The Donahoe laboratory has worked in the area of neuroimmune pharmacology for 27 years. Most of this effort has been directed at understanding how drugs of abuse affect immune functions and the course of infectious diseases. The principle drug-class studied over the years has been opiates, but cocaine, alcohol and marijuana (cannabinoids) have also been of interest, especially when these various drugs are present or used conjunctively, as often occurs in settings of street addiction. These studies have assessed the neuroimmune consequences of drug exposure in various aspects: human clinical aspects where drug addicts are studied, effects in nonhuman primates (rhesus macaques) exposed to morphine as a model of human addiction, and various in vitro cell culture systems that serve as models of in vivo (i.e., in the animal or human host) circumstances. The principle infection studied by these various means has been that caused by Human Immunodeficiency Virus-1 (HIV) or its close relative in monkeys, the Simian Immunodeficiency Virus (SIV). Alterations in immune parameters as well as neural parameters caused by opiates in the context of infection with AIDS viruses have been studied from virological, immunological and host-pathological perspectives.

Among the main accomplishments of these endeavors over the years has been the demonstration that morphine, in vitro, in cell culture, alters the immune properties of circulating blood cells called T-cell lymphocytes (T-cells) which are elemental to proper immune functioning, especially against HIV-SIV/AIDS. In fact it is the T-cell that is the primary target of AIDS viruses. Furthermore, clinical data from the study of opiate addicts showed that T-cells were also functionally altered by opiates. Moreover, it was shown that such effects could be countered when an addict co-abuses cocaine and/or alcohol. This latter finding is important since street addicts seldom abuse one drug alone even though they may well have a preferential drug of choice. Consequently, the finding of counter effects between various drugs highlighted a major difficulty in studying drug effects using subjects who are street addicts. That is, the singular effects of the many drugs frequently found in drug abuse are very difficult to separate. This finding led to the use of the monkey model where opiates could be administered in a controlled fashion, by themselves. Also, the use of the monkey model opened the door for controlled study of opiate effects in SIV/AIDS as a model of the human AIDS syndrome—-an important model since human addicts that inject drugs comprise about a third of the subjects who contract AIDS in western societies.

Studying monkeys made dependent on morphine and infected with SIV led to some unexpected (at the time) findings—-that is, that a well-maintained opiate dependency actually retards progression of SIV to AIDS. Through continued study of this phenomenon, it has been concluded that the likely cause for the ability of opiates to protect monkeys against progression of AIDS virus infections is attributable to various factors. One seems to be the virus type used. Our studies used a fairly slowly growing SIV (SIVsmm9). Other subsequent studies with monkeys that have used more virulent virus strains have found that opiates exacerbate AIDS progression. Another factor is stress and the way that opiates are administered. We and others have found that low stress environments slow progression of AIDS relative to high-stress environments. It seems that our well-controlled administration of opiates in our monkeys reduced their stress levels which could help in reducing the AIDS progression rate. Interestingly, since we found that opiates may slow AIDS progression under certain circumstances in the monkey model, others have found similar findings with human heroin addicts whose dependencies to opiates are reasonably well maintained; and still others have shown that similar viral infections in cats, pigs and mice can be retarded by well-maintained opiate exposures. Studies on these phenomena and their neuroimmune basis continue.