Workshop

Introduction

This workshop was planned, organized and conducted by Walter Royal, M.D., visiting neurologist from Johns Hopkins University School of Medicine, Baltimore, Jag H. Khalsa, Ph.D., Center on AIDS and Other Medical Consequences of Drug Abuse (CAMCODA), and Henry Francis, Director, CAMCODA, both within the National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH). A group of nationally and internationally recognized neuroscientists/neurologists presented/discussed (i) current data on metabolic complications in the CNS of HIV-infected or AIDS patients using drugs of abuse; (ii) in-vitro tests and in-vivo models for the study of interactions-effects on P450 and other metabolic pathways; (iii) pharmacokinetic/pharmacodynamic aspects of drug action; (iv) the problems of design and conducting such studies in clinical populations; and (v) developing new drugs for the treatment of AIDS and drug addiction. Finally, they made recommendations for future research.

Since many investigators presented new and unpublished data, it was agreed that the abstracts could be placed on the NIDA's web site and only a brief executive summary should be published in a professional journal.

Agenda

Abstracts

Participants

Future Research

The workshop participants recommended the following research on: "Metabolic Disorders in the Pathogenesis of Nervous System Damage in HIV-Infected Drug Abusers."

Research areas:

1. Development of a brief Neuro-AIDS Clinical Rating Scale that combines assessments that can identify abnormalities which can occur specifically secondary to drug use (e.g. motor abnormalities that result from basal ganglia involvement) with tests that are useful for identifying abnormalities that also occur in other risk groups.

2. Development of drug user cohorts that reflect regional differences in drug use patterns and behavior, realizing that these factors may potentially change over time.

3. Support infrastructure for making animals available which are needed for performing in vivo and in vitro studies of SIV infection.

4. Development of surrogate markers for nervous system involvement in drug users. This would include techniques such as MR spectroscopy.

5. Identification of common and unique immunologic and pathologic mechanisms that are important in the pathogenesis of HIV related neurologic disease in drug users.

6. Drug development.

7. Elucidate neurotransmitter abnormalities.

8. Examine neuroendocrine effects (HPA, autonomic disturbances).

9. Examine the role of oxidative stress.

10. Modulation of viral replication in brain by drugs of abuse.

11. Examine neuroimmune mechanisms.

12. Determine the effects of age, gender, ethnicity and genetics on the risk of developing neurologic complications and on the course of the nervous system disease.

The following specific projects were recommended:

1. Effects of estrogen on risk of developing cognitive impairment and motor dysfunction.

2. Examine evidence for illicit drug-induced mutagenesis in brain cells.

3. Interactive effects of drug use and HIV infection on apoptotic pathways in the CNS.

4. In vivo effects of drugs of abuse on the blood-brain barrier and CNS immune responses in humans and primates.

5. Effects of neuroprotective compounds (e.g. cyclophilins) in animal models and humans.

6. Studies of regional localization of virus in brains from drug users.

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