Brief 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).
Brief Title
Acute Effects of Cannabis on Cognition and Mobility in Older HIV-infected and HIV-Un-infected Women
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.
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.
Completion Date
Completion Date Type
Actual
Conditions
HIV
AIDS
Aging
Eligibility Criteria
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).
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).
Inclusion Criteria
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.
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.
Gender
Female
Gender Based
false
Keywords
mobility
cognition
WIHS
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
40 Years
NCT Id
NCT03633721
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2018-9188
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Acute Effects of Cannabis on Cognition and Mobility in Older HIV-infected and Uninfected Women
Primary Outcomes
Outcome Description
Mobility will be tested using the timed gait test. Gait speed is measured under normal walking and attention demanding measures.
Outcome Measure
Acute effects of cannabis on mobility
Outcome Time Frame
Change in mobility as a function of timed gait from before cannabis to after cannabis which is the average of the 15 minute and 60 minute result.
Outcome Description
Balance will be tested using functional reach test. Functional reach measures the distance the subject can reach in front of her from a standing position without losing balance.
Outcome Measure
Acute effects of cannabis on balance
Outcome Time Frame
The change in functional reach (in centimeters) will be measured from time 1 (30 minutes prior to cannabis) to the average of times 2 and 3 (15 min and 60 after cannabis)
Outcome Description
Cognition will be tested using the number of correct suppressions on the sustained Attention to Response Task (SART). The hypothesis is that following active cannabis administration, HIV+ women will perform worse than HIV- women on cognitive testing of attention. The groups will not differ following inactive cannabis administration.
Outcome Measure
Acute effects of cannabis on cognition
Outcome Time Frame
The change on the Sustained Attention to Response Task (number of correct suppressions) will be measured from time 1 (30 minutes prior to cannabis) to the average of times 2 and 3 (15 min and 60 after cannabis)
Secondary Ids
Secondary Id
R21AG059505-01
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
40
Investigators
Investigator Type
Principal Investigator
Investigator Name
Anjali Sharma
Investigator Email
anjali.sharma@einsteinmed.org