| Eligibility |
- INCLUSION CRITERIA:
All participants must:
1. Be between the ages of 18-60. Assessment tool(s): Edinburgh Handedness Inventory.
Although left-handed individuals will not be excluded, we will track handedness.
Justification: Some of the neural processes assessed in this protocol may be
lateralized in the brain. In order to assess potential variance, participants
handedness will be documented.
2. Be in good health. Justification: Many illnesses may alter fMRI signals as well as
cognitive processes and neural functioning. Assessment tool(s): Participants will
provide a brief health history during phone screening, and undergo a medical history
and physical examination with a qualified IRP clinician.
3. Be free of active DSM-IV dependence, on alcohol or any drug except nicotine. Past
active dependence is acceptable provided it is at least two years in the past. Those
with past dependence on substances other than alcohol or marijuana may not have any
current use (past 6 months) of the substance on which they were dependent. Individuals
with past dependence on either alcohol or marijuana who report current use of the
previously dependent substance may be included, provided they do not currently meet
any criteria for dependence, with the exception of tolerance. MAI may exclude on a
case-by-case basis for heavy alcohol or drug use not meeting dependence criteria but
likely to interfere with data quality. Justification: Dependence on other substances
(drugs or alcohol) may result in unique CNS deficits that could confound results and
introduce excessive variance. Assessment tool(s): The SCID and/or the Mini
International Neuropsychiatric Interview (M.I.N.I) and clinical substance
abuse/dependence assessment. While recreational/intermittent use of alcohol and/or
marijuana will be tolerated in all participant groups, individuals will be excluded if
they meet current or recent (within 2 years) DSM-IV diagnostic criteria for dependence
on any substances. A positive drug test for marijuana will not be exclusionary as long
as participants have not used in the 24hrs preceding the imaging visits. In the event
of a positive drug test for marijuana, self-reports of current marijuana use will be
used to differentiate intermittent/infrequent from chronic/frequent users.
4. Be able to abstain from alcohol 24hrs before each of the imaging sessions and able to
abstain from caffeine 24hrs before each session. Justification: Alcohol and caffeine
modulate neural functioning in a way that would complicate data interpretation.
Assessment tool(s): Self-report and breathalyzer.
5. For the treatment and non-treatment seeking groups, must have a urine cotinine level
corresponding to smoker/nicotine user status for the specific test being used
(typically corresponding to a urine cotinine above about 200 ng/ml) and have been
smoking or vaping consistently for at least the past year (excluding quit attempts).
Based on the correlation between self-reported cpd/FTND and urine cotinine levels
[85a, 85b], a single inclusion criterion will be easier to manage and provide adequate
characterization of nicotine dependent participants. Urine cotinine level provides a
biomarker that does not rely on self-report/memory. Quit attempts will be assessed via
clinical interview and judgment. Justification: The present protocol is interested in
neurobiological mechanisms that underlie nicotine dependence-induced plasticity and is
thus contingent on the presence of nicotine dependence. Assessment tool(s):
Self-report, commercial urine cotinine test corresponding to smoker/nicotine user
status for the specific test being used, typically corresponding to a urine cotinine
above about 200 ng/ml.
6. For the treatment and non-treatment seeking groups, must be willing to attempt an
acute abstinence period lasting approximately 48 hours.
7. For the treatment seeking group, be actively seeking treatment for nicotine cessation
and willing to engage in 12-weeks of treatment involving weekly counseling sessions,
as well as follow-up imaging and behavioral assessments following treatment onset.
8. For the ex-smoker group, must have smoked approximately 8 or more cigarettes per day
for at least 1 year, and have remained abstinent continuously for at least the last 12
months. Justification: While serum cotinine level has been shown to be a more accurate
measure of cigarette smoking than CPD [85c], it is impossible in the current design to
collect retroactive serum cotinine levels from exsmokers. Instead, CPD must be equated
with the urine cotinine levels of current treatment and nontreatment seeking groups.
