All Things Ketamine, The Most Comprehensive Podcast Episode Ever — 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.

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!

00:00 Start
03:08 The challenges faced by John’s late father, Henry Krystal.
11:28 Was Henry’s work discussed around the Krystal dinner table?
15:05 What people frequently misunderstand about depression.
23:35 Why partial response and non-response occur commonly in psychiatry.
30:22 From the serotonin hypothesis to “what’s really exciting” about antidepression research.
33:26 How monoamine oxidase inhibitors reduce symptoms of depression.
35:02 MAOI Side effects and risks.
37:23 When Western medicine duplicates centuries-old shamanic wisdom.
40:29 How pre-imaging neuroscience of the ’80s was like Ptolemaic astronomy.
45:03 The reason for depression isn’t as simple as a lack of serotonin.
47:32 The change in perspective that illustrated ketamine as a potential therapy.
52:57 From first studies to overcoming skepticism.
01:01:33 How ketamine went from “horse tranquilizer” to antidepressant candidate.
01:18:49 The dose makes the difference.
01:23:14 What is dissociation, and is it an essential part of ketamine’s healing process?
01:39:42 Recommendations for optimal treatment of a close friend (frequency, duration, psychotherapy, etc.).
01:54:05 Reducing the potency of maladaptive memories.
01:59:58 Best dosage practices.
02:07:18 I.M. vs. I.V.
02:08:52 Common in-session side-effects (and remedies).
02:13:34 What my ketamine experience was like.
02:16:52 Optimal settings.
02:22:51 Ketamine risks.
02:35:57 Decreasing the opportunities for abuse and addiction.
02:43:25 Enantiomers: r-ketamine vs. s-ketamine
02:50:33 How effective is ketamine for chronic pain relief?
02:59:05 Why might the durability of relief outlast the presence of ketamine in the body?
03:03:09 What is s-methadone?
03:04:31 Does s-ketamine have the same abuse potential as r-ketamine?
03:07:56 Opiate receptor interaction with ketamine and other compounds.
03:09:58 What is Salvinorin A?
03:14:34 Exploring the ups and downs of optimizing ketamine with rapamycin.
03:32:06 Ketamine doesn’t have a lot in common with other psychedelics.
03:36:02 The effect of ketamine and other hallucinogens on the thalamus.
03:38:56 How important is the role of brain-derived neurotrophic factor (BDNF)?
03:41:44 BHB, ethanol-free alcohol, and exercise vs. depression.
03:45:13 Ketamine’s impact on sleep, and the potential dangers of too much exercise.
03:47:19 What John anticipates for the future of ketamine research and application.
03:52:05 Giving credit to the pioneers of the field.
03:53:48 Parting thoughts.

About Tim Ferriss:
Tim Ferriss is one of Fast Company’s “Most Innovative Business People” and an early-stage tech investor/advisor in Uber, Facebook, Twitter, Shopify, Duolingo, Alibaba, and 50+ other companies. He is also the author of five #1 New York Times and Wall Street Journal bestsellers: The 4-Hour Workweek, The 4-Hour Body, The 4-Hour Chef, Tools of Titans and Tribe of Mentors. The Observer and other media have named him “the Oprah of audio” due to the influence of his podcast, The Tim Ferriss Show, which has exceeded 800 million downloads and been selected for “Best of Apple Podcasts” three years running.

Connect with Tim Ferriss:

[nonebizz]

i have used ketamine therapy over the last 6 months not only has it helped my depression that was untreatable till now. i also am a methadone patient i have detoxed from 220mg daily to 10mg as of 3 days ago and hopefully completely off by Christmas. ketamine has allowed me to detox with little to no withdrawals. completely saving my life.

[iamshellymarie]

I just had my second ketamine treatment today for ptsd, anxiety & depression. I have spent 23 years using spiritual healing and lifestyle strategies to combat the affects of traumatic events and anxiety disorders. I have never heard of it before but when my psychiatrist recommended it, I was willing to try it. It is working in a way I’ve never experienced before.

