Journal of Substance Abuse Treatment, Vol. 6, pp. 71-73, 1989 Printed in the USA. All rights reserved.

0740-5472/89 $3.00 + Ml Copyright 0 1989 Pergamon Press plc

REPORTS FROM ADAMHA *

MODELS DEVELOPED FOR STUDYING are refining their animal model to study a full range ALCOHOL AND AGGRESSIVE BEHAVIOR of natural and functional defense-anxiety patterns

It has been shown in many criminological, sociologi- cal, and psychological studies that alcohol consump- tion often enhances aggressive behavior. However, the interaction between alcohol and aggression is com- plex, varying among individuals, sexes, cultural and social groups, and their functional settings. Under- standing the interaction requires experimental models

associated with alcohol use. Further research is expected to generate new knowledge on the role of social stress in individual differences in ethanol drink- ing. The findings are reported in Physiology and Behavior, 1986, Vol. 38, and Pharmacology, Bio- chemistry and Behavior, in press.

that consider these variables and permit quantitative evaluation of various aspects of aggressive behavior. FINDINGS SUPPORT DRUG TREATMENT

NIAAA grantee Dr. Robert Blanchard, and co- FOR BORDERLINE PERSONALITY DISORDER

workers at the University of Hawaii at Honolulu, have successfully designed and utilized a set of such

In one of the first studies to provide empirical evidence

models for studying changes in aggressive behavior for the use of pharmacotherapy in the management of

following alcohol consumption. borderline personality disorder (BPD), NIMH in-

Their findings indicate that aggressiveness responses tramural scientists compared the efficacy of four dif-

to alcohol depend not only on dose of alcohol, but ferent psychoactive medications in 16 women with this

also on pre-alcohol level of aggressiveness. diagnosis. The medications represent the classes of

The aggression models are based on what the inves- drugs believed to be effective in patients with this dis-

tigators call “ethoexperimental analysis;” namely, the order. Results of this double-blind study showed that

analysis of changes in natural behaviors of animals in two of the drugs had clear-cut beneficial effects on the

relevant experimental situations. patients, while responses to the other two drugs were

Using this approach, Blanchard’s group has found less positive.

that while very high doses (1.2-1.8 g/kg) of ethanol Although clinicians frequently prescribe psychoac-

decreased attacks, low and intermediate doses (0.6 tive medications for this disorder, until now they have

g/kg or less) potentiated aggression. However, this had little or no scientific rationale for choosing spe-

effect was observed only in rats showing low to mod- cific drugs.

erate levels of aggressiveness before alcohol. For BPD is an easily identified illness, but its biologi-

example, the high aggressive group tended to show cal mechanisms are poorly understood. The disorder

less aggression, while nonaggressive groups showed no is characterized by sudden mood changes, unstable

aggression under any ethanol dose. Similarly, some personal relationships, and other unpredictable pat-

humans remain nonaggressive after alcohol consump- terns of behavior. Patients also may exhibit a number

tion while others are consistently aggressive or hostile. of affective symptoms (such as depression, anxiety,

The investigators also found that in colony studies, and rage), brief psychotic episodes, or self-injurious

the target of attacks switched from other males to behavior. The heterogenous nature of BPD has re-

group females, particularly familiar females, with sulted in the use of a wide range of medications.

increasing alcohol dose. The alcohol-enhanced aggres- In the study the four drugs-alprazolam (an anti-

sion was not associated with increased sexual activity, anxiety drug), carbamazepine (an anti-convulsant drug),

however. This animal model may provide useful infor- trifluoperazine hydrochloride (a neuroleptic), and

mation applicable to spouse abuse, which is strongly tranylcypromine sulfate (an MAO anti-depressant) -

associated with alcohol consumption. were compared to a placebo. They were given in con-

Thus far, the results point to a potentially power- secutive 6-week trials to the 16 severely ill patients.

