gamma-aminobutyric acid and Smoking Cessation studies

gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.
gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.

Research Excerpts

Excerpt	Relevance	Reference
"Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation."	9.24	The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. ( Goudriaan, AE; Kaag, AM; Kooi, DP; Schmaal, L; Schulte, M; van den Brink, W; Wiers, RW, 2017)
"This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study."	9.11	A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation. ( Crockford, D; El-Guebaly, N; Patten, S; White, WD, 2005)
"Gabapentin-treated participants exhibited lower abstinence rates than placebo-treated participants; however, this difference was not significant."	6.75	Gabapentin for smoking cessation. ( Croghan, IT; Ebbert, JO; Hays, JT; Schroeder, DR; Sood, A; Sood, R; Wyatt, KD, 2010)
"Although not definitive, our findings suggest that gabapentin administered at these doses with this dosing regimen holds little promise for the treatment of tobacco dependence in a population of smokers seeking treatment."	6.75	Gabapentin for smoking cessation. ( Croghan, IT; Ebbert, JO; Hays, JT; Schroeder, DR; Sood, A; Sood, R; Wyatt, KD, 2010)
"Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects."	6.71	A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation. ( Crockford, D; El-Guebaly, N; Patten, S; White, WD, 2005)
"Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors."	5.51	Prolonged exposure of rats to varenicline increases anxiety and alters serotonergic system, but has no effect on memory. ( de Abreu, GR; de Souza Spinosa, H; Faria Waziry, PA; Flório, JC; Fukushima, AR; Lebrun, I; Moreira, N; Petrocelli, BM; Reis-Silva, TM; Ricci, EL; Sandini, TM; Zaccarelli-Magalhães, J, 2019)
"Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation."	5.24	The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. ( Goudriaan, AE; Kaag, AM; Kooi, DP; Schmaal, L; Schulte, M; van den Brink, W; Wiers, RW, 2017)
"These findings provide limited support for pregabalin as a treatment for nicotine addiction."	5.16	Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive performance in smokers. ( Herman, AI; McKee, SA; Sofuoglu, M; Waters, AJ, 2012)
"This 6-week, randomized, open-label pilot study estimated the treatment effect size of gabapentin (n = 17) compared with bupropion SR (n = 19) for smoking cessation, thereby allowing sample size calculations for a definitive comparison study."	5.11	A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation. ( Crockford, D; El-Guebaly, N; Patten, S; White, WD, 2005)
"Gabapentin-treated participants exhibited lower abstinence rates than placebo-treated participants; however, this difference was not significant."	2.75	Gabapentin for smoking cessation. ( Croghan, IT; Ebbert, JO; Hays, JT; Schroeder, DR; Sood, A; Sood, R; Wyatt, KD, 2010)
"Although not definitive, our findings suggest that gabapentin administered at these doses with this dosing regimen holds little promise for the treatment of tobacco dependence in a population of smokers seeking treatment."	2.75	Gabapentin for smoking cessation. ( Croghan, IT; Ebbert, JO; Hays, JT; Schroeder, DR; Sood, A; Sood, R; Wyatt, KD, 2010)
"Tiagabine treatment did not affect the heart rate or blood pressure changes induced by nicotine."	2.71	Effects of tiagabine in combination with intravenous nicotine in overnight abstinent smokers. ( Culligan, K; Kosten, T; Mouratidis, M; Sofuoglu, M; Yoo, S, 2005)
"Gabapentin was less efficacious than bupropion for smoking cessation but was associated with fewer dropouts from adverse effects."	2.71	A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation. ( Crockford, D; El-Guebaly, N; Patten, S; White, WD, 2005)
"Nicotine plays an important role in the initiation and maintenance of tobacco smoking."	2.49	The "stop" and "go" of nicotine dependence: role of GABA and glutamate. ( D'Souza, MS; Markou, A, 2013)
"Understanding the neural substrates of nicotine dependence is essential for the development of more effective antismoking medications than those currently available."	2.47	Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments. ( D'Souza, MS; Markou, A, 2011)
"Varenicline is a drug used for smoking addiction cessation treatment and acts as a partial agonist of nicotinic cholinergic receptors."	1.51	Prolonged exposure of rats to varenicline increases anxiety and alters serotonergic system, but has no effect on memory. ( de Abreu, GR; de Souza Spinosa, H; Faria Waziry, PA; Flório, JC; Fukushima, AR; Lebrun, I; Moreira, N; Petrocelli, BM; Reis-Silva, TM; Ricci, EL; Sandini, TM; Zaccarelli-Magalhães, J, 2019)

