Cocaine Abuse and Dependence
Conditions
Keywords
Acetylcholine, Acetylcholinesterase, Butyrylcholinesterase, Cholinesterase Inhibitor
Brief summary
The purpose of this study is to determine the safety of intravenous cocaine in subjects receiving oral donepezil.
Detailed description
This is a randomized, double-blind, double-dummy, placebo controlled, inpatient, single-center, parallel group evaluation of the potential for oral donepezil to attenuate cocaine-induced craving. Non-treatment-seeking cocaine-experienced volunteers will receive baseline treatment with intravenous cocaine (30Mg). Forty-two subjects that tolerate baseline cocaine infusions will then receive two subsequent intravenous doses of cocaine during double-blind treatment with oral placebo or 5 mg daily of donepezil. Each dose of cocaine will be preceded or followed by administration of intravenous placebo (saline) in a random order.
Interventions
DRUGDonepezil, 5 mg daily
This is a commercially available cholinesterase inhibitor that is approved for use in Alzheimer's disease.
OTHEROral Placebo
Inactive Comparator with Similar Appearance to Active Medication
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Non-treatment seeking, experienced cocaine users, who have used cocaine by smoking or intravenous injection within the four weeks prior to screening, and must supply a cocaine-positive urine obtained within four weeks of entry into the study.
Exclusion criteria
* Shows signs of psychostimulant toxicity, or has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure. * Has a current psychiatric disorder other than drug abuse or dependence or dementia. * Meets the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for dependence to opiates, benzodiazepines, alcohol, or other sedative-hypnotics. * Has received opiate-substitution therapy (methadone or buprenorphine) within two months prior to enrollment. * Has current or past history of seizure disorder, including alcohol- or psychostimulant- related seizures, or family history of seizure disorder. * Has a diagnosis of adult asthma, or chronic obstructive pulmonary disease, including a history of acute asthma within the past two years, and those with current or recent (with the past two years) treatment with an inhaled or oral beta-adrenergic agonist. * Has had head trauma that resulted in neurological sequelae. * Has an unstable medical condition, which, in the judgement of investigators, would make participation hazardous.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Safety in Subjects Receiving Donepezil | Two weeks | Patients evaluated for clinical and laboratory adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Subjective Effects | 3 to 30 minutes | Cocaine Induced 'High' by VAS (visual analogue scale, between 3 and 30 minutes after intravenous dosing, in mm). VAS results ranged from 0 (minimum effect) to 100 (maximum effect). |
| Cocaine Pharmacokinetics | 0 to 8 hours | Area-Under-the-Curve for Plasma Concentration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All recruited subjects | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 46.4 Years STANDARD_DEVIATION 0.8 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Cocaine Safety in Subjects Receiving Donepezil
Patients evaluated for clinical and laboratory adverse events
Time frame: Two weeks
Population: All participants included
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Treatment Period | Cocaine Safety in Subjects Receiving Donepezil | 0 Participants with an Adverse Event |
| Donepezil Treatment Period | Cocaine Safety in Subjects Receiving Donepezil | 2 Participants with an Adverse Event |
Secondary
Cocaine Pharmacokinetics
Area-Under-the-Curve for Plasma Concentration
Time frame: 0 to 8 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo Treatment Period | Cocaine Pharmacokinetics | 34,503 ng-hr/ml |
| Donepezil Treatment Period | Cocaine Pharmacokinetics | 40,812 ng-hr/ml |
Secondary
Cocaine Subjective Effects
Cocaine Induced 'High' by VAS (visual analogue scale, between 3 and 30 minutes after intravenous dosing, in mm). VAS results ranged from 0 (minimum effect) to 100 (maximum effect).
Time frame: 3 to 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Treatment Period | Cocaine Subjective Effects | 44.1 mm | Standard Error 17.8 |
| Donepezil Treatment Period | Cocaine Subjective Effects | 89.9 mm | Standard Error 35.3 |