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; 2006-2011; most recently renewed 2011-2016) of which I was Director and Principal Investigator till 2011 when R. Heaton became PI; currently I direct the Coordinating Core of the HNRC, funded through 2021.
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. I transferred the PI from myself to multiple PIs David Moore and Cristian Achim in 2014 when I accepted the position as Chair of the UCSD Department of Psychiatry.
In 2002 we were awarded the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) contract from NIMH and NINDS. Funding for the original CHARTER ended in 2015; a new award, with Robert Heaton as PI, and myself as a co-investigator, is extending the CHARTER work into exploration of age X HIV interactions on brain and behavior. Funded as R01 2015-2020.
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 2019).
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 2007-2013; 2014-2019 with I. Grant and B. Mausbach as multiple PIs).
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 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. Currently the CMCR is conducting a number of studies on both therapeutic potentials (e.g., with pain, autism, tremor) and potential risks of medicinal cannabis.