Research

Studies (16)

Authors

Clinical Trials (4)

Trial Overview

Trial Outcomes

Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (6.25)	18.2507
2000's	7 (43.75)	29.6817
2010's	8 (50.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Domi, E	1
Caputi, FF	1
Romualdi, P	1
Domi, A	1
Scuppa, G	1
Candeletti, S	1
Atkins, A	1
Heilig, M	1
Demopulos, G	1
Gaitanaris, G	1
Ciccocioppo, R	1
Ubaldi, M	1
Schulte, M	1
Goudriaan, AE	1
Kaag, AM	1
Kooi, DP	1
van den Brink, W	1
Wiers, RW	1
Schmaal, L	1
Zaccarelli-Magalhães, J	1
Sandini, TM	1
de Abreu, GR	1
Petrocelli, BM	1
Moreira, N	1
Reis-Silva, TM	1
Lebrun, I	1
Flório, JC	1
Ricci, EL	1
Fukushima, AR	1
Faria Waziry, PA	1
de Souza Spinosa, H	1
D'Souza, MS	3
Markou, A	4
Li, X	1
Semenova, S	2
Stoker, AK	1
Sood, A	2
Ebbert, JO	2
Wyatt, KD	1
Croghan, IT	2
Schroeder, DR	2
Sood, R	2
Hays, JT	2
Herman, AI	1
Waters, AJ	1
McKee, SA	1
Sofuoglu, M	2
Paterson, NE	1
Epperson, CN	2
O'Malley, S	1
Czarkowski, KA	1
Gueorguieva, R	1
Jatlow, P	1
Sanacora, G	1
Rothman, DL	2
Krystal, JH	2
Mason, GF	2
Mouratidis, M	1
Yoo, S	1
Culligan, K	1
Kosten, T	1
White, WD	1
Crockford, D	1
Patten, S	1
El-Guebaly, N	1
Amin, Z	1
Cavus, I	1
Vander Weg, MW	1
Wong, GY	1
Wickelgren, I	1
Myrick, H	1
Malcolm, R	1
Henderson, S	1
McCormick, K	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Effectiveness of N-Acetylcysteine in Motivational Enhancement Therapy for Nicotine Addiction: Study on the Dopaminergic Pathways, Changes in Functional Connectivity of fMRI Bold, and Changes in Smoking Abstinence[NCT05903014]	Phase 4	88 participants (Anticipated)	Interventional	2023-01-01	Recruiting
Gabapentin for Smoking Abstinence[NCT00578552]	Phase 2	80 participants (Actual)	Interventional	2007-10-31	Completed
Multimodal Imaging of Progesterone/Neurosteroid Effects in Nicotine Addiction[NCT01954966]	Phase 4	81 participants (Actual)	Interventional	2010-11-30	Completed
Sex, GABA and Nicotine: A 1H-MRS Study[NCT01227343]		54 participants (Actual)	Observational	2010-03-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"Point prevalence tobacco abstinence was adjudicated if the following conditions were met: (a) self-reported tobacco abstinence for the previous 7 days with a negative response to the question Have you used any type of tobacco, even a puff, in the past 7 days? and (b) Expired Carbon Monoxide equal or less then 8 parts per million." (NCT00578552)
Timeframe: 12 weeks following start of medication

Brief Questionnaire on Smoking Urges (BQSU)

Intervention	participants (Number)
Placebo	5
Gabapentin - 1800 mg /Day	4
Gabapentin - 2700 mg/Day	0

Craving will be assessed using the Brief Questionnaire on Smoking Urges (BQSU). It ranges from 7-70 with higher levels indicating higher levels of nicotine craving. (NCT01954966)
Timeframe: Day 1 (pre and post smoking session, day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

