Opioid Abuse, Opioid Addiction, Stimulant Abuse, Stimulant Addiction
Conditions
Keywords
drug discrimination, opioid pharmacology, behavioral pharmacology, human research
Brief summary
This research is part of a set of studies whose purpose is to test whether tramadol can be used for the treatment of opioid addiction. Tramadol is already available in the United States as a pain medicine marketed as Ultram. It has effects similar to morphine, and it may also have effects similar to other drugs like stimulants. The doses of tramadol used in this study are higher than those generally used for the treatment of pain. To be in this study a participant must be a user of opioids (drugs like heroin) and stimulants (drugs like cocaine), but cannot be addicted to either. The person must be between 21-55 years old, and generally healthy. Up to 12 people will take part in this study.
Detailed description
This is a human laboratory study that tests the effects of tramadol as a step in the possible development of this medication as a new treatment for opioid dependence. Tramadol is a mild/moderate mu agonist opioid currently marketed as an analgesic that has a unique profile of effects. One of the primary metabolites of tramadol, mono-O-demethyltramadol (referred to as M1) exerts opioid agonist effects at the mu receptor. In addition, tramadol and M1 produce reuptake blockade of monoamines, and this latter effect may positively influence its analgesic efficacy, in addition to influencing the subjective effects produced by tramadol. Preclinical evidence suggests that tramadol's effects on monoamine reuptake may have antidepressant qualities as well. Given tramadol's diverse pharmacodynamic profile, a systematic characterization of its subjective effects in opioid-experienced subjects would provide valuable information regarding its abuse liability, and its potential utility as a treatment for opioid dependence. The characterization of an opioid medication's profile can be accomplished through a variety of experimental procedures. One useful procedure for assessing the profile of an opioid is a drug discrimination procedure. In this methodology, subjects are first trained to discriminate reference drugs such as placebo and an opioid agonist, and then administered doses of a novel compound to determine how like (or unlike) it is to the reference training conditions. Our laboratory has a long history of using this drug discrimination methodology to study and to characterize opioids with varying opioid receptor activity profiles. Studies have generally included either two or three training conditions in humans. Using this technique in volunteers, studies have characterized the profile of a number of opioids including (for example) butorphanol, nalbuphine, pentazocine, and buprenorphine. While most of these studies testing the effects of mixed agonist-antagonist opioids have used an opioid agonist and placebo as the training conditions, tramadol's profile of effects suggests that there may be a non-opioid component of action at serotonin and norepinephrine sites that will be useful to distinguish. In particular, it is of interest to determine the extent to which tramadol is identified as being like a prototypic mu agonist opioid, whether it is substantially identified as being like a non-opioid compound, and if this non-opioid component is related to enhancement of monoamine effects. In order to provide a meaningful non-opioid contrast training condition, this study will compare different doses of tramadol to training conditions of placebo, a mu agonist opioid, and a prototypic stimulant. Overall, this evaluation will provide a greater understanding of the subjective effect profile of tramadol in comparison to a prototypic mu opioid and a prototypic stimulant. If tramadol is to be useful in the treatment of opioid dependence, a thorough assessment of its subjective effects in experienced opioid and stimulant abusers is warranted.
Interventions
DRUGtramadol
oral dose, once per day
DRUGplacebo
oral dose, once per day
DRUGHydromorphone
oral dose, once per day
DRUGMethylphenidate
oral dose, once per day
Sponsors
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Months to 55 Years
Healthy volunteers
No
Inclusion criteria
* Study subjects are male and female non-dependent opioid users with active stimulant use. * Between the ages of 21-55 * In good physical health * Without significant psychiatric illness besides their drug use. * Females are required to provide a negative pregnancy test prior to study participation.
