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Psychedelics — Microdosing, Mind Enhancing Methods, and More | The Tim Ferriss Show (Podcast)

This episode features a panel that I moderated in front of a standing-room-only crowd at the Milken Institute’s Global Conference 2019.

Tim FerrisshostAyelet WaldmanguestMatthew JohnsonguestRobin Carhart-HarrisguestChristian Angermayerguest

Aug 7, 20191h 3mWatch on YouTube ↗

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Chapter summaries

Panel setup at Milken: why psychedelics, who’s on stage, and what to expect
Tim Ferriss sets the scene for a live panel on psychedelic science recorded at the Milken Institute Global Conference. He describes the unusual level of interest in the room, notes that some visuals were referenced, and introduces the mix of scientists, an investor, and a writer with firsthand experience.
- •The conversation was recorded live at the 2019 Milken Institute Global Conference with a packed audience
- •Tim notes slides are referenced early but aren’t required to follow the discussion; links are available on his site
- •Tim explains the panel includes scientists, an investor, and a writer who has experimented with microdosing
- •Panelists are introduced: Christian Angermayer, Robin Carhart-Harris, Matthew Johnson, and Ayelet Waldman
Audience framing and an “uncrowded bet” story to motivate the moment
Tim asks the audience about depression despite antidepressants and about addiction, getting near-universal hands. He then tells the story of Katharine McCormick funding development of the oral contraceptive as an example of how focused support can change history, and shares his own shift toward supporting psychedelic science.
- •Tim polls the room on depression despite antidepressants and on addiction; most attendees relate personally
- •Tim recounts Katharine McCormick’s financing of oral contraceptive development as a model for leveraged impact
- •Tim discloses that he redirected much of his investing focus toward psychedelic science starting in 2015
- •Tim frames the discussion as both scientific and practical, including legal and funding realities
Responsible psychedelic research: risk management and trial guidelines
Matthew Johnson emphasizes that the field has been explicit about risks and has developed standardized methods to conduct studies safely. He describes published guidelines used by institutional review boards and referenced by the FDA when evaluating protocols.
- •Psychedelics have real downsides; researchers aim to understand and mitigate risks
- •A published set of safety/conduct guidelines has become a widely used reference for running studies
- •Matthew says the FDA is using these guidelines to evaluate novel protocols
- •He mentions a review assessing abuse liability and risks of psilocybin and arguing scheduling should reflect the data
Clinical outcomes with high-dose psilocybin: cancer-related depression and anxiety
Matthew presents results from a large study using a high dose of psilocybin for depression and anxiety linked to life-threatening cancer diagnoses. He describes rapid symptom reductions and sustained improvements months after a single session, contrasting the duration with other antidepressant approaches.
- •The study involved clinically severe depression and anxiety in people facing serious cancer diagnoses
- •The therapeutic dose discussed is not a microdose; it is a large, overwhelming dose
- •Participants showed large reductions in depression and anxiety after sessions, including sustained effects at six months
- •Matthew contrasts the durability of psilocybin effects with shorter-lasting antidepressant effects seen elsewhere
Addiction angle: early smoking-cessation results and why follow-up trials matter
Matthew describes a pilot study exploring psilocybin-assisted treatment for tobacco smoking cessation and reports high abstinence rates in follow-up. He stresses the study design limits (open-label) while arguing the signal is strong enough to justify randomized trials now underway.
- •Matthew frames psychedelic anti-addiction effects as potentially broad-based rather than drug-specific
- •In a pilot smoking-cessation study, abstinence was biologically confirmed via breath and urine samples
- •He reports abstinence outcomes at multiple follow-ups (six months, one year, and longer-term averages)
- •He emphasizes the need for caution due to open-label design and notes a randomized trial is in progress
What microdosing is and why Ayelet Waldman tried it
Ayelet Waldman defines microdosing as taking a sub-perceptual dose that does not produce a classic psychedelic “trip.” She explains that she pursued it after severe depression and limited benefit from prior medications, and describes steps she took to reduce risks associated with illegality and drug purity.
- •Microdosing is described as sub-perceptual dosing: no hallucinatory experience, but possible metabolic effects
- •Ayelet says she tried microdosing amid serious depression after SSRIs and other meds didn’t work effectively
- •She links her interest to reading psychedelic research while teaching a course on the war on drugs
- •She highlights purity/verification as a major safety issue when substances are illegal
Ayelet’s 30-day LSD microdosing experiment: mood shift, beauty returning, and productivity
