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Trial registered on ANZCTR


Registration number
ACTRN12610000182099
Ethics application status
Approved
Date submitted
18/02/2010
Date registered
1/03/2010
Date last updated
23/05/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Double blind, randomised, placebo controlled trial of lithium carbonate for the management of cannabis withdrawal in adult humans
Scientific title
In cannabis dependent adults does lithium carbonate, compared to placebo, assist in the management of cannabis withdrawal?
Secondary ID [1] 1441 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cannabis dependence 256852 0
Condition category
Condition code
Mental Health 256998 256998 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This project aims to explore the safety and effectiveness of lithium carbonate in reducing the severity of withdrawal that often occurs on cessation of dependent cannabis use. The trial will utilise a double-blind, randomised, placebo controlled design. Participants will be admitted to an inpatient drug treatment unit for 7 days and will be randomly assigned to receive either lithium or placebo. Participants randomised to the treatment condition will be administered two capsules containing 250mg lithium carbonate twice a day (i.e., 1000mg per day) for 6 days.
Intervention code [1] 256044 0
Treatment: Drugs
Comparator / control treatment
Participants randomised to the placebo condition will be administered placebo medication on the same dosing schedule as participants in the treatment condition (i.e., two capsules twice a day for six days in inpatient setting). Placebo capsules will be an exact match to lithium capsules in terms of shape, size, colour and degree of opaqueness.
Control group
Placebo

Outcomes
Primary outcome [1] 257895 0
The efficacy of lithium carbonate compared to placebo in reducing the severity of cannabis withdrawal among dependent cannabis users abstaining from cannabis use.
Timepoint [1] 257895 0
Severity of cannabis withdrawal will be measured using a modified version on the Marijuana Withdrawal Checklist, a 32-item self-report measure with reference to previous 24 hours.
Primary outcome [2] 257896 0
Detoxification completion rates among participants randomised to lithium carbonate compared to placebo.
Timepoint [2] 257896 0
Treatment completion, defined as completing 7 days of inpatient treatment under protocol conditions (categorical yes/no); and number of days of inpatient treatment completed (range: 0-7).
Primary outcome [3] 257897 0
Comparison of adverse events (e.g., nausea, vomiting, loss of appetite, fatigue, diarrhea) during detoxification in the two randomised groups.
Timepoint [3] 257897 0
Adverse events during the inpatient treatment period. This will be assessed daily by a self-report adverse effects checklist administered by a clinician (developed for the previous open-label trial conducted by Winstock et al., 2009), and by clinician assessment. Serum lithium levels at day 4 and day 7 will determine whether trough serum lithium levels are in the therapeutic range (0.5-1.5 mmol/L) on day 4 and day 7.
Secondary outcome [1] 263346 0
Determine whether the provision of lithium carbonate for the management of cannabis withdrawal is associated with reduced levels of cannabis use during a 3-month follow-up period.
Timepoint [1] 263346 0
Self-reported cannabis use with total days used cannabis (range 0-90) and longest period of continuous abstinence (range 0-90) during the follow-up period. Cannabis use will be assessed at each follow-up point (days 14, 30 and 90 after discharge from inpatient unit) using the Timeline Followback Method (TLFB) (Sobell et al., 1996). Self-reported cannabis use will be corroborated with serial urinalysis of carboxy-tetrhydrocannabinol (THC): creatinine ratio using Gas Chromatography/Mass Spectrometry (GC/MS), saliva and blood tests at 30 and 90 day follow-up.
Secondary outcome [2] 263347 0
Examination of the potential role of oxytocin in mediating the effects of lithium on cannabis withdrawal.
Timepoint [2] 263347 0
In order to determine whether there is an association between lithium administration and oxytocin levels, plasma oxytocin levels will be assayed on day 1 (baseline), day 4 and day 7 of the inpatient admission.
Secondary outcome [3] 263348 0
Determine whether baseline patient characteristics (including demographics, substance use and psychosocial parameters) predict the severity of cannabis withdrawal and subsequent post-withdrawal outcomes (cannabis use, psychosocial outcomes, sleep disturbances and cannabis-related problems).
Timepoint [3] 263348 0
Self-reported measures of cannabis-related problems assessed at study entry and at each follow-up point (days 14, 30 and 90 after discharge for inpatient unit) using the Cannabis Problems Questionnaire (CPQ).
Secondary outcome [4] 263349 0
Determine the relationship between the attainment and maintenance of abstinence from cannabis and changes in measures of psychological functioning (assessed using the Depression, Anxiety, Stress Scale (DASS) 21, the Social Interaction Anxiety Scale (SAIS) and the Social and Occupational Functioning Assessment Scale), neuropsychological functioning (assessed using the Rey Auditory Verbal Learning Test, the Rey Complex Figure Test, the Trail Making Test, the Wechsler Test of Adult Reading, the Wechsler Memory Scale IV (WMS-IV) Logical Memory, Digit Span, and Spatial working memory using CANTAB), social cognition (assessed using Movie Stills Task and Reading the Mind in the Eyes), functioning and disability (assessed using the Short Form Health Survey (SF-12), World Health Organisation Disability Assessment Schedule II, and World Health Organisation Quality of Life) ? BREF, sleep disturbance (using the Athens Insomnia Scale), other substance use, and cannabis-related problems (using the CPQ).
Timepoint [4] 263349 0
Psychological and neuropsychological functioning, social cognition, functioning and disability, sleep disturbance, other substance use and cannabis-related problems will be measured on day 1 and day 7 of inpatient admission, and at 30- and 90 -day follow-up.
Secondary outcome [5] 263355 0
Determine whether certain single nucleotide polymorphisms (genetic variants) are over-represented in heavy cannabis users relative to the overall Australian population. This might include (but is not limited to) single-nucleotide polymorphisms (SNPs) in genes such as cannabinoid receptor 1, catechol-o-methy transferase and adenosine-triphosphate (ATP)-binding cassette (ABC) transporters.
Timepoint [5] 263355 0
Blood samples taken at study admission will be used to assess whether certain single nucleotide polymorphisms (genetic variants) are over-represented in heavy cannabis users relative to a normative sample collected at the Brain and Mind Institute, University of Sydney. This might include (but is not limited to) SNPs in genes such as cannabinoid receptor 1, catechol-o-methy transferase and ABC transporters.