Exclusion criteria
* Subjects are excluded if they have evidence of significant medical (e.g., insulin dependent diabetes mellitus) or psychiatric (e.g., schizophrenia) illness. * Subjects with a history of seizures will be excluded. * Persons with current history of significant alcohol or sedative/hypnotic drug use will be excluded from study participation. * Applicants seeking treatment for their substance abuse will not be admitted to the study, and will be provided information about treatment services available.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Discrimination Effects Assessed by Discrete Choice | 1 day | During discrete choice, volunteers were given three choices (placebo, hydromorphone, methylphenidate) and were asked to choose which of the training drugs they thought they received. The outcome measure illustrates the percentage of participants who chose either placebo, hydromorphone, or methylphenidate during each drug condition (i.e., Placebo, Hydromorphone 8 mg, Tramadol 50 mg, etc.), ranging from 0-100. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition. |
| Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test | 1 day | The acquisition of discrimination was to test whether volunteers could identify each training drug condition by the correct letter code. Results are the percentage of correct responses with a range of 0% to 100%. |
| Discrimination Effects Assessed by Operant Responses | 1 day | Volunteers emitted operant responses on computer keys that corresponded to the training letter, on a fixed interval 1 second schedule for 8.5 minutes. The range is from 0 to 500 operant responses. |
| Discrimination Effects Assessed by Point Distribution | 1day | In point distribution, volunteers distributed 50 points among three training drug letters depending on how certain they were of the identity of the administrated drug. Maximum total is 50 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Measure at 120 min after drug administration | During the peak (assessed at 120 min) of each drug administration, participants were asked to complete the pharmacological class questionnaire. The pharmacological class questionnaire had volunteers indicate which drug class was most similar to the drug condition they received. Ten drug classes were listed with descriptive labels and examples of each: placebo, opiates (or opioid agonist), phenothiazines, barbiturates, antidepressants, opiate antagonists, hallucinogens, benzodiazepines, stimulants, and other. Of these choices, participants chose 3: placebo, opioid agonist, and stimulant. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition. |
| Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | Measure at 120 min after drug administration | Change in pupil diameter (mm) at peak (120 min) compared to baseline measure of pupil diameter |
| Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | Measure at 120 min after drug administration | The Visual Analog Scale (VAS) measures subjective ratings of opioid agonist effects. The scale on this measure ranges from 0 being Not at all to 100 being Extremely. On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure on VAS. |
| Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | Measure at 120 min after drug administration | The Visual Analog Scale (VAS) measures subjective ratings of stimulant effects. The scale on this measure ranges from 0 being Not at all to 100 being Extremely. On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1(6-9 One Day Sessions) | Failed to perform study task | 7 |
| Phase 1(6-9 One Day Sessions) | Investigator decision | 1 |
| Phase 1(6-9 One Day Sessions) | Unable to determine | 1 |
| Phase 1(6-9 One Day Sessions) | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Group 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 40.3 years STANDARD_DEVIATION 2.3 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test
The acquisition of discrimination was to test whether volunteers could identify each training drug condition by the correct letter code. Results are the percentage of correct responses with a range of 0% to 100%.
Time frame: 1 day
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo 0 mg | Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test | 87 percent of correct response |
| Hydromorphone 8 mg | Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test | 87.5 percent of correct response |
| Methylphenidate 60 mg | Acquisition of Discrimination Assessed by Accuracy of the Discrimination Test | 90 percent of correct response |
Primary
Discrimination Effects Assessed by Discrete Choice
During discrete choice, volunteers were given three choices (placebo, hydromorphone, methylphenidate) and were asked to choose which of the training drugs they thought they received. The outcome measure illustrates the percentage of participants who chose either placebo, hydromorphone, or methylphenidate during each drug condition (i.e., Placebo, Hydromorphone 8 mg, Tramadol 50 mg, etc.), ranging from 0-100. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.
Time frame: 1 day
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo 0 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 0 percentage of drug identification |
| Placebo 0 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 100 percentage of drug identification |
| Placebo 0 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 0 percentage of drug identification |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 25 percentage of drug identification |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 75 percentage of drug identification |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 0 percentage of drug identification |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 100 percentage of drug identification |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 0 percentage of drug identification |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 0 percentage of drug identification |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 0 percentage of drug identification |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 100 percentage of drug identification |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 0 percentage of drug identification |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 0 percentage of drug identification |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 0 percentage of drug identification |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 100 percentage of drug identification |
| Tramadol 50 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 100 percentage of drug identification |
| Tramadol 50 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 0 percentage of drug identification |
| Tramadol 50 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 0 percentage of drug identification |
| Tramadol 100 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 25 percentage of drug identification |
| Tramadol 100 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 75 percentage of drug identification |
| Tramadol 100 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 0 percentage of drug identification |
| Tramadol 200 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 0 percentage of drug identification |
| Tramadol 200 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 25 percentage of drug identification |
| Tramadol 200 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 75 percentage of drug identification |
| Tramadol 400 mg | Discrimination Effects Assessed by Discrete Choice | Hydromorphone | 63 percentage of drug identification |
| Tramadol 400 mg | Discrimination Effects Assessed by Discrete Choice | Placebo | 25 percentage of drug identification |
| Tramadol 400 mg | Discrimination Effects Assessed by Discrete Choice | Methylphenidate | 12 percentage of drug identification |
Primary
Discrimination Effects Assessed by Operant Responses
Volunteers emitted operant responses on computer keys that corresponded to the training letter, on a fixed interval 1 second schedule for 8.5 minutes. The range is from 0 to 500 operant responses.