GABA Pre and Post Progesterone Administration (Dorsal Anterior Cingulate Cortex [DACC])

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 1; post-1st smoking session	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	40.89	30.45	38.47	38.81	41.91	40.84	40.90	39.23	41.95	27.64
Progesterone 200 mg Look-alike Capsules	41.94	25.77	34.34	37.98	41.82	42.03	40.29	37.68	42.38	28.22

"GABA concentrations (collected in the Dorsal Anterior Cingulate Cortex [DACC]) will be obtained using the non-invasive neuroimaging method of proton magnetic resonance spectroscopy (1H-MRS) both before and after placebo administration and smoking abstinence. In total subjects will undergo 6 1H-MRS scans. The 6 1H-MRS scans take place over a period of approximately 1-2 months. Each paradigm (placebo/progesterone) takes approximately one week, with an approximately two-week wash in between paradigms for men and an approximately 1-month wash in between paradigms for women. The subject will undergo a smoking session on Test Day #1 and Test Day #5, MRS scans are conducted on Test Day #2 (2 scans) and Test Day #5 (1 scan).~Minimal data is available for the primary outcome due to substantial issues with the 7T scanner. All subsequent scans were conducted on a 3T scanner which does not have the capacity to collect data on GABA." (NCT01954966)
Timeframe: Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.

GABA Pre and Post Progesterone Administration (Dorsolateral Pre-Frontal Cortex [DLPFC])

Intervention	mg/dl (Mean)
	Test day 2 (baseline, pre-scan)	Test day 2 (post-scan)	Test day 5 (pre-smoking)
Progesterone 200 mg Capsules	1.23	1.28	1.21
Progesterone 200 mg Look-alike Capsules	1.17	1.24	1.17

"GABA concentrations (collected in the Dorsolateral Pre-Frontal Cortex [DLPFC]) will be obtained using the non-invasive neuroimaging method of proton magnetic resonance spectroscopy (1H-MRS) both before and after placebo administration and smoking abstinence. In total subjects will undergo 6 1H-MRS scans. The 6 1H-MRS scans take place over a period of approximately 1-2 months. Each paradigm (placebo/progesterone) takes approximately one week, with an approximately two-week wash in between paradigms for men and an approximately 1-month wash in between paradigms for women. The subject will undergo a smoking session on Test Day #1 and Test Day #5, MRS scans are conducted on Test Day #2 (2 scans) and Test Day #5 (1 scan).~Minimal data is available for the primary outcome due to substantial issues with the 7T scanner. All subsequent scans were conducted on a 3T scanner which does not have the capacity to collect data on GABA." (NCT01954966)
Timeframe: Test Day #2 and Test Day #5 - 6 total scans over the period of 2-3 months.

Nicotine Effects Questionnaire (NEQ) Question: Feels Bad Effects of Nicotine

Intervention	mg/dl (Mean)
	Day 2- pre scan	Day 2- post scan	Day 5- after scan, pre smoking
Progesterone 200 mg Capsules	1.18	1.05	1.06
Progesterone 200 mg Look-alike Capsules	1.20	0.98	1.11

Nicotine Effects Questionnaire (NEQ) question: feels bad effects of nicotine. Score ranges from 0 to 100 with higher levels indicating feeling more bad effects of nicotine after smoking. (NCT01954966)
Timeframe: Day 1 (pre smoking session), Day 5 (post smoking session)

Nicotine Effects Questionnaire (NEQ) Question: Feels Good Effects of Nicotine

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 5; after smoking
Progesterone 200 mg Capsules	26.25	25.39
Progesterone 200 mg Look-alike Capsules	25.92	28.70

NEQ question: feels good effects of nicotine. Score ranges from 0 to 100 with higher levels indicating feeling more good effects of nicotine after smoking. (NCT01954966)
Timeframe: Day 1 (pre smoking session), Day 5 (post smoking session)

Nicotine Effects Questionnaire (NEQ) Question: Feels Strength of Nicotine

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 5; after smoking
Progesterone 200 mg Capsules	67.72	67.84
Progesterone 200 mg Look-alike Capsules	67.84	64.72

