#625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever

Dr. John Krystal — All Things Ketamine, The Most
Comprehensive Podcast Episode Ever | Brought to you
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Dr. John Krystal is the Robert L. McNeil, Jr.,
Professor of Translational Research; Professor of Psychiatry,
Neuroscience, and Psychology; Chair of the Department of
Psychiatry at Yale University; and Chief of Psychiatry and
Behavioral Health at Yale-New Haven Hospital.


Dr. Krystal is a leading expert in the areas of alcoholism,
post-traumatic stress disorder, schizophrenia, and depression.
His work links psychopharmacology, neuroimaging, molecular
genetics, and computational neuroscience to study the
neurobiology and treatment of these disorders. He is best
known for leading the discovery of the rapid antidepressant
effects of ketamine in depressed patients.


He directs/co-directs the Yale Center for Clinical Investigation
(CTSA), NIAAA Center for the Translational Neuroscience of
Alcoholism, and Clinical Neuroscience Division of the National
Center for PTSD (VA).


Dr. Krystal is a member of the U.S. National Academy of Medicine;
co-director of the Neuroscience Forum of the U.S. National
Academies of Sciences, Engineering, and Medicine; Fellow of the
American Association for the Advancement of Science (AAAS); and
editor of Biological Psychiatry, one of the most selective and
highly cited journals in the field of psychiatric neuroscience.


He is the co-founder and Chief Scientific Advisor of
Freedom Biosciences, a clinical-stage
biotechnology platform developing next-generation ketamine and
psychedelic therapeutics that recently emerged from stealth in
August 2022.


ONE VERY IMPORTANT DISCLAIMER: I’m not a doctor,
nor do I play one on the Internet. None of the content in this
podcast constitutes medical advice or should be construed as a
recommendation to use ketamine or psychedelics. There are
psychological, physical, and sometimes legal risks with such
usage. Please consult your doctor before considering anything we
discuss in this episode.


Please enjoy!


*


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*


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*


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*


[07:30] The challenges faced by John’s late father, Henry
Krystal.


[14:44] Was Henry’s work discussed around the Krystal dinner
table?


[18:10] What people frequently misunderstand about depression.


[25:53] Why partial response and non-response occur commonly in
psychiatry.


[32:15] From the serotonin hypothesis to “what’s really exciting”
about antidepression research.


[35:08] How monoamine oxidase inhibitors reduce symptoms of
depression.


[36:41] MAOI Side effects and risks.


[40:14] When Western medicine duplicates centuries-old shamanic
wisdom.


[43:13] How pre-imaging neuroscience of the ’80s was like
Ptolemaic astronomy.


[47:24] The reason for depression isn’t as simple as a lack of
serotonin.


[49:42] The change in perspective that illustrated ketamine as a
potential therapy.


[54:35] From first studies to overcoming skepticism.


[1:02:39] How ketamine went from “horse tranquilizer” to
antidepressant candidate.


[1:18:46] The dose makes the difference.


[1:23:02] What is dissociation, and is it an essential part of
ketamine’s healing process?


[1:37:32] Recommendations for optimal treatment of a close friend
(frequency, duration, psychotherapy, etc.).


[1:50:42] Reducing the potency of maladaptive memories.


[1:56:15] Best dosage practices.


[2:03:23] I.M. vs. I.V.


[2:04:55] Common in-session side-effects (and remedies).


[2:09:19] What my ketamine experience was like.


[2:12:41] Optimal settings.


[2:18:05] Ketamine risks.


[2:30:22] Decreasing the opportunities for abuse and addiction.


[2:37:28] Enantiomers: r-ketamine vs. s-ketamine


[2:44:19] How effective is ketamine for chronic pain relief?


[2:52:28] Why might the durability of relief outlast the presence
of ketamine in the body?


[2:56:12] What is s-methadone?


[2:57:31] Does s-ketamine have the same abuse potential as
r-ketamine?


[3:00:46] Opiate receptor interaction with ketamine and other
compounds.


[3:05:56] What is Salvinorin A?


[3:07:05] Exploring the ups and downs of optimizing ketamine with
rapamycin.


[3:23:28] Ketamine doesn’t have a lot in common with other
psychedelics.


[3:26:47] The effect of ketamine and other hallucinogens on the
thalamus.


[3:29:57] How important is the role of brain-derived neurotrophic
factor (BDNF)?


[3:32:20] BHB, ethanol-free alcohol, and exercise vs. depression.


[3:35:31] Ketamine’s impact on sleep, and the potential dangers
of too much exercise.


[3:37:27] What John anticipates for the future of ketamine
research and application.


[3:41:51] Giving credit to the pioneers of the field.


[3:43:21] Parting thoughts.


*


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