Acute Effects of Cannabis on Cognition and Mobility in Older HIV-infected and HIV-Un-infected Women
Acute Effects of Cannabis on Cognition and Mobility in Older HIV-infected and HIV-Un-infected Women
The purpose of this study is to try to understand and explain why HIV-infected and uninfected
 women who use cannabis (marijuana) currently, or have used cannabis in the past, have higher
 risk of having experienced a fall in our earlier analyses in WIHS. This study will compare
 what happens when women are given cannabis compared with placebo, on measures of mobility,
 including walking speed under walking conditions that vary in terms of difficulty; for
 example normal walking and walking while reciting alternate letters of the alphabet, as well
 as measures of balance and cognition (for example attention, memory).
Cannabis is the most prevalent drug used by adults aged 50 and older in the U.S., after
 alcohol and tobacco. Recent trends show dramatic increases in cannabis use among older U.S.
 adults, and rising cannabis tetrahydrocannabinol (THC) content. Cannabis intoxication acutely
 alters short-term memory, attention span, verbal fluency, reaction time, and psychomotor
 control. Heavy long term cannabis use has been associated with lasting impairments in verbal
 learning, memory, and attention that correlate with duration of use; however, other studies
 have found that cognitive deficits from cannabis are reversible and related to recent
 exposure. But studies on cannabis exposure and cognition are age limited by including only
 adolescents through middle-aged adults; effects of acute and long-term cannabis use on
 cognition among older adults are virtually unknown. Given the rising potency and increasing
 frequency of cannabis use among older adults, studies systematically examining the risks and
 benefits of cannabis use in older adults are urgently needed.

 Cannabis use is particularly common in people living with HIV (PLWH), with 12- 56% prevalence
 rates compared to 9.5% in the general U.S. population. HIV has detrimental effects on both
 mobility and cognition, and similar to normal aging, mobility in patients with HIV may be
 influenced by cognitive function. Mild-to-moderate neurocognitive impairments (NCI), notably
 in attention and executive functions, remain highly prevalent and persist despite suppressive
 antiretroviral therapy, affecting almost half of PLWH. Little is known about the combined
 effects of cannabis use and HIV infection on cognition and mobility, particularly among older
 individuals. As the population of older PLWH continues to grow, co-occurring aging and HIV
 related declines in cognition and mobility will coincide; the effects of continued cannabis
 use In the Women's Interagency HIV Study (WIHS), it was found that current cannabis use was
 associated with over double the odds of single fall, and over 2.5 times the odds of multiple
 falls in 6 months; past cannabis use was associated with over 1.5 greater odds of single fall
 and multiple falls. Preliminary data shows that 40% of WIHS women (mean age 48) reported at
 least one fall over 2 years; current cannabis users had 1.7 times greater fall risk among
 HIV+ but not HIV-women. The hypothesis is that falls are related to acute effects of cannabis
 on attention and mobility, and that given subtle, pre-existing deficits associated with HIV
 infection, these acute cannabis effects may be more pronounced in HIV+ women, placing them at
 increased risks of falls. Whether this observed fall risk associated with cannabis use
 represents acute effects, or persistent effects of past cannabis use on cognition, balance,
 or mobility, or whether adverse effects of cannabis differ by HIV status merits further study
 in this aging population.

 The "Walking While Talking" (WWT) test requires individuals to walk while performing a
 secondary attention-demanding task (dual task), has been used to assess the interactions
 between cognition and gait, and provides a framework for evaluating the effect of divided
 attention, a facet of executive functions, on mobility. Increased dual task costs measured
 using WWT may help unmask subtle and latent cognitive abnormalities before they become
 clinically apparent by increasing the complexity of the walking condition, and predict falls,
 frailty, disability, and mortality among older community-residing adults. Because both
 cannabis use and HIV have been implicated in impairments in attention and executive
 functions, the WWT may be a quick and simple mobility stress test to identify subtle
 cognitive and motor effects of acute cannabis administration as a function of HIV status.

 The objective is to explore the mechanisms that underlie the increased fall risk associated
 with cannabis use. The effects of controlled administration of active (7.0% THC) and inactive
 (0.0%) cannabis in aging HIV+ women on stable HAART and HIV- controls enrolled on the WIHS
 will be compared. Endpoints will be balance, mobility, and cognition, including a
 cognitive-motor divided attention task (WWT). Specific aims and hypotheses are:

 1. To determine the acute effects of cannabis on balance and mobility among older HIV+ and
 HIV- women. These test will be performed within subject comparisons of performance on
 balance and mobility tests at two supervised visits, with administration of placebo vs.
 active cannabis in counter-balanced order. The hypothesis is that HIV+ women will have
 greater impairment on balance and mobility, especially on complex walking conditions
 that demand attention, with administration of active cannabis than HIV- women

 2. To determine the acute effects of cannabis on cognition among older HIV+ and HIV-
 women.HIV+ women will have greater impairment on cognitive testing, especially in
 attention, with administration of active cannabis than HIV- women.
Inclusion Criteria:

 1. current cannabis use (within 6 months) based on self-report

 2. able to perform study procedures, including ability to ambulate independently

 3. adequate hearing and vision

 4. for HIV+ women use of stable HAART for at least 6 months.

 Exclusion Criteria:

 1. pregnancy

 2. current illicit drug use other than cannabis

 3. request for substance use treatment

 4. current parole or probation

 5. recent history of significant violent behavior (within 12 months)

 6. major current Axis I psychopathology (e.g.,bipolar disorder, suicide risk,
 schizophrenia)

 7. current use of psychiatric medication known to influence cognition

 8. significant uncontrolled medical illness (such as uncontrolled diabetes or
 hypertension, clinically significant laboratory abnormalities, liver function tests
 (LFTs)>3x upper limit of normal)

 9. history of active heart disease within 12 months

 10. history of dementia

 11. severe hand tremor

 12. history of Central Nervous System (CNS) diseases or injury

 13. poor English fluency.

 All participants will be consented and compensated for their effort as approved by the
 Institutional Review Boards (IRBs) of each participating institution (see human subjects).