Nicotine Effects Questionnaire (NEQ) question: feels strength of nicotine. Score ranges from 0 to 100 with higher levels indicating feeling stronger effects of nicotine after smoking. (NCT01954966)
Timeframe: Day 1 (pre smoking session), Day 5 (post smoking session)

Nicotine Effects Questionnaire (NEQ) Question: Head Rush

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 5; after smoking
Progesterone 200 mg Capsules	71.45	74.87
Progesterone 200 mg Look-alike Capsules	71.01	75.25

Nicotine Effects Questionnaire (NEQ) question: feels head rush. Score ranges from 0 to 100 with higher levels indicating feeling stronger/more intense head rush after smoking. (NCT01954966)
Timeframe: Day 1 (pre smoking session), Day 5 (post smoking session)

Positive and Negative Affect Schedule (PANAS) Negative Affect

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 5; after smoking
Progesterone 200 mg Capsules	30.58	40.23
Progesterone 200 mg Look-alike Capsules	29.38	42.48

Positive and Negative Affect Schedule (PANAS) Negative Affect Score. Ranges from 10-50 with higher scores representing higher levels of negative affect. (NCT01954966)
Timeframe: Day 1 (pre and post smoking session, day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Positive and Negative Affect Schedule (PANAS) Positive Affect

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 1; post-1st smoking session	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	11.94	10.64	11.25	11.59	12.31	13.07	12.51	12.90	12.55	11.41
Progesterone 200 mg Look-alike Capsules	11.43	10.57	11.03	11.49	13.01	12.89	13.06	13.16	12.18	11.94

Positive and Negative Affect Schedule (PANAS) Positive Affect Score. Ranges from 10-50 with higher scores representing higher levels of positive affect. (NCT01954966)
Timeframe: Day 1 (pre and post smoking session, day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Profile of Mood State (POMS) Subscale: Vigor

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 1; post-1st smoking session	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	37.10	35.72	36.08	33.51	32.57	32.34	32.56	33.25	33.45	33.10
Progesterone 200 mg Look-alike Capsules	37.23	36.11	36.55	34.17	33.30	32.81	32.03	32.61	32.53	33.76

Profile of Mood State (POMS) Subscale: Vigor. Subscale ranges from 0 to 32, with higher levels indicating higher levels of vigor. (NCT01954966)
Timeframe: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Anger-Hostility

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	18.71	16.74	16.71
Progesterone 200 mg Look-alike Capsules	18.71	16.73	16.39

Profile of Mood States (POMS) Subscale: Anger-Hostility. This scale ranges from 0 to 48 with higher levels indicating higher levels of anger/hostility. (NCT01954966)
Timeframe: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Confusion-Bewilderment

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	0.94	1.55	2.70
Progesterone 200 mg Look-alike Capsules	0.83	1.41	2.36

Profile of Mood States (POMS) Subscale: Confusion-Bewilderment. Ranges from 0 to 28 with higher levels indicating higher levels of confusion/bewilderment. (NCT01954966)
Timeframe: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Depression-Dejection

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	2.47	2.95	3.46
Progesterone 200 mg Look-alike Capsules	2.31	2.98	2.80

Profile of Mood States (POMS) Subscale: Depression-Dejection. This subscale ranges from 0-60 with higher levels indicating greater depression/dejection. (NCT01954966)
Timeframe: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Fatigue

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	1.09	1.30	1.66
Progesterone 200 mg Look-alike Capsules	0.64	0.88	1.81

Profile of Mood States (POMS) Subscale: Fatigue. This subscale ranges from 0 to 28 with higher scores indicating higher levels of fatigue. (NCT01954966)
Timeframe: Day 2 (pre and post scan), Day 5 (pre smoking session)

Profile of Mood States (POMS) Subscale: Tension-Anxiety

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	2.17	2.84	3.66
Progesterone 200 mg Look-alike Capsules	1.77	3.63	3.10

Profile of Mood States (POMS) Subscale: Tension-Anxiety. This subscale ranges from 0-28 with higher levels indicating greater tension/anxiety. (NCT01954966)
Timeframe: Day 2 (pre and post scan), Day 5 (pre smoking session)