[KenjiBoss]

I am a pain patient who also had significant childhood trauma. I put my headphones on, played a 4 hour guided meditation with positive affirmations while having treatment. The benefit of being able to turn inward using ketamine has been an unexpected side effect. I become the music and meditation I was listening to and etched acceptance and positivity into my core being. I’d love to share my experience.

[KenjiBoss]

My trauma was stored in my body. My body holds the emotional remembrance of the trauma. That’s why early childhood trauma is so sticky to overcome. Ketamine is a game changer!

[cherylnathanodette]

I hope anyone struggling with addiction of any kind finds the strength and support they need.

[MrBungle]

This is by far my favourite video from you. I’m a therapist and have had ten ketamine infusions to date. It’s been incredible at helping me to gain momentum out of my suffering.
Only downside it it’s so expensive. Especially over here in the UK where we have to pay for it privately. I hope one day this can be accessible for all as it’s so effective and user friendly.

Great work, fella.

[stoicselfie]

Please Tim! Can you work with some people to help you getting subtitles in many languages for your interview videos... The information is so valuable but all the non english speakers in the world are missing on it. I would love to share it with so many people I know, but they do not speak english.... You got to a point in your craft and structure that this should not be a big problem... please do it... 🙏

[kimburleejostewart]

I can't believe I sat through this 4 hour video! It was so informative, I am saving for a future viewing! I am planning my first ketamine sessions in a clinical setting, I am not nervous about it after all the information! THANK YOU!

[rebeccashifflet]

Granted I’ve only used ketamine recreationally but it has changed my life!!! My perspective on life is completely different! I’ve dealt with depression and ptsd for most of my life. Ketamine has completely changed my perspective on life. It’s amazing how different I feel! I feel so connected to myself and my body now it’s absolutely amazing! Ive felt disconnected from myself for almost all of my life. Life has new meaning to me now and i am so happy and at peace with all aspects of life now. What a wonderful substance!

[anthonyaskew]

I have been using ketamine for 3 months and I was able to finally quit drinking and my Anxiety and PTSD is 90% better.

[tompatterson]

Intermittent fasting has completely destroyed my depression. I have been having lots of energy to walk 10000 + steps daily and now I work on projects that I’ve been putting off for months.Depression sucks no doubt. I quit drinking two years ago. Thanks to the state of South Dakota. God bless them.

[BallietBran]

Ketamine changed my life and healed my CPTSD

[andreacatura]

I have multiple sclerosis, and I am about to join a study to see if ketamine treatment can actually improve fatigue in people with MS 🤞 Wouldn’t it be fantastic if it also helped my depression and anxiety 😮

[spartanmgmt]

I have traumatic brain injury which affected my spatial memory due to an intentional drug overdose. Ketamine is helping to repair that. It’s helped my depression, anxiety, bipolar and trauma. I’m much more connected to my body and aware of present events in a way that I’ve never experienced.

[khilden]

Such great information! It’s so sad for me though. I’ve had severe depression for 70 years, attempting suicide twice, cutting and various other coping mechanisms. I had my first ketamine treatment two weeks ago and will have my fifth next week. I will be 81 in three weeks and have spent a life time in survival mode. How I wish I could have been a trial patient 25 years ago! I’m experiencing some improvement but due to numerous health conditions with inflammation and heart disease I fear my life will end before I can enjoy any long term benefits. Please go NOW and find a doctor who will try ketamine!!

[HappyCat]

I’ve had 10 ketamine sessions and only had a moderate improvement, no breakthrough moments or epiphanies about life. I may need to try a different modality to lift my depression and complex PTSD. Many people have miraculous recovery but I’m one of the few that hasn’t been blown away by ketamine therapy.

[philforrence]

This is one of the BEST Tim Ferriss episodes I've ever heard. Thank you so much for your amazing work, Tim and John!

[oerjanlothe]

Ketamine - Here I come! What a great video. Will start my treatment in Thailand very soon

[sebastianfelipe]

I can't find a source anywhere for any good psychedelics in my area, I suffer some pretty bad depression and i got a chance to try K and man it was a miracle substance, I felt free, the only high or euphoria was from the relief of my vices being released, that's exactly what it did

[SortaSalty]

I appreciate what was said of awareness to inflammation and depression. I feel this isn’t addressed enough.