Eligibility
Key inclusion criteria
* At least (=) 18 years of age.
* Meet Diagnostic Statistical Manual of Mental Disorders (DSM)-IV-TR criteria for cannabis dependence.
* Have identified withdrawal symptoms as a barrier to achieving abstinence from cannabis.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* People who are alcohol dependent. This will be assessed by clinical assessment
* People who use drugs other than cannabis, caffeine and tobacco more than twice weekly, or inject drugs more than once per week (on average) in the 30 days prior to recruitment.
* People on methadone or buprenorphine treatment for opioid dependence.
* People with documented lactose intolerance.
* People with a documented intolerance of lithium.
* People with a history of schizophrenia, bipolar affective disorder or recent psychosis (within preceding 3 months); or admission to mental health unit within the 3 months prior to recruitment.
* People assessed as being at significant risk of suicide.
* People with renal or thyroid function outside the normal range. People with severe liver disease (as identified by clinical assessment and liver function tests (Gamma Glutamyl Transpeptidase (GGT), Aspartate Transaminase (AST) and Alanine Transaminase (ALT) levels 3-fold above the normal range). This will be assessed prior to study entry.
* People with significant cardiovascular disease (myocardial infarction in past 6 months, cardiomyopathy, significant hypertension (> 180/120), major arrhythmias). Assessed clinically and by electrocardiography (ECG) in those >45 years of age.
* People with current prescriptions (within past month) for mood stabilising medications (e.g., Valproate and Carbamazepine).
* People with current prescriptions (within past month) for antidepressant and/or antipsychotic medications assessed as clinically unstable.
* Females who are breastfeeding or pregnant at recruitment (screened using blood test for human chorionic gonadotropin (hCG) in women of child bearing potential), or planning on becoming pregnant or not using adequate contraception in the month following study entry.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
12/04/2010
Actual
13/12/2010
Date of last participant enrolment
Anticipated
Actual
24/08/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256547 0
Government body
Name [1] 256547 0
NHMRC
Country [1] 256547 0
Australia
Primary sponsor type
University
Name
Brain & Mind Research Institute (BMRI), University of Sydney
Address
BMRI, University of Sydney
100 Mallett St
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 255874 0
None
Name [1] 255874 0
Address [1] 255874 0
Country [1] 255874 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258590 0
Sydeny South West Area Health Service (SSWAHS) Ethics Review Committee - Royal Prince Alfred Hospital (RHAH) Zone
Ethics committee address [1] 258590 0
Ethics committee country [1] 258590 0
Australia
Date submitted for ethics approval [1] 258590 0
Approval date [1] 258590 0
27/08/2009
Ethics approval number [1] 258590 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30682 0
A/Prof Nicholas Lintzeris
Address 30682 0
The Langton Centre
591 South Dowling Street
Surry Hills NSW 2010
Country 30682 0
Australia
Phone 30682 0
+ 61 2 9332 8777
Fax 30682 0
Email 30682 0
[email protected]
Contact person for public queries
Name 13929 0
Dr Jennifer Johnston
Address 13929 0
care of
Riverlands Drug and Alcohol Centre
Locked Bag 11
Lismore, NSW 2480
Country 13929 0
Australia
Phone 13929 0
+61 2 6688 2391
Fax 13929 0
Email 13929 0
[email protected]
Contact person for scientific queries
Name 4857 0
Associate Professor Nicholas Lintzeris
Address 4857 0
The Langton Centre
591 South Dowling Street
Surry Hills, NSW 2010
Country 4857 0
Australia
Phone 4857 0
+ 61 2 9332 8777
Fax 4857 0
Email 4857 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe effects of lithium carbonate supplemented with nitrazepam on sleep disturbance during cannabis abstinence.2015https://dx.doi.org/10.5664/jcsm.5090
N.B. These documents automatically identified may not have been verified by the study sponsor.