The low-end cotinine level for the inclusion of smokers/vapers in this protocol is
about 200 ng/mL. In adult smokers, a nicotine intake of approximately 1 mg can be
estimated from a blood cotinine level of 12.5 ng/mL) [85d]. Thus, to have achieved a
blood cotinine level of 200ng/mL, ex-smokers would have to self-report consumption of
16 mg of nicotine per day which equates to approximately 8 CPD (0.36-2.62 mg nicotine
yield per cigarette [85e]. Given these calculations, the inclusion criterion for the
ex-smoker group has been lowered to 8 CPD. Assessment tool(s): Self-report, commercial
urine cotinine test corresponding to non-smoker status for the specific test being
used, typically corresponding to a urine cotinine under about 20 ng/ml, CO < 6.
9. For the non-smoking/vaping control group, less than 20 times of lifetime use of
nicotine containing products and vaping of non-nicotine containing products, none in
past year and no history of daily nicotine use. Justification: Minimal nicotine
exposure in the control group is required to assess differences between controls and
the nicotine groups. Assessment tool(s): Self-report, commercial urine cotinine test
corresponding to non-smoker status for the specific test being used, typically
corresponding to a urine cotinine under about 20 ng/ml, CO < 6.
EXCLUSION CRITERIA:
3.3 Exclusion criteria:
Participants will be excluded if they:
1. are not suitable to undergo an fMRI experiment due to certain implanted devices
(cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical
clips or other implanted metal parts), body morphology, or claustrophobia.
Justification: MR scanning is one of the primary measurement tools used in the
protocol. Assessment tool(s): Prospective participants will fill out an MRI screening
questionnaire and undergo an interview with an MR technologist. Questions concerning
suitability for scanning will be referred to the MR Medical Safety Officer.
Prospective participants will be questioned about symptoms of claustrophobia and
placed in the mock scanner during their first visit to assess for possible difficulty
tolerating the confinement of the scanner and for ability to fit into the scanner.
2. have coagulopathies, history of, current superficial, or deep vein thrombosis,
musculoskeletal
abnormalities restricting an individual s ability to lie flat for extended periods of
time. Justification: MR scanning sessions require participants to lie flat on their
backs and remain perfectly still for approximately two hours. Therefore, conditions
that would make that difficult (e.g. chronic back pain, significant scoliosis) or
dangerous (e.g. familial hypercoagulability syndrome, history of thrombosis) will be
exclusionary. Assessment tool(s): History and physical examination by a qualified IRP
clinician, supplemented with a trial of lying in the mock scanner to assess comfort
issues.
3. have HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous
system (CNS) sequelae, thus introducing unnecessary variability into the data.
Assessment tool(s): Oral HIV blood test if oral test is + and STS+ without adequate
prior treatment
4. regularly use any prescription (e.g., benzodiazepines, antipsychotics,
anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal
medication (e.g., Kava, Gingko biloba, St. John s wort) that may alter CNS function,
cardiovascular function, or neuronal-vascular coupling. Antidepressant use will be
allowed if an individual is on a stable dose of an SSRI or SNRI for ~6 weeks. As
needed, benzodiazepine use is also allowed, but the individual must test negative for
benzodiazepines on the drug screen. Justification: The use of some medications may
alter the fMRI signal and/or neural functions of interest in the current study.
Consistent antidepressant use or infrequent use of benzodiazepines is unlikely to
drive study-related changes in brain function. Allowing such medication use will also
make it possible to study nicotine dependent individuals who continue to smoke despite
receiving treatment for a mood disorder. Assessment tool(s): History and comprehensive
urine drug screening to detect antidepressants, benzodiazepines, antipsychotics,
anticonvulsants, and barbiturates.