Symptoms During Nicotine Abstinence (NWSC)

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post- 2nd scan	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	2.88	3.55	4.85
Progesterone 200 mg Look-alike Capsules	2.57	3.11	3.70

Withdrawal symptoms will be measured using the Nicotine Withdrawal Symptoms Checklist (NWSC). The scale ranges from a minimum of 0 to a maximum of 28, with higher scores indicating greater withdrawal (more withdrawal symptoms, higher intensity/severity of withdrawal). (NCT01954966)
Timeframe: Day 1 (pre and post smoking session, day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Tiffany Questionnaire on Smoking Urges (TQSU)

Intervention	score on a scale (Mean)
	Nicotine withdrawal symptoms checklist (NWSC); day 1 pre 1st smoking session	Nicotine withdrawal symptoms checklist (NWSC); day 1 post 1st smoking session	Nicotine withdrawal symptoms checklist (NWSC); day 2 pre-scan	Nicotine withdrawal symptoms checklist (NWSC); day 2 post-scan	Nicotine withdrawal symptoms checklist (NWSC); day 3 abstinence AM	Nicotine withdrawal symptoms checklist (NWSC); day 3 abstinence PM	Nicotine withdrawal symptoms checklist (NWSC); day 4 abstinence AM	Nicotine withdrawal symptoms checklist (NWSC); day 4 abstinence PM	Nicotine withdrawal symptoms checklist (NWSC); day 5 pre-smoking	Nicotine withdrawal symptoms checklist (NWSC); day 5 post-smoking
Progesterone 200 mg Capsules	6.00	4.84	5.67	5.37	7.07	6.99	7.33	7.19	7.01	4.60
Progesterone 200 mg Look-alike Capsules	6.15	4.48	4.92	5.25	7.62	7.88	7.66	7.32	7.34	4.82

Craving will also be assessed using the Tiffany Questionnaire for Smoking Urges. It ranges from 32 to 224 with higher scores indicated higher levels of smoking urges/craving. (NCT01954966)
Timeframe: Day 1 (pre smoking session, day 3 (PM), day 4 (PM), day 5 (pre smoking session)

Visual Analog Scale (VAS) Question: Anxious

Intervention	score on a scale (Mean)
	Day 1; pre-1st smoking session	Day 3; abstinence PM	Day 4; abstinence PM	Day 5; after scan, pre-smoking
Progesterone 200 mg Capsules	143.45	138.46	139.11	146.22
Progesterone 200 mg Look-alike Capsules	140.31	140.77	135.88	141.08

Visual Analog Scale (VAS) question: Anxious. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Calm

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	16.69	15.02	20.20	16.38	18.46	15.88	17.81	16.26
Progesterone 200 mg Look-alike Capsules	15.62	12.65	17.38	20.23	15.08	15.63	19.05	15.30

Visual Analog Scale (VAS) question: Calm. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Depressed

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	74.35	73.15	65.65	58.92	60.23	65.47	67.60	69.27
Progesterone 200 mg Look-alike Capsules	76.52	69.23	61.15	52.44	57.97	62.48	61.02	70.52

Visual Analog Scale (VAS) question: Depressed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Drowsy

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	3.97	4.99	6.43	4.61	5.51	5.67	2.64	2.53
Progesterone 200 mg Look-alike Capsules	2.87	5.55	6.85	4.58	5.17	5.73	5.26	4.89

Visual Analog Scale (VAS) question: Drowsy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Energetic

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	16.63	24.25	17.14	24.71	19.56	19.84	23.01	20.45
Progesterone 200 mg Look-alike Capsules	14.29	30.17	15.43	24.36	18.32	20.50	21.01	21.45

Visual Analog Scale (VAS) question: Energetic. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Happy

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	54.86	55.18	56.14	56.13	55.62	53.45	51.47	54.79
Progesterone 200 mg Look-alike Capsules	67.01	21.03	58.11	50.12	54.89	56.77	56.64	54.70

Visual Analog Scale (VAS) question: Happy. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Headache

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	76.62	70.98	66.22	65.10	62.76	61.99	66.59	70.07
Progesterone 200 mg Look-alike Capsules	79.70	71.34	64.04	61.30	60.58	63.95	63.46	67.87

Visual Analog Scale (VAS) question: Headache. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Heartburn.

