Table 1.

Drug Type	Participants	Study Type	Treatment	Results	Authors
Amphetamine	18 females	Randomized, placebo- controlled, within- subjects study	Chronic treatment; oral micronized PROG (200mg/day) vs. placebo administered over 3 days in the F phase	PROG pretreatment increased positive subjective ratings of drug and choice of drug over money in study paradigm.	Reed et al., 2010 [97]
Benzodiazepine	35 daily benzodiazepine users (gender not reported)	Randomized, double-blind, between- subjects study	Chronic treatment; Oral micronized PROG titrated to a mean dose of 1,983mg/day in 3 weeks and given for an additional 4 weeks vs. placebo.	PROG treatment did not have a significant effect on severity of withdrawal symptoms or in the discontinuation of benzodiazepines.	Schweize et al., 1995 [105]
Cocaine	46 treatment- seeking cocaine dependent participants (17 females; 29 males)	Randomized, double-blind, within- subjects study; three cued stress conditions: stressed, drug and relaxed	Chronic treatment; 400mg/day micronized PROG vs. placebo for 7 days	Participants’ results were group utilizing a median spilt based upon ALLO level (high vs. low). The high ALLO group reported lower post- stress imagery cocaine craving scores on all three study sessions. High ALLO reported higher positive emotion at baseline and overall lower peak cocaine craving. Increased levels of ALLO were associated with reduced cortisol levels at pre-imagery.	Milivojevic et al., 2016 [99]
	28 participants (19 males; 9 females)	Randomize	Chronic treatment; 400mg/day PROG vs. placebo for 7 days	PROG improved scores on the Thought Facilitation Task scale.	Milivojevic et al., 2014 [106]
	50 postpartum females with cocaine use disorders	Randomized, double- blinded, placebo controlled study	Chronic treatment; 200mg PROG/day vs. placebo for 12 weeks	Placebo group had more self-reported cocaine use during the study; there were no significant differences between groups at 3- month follow-up. There were no group differences between positive urine drug screens. The placebo group relapsed more quickly and among participants who did not reported drug use, the placebo group had more positive urine samples.	Yonkers et al., 2014 [101]
	42 early abstinent, treatment- seeking cocaine users (24 males; 18 females)	Randomized, double-blind, placebo- controlled study; three cued stress conditions: stressed, drug and relaxed	Chronic treatment; 400mg PROG vs. placebo for 7 days	PROG group selectively demonstrated efficacy to attenuate drug craving and stress arousal in early abstinent cocaine dependent individuals; this effect was more robust in females.	Fox et al., 2013 [98]
	10 non- treatment seeking female cocaine smokers	Randomized, placebo controlled study	Chronic treatment; 300mg/day PROG vs. placebo for three days	Smoked cocaine administration did not differ across treatment groups and PROG did not attenuate administration or subjective ratings	Reed et al., 2011 [101]
	45 male cocaine users, maintained on methadone	Randomized, double-blind, placebo- controlled study	Chronic treatment; 200 increased to 600mg/day over 4 weeks PROG vs. placebo for 6 additional weeks	PROG group demonstrated a slight reduction in probability of UDS positive for cocaine, while the placebo group showed a slight increase. No medication differences were observed for opioid drug screens.	Sofuoglu et al., 2007 [102]
	21 smoked cocaine participants (11 females in F/L phases; 10 males)	Randomized study	Chronic treatment; 150mg/day PROG vs. placebo for 4 days	PROG attenuated positive subjective effects in females. There were no group or gender differences in terms of cocaine use within the study paradigm.	Evans et al., 2006 [94]
	10 female cocaine users (early F phase)	Double-blind, placebo- controlled crossover study	Single dose; 400mg/study session PROG vs. placebo	Subjective ratings of “high” and “feel the effects of the last dose” were attenuated in the PROG group.	Sofuoglu et al., 2004 [96]
	5 smoked- cocaine female users	Randomized, within- subjects	Single dose; 200mg/study session micronized PROG vs. placebo	Reduced subjective responses in PROG group.	Sofuoglu et al., 2002 [95]
Tobacco/Nicotine	41 postpartum female smokers	Randomized, double-blind, between- subjects, placebo controlled study	Chronic treatment; 400mg/day micronized PROG vs. placebo for 8 weeks	PROG group had higher proportion of participants achieving abstinence at week 8 and a slower rate of relapse*; PROG group also endorsed lower craving scores.	Forray et al., 2017 [100]
	46 nicotine abstinent, postpartum women	Randomized, within- subjects	Chronic treatment; 400mg/day micronized PROG vs. placebo for 4 weeks	PROG group exhibited higher rates of abstinence at weeks 4 and 7*. These participants also exhibited more median days until relapse*.	Allen et al., 2016 [104]
	64 smokers (30 females; 34 males)	Randomized, within- subjects study	Chronic treatment; 200mg/day micronized PROG vs. 400mg/day micronized PROG vs. placebo over 4 days	No PROG treatment differences were observed for adlib smoking; 200mg groups had more correct responses on DSST. PROG groups demonstrated decreased positive subjective ratings and increased negative ratings.	Sofuoglu et al., 2011 [7]
	12 participants (6 males; 6 females in early F phase)	Randomized; within- subjects, placebo- controlled study	Single dose; 200mg/study session micronized PROG vs. placebo over two study sessions	PROG treatment increased negative subjective ratings and decreased urges to smoke when compared to placebo condition.	Sofuoglu et al., 2009 [55]
	12 female smokers	Double-blind, within- subjects, placebo- controlled study	Single dose; 200mg/study session micronized PROG vs. placebo	PROG treatment diminished subjective ratings of good effects and decreased craving for cigarettes. Progesterone decreased smoking*.	Sofuoglu et al., 2001 [93]

ALLO= allopregnanolone; DSST= Digit Symbol Substitution Test; F=follicular phase; HPW= high progesterone week; LPW= low progesterone week; L= luteal phase; PROG= progesterone; UDS= urine drug screen; *= not statistically significant