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A randomized controlled trial of 3,4-methylenedioxymethamphetamine (MDMA) and fear extinction retention in healthy adults

Maples-Keller, Jessica L; Norrholm, Seth D; Burton, Mark; Reiff, Collin; Coghlan, Callan; Jovanovic, Tanja; Yasinski, Carly; Jarboe, Kathleen; Rakofsky, Jeffrey; Rauch, Sheila; Dunlop, Boadie W; Rothbaum, Barbara O
BACKGROUND/UNASSIGNED:Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention. AIMS/UNASSIGNED:This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans. METHODS/UNASSIGNED: = 34; 70.6% male and 29.4% female) were randomly assigned in 1:1 ratio to 100 mg MDMA or placebo. All randomized participants completed the trial and were included in primary analyses. Safety was monitored via adverse events and vital signs. MDMA was well-tolerated with no serious adverse events. RESULTS/UNASSIGNED: = 0.007). CONCLUSION/UNASSIGNED:Although we did not observe the hypothesized facilitation of extinction retention, the findings from this initial human trial provide compelling rationale to continue to explore the potential for MDMA to impact extinction retention.Clinical Trials Registry Name and Identifier: Evaluation of MDMA on Startle Response (NCT0318176) = MDMA&draw = 2&rank = 9.
PMID: 35166140
ISSN: 1461-7285
CID: 5167412

MDMA-assisted psychotherapy for the treatment of PTSD [Editorial]

Reiff, Collin M; McDonald, William M
PMID: 33053043
ISSN: 1809-452x
CID: 4702622

Psychedelics and Psychedelic-Assisted Psychotherapy

Reiff, Collin M; Richman, Elon E; Nemeroff, Charles B; Carpenter, Linda L; Widge, Alik S; Rodriguez, Carolyn I; Kalin, Ned H; McDonald, William M
(Reprinted with permission from The American Journal of Psychiatry 2020; 177:391-410).
PMID: 34483775
ISSN: 1541-4094
CID: 5112812


Chapter by: Ross, Stephen; Franco, Silvia; Reiff, Collin; Agin-Liebes, Gabrielle
in: Handbook of medical hallucinogens by Grob, Charles S; Grigsby, Jim (Eds)
New York, NY : The Guilford Press, [2021]
pp. 181-214
ISBN: 1462545440
CID: 5069562

Psychedelics and Psychedelic-Assisted Psychotherapy

Reiff, Collin M; Richman, Elon E; Nemeroff, Charles B; Carpenter, Linda L; Widge, Alik S; Rodriguez, Carolyn I; Kalin, Ned H; McDonald, William M
OBJECTIVE/UNASSIGNED:The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders. METHODS/UNASSIGNED:-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care. RESULTS/UNASSIGNED:The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as "breakthrough therapies" for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders. CONCLUSIONS/UNASSIGNED:Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.
PMID: 32098487
ISSN: 1535-7228
CID: 4324312

Brain mechanisms of stress and depression in coronary artery disease

Bremner, J Douglas; Campanella, Carolina; Khan, Zehra; Fani, Negar; Kasher, Nicole; Evans, Sarah; Reiff, Collin; Mishra, Sanskriti; Ladd, Stacy; Nye, Jonathon A; Raggi, Paolo; Vaccarino, Viola
INTRODUCTION/BACKGROUND:Major depression is associated with an increased risk for and mortality from coronary artery disease (CAD), however the mechanisms by which this occurs are not clear. Depression, which is linked to stress, is associated with changes in brain areas involved in memory and the stress response, and it is likely that these regions play an important role in this increased risk. This study assessed the effects of stress on brain and cardiac function in patients with CAD with and without depression. METHODS:CAD patients with (N = 17) and without (N = 21) major depression based on the Structured Clinical Interview for DSM-IV (DSM-IV) and/or a Hamilton Depression Scale score of nine or greater underwent imaging of the brain with high resolution positron emission tomography (HR-PET) and [O-15] water and imaging of the heart with single photon emission tomography (SPECT) and [Tc-99 m] sestamibi during mental stress (mental arithmetic) and control conditions. RESULTS:Patients with CAD and major depression showed increased parietal cortex activation and a relative failure of medial prefrontal/anterior cingulate activation during mental stress compared to CAD patients without depression. Depressed CAD patients with stress-induced myocardial ischemia, however, when compared to depressed CAD patients without showed increased activation in rostral portions of the anterior cingulate. CONCLUSIONS:These findings are consistent with a role for brain areas implicated in stress and depression in the mechanism of increased risk for CAD morbidity and mortality in CAD patients with the diagnosis of major depression.
PMID: 30508746
ISSN: 1879-1379
CID: 3781302

Case study 6: Treatments for alcohol use disorder

Chapter by: Reiff, Collin M
in: Treating adolescent substance use: A clinician's guide by Welsh, Justine W [Ed]; Hadland, Scott E [Ed]
Cham, Switzerland: Springer Nature Switzerland AG; Switzerland, 2019
pp. 161-164
ISBN: 978-3-030-01892-4
CID: 4883362

Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions

Riva-Posse, Patricio; Reiff, Collin M; Edwards, Johnathan A; Job, Gregory P; Galendez, Gail C; Garlow, Steven J; Saah, Tammy C; Dunlop, Boadie W; McDonald, William M
BACKGROUND:The dissociative anesthetic agent ketamine is increasingly being utilized to treat depression, despite not having FDA (Food and Drug Administration) approval for this indication. There are many questions about the potential risks of this treatment and hence the proper setting and degree of monitoring required to ensure patient safety. There is limited data about the cardiovascular safety of ketamine when administered at subanesthetic doses to treat depression. METHODS:66 patients in the Department of Psychiatry at Emory University received a total of 684 ketamine infusions between 2014 and 2016. Ketamine was dosed at 0.5 mg/kg body weight and infused over 40 min. Blood pressure was measured every 10 min during the infusions and every 15 min thereafter. RESULTS:Mean age of the patients was 56.7 years, 87.9% had unipolar depression and 36.1% had essential hypertension. No infusions were discontinued due to instability of vital signs, adverse physiological consequences or acute psychotomimetic effects. The biggest increases in blood pressure were measured at 30 min (systolic 3.28 mmHg, diastolic 3.17 mmHg). Hypertensive patients had higher blood pressure peaks during the infusions. Blood pressures returned to baseline during post-infusion monitoring. There was no development of tolerance to the blood pressure elevating effects of ketamine between the first and sixth infusions. LIMITATIONS/CONCLUSIONS:This is a single site, retrospective analysis, of patients who were spontaneously seeking clinical care. CONCLUSIONS:The blood pressure changes observed when ketamine is administered over 40 min at 0.5 mg/kg for the treatment of depression are small, well tolerated and clinically insignificant.
PMID: 29525051
ISSN: 1573-2517
CID: 3221232


Bremner, J. Douglas; Campanella, Carolina; Khan, Zehra; Fani, Negar; Kasher, Nicole; Evans, Sarah; Reiff, Collin; Mishra, Sanskriti; Ladd, Stacy; Nye, Jonathon A.; Garcia, Ernest; Vaccarino, Viola
ISSN: 0033-3174
CID: 3221262

Cardiovascular Effects of Intravenous Ketamine for Depression: Analysis of 684 Consecutive Infusions [Meeting Abstract]

Posse, Patricio Riva; Reiff, Collin; Job, Gregory; Galendez, Gail; Edwards, Johnathan; McDonald, William
ISSN: 0893-133x
CID: 3221252