Evaluation of MDMA on Startle Response

Study Overview
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Brief Summary
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This study will examine how the drug methylenedioxymethamphetamine (MDMA) impacts response to different types of memory in humans compared to placebo. MDMA is an experimental drug and is illegal to possess outside of research; when sold illegally it is referred to as Ecstasy or Molly (material supposedly containing MDMA). MDMA may make it easier to face unpleasant memories and reduce anxiety, and it may do so in part by influencing response to memories. This study will enroll healthy adults who will need to come in for three visits over four days. At visit 1, participants will undergo a 1-hour startle test. The startle test measures eye-blink response to loud sounds. After this, the participant will also view different colored shapes presented on a computer monitor. While watching the computer monitor, the participant will experience several brief blasts of air directed at the throat, while eye-blink is measured with sensors under the eye. The following day at visit 2, participants will be randomized to receive placebo or 100 mg MDMA and will complete tasks similar to the ones completed the previous day. Participants who agree to do so will have blood drawn to measure the neurohormones oxytocin and cortisol and brain-derived neurotrophic factor (BDNF) before and after drug administration on Visit 2. The researchers will measure pulse, blood pressure and temperature once before and seven times after receiving MDMA or placebo, and study participants will complete a questionnaire about their experience. Two days after receiving MDMA or placebo, participants will return for a third visit to complete similar tasks to previous visits. This study will also measure sleep through a sleep diary and actigraphy, which is a device worn on the wrist like a watch that records movement during sleep and lets researchers see how much sleep a person is getting.

Detailed Description
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This is a randomized, blinded, placebo-controlled Phase 1 study that aims to evaluate the impact of 3,4-methylenedioxymethamphetamine (MDMA) on startle response . MDMA is an experimental drug and is illegal to possess outside of research; when sold illegally it is referred to as Ecstasy or Molly (material supposedly containing MDMA). MDMA may make it easier to face unpleasant memories and reduce anxiety. This study will enroll healthy participants. At visit 1 all participants will undergo a 1-hour startle test. Acoustic startle will be measured through assessing eye-blink response from the orbicularis oculi muscles in response to a 106 dB noise, using sensors under the eye. While watching the computer monitor, the participant will also experience several brief blasts of air directed at the throat. At visit 2, 24 hours later, participants will be randomized to receive 100 mg of MDMA or inactive placebo, after which they will undergo another startle task. Participants enrolled in the study who agree to do this will have their blood drawn to measure levels of oxytocin, and possibly other hormones or proteins, such as cortisol or brain-derived neurotrophic factor (BDNF). Measuring oxytocin will be blind to condition, and the decision will happen before randomization to either condition. Blood will be drawn before MDMA or placebo administration, and eight times afterwards.The researchers will measure pulse, blood pressure and temperature once before and six times after receiving MDMA or placebo, and study participants will complete a questionnaire about their experience. At visit 3, participants will return for a final startle test and recall task. Sleep will be measured via self-report and Fittbit during study participation. The primary objective of this study is to assess whether MDMA affects startle response

Official Title
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Evaluation of 3,4-methylenedioxymethamphetamine (MDMA) on Startle Response