Time frame: 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo 0 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 455.5 Responses | Standard Error 9.6 |
| Placebo 0 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 0.0 Responses | Standard Error 0 |
| Placebo 0 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 0.0 Responses | Standard Error 0 |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 0.0 Responses | Standard Error 0 |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 341.3 Responses | Standard Error 74.7 |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 116.6 Responses | Standard Error 76.4 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 453.4 Responses | Standard Error 9 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 0.0 Responses | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 0.0 Responses | Standard Error 0 |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 465.4 Responses | Standard Error 4.7 |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 0.0 Responses | Standard Error 0 |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 0.0 Responses | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 0.0 Responses | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 0.0 Responses | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 465.8 Responses | Standard Error 3 |
| Tramadol 50 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 0.0 Responses | Standard Error 0 |
| Tramadol 50 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 464.1 Responses | Standard Error 4.2 |
| Tramadol 50 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 0.0 Responses | Standard Error 0 |
| Tramadol 100 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 0.0 Responses | Standard Error 0 |
| Tramadol 100 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 341.3 Responses | Standard Error 74.8 |
| Tramadol 100 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 118.1 Responses | Standard Error 77.3 |
| Tramadol 200 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 367.0 Responses | Standard Error 60.2 |
| Tramadol 200 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 0.0 Responses | Standard Error 0 |
| Tramadol 200 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 86.6 Responses | Standard Error 62 |
| Tramadol 400 mg | Discrimination Effects Assessed by Operant Responses | Hydromorphone | 282.9 Responses | Standard Error 83.4 |
| Tramadol 400 mg | Discrimination Effects Assessed by Operant Responses | Methylphenidate | 59.9 Responses | Standard Error 59.9 |
| Tramadol 400 mg | Discrimination Effects Assessed by Operant Responses | Placebo | 115.6 Responses | Standard Error 75.7 |
Primary
Discrimination Effects Assessed by Point Distribution
In point distribution, volunteers distributed 50 points among three training drug letters depending on how certain they were of the identity of the administrated drug. Maximum total is 50 points.
Time frame: 1day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo 0 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 0.0 Points distributed | Standard Error 0 |
| Placebo 0 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 0.0 Points distributed | Standard Error 0 |
| Placebo 0 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 50.0 Points distributed | Standard Error 0 |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 0.0 Points distributed | Standard Error 0 |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 11.9 Points distributed | Standard Error 7.8 |
| Hydromorphone 8 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 38.1 Points distributed | Standard Error 7.8 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 0.0 Points distributed | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 0.0 Points distributed | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 50.0 Points distributed | Standard Error 0 |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 50.0 Points distributed | Standard Error 0 |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 0.0 Points distributed | Standard Error 0 |
| Methylphenidate 30 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 0.0 Points distributed | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 0.0 Points distributed | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 0.0 Points distributed | Standard Error 0 |
| Methylphenidate 60 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 50.0 Points distributed | Standard Error 0 |
| Tramadol 50 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 0.0 Points distributed | Standard Error 0 |
| Tramadol 50 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 50.0 Points distributed | Standard Error 0 |
| Tramadol 50 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 0.0 Points distributed | Standard Error 0 |
| Tramadol 100 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 0.0 Points distributed | Standard Error 0 |
| Tramadol 100 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 37.5 Points distributed | Standard Error 8.2 |
| Tramadol 100 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 12.5 Points distributed | Standard Error 8.2 |
| Tramadol 200 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 38.3 Points distributed | Standard Error 6.5 |
| Tramadol 200 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 0.0 Points distributed | Standard Error 0 |
| Tramadol 200 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 9.4 Points distributed | Standard Error 6.6 |
| Tramadol 400 mg | Discrimination Effects Assessed by Point Distribution | Hydromorphone | 31.3 Points distributed | Standard Error 9.1 |
| Tramadol 400 mg | Discrimination Effects Assessed by Point Distribution | Methylphenidate | 6.3 Points distributed | Standard Error 6.3 |
| Tramadol 400 mg | Discrimination Effects Assessed by Point Distribution | Placebo | 12.5 Points distributed | Standard Error 8.2 |
Secondary
Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS)
The Visual Analog Scale (VAS) measures subjective ratings of opioid agonist effects. The scale on this measure ranges from 0 being Not at all to 100 being Extremely. On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure on VAS.
Time frame: Measure at 120 min after drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo 0 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 1.4 units on a scale | Standard Error 0.7 |
| Hydromorphone 8 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 2.9 units on a scale | Standard Error 1 |
| Methylphenidate 60 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 4.8 units on a scale | Standard Error 2.1 |
| Methylphenidate 30 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 2.1 units on a scale | Standard Error 0.5 |
| Methylphenidate 60 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 3.4 units on a scale | Standard Error 1.2 |
| Tramadol 50 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 0.4 units on a scale | Standard Error 0.4 |
| Tramadol 100 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 1.6 units on a scale | Standard Error 0.7 |
| Tramadol 200 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 2.1 units on a scale | Standard Error 1 |
| Tramadol 400 mg | Peak Change From Baseline Opioid Agonist Effects Assessed by the Visual Analog Scale (VAS) | 3.8 units on a scale | Standard Error 1.8 |
Secondary
Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS)
The Visual Analog Scale (VAS) measures subjective ratings of stimulant effects. The scale on this measure ranges from 0 being Not at all to 100 being Extremely. On this scale, higher scores indicate a stronger drug effect. The outcome measure illustrates a difference from peak (120 min) to baseline measure.
