Psychedelics: Microdosing, Mind-Enhancing Methods, and More – The Tim Ferriss Show

Check out The Tim Ferriss Show Episode Page & Show Notes

Key Takeaways

  • Psilocybin appears to be useful for mitigating symptoms of depression and anxiety associated with a life-threatening cancer diagnosis
  • Psilocybin appears to be useful at treating an addiction to smoking
  • Psychedelics relax harmful beliefs and open a window for revision (like someone with depression feeling and believing they’re worthless)
  • 320 million people worldwide suffer from depression
    • Depression is the single most costly illness in the Western world (if you count all the side effects, like people not showing up at work)
  • Rather than thinking of it as a good vs. bad trip, think of it as a safe vs. unsafe trip
    • “In many cases, the difficult experiences are when you see the truths you prefer not to see and look at the behaviors that may be in your blind spot. That can be very uncomfortable.” – Tim
  • When brains of people on psychedelics are imaged, activity in the Default Mode Network (DMN) has been shown to be diminished
    • The DMN is a master regulator and it’s very involved in self-reflection, self-criticism, and worry
    • If the ego has an address, it’s in the DMN
  • Our brains function along a spectrum, from entropy to rigidity
    • The entropy end = childhood consciousness
    • The rigidity end = ailments consistent with too much order (anxiety, obsession, addiction, depression)
    • You ideally want to be in the middle
    • Psychedelics work by increasing the amount of entropy in the brain
  • Psychedelics should NOT be available over-the-counter
    • Proper guidance, in conjunction with the correct set and setting, is needed for the success of these therapies

Books Mentioned

Intro

Using Psilocybin to Treat Depression and Anxiety (Matthew)

  • (Slides be found here to reference the below  – see slide 2, where the above image was taken from)
  • Check out the following study examining psilocybin for the treatment of depression/anxiety associated with a life-threatening cancer diagnosis:
    • Examine the graph above
      • (Looking at the red group) – A huge reduction in anxiety and depression was observed after taking a very high dose of psilocybin – Matt calls it “a very high overwhelming, dose… something you don’t want to be at a concert on”
      • (Looking at the blue group) – A minor reduction in anxiety/depression was observed for participants who received a small initial microdose
      • BOTH groups received a second high dose a month after the first dose – everyone had dramatically decreased their depression/anxiety by this point
      • 6 months after treatment, sustained reductions in depression and anxiety are still observed (all from a single high-dose psilocybin session)

Using Psilocybin to Treat Smoking Addiction (Matthew)

  • (Slides be found here to reference the below  – see slide 3, where the above image was taken from)
  • “The anti-addiction effects of psychedelics seem to be broad based. They get to the psychological meat of addiction.”
  • Check out this study examining the effectiveness of psilocybin at treating tobacco addiction
    • Examine the graph above
      • At 6 months (after a third high-dose psilocybin session), 80% of participants in the study were biologically confirmed as “smoke-free” with breath and urine samples (67% at a year and 60% at 2.5 years)
        • For comparison – the best medications that exist on the market for treating nicotine addiction (such as Varenicline) have a quit rate of about 35% at 6 months

Microdosing (Ayelet)

  • Microdosing involves taking a sub-perceptual dose of a psychedelic 
    • With a microdose, you’re NOT tripping or perceiving any effects, but there’s still something going on metabolically 
  • Ayelet was experiencing significant depression and had tried everything – from SSRIs to mood stabilizers and various other medications – and nothing was working (which led her to try microdosing with LSD as a 30-day experiment)
    • How much LSD did she take? – 10 micrograms every 3 days (a hallucinogenic dose of LSD ranges from 100-200 micrograms)
    • “The effects were profound”
      • On the first day, Ayelet went from a full-on suicidal depression to being able to appreciate the beauty a flower for the first time in a long while
      • “Over the course of the next 30 days, it wasn’t like every day was a really good day, but many days were really good days”
      • Ayelet also claims her productivity dramatically increased
        • The first draft of her book recounting her experience, A Really Good Day, was written in just one month

The Science | Why Psychedelics Do What They Do (Robin)

  • MONTHS on from psychedelic experiences, people are reporting improvements in psychological well-being as well as drops in depression (despite the drug being washed out of the body)
  • Psychedelics bind to the 5-HT2A receptors of the serotonin system (which are largely present in the cortex)
    • Stimulating these receptors seems to have an interesting effect on the regularity and quality of brain activity
      • They appear to enhance the “richness” of our brain waves 
  • Robin adds that the quality of the experience someone has under a psychedelics appears to predict, very reliably, the therapeutic outcome
  • Psychedelics relax harmful beliefs and open a window for revision (like someone with depression feeling and believing they’re worthless)

Investment in the Psychedelic Space (Christian)

