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C. Reiff

Psychedelics and Psychedelic-Assisted Psychotherapy

May 1, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.
Methods: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on “psilocybin,” “lysergic acid diethylamide,” “LSD,” “ayahuasca,” “3,4-methylenedioxymethamphetamine,” and “MDMA,” in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms “clinical trial,” “therapy,” or “imaging” in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-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: 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: 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.

Keywords: Ayahuasca; Drug-Psychotherapy Combination; Lysergic Acid Diethylamide; MDMA; Psilocybin; Psychedelics.
Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodriguez, C. I., … & Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. (2020). Psychedelics and psychedelic-assisted psychotherapy. American Journal of Psychiatry, 177(5), 391-410., https://doi.org/10.1176/appi.ajp.2019.19010035
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Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions

July 19, 2018 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

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:
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.
Riva-Posse, P., Reiff, C. M., Edwards, J. A., Job, G. P., Galendez, G. C., Garlow, S. J., … & McDonald, W. M. (2018). Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions. Journal of affective disorders, 236, 291-297. 10.1016/j.jad.2018.02.025
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Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

July 24, 2017 / Anxiety Disorders / PTSD, MDMA, Neuroscience, Papers, Psychology / By / , , , , , ,

Abstract

Rationale

3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA’s broad pharmacological profile, further investigation is warranted before moving to a complex clinical population.

Objectives

We aimed to inform clinical research by providing a translational model of MDMA’s effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction.

Methods

We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training.

Results

MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA’s effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA’s effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA’s effect on extinction.

Conclusions

We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

Young, M. B., Norrholm, S. D., Khoury, L. M., Jovanovic, T., Rauch, S. A., Reiff, C. M., … & Howell, L. L. (2017). Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3, 4-methylenedioxymethamphetamine (MDMA). Psychopharmacology, 234(19), 2883-2895. 10.1007/s00213-017-4684-8
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