Acute Effects of Cannabis on Cognition and Mobility in Older HIV-infected and HIV-Un-infected Women
Condition: HIV; AIDS; Aging
MeSH terms: Marijuana Abuse
Study type: Interventional
Phase: Phase 2

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Cannabis; Placebo
Intervention type(s): Drug; Other
Intervention description(s): 7% delta9-THC cigarettes will be smoked by 'light the cigarette' (30 sec), 'get ready' (5 sec), 'inhale' (5 sec), 'hold smoke in lungs' (10 sec) and 'exhale.' Participants will smoke 3 puffs in this manner, with a 40-sec interval between each puff.; 0% THC cigarettes will be administered to HIV negative women. Participants will be instructed to 'light the cigarette' (30 sec), 'get ready' (5 sec), 'inhale' (5 sec), 'hold smoke in lungs' (10 sec) and 'exhale.' Participants will smoke 3 puffs in this manner, with a 40-sec interval between each puff.
Other intervention name(s): Cannabis administered to HIV+ and HIV- women; Placebo administered to HIV+ and HIV- women
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants will receive either cannabis or placebo on 1st visit and the opposite on the 2nd visit.
Masking: Double (Participant, Care Provider)
Primary purpose: Other
Keywords: mobility; cognition; WIHS