Trial Outcomes & Findings for Gabapentin Treatment of Cannabis Dependence (NCT NCT00395044)

Results Overview

Urinary THC/Cr ratio, also known as CN-THCCOOH (creatinine normalized tetrahydrocannabinol carboxylic acid), is a highly sensitive and specific quantitative analytic procedure to determine current marijuana metabolite levels in the urine as well as new marijuana use or abstinence. Gas chromatography-mass spectrometric levels of 11-nor-9-carboxy-9-THC (THC-COOH), the primary marijuana metabolite, are normalized to the urine creatinine (CN) concentration to reduce the variability of drug measurement attributable to urine dilution. Negative values indicate decreased use.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Week 0 and Week 12

Results posted on

2017-02-10

Participant Flow

50 subjects were recruited. An initial phone screen was conducted followed by an in-person clinical screening and interview in the research laboratory.

Subjects were excluded from enrollment if they did not meet Inclusion criteria or if they met one or more of the Exclusion criteria.

Participant milestones

Participant milestones
Measure	Gabapentin 1200 mg/daily of Gabapentin	Placebo Matched Placebo
Overall Study STARTED	25	25
Overall Study COMPLETED	7	11
Overall Study NOT COMPLETED	18	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Gabapentin Treatment of Cannabis Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants 1200mg/d of Placebo	Total n=50 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	33.4 years STANDARD_DEVIATION 8.5 • n=5 Participants	34.4 years STANDARD_DEVIATION 10.8 • n=7 Participants	33.9 years STANDARD_DEVIATION 9.7 • n=5 Participants
Gender Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Gender Male	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 0 and Week 12

Urinary THC/Cr ratio, also known as CN-THCCOOH (creatinine normalized tetrahydrocannabinol carboxylic acid), is a highly sensitive and specific quantitative analytic procedure to determine current marijuana metabolite levels in the urine as well as new marijuana use or abstinence. Gas chromatography-mass spectrometric levels of 11-nor-9-carboxy-9-THC (THC-COOH), the primary marijuana metabolite, are normalized to the urine creatinine (CN) concentration to reduce the variability of drug measurement attributable to urine dilution. Negative values indicate decreased use.

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants Matched Placebo
Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 12	-966.00 ng/ml Standard Deviation 1175.25	-532.81 ng/ml Standard Deviation 422.15

SECONDARY outcome

Timeframe: Week 0 and Week 12

The MWC is an instrument to assess the severity of frequently reported cannabis withdrawal symptoms. Each question on the measure is recorded as a severity rating between 0-3: 0=best outcome; 3=worst outcome. The severity rating of each question was averaged to obtain a single marijuana withdrawal severity score. Change = (Week 12 score - Week 0 score).

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants Matched Placebo
Change From Week 0 in Withdrawal Symptom Severity on the Marijuana Withdrawal Checklist (MWC) at Week 12	1.42 units on a scale Standard Deviation 1.13	2.12 units on a scale Standard Deviation 1.50

SECONDARY outcome

Timeframe: Week 0 and Week 12

The PSQI is an instrument to assess subjective sleep quality and disturbance. The range on the measure is from 0-21: 0=best outcome; 21=worst outcome. Change = (Week 12 score - Week 0 score).

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants Matched Placebo
Change in Sleep Quality on the Pittsburgh Sleep Quality Index (PSQI) at Week 12	-4.27 units on a scale Standard Deviation 3.07	-1.72 units on a scale Standard Deviation 2.80

SECONDARY outcome

Timeframe: Week 0 and Week 12

The BDI-II is a self-rating of severity of depressive symptoms. The Total score range on the BDI-II is from 0-63; 0=best outcome; 63=worst outcome. Change = (Week 12 score - Week 0 score).

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants Matched Placebo
Change From Week 0 in Mood on the Beck Depression Inventory (BDI-II) at Week 12	3.71 units on a scale Standard Deviation 1.98	5.22 units on a scale Standard Deviation 2.36

SECONDARY outcome

Timeframe: Week 0 and Week 12

The Marijuana Craving question of the Marijuana Withdrawal Checklist assesses severity of craving to smoke marijuana. The craving question is rated on a scale of 0-3 where 0=best outcome (no symptoms) and 3=worst outcome (severe symptoms). Change = (Week 12 score - Week 0 score).

