Evaluation of MDMA on Startle Response

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

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.

Study Overview

• Status: Completed
• Conditions: Startle Response
• Intervention / Treatment: Behavioral: Acoustic startle; Drug: Placebo; Drug: Midomafetamine

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDMA; Participants receive 100 mg MDMA	Behavioral: Acoustic startle; Startle assessment; Drug: Midomafetamine; Participant will receive 100 mg MDMA one day after startle assessment; Other Names: MDMA; 3,4-methylenedioxymethamphetamine
Placebo Comparator: Placebo; Participants receive inactive placebo	Behavioral: Acoustic startle; Startle assessment; Drug: Placebo; Placebo given day after startle assessment

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lykos Therapeutics
• Investigators: Principal Investigator: Barbara Rothbaum, Emory University

Publications and helpful links

General Publications

• Maples-Keller JL, Norrholm SD, Burton M, Reiff C, Coghlan C, Jovanovic T, Yasinski C, Jarboe K, Rakofsky J, Rauch S, Dunlop BW, Rothbaum BO. A randomized controlled trial of 3,4-methylenedioxymethamphetamine (MDMA) and fear extinction retention in healthy adults. J Psychopharmacol. 2022 Mar;36(3):368-377. doi: 10.1177/02698811211069124. Epub 2022 Feb 15.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2017
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: June 7, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: sleep; Oxytocin; MDMA; Startle response
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: MPVA-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share data after quality analysis and upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No