HIV Studies
In collaboration with UCSD and VA investigators in Psychiatry, Medicine, Neurosciences, Radiology, Pediatrics, and Pathology, I am examining neuropsychological, neuroradiological, neurological, psychiatric, and neuropathological change in persons with HIV infection. I am collaborating with UCSD AIDS Study Group investigators on other studies of experimental treatments of HIV infection. The work is supported by an NIMH Center Grant (San Diego HIV Neurobehavioral Research Center: HNRC, 1989-1995; 2000-2005; most recently renewed 2006-2011) of which I am Director and Principal Investigator.

I also direct the California NeuroAIDS Tissue Network (CNTN). The CNTN was established with NIMH funding (current period 2003-2008; renewed 2008-2013) to maintain a bank of neurologic and other tissues gathered from well characterized persons who died from AIDS, and to make such tissues and data available for research nationally.

In 2002 we were awarded the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) contract from NIMH and NINDS. I am Director and Principal Investigator of this six-center 8 year study.

Methamphetamine and HIV
In 1999 we began evaluating the possible combined effects of methamphetamine abuse and HIV infection on brain function (NIDA Program Project "NeuroAIDS: Effects of Methamphetamine" funded 1999-2004). In the current phase of our research we are also looking at the added effects of hepatitis C virus (NIDA Program Project "NeuroAIDS: Effects of Methamphetamine and HCV" funded 2005-2010).

In 2009 we were awarded a P50 NIDA Center of Excellence (Translational Methamphetamine AIDS Research Center [TMARC]) to continue examining the interactions between drug abuse and HIV on CNS outcomes, and the implications for therapy and prevention, using laboratory, preclinical animal, and human models (funded through 2014).

Alcohol and the Brain
From 1976-1979 I was principal investigator of a V.A. funded prospective study of younger alcoholics. The results suggested surprising intactness in late thirties alcoholics, but with early evidence of very subtle dysfunction. Since 1980 I have been examining a broader age range of recently detoxified and long-term abstinent alcoholics with a view to unraveling the relationships of drinking, abstinence, and aging to neuropsychologic outcome (VA funded 1980-1983; renewed, 1983-1988; 1988-1993; 1993-1998).

Additional neuropsychological studies have been conducted in collaboration with N. Butters as part of the VA Alcoholism Center (M. Schuckit, M.D., P.I., funded 1984-1989), and studies on MRI change in alcoholics in collaboration with Nelson Butters and Terry Jernigan. New studies are ongoing relating neuropsychological performance to proton NMR spectroscopic and MRI structural brain changes (VA funded 1998-2003, renewed 2003-2008, I. Grant, P.I., and G. Brown, M.J. Taylor, co-investigators).

Alzheimer Caregiving and Alzheimer's Disease
We are exploring medical, psychological, neuroendocrinological and neuroimmunological consequences to the caregiver of the stress of looking after a patient with Alzheimer's Disease (NIMH funded 1988-1991; renewed again, 1992-1997; with T. Patterson, M. Irwin and R. Hauger); renewed with funding from NIA 1997-2001, to study cardiovascular reactivity and respite effects in caregivers, with T. Patterson, J. Dimsdale, M. Ziegler, P. Mills, R. Sloan, L. Pearlin.

The most recent work focuses on physiologic and molecular changes in caregiving stress with an emphasis on factors that may predict vulnerability to cardiovascular disease and stroke. These include sympathoadrenal medullary mediated alterations in expression of cellular adhesion molecules and hemostasis factors (with T. Patterson, J. Dimsdale, P. Mills, S. Ancoli-Israel, M. Ziegler; NIA funded 2001-2006; renewed 2007-2012).

We are also exploring the impact of psychosocial stress, including expressed emotion, on relapse and remission in elderly psychotic patients (with Tom Patterson, Ph.D.; funded as part of Dilip Jeste's Geropsychiatry Research Center, 1992-1996); renewed with Tom Patterson as core director, 1996-2001.

In collaboration with R. Katzman and N. Butters, and more recently with L. Thal, I have been a co-investigator in the NIA-funded Alzheimer's Disease Research Center (funded 1984-1989, renewed 1989-1994, renewed again 1994-1999; 1999-2004). I have been particularly involved in examining the prevalence of affective, psychotic, and alcohol disorders preceding development of Alzheimer's disease.

Cannabis Studies
As Director of the University of California Center for Medicinal Cannabis Research, I oversee clinical trials exploring the possible utility of cannabis compounds in the amelioration of certain severe manifestations of disease. Our current study, "A Randomized, Cross-Over Controlled Trial of Dronabinol and Vaporized Cannabis in Neuropathic Low Back Pain", aims to demonstrate analgesic response to oral and/or inhaled cannabis in patients with neuropathic low back pain. In 2016, we were authorized by the California Legislature (Assembly Bill 266, the Medical Marijuana Regulation and Safety Act) to help with detection of driving under the influence of cannabis.