Staccato Alprazolam Abuse Liability

Abuse Liability Study of Staccato® Alprazolam for Inhalation in Subjects With Histories of Sedative Abuse

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00603980

Enrollment

Registered

2008-01-29

Start date

2008-01-01

Completion date

2009-01-01

Last updated

2026-04-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Abuse Liability of Staccato Alprazolam

Brief summary

Compare the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo.

Detailed description

The Phase 1 clinical study compared the abuse liabilities of Staccato Alprazolam, oral immediate-release alprazolam, and Staccato Placebo in 14 subjects with a history of sedative abuse. Subjects who met the inclusion/exclusion criteria received 2 mg of oral alprazolam and matching placebo over 2 sessions. Those who demonstrated greater liking for alprazolam versus placebo were eligible to participate in the study.

Interventions

DRUGInhaled placebo + oral placebo

Inhaled Staccato placebo + oral placebo

DRUGInhaled alprazolam 0.5 mg

Inhaled Staccato alprazolam 0.5 mg + oral placebo

DRUGInhaled alprazolam 1 mg

Inhaled Staccato alprazolam 1 mg + oral placebo

DRUGInhaled alprazolam 2 mg

Inhaled Staccato alprazolam 2 mg + oral placebo

DRUGOral alprazolam 1 mg

Oral alprazolam 1 mg + Inhaled placebo

DRUGOral alprazolam 2 mg

Oral alprazolam 2 mg + Inhaled placebo

DRUGOral alprazolam 4 m

Oral alprazolam 4 mg + Inhaled placebo

DRUGOral alprazolam 2 mg qualifying session

Qualifying session (2 mg oral alprazolam)

DRUGOral placebo qualifying session

Qualifying control session (oral placebo)

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Masking description

In order to reduce discrimination between placebo and active Staccato Alprazolam, taste blinding will be accomplished using a rapidly dissolving, intensely flavored product (candy, strip or breath spray). The product will be administered immediately after each oral capsule dosing (at the -60-min and 0- min time points).

Intervention model description

The crossover schedule is planned according to a 7-treatment, 7-period Latin Square design due to E.J. Williams (1949), which is balanced for first-order carryover effects (Fleiss, 1986). Each subject will receive all treatments in this 7-treatment, 7- period Williams Square crossover design as suggested by Chen & Tsong (2007). This Williams Square will include one replication by 1 subject of each of the 14 sequences

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Male and female subjects between the ages of 18 to 55 years, inclusive, who have a history of substance abuse or dependence on barbiturates and/or benzodiazepine receptor agonists for their intoxicating effects

Exclusion criteria

* Subjects with a significant current psychiatric illness or taking any psychotropic prescription medications for therapeutic uses.

Design outcomes

Primary

Measure	Time frame	Description
Response to EDQ Question Number 5, "Rate the Degree to Which You Would Like to Take the Drug Again"	End of day for each of the 7 crossover treatments	The End of Day Questionnaire (EDQ) is a 7-question computerized instrument in which subjects rate the overall effect of the drug they received that day. The primary outcome measure for this trial is the categorical response to question number 5, "Rate the degree to which you would like to take the drug again", with a numerical value assigned to each of the responses allowed: 0=Not at all, 1=A little, 2=Moderately, 3=Quite a bit, 4=Very much

