Nicotine for Marijuana Withdrawal

The aim of this proposal is to accurately assess the effects of TNP on MJ withdrawal
symptoms across 15 days of biochemically confirmed MJ abstinence using a placebo-controlled,
double-blind, randomly assigned treatment design, while closely monitoring any potential
adverse effects, including changes in nicotine use and dependence.

To achieve these goals, 116 carefully screened cannabis-dependent individuals (58 female)
will be randomly assigned to one of two doses (0 mg or 7mg nicotine) of TNP (transdermal
nicotine patch) while they abstain from MJ for 15 days. Subjects will be administered a
follow-up phone interview 30 days after the termination of treatment to assess the effects
of nicotine-patch treatment on: 1) frequency of nicotine and tobacco smoking intake, 2)
FTND-assessed nicotine dependence, 3) new use of nicotine during the time since completion
of the study, and 4) marijuana and other drug use patterns. Large financial contingencies
will be used to provide a high degree of abstinence and study completion. This will be the
first adequately powered study to assess the effects of TNP on MJ negative affect-related
withdrawal symptoms and urges to use MJ. Withdrawal patterns and abstinence will be assessed
in two groups of MJ-dependent individuals: 1) those who rarely or never smoke tobacco, and
2) those who smoke four or fewer tobacco cigarettes per day (very-light tobacco smokers). A
stratified randomization method will be used to control for gender and tobacco-smoker
status. It is hypothesized that MJ withdrawal symptoms will be less severe in the group
assigned to the 7 mg patch than in the group assigned to the placebo. It is also
hypothesized that individuals high in anxiety/neuroticism and those high in
aggression/hostility will exhibit greater benefits from TNP than those low in these traits.
Given that no gender differences were observed in our preliminary study, gender differences
are not predicted. The over-the-counter availability, minimal abuse risks, and minimal
adverse side-effects associated with TNP would make it an ideal and highly implementable
treatment for MJ dependence if it can be demonstrated to be efficacious in reducing MJ
withdrawal symptoms.

Inclusion Criteria: Female and male cannabis-dependent MJ smokers aged 18 years or older
will be recruited. Inclusion criteria include cannabis dependence as assessed by a
DSM-IV-based structured interview and MJ use on 10-28 occasions per week and be willing to
abstain for 15 days. Only individuals who are in good mental and physical health, with a
BMI of 17-30 kg/m2, as verified by health questionnaires and the Structured Clinical
Interview for DSM-IV (SCID), will participate in this study. Potential subjects will be
asked to indicate, on a scale of 1-10, how strong they currently want to quit smoking MJ
(from "1" = "not at all" to "10" = "very strong") and will also be assessed with the
four-item MJ Stages of Change. Additionally, subjects will fulfill one of two criteria: 1)
not smoke or use other tobacco products or 2) smoke tobacco cigarettes or use other
nicotine delivery systems (e.g., hookah, cigars, chewing tobacco) fewer than 5 times per
day (on average) for the past year. Current use of MJ and tobacco will be verified by
detectable urine THC and nicotine metabolites. All subjects will be required to provide
four pre-quit baseline urine samples. The mean creatinine-normalized THC concentration
across these samples must be of 175 ng/ml or greater based. -

Exclusion Criteria:

Criteria include meeting DSM-IV criteria for current abuse or dependence on a substance
other than MJ, nicotine, or caffeine, using psychoactive substances (other than MJ,
alcohol, nicotine, & caffeine) 6+ times/month, testing positive for stimulants,
antidepressants, anxiolytics, and/or opiates (10-panel urine drug test), testing above a
salivary cotinine concentration of 150 ng/ml during the initial screening, using
creatinine or creatinine-containing supplements, testing positive for adulteration of
urine samples, consuming more than 6 alcoholic drinks per day continuously for a month,
mental disorders including bipolar disorder, schizophrenia, psychotic symptoms, currently,
recently, or ever chronically at significant suicidal risk or experiencing violent
thoughts or current major depression. Others that will be excluded include women who are
pregnant, lactating, not taking precautions to avoid pregnancy, individuals with
significant physical disorders or unstable physical disorders that may represent a severe
untreated condition, such as hypertension, as well as those with less than a high school
education or equivalent, primary language other than English, and those with significant
cognitive impairment.