The proposed studies will determine the clinical significance of marijuana withdrawal among daily marijuana smokers in their usual living environments. Although marijuana withdrawal has been observed in non- humans and in human inpatient studies, the absence of generalizable has been observed in assessment of its clinical relevance as evidenced by the omission of Cannabis Withdrawal in DSM-IV. Three outpatient studies will determine (a) the physical, behavioral, and emotional symptoms that occur following the withdrawal syndrome; and (d) the initial efficacy of an agonist therapy for relieving such withdrawal. Study 1 will use a within-subject ABAB design (A: smoking-as-usual; B. marijuana-abstinence) to examine the clinical significance and reliability of symptoms that occur during the first 3 days of cessation from daily severity of marijuana withdrawal to symptoms experienced by psychiatric outpatients and to withdrawal observed in studies of other substances. Study 2 will examine the time-course of marijuana withdrawal. An incentive-based intervention will be used to engender a 45-day abstinence period in daily marijuana users. Interactive Voice Response technology will be used to obtain daily assessments of self-reported and observer- rated signs and symptoms of withdrawal. A comparison group of former daily marijuana smokers will be used to help interpret whether the post- cessation effects are true, time-limited withdrawal or simply offset effects. Study 3B will utilize a modified Latin Square design to examine the pharmacological specificity of marijuana withdrawal and provide initial information on a potential agonist therapy. Daily smokers will participate in three cessation conditions: high dose dronabinol (oral THC), low dose dronabinol, and placebo. This study will determine if delta9-THC can relieve the symptoms of withdrawal. The doses to be used in Study 3B will be determined in Study 3A, a preliminary, inpatient dose runup study. These studies will be the first outpatient studies to systematically describe and validate the specific signs and symptoms of marijuana withdrawal. This information will be vital to deciding whether marijuana withdrawal should be included in the DSM, should be a focus on treatment, and should be further studied to examine its role in marijuana relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012471-03
Application #
6475995
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Khalsa, Jagjitsingh H
Project Start
1999-12-15
Project End
2003-09-14
Budget Start
2001-12-01
Budget End
2003-09-14
Support Year
3
Fiscal Year
2002
Total Cost
$246,883
Indirect Cost
Name
University of Vermont & St Agric College
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
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Budney, Alan J; Hughes, John R (2006) The cannabis withdrawal syndrome. Curr Opin Psychiatry 19:233-8

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