Secondary

Measure	Time frame	Description
EDQ Question Number 2 "Rate Your Overall Liking of the Drug Effect"	End of day for each of the 7 crossover treatments	The within patient rank (1-7) of End of Day question number 2 (of primary interest), "Rate your overall liking of the drug effect", response options range from -4 to +4: * 4=Dislike very much * 3=Dislike quite a bit * 2=Dislike somewhat * 1=Dislike, but not very much 0=NEUTRAL OR NO EFFECT * 1=Like, but not very much * 2=Like somewhat * 3=Like quite a bit * 4=Like very much Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
EDQ Question Number 6 " Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street".	End of day for each of the 7 crossover treatments	EDQ question number 6 (of primary interest)," Estimate the amount of money you think the drug you took today would be worth on the street".
EDQ Question Number 1, "Rate the Overall Strength of the Drug Effect"	End of day for each of the 7 crossover treatments	The within patient rank (1-7) of End of Day question number 1, "Rate the overall strength of the drug effect", response options range from 0-4: 0=No drug effect at all 1. Possible mild effect, but not sure 2. Definite mild effect 3. Moderate strong drug effect 4. Very strong drug effect Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
EDQ Question Number 7,"What Would You be Willing to Pay for Today's Drug?"	End of day for each of the 7 crossover treatments	EDQ question number 7," What would you be willing to pay for today's drug?"
Maximum of DEQ Question 1 "Rate the Strength of the Drug Effect" (at the 10 Time Points, Predose Through 9 Hours)	DEQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of Drug Effect Questionnaire question number 1: Rate the STRENGTH of the drug effect you are feeling RIGHT NOW; response options range for 0 to 4: "No drug effect at all"=0, "Possible mild effect, but not sure"=1, "Definite mild effect"=2, "Moderate strong drug effect"=3, "Very strong drug effect"=4 Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Maximum of DEQ Question 2 "Rate Your Liking of the Drug Effect" at the 10 Time Points (Predose Through 9 Hours)	DEQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the Rate your LIKING of the drug effect you are feeling RIGHT NOW; response options range from -4 to +4: "Dislike very much"=-4, "Dislike quite a bit"=-3, "Dislike somewhat"=-2, "Dislike, but not very much"=-1, "NEUTRAL OR NO EFFECT"=0, "Like, but not very much"=1, "Like somewhat"=2, "Like quite a bit"=3, "Like very much"=4 Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 1) Maximum of Sedation/Sleepiness	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of Maximum of Observer Rated Questionnaire (ORQ): A trained and blinded staff member completed observer ratings as the subject completed the questionnaires and psychomotor assessment testing at each time point. The observer rated the subject on sedation/sleepiness, muscle relaxation, impaired posture, impaired speech, confusion/disorientation, stimulation/arousal and strength of drug effect on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 2) Maximum of Muscle Relaxation Locomotor	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (locomotor) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 3) Maximum of Muscle Relaxation Non-locomotor	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (non-locomotor) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 4) Maximum of Muscle Relaxation Posture	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on muscle relaxation (posture) on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 5) Maximum of Speech	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on speech on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 6) Maximum of Confusion/Disorientation	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on Confusion/Disorientation on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 7) Maximum of Stimulation/Arousal	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on Stimulation/Arousal on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect
Observer Rated Questionnaire 8) Maximum of Drug Strength	ORQ was assessed at the 10 time points (predose through 9 hours)	The within patient rank (1-7) of maximum of the observer rated the subject on Drug Strength on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORRoland R Griffiths, PhD

Johns Hopkins University

Participant flow

Pre-assignment details

Each participants was to receive all 7 interventions in a randomized order in a crossover design

Participants by arm

Arm	Count
Qualifying Session (Includes Crossover Group) All subjects received Placebo and Oral alprazolam 2 mg in a randomized order to Qualify Each subject was to receive all 7 interventions (Placebo, Oral alprazolam 1, 2 & 3 mg, Inhaled alprazolam 0.5, 1, & 2 mg) in a randomized order in a crossover design	31
Total	31

Baseline characteristics

Characteristic	Qualifying Session (Includes Crossover Group)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	31 Participants
Age, Continuous	38.032 years STANDARD_DEVIATION 38.032
Region of Enrollment United States	31 participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 15	0 / 14	0 / 15	0 / 14	0 / 15	0 / 15	0 / 28	0 / 28
other Total, other adverse events	0 / 15	0 / 15	0 / 14	1 / 15	0 / 14	0 / 15	0 / 15	0 / 28	1 / 28
serious Total, serious adverse events	0 / 15	0 / 15	0 / 14	0 / 15	0 / 14	0 / 15	0 / 15	0 / 28	0 / 28

Outcome results

Primary

Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again

The End of Day Questionnaire (EDQ) is a 7-question computerized instrument in which subjects rate the overall effect of the drug they received that day. The primary outcome measure for this trial is the categorical response to question number 5, Rate the degree to which you would like to take the drug again, with a numerical value assigned to each of the responses allowed: 0=Not at all, 1=A little, 2=Moderately, 3=Quite a bit, 4=Very much

Time frame: End of day for each of the 7 crossover treatments

Population: Efficacy (crossover) Population, n=14. LSM \& SEM are based on all 14 subjects completing all 7 treatments. PROC MIXED model used assigns the same SEM to all 7 treatments.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	0 units on a scale	Standard Error 0.349
Oral Alprazolam 1 mg	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	1.714 units on a scale	Standard Error 0.349
Oral Alprazolam 2 mg	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	2.143 units on a scale	Standard Error 0.349
Oral Alprazolam 4 mg	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	2.286 units on a scale	Standard Error 0.349
Inhaled Alprazolam 0.5 mg	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	1.00 units on a scale	Standard Error 0.349
Inhaled Alprazolam 1 mg	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	1.714 units on a scale	Standard Error 0.349
Inhaled Alprazolam 2 mg	Response to EDQ Question Number 5, Rate the Degree to Which You Would Like to Take the Drug Again	2.214 units on a scale	Standard Error 0.349