Conditions
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Startle Response

Intervention / Treatment
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* Drug: Placebo
* Drug: Midomafetamine
* Behavioral: Acoustic startle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persons aged 21 to 55. Ability to visually read and understand English language. Live within in metro Atlanta area Previously used MDMA in a recreational or research setting If a person is of childbearing potential (able to bear children), they must have a negative pregnancy test at study entry and prior to the Experimental Session. They must agree to use adequate birth control through 10 days after the last dose of MDMA. Adequate birth control methods include intrauterine device (IUD), injected or implanted hormonal methods, abstinence, oral hormones plus a barrier contraception or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e. condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Not of childbearing potential is defined as permanent sterilization, postmenopausal, or male. (For sub-study measuring serum oxytocin) Willing to have periodic blood draws Exclusion Criteria: Upon review of medical or psychiatric history, have any current or past diagnosis that would be considered a risk to participating in the study. Are abusing illegal drugs. Current use of any psychoactive medications, including antidepressants, mood stabilizers, sedatives, stimulants, antipsychotics, anxiolytics, or beta-blockers Are not able to give adequate informed consent. Uncontrolled hypertension, or clinically significant cardiac arrhythmia, as detected by electrocardiogram. Currently pregnant or breast-feeding. History of acute angle glaucoma. Hearing impairment as assessed by audiometer; unable to detect tones below 40 dB in right or left ear.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Blinded, placebo between group; all participants undergo fear conditioning, with half randomized to receive 100 mg MDMA and half receiving inactive placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDMA<br>Participants receive 100 mg MDMA | Drug: Midomafetamine<br>* Participant will receive 100 mg MDMA one day after startle assessment<br>* Other names: MDMA;Behavioral: Acoustic startle<br>* Startle assessment<br>|
| Placebo Comparator: Placebo<br>Participants receive inactive placebo | Drug: Placebo<br>* Placebo given day after startle assessment<br>Behavioral: Acoustic startle<br>* Startle assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EMG of right orbicularis oculi muscle | Description: Measure of startle response to noise after fear extinction training | Four days post-enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure pre-drug | Systolic blood pressure measured prior to administration of MDMA or placebo | 5 minutes pre-drug | 
| Systolic blood pressure 45 min post-drug | Systolic blood pressure measured 45 minutes after MDMA or placebo administration | 45 minutes post-drug | 
| Systolic blood pressure 1 h 15 min post-drug | Systolic blood pressure measured 1 hour 15 minutes after MDMA or placebo administration | 1 hour 15 minutes post drug | 
| Systolic blood pressure 1 h 45 min post-drug | Systolic blood pressure measured 1 hour 45 minutes after MDMA or placebo administration | 1 hour 45 minutes post drug | 
| Systolic blood pressure 3 h post-drug | Systolic blood pressure measured 3 hours after MDMA or placebo administration | 3 hours post-drug | 
| Systolic blood pressure 4 h post-drug | Systolic blood pressure measured 4 hours after MDMA or placebo administration | 4 hours post-drug | 
| Systolic blood pressure 5 h post-drug | Systolic blood pressure measured 5 hours after MDMA or placebo administration | 5 hours post-drug | 
| Systolic blood pressure 6 h post-drug | Systolic blood pressure measured 6 hours after MDMA or placebo administration | 6 hours post-drug | 
| Diastolic blood pressure pre-drug | Diastolic blood pressure measured prior to MDMA or placebo administration | 5 minutes pre-drug | 
| Diastolic blood pressure 45 min post-drug | Diastolic blood pressure measured 45 minutes after MDMA or placebo administration | 45 minutes post-drug | 
| Diastolic blood pressure 1 h 15 min post-drug | Diastolic blood pressure measured 1 h 15 minutes after MDMA or placebo administration | 1 hour 15 minutes post-drug | 
| Diastolic blood pressure 1 h 45 min post-drug | Diastolic blood pressure measured 1 h 45 minutes after MDMA or placebo administration | 1 hour 45 minutes post drug | 
| Diastolic blood pressure 3 h post-drug | Diastolic blood pressure measured 3 hours after MDMA or placebo administration | 3 hours post-drug | 
| Diastolic blood pressure 4 hours post-drug | Diastolic blood pressure measured 4 hours after MDMA or placebo administration | 4 hours post-drug | 
| Diastolic blood pressure 5 hours post-drug | Diastolic blood pressure measured 5 hours after MDMA or placebo administration | 5 hours post-drug | 
| Diastolic blood pressure 6 hours post-drug | Diastolic blood pressure measured 6 hours after MDMA or placebo administration | 6 hours post-drug | 
| Pulse pre-drug | Pulse (assessing heart rate) measured prior to MDMA or placebo administration | 5 minutes pre-drug | 
| Pulse 45 min post-drug | Pulse (assessing heart rate) measured 45 min after MDMA or placebo administration | 45 minutes post-drug | 
| Pulse 1 h 15 min post-drug | Pulse (assessing heart rate) measured 1 hour 15 min after MDMA or placebo administration | 1 hour 15 minutes post-drug | 
| Pulse 1 h 45 min post-drug | Pulse (assessing heart rate) measured 1 hour 45 min after MDMA or placebo administration | 1 hour 45 minutes post-drug | 
| Pulse 3 h post-drug | Pulse (assessing heart rate) measured 3 hours after MDMA or placebo administration | 3 hours post-drug | 
| Pulse 4 h post-drug | Pulse (assessing heart rate) measured 4 hours after MDMA or placebo administration | 4 hours post-drug | 
| Pulse 5 h post-drug | Pulse (assessing heart rate) measured 5 hours after MDMA or placebo administration | 5 hours post-drug | 
| Pulse 6 h post-drug | Pulse (assessing heart rate) measured 6 hours after MDMA or placebo administration | 6 hours post-drug | 
| Body temperature pre-drug | Body temperature measured before MDMA or placebo administration | 5 minutes pre-drug | 
| Body temperature 45 minutes post-drug | Body temperature measured 45 minutes after MDMA or placebo administration | 45 minutes post-drug | 
| Body temperature 1 h 15 minutes post-drug | Body temperature measured 1 hour 15 minutes after MDMA or placebo administration | 1 hour 15 minutes post-drug | 
| Body temperature 1 h 45 minutes post-drug | Body temperature measured 1 hour 45 minutes after MDMA or placebo administration | 1 hour 45 minutes post-drug | 
| Body temperature 3 hours post-drug | Body temperature measured 3 hours after MDMA or placebo administration | 3 hours post-drug | 
| Body temperature 4 hours post-drug | Body temperature measured 4 hours after MDMA or placebo administration | 4 hours post-drug | 
| Body temperature 5 hours post-drug | Body temperature measured 5 hours after MDMA or placebo administration | 5 hours post-drug | 
| Body temperature 6 hours post-drug | Body temperature measured 6 hours after MDMA or placebo administration | 6 hours post-drug | 
| Plasma oxytocin (OT) levels predrug | In people who agree to it, blood collected to assess levels of oxytocin prior to MDMA or placebo administration on day of drug administration | 5 min prior to drug administration | 
| Plasma oxytocin (OT) levels 5 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 5 minutes after MDMA or placebo administration | 5 min post-drug administration | 
| Plasma oxytocin (OT) levels 20 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 20 minutes after MDMA or placebo administration | 20 min post-drug administration | 
| Plasma oxytocin (OT) levels 95 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 95 minutes (approximately 1.5 h) after MDMA or placebo administration | 95 min post-drug administration | 
| Plasma oxytocin (OT) levels 110 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 110 minutes after MDMA or placebo administration | 110 min post-drug administration | 
| Plasma oxytocin (OT) levels 185 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 185 minutes after MDMA or placebo administration | 185 min post-drug administration | 
| Plasma oxytocin (OT) levels 200 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 200 minutes after MDMA or placebo administration | 200 min post-drug administration | 
| Plasma oxytocin (OT) levels 240 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 240 minutes after MDMA or placebo administration | 240 min post-drug administration | 
| Plasma oxytocin (OT) levels 300 min post-drug | In people who agree to it, blood collected to assess levels of oxytocin approximately 300 minutes after MDMA or placebo administration | 300 min post-drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA, Startle response, sleep, Oxytocin