  • Christians biotech company is one of the largest investors aiming to bring psychedelics back into the legal realm
  • After not taking a single drug throughout his whole life, Christian had his first experience with psilocybin
    • “It was the single most meaningful thing I’ve ever done and experienced, full stop. Nothing comes close to it.”
      • In studies at Johns Hopkins, ~2/3 participants rank their psilocybin session as one of the 5 most meaningful experiences of their life and ~1/3 rank it as the most meaningful experience
    • Coming out of his trip – Christian knew more people needed to experience the benefits of psilocybin/psychedelics
  • “The whole mental health area… has completely more or less been neglected over the last 30 years”
    • Why? – Pharma companies recognized how difficult the mind was to understand and instead preferred to focus on the more tangible illnesses
    • But this is now changing
      • “Mental health is becoming a problem because our world is bad for our minds, especially for young people”
      • 320 million people worldwide suffer from depression
      • Depression is the single most costly illness in the Western world (if you count all the side effects, like people not showing up at work)
      • The current drugs on the market don’t cure depression, they just numb it – the space hasn’t seen innovation in 20-30 years

The Benefits of MDMA (Ayelet)

  • Ayelet and her husband have used MDMA as a tool for marital therapy for a number of years now
    • “We have the strongest marriage of anyone I know”
  • MDMA allows you to talk about your issues (and every couple has them) from a place of connection and love
    • MDMA disconnects the emotional experience from a memory which then allows someone to deal with a specific trauma without the negative emotional content

Psychedelic Risk and Toxicity (Matt)

  • For psilocybin, LSD, and DMT – there is no known lethal overdose threshold (or a known threshold for which organ damage appears to result) (or a known dose that causes neurotoxicity)
    • Cannabis is similar
    • “You’d be hard-pressed to find anything sold over-the-counter that you’d be able to say this about” 
      • I.e., caffeine, Asprin, or even cold medicine
  • But that said, one can certainly have a negative experience when using a psychedelic (AKA a bad trip)
    • This can be minimized with proper preparation and taking the drug in the proper set/setting
  • To add – a very small percentage of the population are prone to psychotic episodes (these people definitely shouldn’t take psychedelics)
    • Tim’s cousin by marriage had a hereditary disposition to schizophrenia and having abused LSD through college, the onset of his symptoms was accelerated 

The Commonality of Mental Illness, the Default Mode Network, and the Entropic Brain (Robin)

  • Perhaps anxiety, depression, OCD, and eating disorders are not as different as we think
    • Why is it that psychedelics have such profound effects with all of the above illnesses? – Maybe they’re rooted in the same areas of the brain and aren’t so different after all
    • The names we give the above are artifacts of the insurance industry – we have to assign a number to every diagnosis, so we tend to separate things
      • Depression is regret about the past, and anxiety is regret about the future, so the only difference, is tense
  • When brains of people on psychedelics are imaged, activity in the Default Mode Network (DMN) has been shown to be diminished
    • The DMN is a master regulator and it’s very involved in self-reflection, self-criticism, and worry
    • If the ego has an address, it’s in the DMN
      • The higher a drop in DMN activity, the more likely someone is liable to report they experienced ego dissolution during a psychedelic session
  • Check out this paper from Robin on the entropic brain
    • Our brains function along a spectrum, from entropy to rigidity
      • The entropy end = childhood consciousness
      • The rigidity end = ailments consistent with too much order (anxiety, obsession, addiction, depression)
      • You ideally want to be in the middle
      • Psychedelics work by increasing the amount of entropy in the brain

The Psychedelic Spa (Christian and Ayelet)

  • Christian doesn’t believe psilocybin should be available over-the-counter, but rather in clinics and within the context of therapy
    • “This is NOT someone should do alone, especially when they’re depressed” – A guide is VERY important
    • An interesting point – psychedelics are legal over-the-counter in the Netherlands and they still have the same mental health issues as every other country in the world
  • In her book, Ayelet talks about the idea of a “psychedelic spa”
  • “In all drug experiences, but particularly with psychedelics, the set and setting are critical”
    • Set = what you bring to the experience
    • Setting = where you experience the drug

Business Models and Single-Dose Psychedelic Therapies (Christian)

  • There’s enough business, even if these turn out to be single-dose therapies
    • The market is HUGE – As mentioned 320 million+ people worldwide have some sort of depression
  • You can then add in pre/post treatment facilitates (like psychedelic spas/clinics)
  • To add – we don’t yet know the correct dosing
    • Perhaps optimal treatments involve repeating a dose every X months or so

Wrapping Up – What would Ayelet hope this field looks like a few years from now?

  • A few years back, the decriminalization of marijuana seemed incomprehensible
    • Now, MANY states have approved the use of recreational marijuana 
  • So – the shift IS possible with psychedelics
    • Perhaps we’ll see some sort of medical psychedelic model somewhere down the line

Additional Notes

  • Matt’s colleague at the University of Alabama is showing initial positive results at using psychedelics to treat cocaine addiction
  • Compass Pathways is in Phase II studies, aiming to bring R-Ketamine to the market for the treatment of depression
  • “Prescription rates for psychiatric medications are going up at record levels yet we’re not chipping into the problem” – Robin
  • Rather than thinking of it as a good vs. bad trip, think of it as a safe vs. unsafe trip
    • “In many cases, the difficult experiences are when you see the truths you prefer not to see and look at the behaviors that may be in your blind spot. That can be very uncomfortable.” – Tim
  • There are quite a few chapters in Tim’s book, Tools of Titans, on psychedelics
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