Secondary

EDQ Question Number 1, Rate the Overall Strength of the Drug Effect

The within patient rank (1-7) of End of Day question number 1, Rate the overall strength of the drug effect, response options range from 0-4: 0=No drug effect at all 1. Possible mild effect, but not sure 2. Definite mild effect 3. Moderate strong drug effect 4. Very strong drug effect Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect

Time frame: End of day for each of the 7 crossover treatments

Population: Efficacy (crossover) Population, n=14~LS Means via SAS PROC MIXED non-parametric model (ranks within subject), treatment and period as fixed effects, ddf=72~LSM \& SEM are based on the ranks of scores within each subject across all 14 subjects completing all 7 treatments.~PROC MIXED model assigns the same SEM to all 7 treatments.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	1.429 Rank across the 7 treatments	Standard Error 0.317
Oral Alprazolam 1 mg	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	3.536 Rank across the 7 treatments	Standard Error 0.317
Oral Alprazolam 2 mg	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	4.821 Rank across the 7 treatments	Standard Error 0.317
Oral Alprazolam 4 mg	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	5.429 Rank across the 7 treatments	Standard Error 0.317
Inhaled Alprazolam 0.5 mg	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	2.893 Rank across the 7 treatments	Standard Error 0.317
Inhaled Alprazolam 1 mg	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	4.143 Rank across the 7 treatments	Standard Error 0.317
Inhaled Alprazolam 2 mg	EDQ Question Number 1, Rate the Overall Strength of the Drug Effect	5.750 Rank across the 7 treatments	Standard Error 0.317

Secondary

EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect

The within patient rank (1-7) of End of Day question number 2 (of primary interest), Rate your overall liking of the drug effect, response options range from -4 to +4: * 4=Dislike very much * 3=Dislike quite a bit * 2=Dislike somewhat * 1=Dislike, but not very much 0=NEUTRAL OR NO EFFECT * 1=Like, but not very much * 2=Like somewhat * 3=Like quite a bit * 4=Like very much Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect

Time frame: End of day for each of the 7 crossover treatments

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	1.679 Rank across the 7 treatments	Standard Error 0.349
Oral Alprazolam 1 mg	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	4.214 Rank across the 7 treatments	Standard Error 0.349
Oral Alprazolam 2 mg	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	4.429 Rank across the 7 treatments	Standard Error 0.349
Oral Alprazolam 4 mg	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	4.607 Rank across the 7 treatments	Standard Error 0.349
Inhaled Alprazolam 0.5 mg	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	2.571 Rank across the 7 treatments	Standard Error 0.349
Inhaled Alprazolam 1 mg	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	4.857 Rank across the 7 treatments	Standard Error 0.349
Inhaled Alprazolam 2 mg	EDQ Question Number 2 Rate Your Overall Liking of the Drug Effect	5.643 Rank across the 7 treatments	Standard Error 0.349

Secondary

EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.

EDQ question number 6 (of primary interest), Estimate the amount of money you think the drug you took today would be worth on the street.

Time frame: End of day for each of the 7 crossover treatments

Population: Efficacy (crossover) Population, n=14. LSM \& SEM are based on all 14 subjects completing all 7 treatments. PROC MIXED model used assigns the same SEM to all 7 treatments.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	1.750 Dollars ($)	Standard Error 0.402
Oral Alprazolam 1 mg	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	3.571 Dollars ($)	Standard Error 0.402
Oral Alprazolam 2 mg	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	7.071 Dollars ($)	Standard Error 0.402
Oral Alprazolam 4 mg	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	8.714 Dollars ($)	Standard Error 0.402
Inhaled Alprazolam 0.5 mg	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	2.857 Dollars ($)	Standard Error 0.402
Inhaled Alprazolam 1 mg	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	4.286 Dollars ($)	Standard Error 0.402
Inhaled Alprazolam 2 mg	EDQ Question Number 6 Estimate the Amount of Money You Think the Drug You Took Today Would be Worth on the Street.	8.571 Dollars ($)	Standard Error 0.402

Secondary

EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?