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	6.50	5.74	9.15	8.86	10.88	11.83	9.05	11.93
Progesterone 200 mg Look-alike Capsules	7.59	9.39	14.71	10.93	7.70	12.78	13.36	11.67

Visual Analog Scale (VAS) question: Heartburn. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Hunger

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	3.11	4.30	5.46	6.00	7.31	5.51	4.33	4.56
Progesterone 200 mg Look-alike Capsules	2.35	4.06	3.27	4.55	6.50	5.56	5.30	6.37

Visual Analog Scale (VAS) question: Hunger. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Irritable

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	34.60	28.63	24.88	27.72	27.94	25.57	28.22	28.63
Progesterone 200 mg Look-alike Capsules	40.23	22.20	33.40	31.95	34.64	29.27	35.22	32.61

Visual Analog Scale (VAS) question: Irritable. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Nauseous

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	7.50	13.20	24.80	23.97	30.79	26.50	23.23	13.45
Progesterone 200 mg Look-alike Capsules	5.71	13.01	24.56	25.49	29.58	30.11	22.96	15.52

Visual Analog Scale (VAS) question: Nauseous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Nervous

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	5.52	6.31	6.01	8.07	6.07	6.60	6.51	8.00
Progesterone 200 mg Look-alike Capsules	4.92	5.43	10.44	9.85	8.22	10.29	10.34	11.41

Visual Analog Scale (VAS) question: Nervous. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Relaxed

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	13.24	10.91	7.19	9.56	9.36	10.83	10.79	7.64
Progesterone 200 mg Look-alike Capsules	10.26	8.46	8.22	9.24	11.37	10.66	12.15	11.94

Visual Analog Scale (VAS) question: Relaxed. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Sad

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	72.66	67.77	63.87	57.69	57.83	63.46	62.45	67.99
Progesterone 200 mg Look-alike Capsules	73.87	63.65	55.85	54.08	55.37	63.45	67.65	67.55

Visual Analog Scale (VAS) question: Sad. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Visual Analog Scale (VAS) Question: Talkative

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	3.95	6.77	5.67	4.36	8.54	7.32	3.87	2.95
Progesterone 200 mg Look-alike Capsules	2.09	4.48	10.51	9.07	8.47	8.65	12.47	5.92

Visual Analog Scale (VAS) Question: Tired

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	54.17	50.61	51.43	48.14	49.67	50.48	52.74	54.26
Progesterone 200 mg Look-alike Capsules	57.46	51.46	50.34	47.04	50.71	49.27	56.19	53.12

Visual Analog Scale (VAS) question: Tired. Scale ranges from 0 to 100 with higher levels indicating greater intensity of symptom/feeling. (NCT01954966)
Timeframe: Day 2 (pre and post scan), day 3 (AM and PM), day 4 (AM and PM), day 5 (pre and post smoking session)

Intervention	score on a scale (Mean)
	Day 2; pre-1st scan	Day 2; post-2nd scan	Day 3; abstinence AM	Day 3; abstinence PM	Day 4; abstinence AM	Day 4; abstinence PM	Day 5; after scan, pre-smoking	Day 5; after smoking
Progesterone 200 mg Capsules	24.15	29.67	21.64	30.82	31.73	30.69	33.94	31.22
Progesterone 200 mg Look-alike Capsules	18.62	40.92	27.24	35.53	27.99	28.51	32.06	34.79

