OPEN Foundation

Day: 25 September 2015

Ketamine for depression: evidence, challenges and promise

Abstract

Major depressive disorder and bipolar depression are among the most prevalent and disabling mental disorders worldwide. Real-world effectiveness trials in major depressive disorder have underscored that most pharmacological options target monoamines, which are involved in a minority (15-20%) of synaptic contacts in the mammalian brain.

Most synapses (∼50%) use the amino acid glutamate as their primary neurotransmitter, and preclinical models of depression have implicated aberrant glutamatergic neurotransmission for 25 years. More recently, the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine was shown to produce rapid and robust antidepressant effects in patients with treatment-resistant major depressive disorder and bipolar depression.

Zarate, C. A., & Niciu, M. J. (2015). Ketamine for depression: evidence, challenges and promise. World Psychiatry, 14(3), 348-350. http://dx.doi.org/10.1002/wps.20269
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The Prosocial Effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled Studies in Humans and Laboratory Animals

Abstract

Users of ±3,4-Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) report prosocial effects such as sociability and empathy. Supporting these apparently unique social effects, data from controlled laboratory studies indicate that MDMA alters social feelings, information processing, and behavior in humans, and social behavior in rodents. Here, we review this growing body of evidence. In rodents, MDMA increases passive prosocial behavior (adjacent lying) and social reward while decreasing aggression, effects that may involve serotonin 1A receptor mediated oxytocin release interacting with vasopressin receptor 1A. In humans, MDMA increases plasma oxytocin and produces feelings of social affiliation. It decreases identification of negative facial expressions (cognitive empathy) and blunts responses to social rejection, while enhancing responses to others’ positive emotions (emotional empathy) and increasing social approach. Thus, consistent with drug folklore, laboratory administration of MDMA robustly alters social processing in humans and increases social approach in humans and animals. Effects are consistent with increased sociability, with mixed evidence about enhanced empathy. These neurobiologically-complex prosocial effects likely motivate recreational ecstasy use.

Kamilar-Britt, P., & Bedi, G. (2015). The Prosocial Effects of 3, 4-methylenedioxymethamphetamine (MDMA): Controlled Studies in Humans and Laboratory Animals. Neuroscience & Biobehavioral Reviews. http://dx.doi.org/10.1016/j.neubiorev.2015.08.016
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30 April - Q&A with Rick Strassman

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