EDQ question number 7, What would you be willing to pay for today's drug?

Time frame: End of day for each of the 7 crossover treatments

Population: Efficacy (crossover) Population, n=14. LSM \& SEM are based on all 14 subjects completing all 7 treatments. PROC MIXED model used assigns the same SEM to all 7 treatments.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	1.607 Dollars ($)	Standard Error 0.387
Oral Alprazolam 1 mg	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	3.821 Dollars ($)	Standard Error 0.387
Oral Alprazolam 2 mg	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	4.571 Dollars ($)	Standard Error 0.387
Oral Alprazolam 4 mg	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	5.179 Dollars ($)	Standard Error 0.387
Inhaled Alprazolam 0.5 mg	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	2.964 Dollars ($)	Standard Error 0.387
Inhaled Alprazolam 1 mg	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	4.107 Dollars ($)	Standard Error 0.387
Inhaled Alprazolam 2 mg	EDQ Question Number 7,What Would You be Willing to Pay for Today's Drug?	5.750 Dollars ($)	Standard Error 0.387

Secondary

Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)

The within patient rank (1-7) of Drug Effect Questionnaire question number 1: Rate the STRENGTH of the drug effect you are feeling RIGHT NOW; response options range for 0 to 4: No drug effect at all=0, Possible mild effect, but not sure=1, Definite mild effect=2, Moderate strong drug effect=3, Very strong drug effect=4 Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect

Time frame: DEQ was assessed at the 10 time points (predose through 9 hours)

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	1.571 Rank across the 7 treatments	Standard Error 0.34
Oral Alprazolam 1 mg	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	3.143 Rank across the 7 treatments	Standard Error 0.34
Oral Alprazolam 2 mg	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	4.714 Rank across the 7 treatments	Standard Error 0.34
Oral Alprazolam 4 mg	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	5.536 Rank across the 7 treatments	Standard Error 0.34
Inhaled Alprazolam 0.5 mg	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	3.036 Rank across the 7 treatments	Standard Error 0.34
Inhaled Alprazolam 1 mg	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	4.250 Rank across the 7 treatments	Standard Error 0.34
Inhaled Alprazolam 2 mg	Maximum of DEQ Question 1 Rate the Strength of the Drug Effect (at the 10 Time Points, Predose Through 9 Hours)	5.750 Rank across the 7 treatments	Standard Error 0.34

Secondary

Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)

The within patient rank (1-7) of maximum of the Rate your LIKING of the drug effect you are feeling RIGHT NOW; response options range from -4 to +4: Dislike very much=-4, Dislike quite a bit=-3, Dislike somewhat=-2, Dislike, but not very much=-1, NEUTRAL OR NO EFFECT=0, Like, but not very much=1, Like somewhat=2, Like quite a bit=3, Like very much=4 Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect

Time frame: DEQ was assessed at the 10 time points (predose through 9 hours)

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	1.607 Rank across the 7 treatments	Standard Error 0.343
Oral Alprazolam 1 mg	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	3.500 Rank across the 7 treatments	Standard Error 0.343
Oral Alprazolam 2 mg	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	4.536 Rank across the 7 treatments	Standard Error 0.343
Oral Alprazolam 4 mg	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	5.536 Rank across the 7 treatments	Standard Error 0.343
Inhaled Alprazolam 0.5 mg	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	2.893 Rank across the 7 treatments	Standard Error 0.343
Inhaled Alprazolam 1 mg	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	4.250 Rank across the 7 treatments	Standard Error 0.343
Inhaled Alprazolam 2 mg	Maximum of DEQ Question 2 Rate Your Liking of the Drug Effect at the 10 Time Points (Predose Through 9 Hours)	5.679 Rank across the 7 treatments	Standard Error 0.343

Secondary

Observer Rated Questionnaire 1) Maximum of Sedation/Sleepiness

The within patient rank (1-7) of Maximum of Observer Rated Questionnaire (ORQ): A trained and blinded staff member completed observer ratings as the subject completed the questionnaires and psychomotor assessment testing at each time point. The observer rated the subject on sedation/sleepiness, muscle relaxation, impaired posture, impaired speech, confusion/disorientation, stimulation/arousal and strength of drug effect on a five-point scale from 0 (indicating normal or no effect) to 4 (indicating extreme drug effect). Maximum of the 10 time points (predose through 9 hours) Thus a higher rank means a stronger drug effect and a lower rank a lesser drug effect