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants Matched Placebo
Change From Week 0 in Craving on the Marijuana Withdrawal Checklist Marijuana Craving Question at Week 12	-1.55 units on a scale Standard Deviation .64	-1.46 units on a scale Standard Deviation .77

SECONDARY outcome

Timeframe: Week 0 and Week 12

The MPS is an instrument to assess the incidence of physical, psychological, social, and functioning problems that can result from cannabis dependence. The Total score ranges from 0-38 where 0=best outcome and 38=worst outcome. Change = (Week 12 score - Week 0 score).

Outcome measures

Outcome measures
Measure	Gabapentin n=25 Participants 1200 mg/daily of Gabapentin	Placebo n=25 Participants Matched Placebo
Change From Week 0 in Cannabis-related Problems on the Marijuana Problem Scale (MPS) at Week 12	-3.40 units on a scale Standard Deviation 2.07	-4.90 units on a scale Standard Deviation 7.09

SECONDARY outcome

Timeframe: Week 0 and Week 4

Population: Cognitive testing was done in a subset of participants enrolled in the study, beginning with randomized subject #21 and continuing until the 50th subject was randomized. The number analyzed is the total number available for analysis that completed both the Baseline and Week 4 assessment.

The D-KEFS is a testing battery designed to measure executive functioning, a critical component of participating in cognitive behavioral therapy used to treat marijuana dependence. Data were obtained from the D-KEFS test instruments completed at baseline and week 4, which included the Trail Making Test, Verbal Fluency Test, and Color-Word Interference Test. Scaled scores range from 1 (worst) to 19 (best). Change = (Week 4 score - Week 0 score). Positive values indicate increased executive functioning.

Outcome measures

Outcome measures
Measure	Gabapentin n=7 Participants 1200 mg/daily of Gabapentin	Placebo n=10 Participants Matched Placebo
Change From Baseline in Cognitive Functioning Using the Delis-Kaplan Executive Function System (D-KEFS) at Week 4	.28 scores on a scale Standard Deviation .50	-.20 scores on a scale Standard Deviation .31

Adverse Events

Gabapentin

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Gabapentin n=25 participants at risk 1200 mg/daily of Gabapentin	Placebo n=25 participants at risk 1200mg/d of Placebo
Nervous system disorders Headache	16.0% 4/25 • 13 weeks, from baseline to week 13	24.0% 6/25 • 13 weeks, from baseline to week 13
Nervous system disorders Insomnia	12.0% 3/25 • 13 weeks, from baseline to week 13	8.0% 2/25 • 13 weeks, from baseline to week 13
Gastrointestinal disorders Nausea	12.0% 3/25 • 13 weeks, from baseline to week 13	4.0% 1/25 • 13 weeks, from baseline to week 13
Respiratory, thoracic and mediastinal disorders Cold symptoms	8.0% 2/25 • 13 weeks, from baseline to week 13	8.0% 2/25 • 13 weeks, from baseline to week 13
Musculoskeletal and connective tissue disorders Pain	0.00% 0/25 • 13 weeks, from baseline to week 13	16.0% 4/25 • 13 weeks, from baseline to week 13
Nervous system disorders Fatigue	4.0% 1/25 • 13 weeks, from baseline to week 13	8.0% 2/25 • 13 weeks, from baseline to week 13
Psychiatric disorders Depression	8.0% 2/25 • 13 weeks, from baseline to week 13	4.0% 1/25 • 13 weeks, from baseline to week 13
Psychiatric disorders Irritability	4.0% 1/25 • 13 weeks, from baseline to week 13	8.0% 2/25 • 13 weeks, from baseline to week 13
Immune system disorders Allergic reaction	8.0% 2/25 • 13 weeks, from baseline to week 13	4.0% 1/25 • 13 weeks, from baseline to week 13
Metabolism and nutrition disorders Appetite decrease	4.0% 1/25 • 13 weeks, from baseline to week 13	4.0% 1/25 • 13 weeks, from baseline to week 13
Psychiatric disorders Anxiety	4.0% 1/25 • 13 weeks, from baseline to week 13	4.0% 1/25 • 13 weeks, from baseline to week 13

Additional Information

Dr. Barbara Mason

The Scripps Research Institute

Phone: (858) 784-7324

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place