5. have any current neurological illnesses including, but not limited to, seizure
disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement
disorders, history of significant head trauma, or CNS tumor. Justification:
Neurological diseases alter CNS function and, possibly, the neuronalvascular coupling
that forms the basis of the fMRI signal. Assessment tool(s): History and physical
examination by a qualified IRP clinician, urine drug screening for anticonvulsants not
disclosed by history. History of head trauma with loss of consciousness of more than
30 minutes or with postconcussive sequelae lasting more than two days, regardless of
loss of consciousness, will be exclusionary. The MAI who will also retain discretion
to exclude based on a history of neurological illness that may compromise data
integrity.
6. Have current major psychiatric disorders to include, but not limited to psychotic
disorders, or substance-induced psychiatric disorders, or risk of suicide or currently
on antipsychotic medication treatment. Individuals with current major depressive
disorder (MDD) and related anxiety will be allowed if currently stable, as assessed by
the MAI. The MAI will reserve the right to exclude on the basis of psychiatric history
not explicitly described in this criterion. Justification: Psychiatric disorders
involve the central neural system (CNS) and, therefore, can be expected to alter the
fMRI measures being used in this study. However, mood disorders such as MDD are highly
comorbid with nicotine dependence. Including this population will generate results
that are more representative of nicotine dependent individuals. Assessment tool(s):
Computerized SCID or M.I.N.I., Beck Depression Inventory, Beck Anxiety Inventory,
Adult ADHD Self-Report Scales and clinical interview confirmation by clinician.
7. Are cognitively impaired or learning disabled. Justification: Cognitive impairment and
learning disabilities may be associated with altered brain functioning in regions
recruited during laboratory task performance. Cognitive impairment may affect one s
ability to give informed consent. Assessment tool(s): History examination and
validated IQ test, such as the Wechsler Abbreviated Scale of Intelligence (WASI) or
Shipley-2. IQ estimate must be 80 or over.
8. have significant cardiovascular, cerebrovascular, or respiratory conditions.
Justification: Such conditions may alter blood flow, the fMRI signal and other
autonomic signals, and increase risks associated with nicotine patch and/or
e-cigarette use. Assessment tool(s): History and physical exam, including 12-lead EKG.
9. have any other major medical condition that in the view of the investigators would
compromise the safety of an individual during participation. Justification: Many
illnesses not explicitly covered here may increase risk or alter important outcome
measures. Assessment tool(s): History and physical examination by a qualified IRP
clinician and CBC, urinalysis, NIDA chemistry panel (liver function tests,
electrolytes, kidney function). The following lab values will result in exclusion from
the study:
i. Hemoglobin < 10 g/dl
ii. White Blood Cell Count < 2400/ l
iii. Liver Function Tests > 3X normal
iv. Serum glucose > 200 mg/dl
v. Urine protein > 2+
vi. Serum creatinine > 2 mg/dl
vii. Estimated creatinine clearance <60ml/min
The MAI will retain discretion to exclude based on less extreme lab results. After the
screening process has been completed, the MAI will take into account all data
collected in order to decide if there is an existing medical illness that would
compromise participation in this research.
10. are pregnant, planning to become pregnant, or breastfeeding. Females are instructed in
the consent to use effective forms of birth control during the study period.
Justification: study procedures and drugs used in the current protocol may complicate
pregnancy or be transferred to nursing children. Assessment tool(s): Urine and/or
serum pregnancy tests, and clinical interview. Urine pregnancy tests will also be
conducted at the beginning of each imaging visit.
11. Are non-English speaking. Justification: To include non-English speakers, we would
have to translate the consent and other study documents and hire and train bilingual
staff, which would require resources that we do not have and could not justify, given
the small sample size for each experiment. Additionally, the data integrity of some of
the cognitive tasks and standardized questionnaires used in this study would be
compromised as they have only been validated in English. Most importantly, ongoing
communication regarding safety procedures is necessary when participants are
undergoing MRI procedures. The inability to effectively communicate MRI safety
procedures in a language other than English could compromise the safety of non-English
speaking participants. Assessment tool(s): self-report....
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