Article	Year
The "stop" and "go" of nicotine dependence: role of GABA and glutamate. Cold Spring Harbor perspectives in medicine, 2013, Jun-01, Volume: 3, Issue:6 Topics: Animals; Behavior, Animal; Brain; Conditioning, Psychological; Dopamine; Excitatory Amino Acid Antag	2013
Involvement of glutamatergic and GABAergic systems in nicotine dependence: Implications for novel pharmacotherapies for smoking cessation. Neuropharmacology, 2014, Volume: 76 Pt B Topics: Animals; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Smoking Cessation; Tobacco Use Disorder	2014
Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments. Addiction science & clinical practice, 2011, Volume: 6, Issue:1 Topics: Behavior, Addictive; Brain; Dopamine Antagonists; Dopaminergic Neurons; gamma-Aminobutyric Acid; Hum	2011
The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacology, biochemistry, and behavior, 2006, Volume: 84, Issue:4 Topics: Affect; Depression, Postpartum; Female; gamma-Aminobutyric Acid; Humans; Menstruation; Mental Disord	2006

Article	Year
The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. Journal of psychopharmacology (Oxford, England), 2017, Volume: 31, Issue:10 Topics: Acetylcysteine; Adult; Craving; Double-Blind Method; gamma-Aminobutyric Acid; Glutamic Acid; Gyrus C	2017
Gabapentin for smoking cessation. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2010, Volume: 12, Issue:3 Topics: Adult; Amines; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Excitatory Amino Acid	2010
Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive performance in smokers. Psychopharmacology, 2012, Volume: 220, Issue:3 Topics: Adult; Cross-Over Studies; Double-Blind Method; Female; gamma-Aminobutyric Acid; Humans; Male; Nicot	2012
Effects of tiagabine in combination with intravenous nicotine in overnight abstinent smokers. Psychopharmacology, 2005, Volume: 181, Issue:3 Topics: Adult; Anticonvulsants; Arousal; Attention; Blood Pressure; Brain; Cross-Over Studies; Double-Blind	2005
A randomized, open-label pilot comparison of gabapentin and bupropion SR for smoking cessation. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2005, Volume: 7, Issue:5 Topics: Adolescent; Adult; Amines; Bupropion; Cyclohexanecarboxylic Acids; Dopamine Uptake Inhibitors; Excit	2005
Gabapentin for smoking cessation: a preliminary investigation of efficacy. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2007, Volume: 9, Issue:2 Topics: Adult; Amines; Analgesics; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid;	2007

Article	Year
Activation of PPARγ Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms through Mechanisms Involving Amygdala and Hippocampus Neurotransmission. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019, 12-04, Volume: 39, Issue:49 Topics: Affect; Amygdala; Anilides; Animals; Anxiety; Behavior, Animal; gamma-Aminobutyric Acid; Hippocampus	2019
Prolonged exposure of rats to varenicline increases anxiety and alters serotonergic system, but has no effect on memory. Pharmacology, biochemistry, and behavior, 2019, Volume: 181 Topics: alpha7 Nicotinic Acetylcholine Receptor; Analysis of Variance; Animals; Anxiety; Behavior, Animal; C	2019
Role of gamma-aminobutyric acid (GABA) and metabotropic glutamate receptors in nicotine reinforcement: potential pharmacotherapies for smoking cessation. Annals of the New York Academy of Sciences, 2004, Volume: 1025 Topics: Animals; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; GABA Agonists; GABA-B	2004
Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biological psychiatry, 2005, Jan-01, Volume: 57, Issue:1 Topics: Adult; Cotinine; Estradiol; Female; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Spectroscopy	2005
Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biological psychiatry, 2005, Jan-01, Volume: 57, Issue:1 Topics: Adult; Cotinine; Estradiol; Female; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Spectroscopy	2005
Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biological psychiatry, 2005, Jan-01, Volume: 57, Issue:1 Topics: Adult; Cotinine; Estradiol; Female; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Spectroscopy	2005
Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biological psychiatry, 2005, Jan-01, Volume: 57, Issue:1 Topics: Adult; Cotinine; Estradiol; Female; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Spectroscopy	2005
Drug may suppress the craving for nicotine. Science (New York, N.Y.), 1998, Dec-04, Volume: 282, Issue:5395 Topics: Animals; Behavior, Animal; Brain; Cocaine-Related Disorders; Conditioning, Psychological; Dopamine;	1998
Gabapentin for misuse of homemade nicotine nasal spray. The American journal of psychiatry, 2001, Volume: 158, Issue:3 Topics: Acetates; Administration, Intranasal; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Gabapent	2001

gamma-aminobutyric acid and Smoking Cessation