ful model which will shed light on mechanisms of The investigators, Dr. Rex Cowdry and Dr. David

emotional behaviors and their pharmacological mod- Gardner, found that carbamazepine and tranylcy-

ification by drugs such as alcohol. The investigators promine brought about statistically significant im- provement in the mood and behavior of the patients. Trifluoperazine proved effective in some women if

*Alcohol, Drug Abuse, and Mental Health Administration, Wash- taken for the full trial period. However, many pa- ington, D.C. tients could not tolerate this drug because of side

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effects. The researchers also found that alprazolam worsened behavior in most patients, although two patients reported that alprazolam helped them more than any of the other medications. There was no improvement when patients took the placebo.

The scientists note several limitations of their study. The relatively homogeneous population was small and did not include patients with less severe BPD or patients with prominent schizotypal symp-

toms. Therefore, the current findings may not be generalizable to other BPD patient subgroups. In ad- dition, although the short-term pharmacotherapy used in this study benefitted the patients, the question of long-term drug treatment was not addressed. The investigators also pointed out that the drugs tested in this pilot study have strong side effects, necessitating close and careful supervision by the physician, as well as a high level of patient involvement in the treatment

course. Nonetheless, the researchers believe that their study

provides needed evidence for the use of pharmaco- therapy for BPD. Drug treatment can reduce some of the negative symptoms of the disorder, such as un- relieved dysphoria and impulsive acting-out, and may allow patients more opportunity to benefit from on-

going psychotherapy. Finally, there is reason to believe that different

aspects of BPD may respond differently to specific drugs, suggesting to the investigators that knowledge about the pattern of drug responses may ultimately help to uncover clues to the underlying mechanisms of the disorder. The study results were published in the February 1988 Archives of General Psychiatry.

“JOINTS” RISKIER THAN CIGARETTES

The regular use of 1 to 3 marijuana joints produces

approximately the same lung damage and potential cancer risk as smoking 5 times as many cigarettes, partly because the two substances are smoked differ- ently, according to research by Drs. Tzu Chin Wu and Donald Tashkin, NIDA grantees, at the University of California at Los Angeles (UCLA).

The scientists wanted to find the reason why, as they reported in an earlier study, people who habitu- ally use only a few marijuana joints show health effects similar to those who smoke a pack or more of cigarettes daily. Included among these problems are bronchitis and damage to the airways in the lungs.

The answers provided by their new study, pub- lished in the February 1988 issue of the New England Journal of Medicine, suggest that the way smokers inhale marijuana in addition to its chemical composi- tion increases the adverse physical effects. These find- ings, says Tashkin, refute the argument that marijuana

Reports from ADAMHA

is safer than tobacco because users only smoke a few joints a day.

The study found that a “take” of marijuana delivers three times more tar to the mouth and lungs than a puff of a filter-tipped tobacco cigarette. It also deposits one-third more tar in the throat and lungs and increases the carbon monoxide levels in the blood by 4 to 5 times.

Users inhale more marijuana smoke, retaining it in the lung four times longer than tobacco, thereby intensifying the physical effects of the marijuana, according to Tashkin and his colleagues. During the lengthened period the smoke stays in the lung, grav- ity causes more particles of tar to settle out and blood vessels to absorb more carbon monoxide.

Wu and coworkers developed a sophisticated new device to trap tar and measure characteristics of smok- ing behavior as subjects smoked joints or cigarettes. It recorded volume of air inhaled, puff duration, and intervals between puffs. At the same time, an instru- ment circling the subject’s rib cage measured physical effects such as total volume of inhaled air and heart

rate. Blood tests determined the uptake of carbon monoxide. Previous studies of smoking dynamics used machines to simulate human smoking behaviors rather than studying actual smokers.

