Posted on by

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

7 Comments
Topics: CategoriesThe Tim Ferriss Show
Illustration via 99designs

“Depression is a disorder of the spirit, if you will—the brain but also the whole body. And that’s one of the reasons why it’s one of the most disabling conditions that we have in the world.”

— Dr. John Krystal

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!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, Google Podcasts, Stitcher, Amazon Music, or on your favorite podcast platform. You can watch the interview on YouTube here.

Brought to you by Athletic Greens all-in-one nutritional supplement, Helix Sleep premium mattresses, and Allform premium, modular furniture. 

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

Listen onApple Podcasts
Listen onSpotify
Listen onOvercast
#625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever

This episode is brought to you by Helix Sleep! Helix was selected as the best overall mattress of 2022 by GQ magazine, Wired, and Apartment Therapy. With Helix, there’s a specific mattress to meet each and every body’s unique comfort needs. Just take their quiz—only two minutes to complete—that matches your body type and sleep preferences to the perfect mattress for you. They have a 10-year warranty, and you get to try it out for a hundred nights, risk-free. They’ll even pick it up from you if you don’t love it. And now, Helix is offering 20% off all mattress orders plus two free pillows at HelixSleep.com/Tim.

This episode is brought to you by Allform! If you’ve been listening to the podcast for a while, you’ve probably heard me talk about Helix Sleep mattresses, which I’ve been using since 2017. They also launched a company called Allform that makes premium, customizable sofas and chairs shipped right to your door—at a fraction of the cost of traditional stores. You can pick your fabric (and they’re all spill, stain, and scratch resistant), the sofa color, the color of the legs, and the sofa size and shape to make sure it’s perfect for you and your home.

Allform arrives in just 3–7 days, and you can assemble it yourself in a few minutes—no tools needed. To find your perfect sofa and receive 20% off all orders, check out Allform.com/Tim.

This episode is brought to you by Athletic Greens. I get asked all the time, “If you could use only one supplement, what would it be?” My answer is usually AG1 by Athletic Greens, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. I do my best with nutrient-dense meals, of course, but AG1 further covers my bases with vitamins, minerals, and whole-food-sourced micronutrients that support gut health and the immune system. 

Right now, Athletic Greens is offering you their Vitamin D Liquid Formula free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit AthleticGreens.com/Tim to claim this special offer today and receive the free Vitamin D Liquid Formula (and 5 free travel packs) with your first subscription purchase! That’s up to a one-year supply of Vitamin D as added value when you try their delicious and comprehensive all-in-one daily greens product.

Want to hear another podcast episode with someone who’s exploring the beneficial properties of mind-altering compounds? Listen to my conversation with Dr. Suresh Muthukumaraswamy, in which we discuss how ketamine differs from other psychedelics, the durability of antidepressant effects, obstacles to getting ketamine labeled as an antidepressant, avoiding another 50 years of psychedelic research darkness, where aspiring psychedelic researchers should focus their education, and much more.

#619: Dr. Suresh Muthukumaraswamy — LSD Microdosing, Classical Psychedelics vs. Ketamine, Science and Speed in New Zealand, Placebo Options, and The Infinite Possibilities of Studying Mind-Altering Compounds

What was your favorite quote or lesson from this episode? Please let me know in the comments.

SCROLL BELOW FOR LINKS AND SHOW NOTES…

SELECTED LINKS FROM THE EPISODE

SHOW NOTES

  • [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.

MORE GUEST QUOTES FROM THE INTERVIEW

“Depression is a disorder of the spirit, if you will—the brain, but also the whole body. And that’s one of the reasons why it’s one of the most disabling conditions that we have in the world.”
— Dr. John Krystal

“The ideal antidepressant would be a drug that acted rapidly and lasted forever. We would call that, basically, cure. And we never use the word ‘cure’ in psychiatry. We don’t even think of the idea of cure. And that’s partly because we don’t really understand the brain well enough to really know how to completely undo the changes that we see there.”
— Dr. John Krystal

PEOPLE MENTIONED

The Tim Ferriss Show is one of the most popular podcasts in the world with more than 900 million downloads. It has been selected for "Best of Apple Podcasts" three times, it is often the #1 interview podcast across all of Apple Podcasts, and it's been ranked #1 out of 400,000+ podcasts on many occasions. To listen to any of the past episodes for free, check out this page.

Leave a Reply

Comment Rules: Remember what Fonzie was like? Cool. That’s how we’re gonna be — cool. Critical is fine, but if you’re rude, we’ll delete your stuff. Please do not put your URL in the comment text and please use your PERSONAL name or initials and not your business name, as the latter comes off like spam. Have fun and thanks for adding to the conversation! (Thanks to Brian Oberkirch for the inspiration.)

7 Replies to “Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever (#625)”

  2. Thank you Tim for making the transcripts available for the hearing impaired. I’m not sure if you get any acknowledgement of the transcripts, just wanted to Kota let you know I am very appreciative oa.
    Thank you sincerely.

    Reply

  3. Dr. Krystal made it sound like insurance will cover these treatments but my brief research indicates this isn’t so. Anyone know the scoop?

    Reply

  4. Dear Tim, thank you for this conversation. Talk can be such a catalyst for change and your podcast with Dr. Krystal was fantastic. Everyone’s Thanksgiving dinner table offers a seating chart of disorder!
    As a former professional athlete who has suffered from sever depression from a young age and who is now pursuing a career in clinical counseling, I really appreciate you and the work you do.

    Reply

  5. I’m wondering why, after talking about dosage/administration routes/abuse potential, they did not discuss sublingual administration (ie rapid dissolve tables). There are so many people taking it at home – it seems deliberate to skip over that method.

    Clinical treatment is not-sustainable – both in cost and the difficulty with scheduling. The advantages of at-home options are immense and will surely save even more lives.

    Reply

  7. What should we give our dogs then? Any additional ideas would be helpful such as dose, frequency, side effects, etc. when giving it to dogs. Thanks so much!

    Reply