OPEN Foundation

B. Heifets

Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine

January 7, 2022 / Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychiatry, Psychopharmacology, Psychotherapy / Leave a Comment / By / , , , , , ,

Abstract

A revamped interest in the study of hallucinogens has recently emerged, especially with regard to their potential application in the treatment of psychiatric disorders. In the last decade, a plethora of preclinical and clinical studies have confirmed the efficacy of ketamine in the treatment of depression. More recently, emerging evidence has pointed out the potential therapeutic properties of psilocybin and LSD, as well as their ability to modulate functional brain connectivity. Moreover, MDMA, a compound belonging to the family of entactogens, has been demonstrated to be useful to treat post-traumatic stress disorders. In this review, the pharmacology of hallucinogenic compounds is summarized by underscoring the differences between psychedelic and nonpsychedelic hallucinogens as well as entactogens, and their behavioral effects in both animals and humans are described. Together, these data substantiate the potentials of these compounds in treating mental diseases.

De Gregorio, D., Aguilar-Valles, A., Preller, K. H., Heifets, B. D., Hibicke, M., Mitchell, J., & Gobbi, G. (2021). Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine. The Journal of neuroscience : the official journal of the Society for Neuroscience, 41(5), 891–900. https://doi.org/10.1523/JNEUROSCI.1659-20.2020

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Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.

August 29, 2019 / Depression, Ketamine, Papers, Psychiatry, Psychology, Psychopharmacology, Publications / By / , , , , , ,

Abstract

We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine’s antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.
Williams, N. R., Heifets, B. D., Bentzley, B. S., Blasey, C., Sudheimer, K. D., Hawkins, J., … & Schatzberg, A. F. (2019). Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism. Molecular psychiatry, 1-8., https://doi.org/10.1038/s41380-019-0503-4
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MDMA as a Probe and Treatment for Social Behaviors

July 14, 2016 / MDMA, Papers, Psychiatry, Psychology, Psychotherapy, Publications / By / ,

Abstract

MDMA, better known as the recreational drug “ecstasy,” is well known for stimulating a feeling of closeness and empathy in its users. We advocate that exploring its mechanism of action could lead to new treatments for psychiatric conditions characterized by impairments in social behavior.

Heifets, B. D., & Malenka, R. C. (2016). MDMA as a Probe and Treatment for Social Behaviors. Cell, 166(2), 269-272. http://dx.doi.org/10.1016/j.cell.2016.06.045
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