcg/kg), morphine and pentobarbital produce changes in “mental set” qualitatively similar to that which characterizes patients with schizophrenia, but that the nature of such impairment is not specific for schizophrenia, except possibly in degree.