Subjects were tested smoking their own brands of tobacco, a marijuana joint, and a placebo cigarette containing marijuana from which the “high” produc- ing chemical had been removed. The same cancer- causing substances found in tobacco smoke have been found in both types of marijuana smoke. Therefore, Tashkin says, the well-known lung cancer risks of tobacco also apply to marijuana users, even though they smoke far fewer joints than the typical tobacco cigarette smoker. The results “justify concern over smoking only a few marijuana cigarettes a day,” he says.

GUIDELINES FOR DRUG TESTING

Mandatory Guidelines for Federal Drug Testing Pro-

grams, which prescribe procedures and standards for conducting drug testing of Federal employees, were published in the Federal Register April 11, 1988.

The Guidelines establish comprehensive standards and procedures for all aspects of drug testing, includ- ing procedures for collecting urine specimens, the drugs employees may be tested for, and eligibility standards for certifying laboratories engaged in drug testing for Federal agencies.

The Guidelines were developed in accordance with Executive Order 12564, Drug-Free Federal Work- place, issued by the President September 15, 1986, and Public Law 100-71, which establish requirements

Reports from ADAMHA 73

for Federal agencies and employees in order to obtain a drug-free Federal workplace.

The Mandatory Guidelines incorporate both the

Scientific and Technical Guidelines for Federal Drug Testing Programs first released by HHS in February 1987, and the proposed Standards for Certification of

Laboratories Engaged in Urine Drug Testing. In ac- cord with PL 100-71, the Guidelines and Standards were published in the Federal Register August 14, 1987. Comments on the proposed Guidelines and Standards were received from approximately 150 indi- viduals, organizations and Federal agencies. The com- ments were reviewed and considered in developing the final Mandatory Guidelines.

Highlights of the Mandatory Guidelines include:

DRUGS TO BE TESTED-The Guidelines require Federal drug testing programs to test, at a minimum, for marijuana and cocaine and also authorize testing for opiates, amphetamines, and phencyclidine (PCP). When conducting tests based on reasonable suspicion,

accident or unsafe practice, an agency may test for any drug listed in Schedule I or II of the Controlled Substances Act.

SPECIMEN COLLECTION PROCEDURES- The Guidelines specify procedures for collecting urine specimens to ensure privacy of employees, unless the agency has reason to believe that an individual may alter or substitute the specimen to be provided.

LABORATORY ANALYSIS PROCEDURES- The Guidelines specify standards which require the use of the best available technology for ensuring the full reliability and accuracy of drug tests and strict procedures governing the chain of custody of speci- mens collected for drug testing. When an initial screening test shows the presence of illegal drugs, the Guidelines require a confirmatory test of a specimen

using gas chromatography/mass spectrometry tech-

niques. Results will be reported as positive only when both the initial and confirmatory tests are positive.

LABORATORY CERTIFICATION-The Guide- lines establish criteria for certification and revocation of certification of laboratories performing drug test- ing and appropriate standards and procedures for periodic review of laboratories. Certification stan-

dards are included to ensure that laboratories engaged in Federal employee drug testing achieve maximum accuracy of test results to protect the rights of the Federal employees being tested.

HANDLING TEST RESULTS -The Guidelines also require each agency to have a physician with knowledge of substance abuse disorders to serve as a Medical Review Officer (MRO). The MRO will review all positive test results with the employee to determine whether alternative medical factors could account for the result. This review must occur prior to the trans- mission of results to agency administrative officials. If alternative medical factors are found by the MRO to be the cause of a positive test result, this test would

be reported as negative. The Guidelines require that employees with positive test results be referred by the MRO to the Employee Assistance Program.

The Guidelines do not apply to drug testing under any legal authority other than Executive Order 12564 and do not apply to testing of military service personnel or applicants to the military.

NIDA’s Office of Workplace Initiatives was delegated the responsibility for developing the guide- lines. Dr. J. Michael Walsh, Office Director, credited the Secretary for strong support of the scientific and technical guidelines and of the laboratory certifica- tion standards. “We expect that these standards will have a broad impact on the quality of the labora- tories offering drug testing services in this country,”

he said.