Time frame: Measure at 120 min after drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo 0 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 1.4 units on a scale | Standard Error 0.8 |
| Hydromorphone 8 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 3.6 units on a scale | Standard Error 1 |
| Methylphenidate 60 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 3.6 units on a scale | Standard Error 1.2 |
| Methylphenidate 30 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 8.0 units on a scale | Standard Error 1.6 |
| Methylphenidate 60 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 10.6 units on a scale | Standard Error 2.3 |
| Tramadol 50 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 0.6 units on a scale | Standard Error 0.4 |
| Tramadol 100 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 0.9 units on a scale | Standard Error 0.5 |
| Tramadol 200 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 4.9 units on a scale | Standard Error 2 |
| Tramadol 400 mg | Peak Change From Baseline Stimulant Effects Assessed by the Visual Analog Scale (VAS) | 6.9 units on a scale | Standard Error 2.1 |
Secondary
Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter
Change in pupil diameter (mm) at peak (120 min) compared to baseline measure of pupil diameter
Time frame: Measure at 120 min after drug administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo 0 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.5 mm | Standard Error 0.2 |
| Hydromorphone 8 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -1.2 mm | Standard Error 0.2 |
| Methylphenidate 60 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -1.9 mm | Standard Error 0.2 |
| Methylphenidate 30 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.6 mm | Standard Error 0.3 |
| Methylphenidate 60 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.3 mm | Standard Error 0.2 |
| Tramadol 50 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.5 mm | Standard Error 0.1 |
| Tramadol 100 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.2 mm | Standard Error 0.1 |
| Tramadol 200 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.8 mm | Standard Error 0.3 |
| Tramadol 400 mg | Physiological Effects Assessed by Peak Change From Baseline Pupil Diameter | -0.8 mm | Standard Error 0.3 |
Secondary
Physiologic Effects Assessed by the Pharmacological Class Questionnaire
During the peak (assessed at 120 min) of each drug administration, participants were asked to complete the pharmacological class questionnaire. The pharmacological class questionnaire had volunteers indicate which drug class was most similar to the drug condition they received. Ten drug classes were listed with descriptive labels and examples of each: placebo, opiates (or opioid agonist), phenothiazines, barbiturates, antidepressants, opiate antagonists, hallucinogens, benzodiazepines, stimulants, and other. Of these choices, participants chose 3: placebo, opioid agonist, and stimulant. The outcome measure represents the percentage of participants who chose either placebo, opioid agonist, or stimulant across each drug condition.
Time frame: Measure at 120 min after drug administration
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo 0 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 100 percentage of drug identification |
| Placebo 0 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 0 percentage of drug identification |
| Placebo 0 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 0 percentage of drug identification |
| Hydromorphone 8 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 0 percentage of drug identification |
| Hydromorphone 8 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 75 percentage of drug identification |
| Hydromorphone 8 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 25 percentage of drug identification |
| Methylphenidate 60 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 100 percentage of drug identification |
| Methylphenidate 60 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 0 percentage of drug identification |
| Methylphenidate 60 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 0 percentage of drug identification |
| Methylphenidate 30 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 100 percentage of drug identification |
| Methylphenidate 30 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 0 percentage of drug identification |
| Methylphenidate 30 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 0 percentage of drug identification |
| Methylphenidate 60 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 0 percentage of drug identification |
| Methylphenidate 60 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 0 percentage of drug identification |
| Methylphenidate 60 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 100 percentage of drug identification |
| Tramadol 50 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 0 percentage of drug identification |
| Tramadol 50 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 100 percentage of drug identification |
| Tramadol 50 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 0 percentage of drug identification |
| Tramadol 100 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 0 percentage of drug identification |
| Tramadol 100 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 75 percentage of drug identification |
| Tramadol 100 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 25 percentage of drug identification |
| Tramadol 200 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 63 percentage of drug identification |
| Tramadol 200 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 0 percentage of drug identification |
| Tramadol 200 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 37 percentage of drug identification |
| Tramadol 400 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Opioid Agonist | 63 percentage of drug identification |
| Tramadol 400 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Stimulant | 12 percentage of drug identification |
| Tramadol 400 mg | Physiologic Effects Assessed by the Pharmacological Class Questionnaire | Placebo | 25 percentage of drug identification |