Ayelet recounts her dosing approach (a fraction of a typical hallucinogenic amount taken every few days) and the first noticeable shift: appreciating beauty again without perceptual distortions. She describes broader changes in her depression “set point” and increased productivity with a calmer sense of flow.
- •She describes taking a very small fraction of a typical LSD dose on a schedule of every three days
- •Her first noticeable change was being able to recognize and feel beauty again after months of depression
- •She reports that while not every day was great, many were, with a marked change in baseline mood
- •She describes a significant productivity increase, including drafting a book quickly without hypomania
How psychedelics may work: serotonin 2A, increased brain “richness,” and belief relaxation
Robin Carhart-Harris explains that classic psychedelics primarily act on the serotonin system, especially the 2A receptor, which he associates with adaptability and plasticity. He describes findings that psychedelics increase the complexity of brain activity beyond normal waking consciousness and proposes that therapeutic benefit relates to relaxing rigid beliefs and enabling revision with psychological support.
- •Psychedelics are described as acting on serotonin, especially the serotonin 2A receptor
- •Robin links 2A receptor stimulation with flexibility, adaptability, and plasticity
- •He describes brain activity under psychedelics as showing increased richness/complexity beyond normal waking states
- •He says the quality of the acute experience predicts therapeutic outcomes and may “open a window” to revise maladaptive beliefs with proper support
Why an investor got involved: personal experience, biotech pathway, and mental health neglect
Christian Angermayer recounts his initial reluctance, the influence of trusted friends and scientific data, and a guided legal psilocybin session he describes as the most meaningful experience of his life. He explains his motivation to pursue FDA/EMA-style approval pathways and argues mental health has been under-innovated for decades despite large and rising need.
- •Christian describes being historically risk-averse with substances before exploring mushrooms
- •He attributes his shift to compelling data and a guided legal session he found profoundly meaningful
- •He argues the way forward is bringing compounds through standard regulatory approval cycles
- •He describes mental health as long neglected by pharma/biotech and suggests modern life is worsening it
MDMA: PTSD relevance and Ayelet’s account of its role in marriage-focused conversations
Tim briefly flags strong-looking PTSD data and notes FDA “breakthrough therapy” status for MDMA and psilocybin. Ayelet adds her experience using MDMA with her husband in structured, infrequent sessions as a tool for difficult conversations, and suggests it helps separate emotional charge from memory, making discussion feel safer and more connected.
- •Tim highlights that MDMA and psilocybin have received breakthrough therapy designation (as he states it)
- •Ayelet describes being generally a non-drug user aside from specific substances discussed
- •She recounts trying MDMA after encouragement from Sasha Shulgin and Ann Shulgin, framed as marital therapy
- •She describes multi-hour conversations characterized by connection and love, with effects she says can last for years
Safety and toxicity: physiological risk, psychological risk, screening, and rare adverse outcomes
Tim asks about risks and contrasts compounds with different risk profiles, then Matthew outlines what is known about physiological toxicity for classic psychedelics and where harms tend to arise. He distinguishes physiological safety from psychological and situational risks, describes who may be vulnerable, and lists key concerns researchers screen for or monitor.
- •Matthew says there is no known lethal overdose or organ damage mechanism for psilocybin, LSD, DMT at physiological levels discussed
- •He emphasizes no drug is universally “safe”; risks depend on the category (physiological vs psychological vs situational)
- •He describes “challenging experiences” and how panic or disorientation can lead to dangerous behavior without proper setting
- •He identifies elevated risk for people with active psychotic disorders or strong predisposition, and notes cardiovascular screening, headaches, and rare persistent perceptual disorder reports tied mainly to polydrug recreational contexts
Opioid addiction and the case for further research; scheduling and treatment limitations
Tim asks whether psychedelics could have applications for opioid addiction, grounding the question in personal loss. Matthew points to limited historical signals and related early work in other addictions, while Ayelet argues current approaches are insufficient without broader medication-assisted treatment and serious evaluation of psychedelics; they discuss the meaning of Schedule I and comparisons to Schedule IV.
- •Tim connects the question to personal experiences with opioid-related deaths in his family and among friends
- •Matthew cites an early LSD study in heroin addiction and describes opioids as a promising area for investigation
- •He mentions initial positive results being explored for cocaine addiction by another researcher
- •Ayelet argues opioid addiction is resistant to traditional treatments and suggests the crisis should increase openness to rescheduling and research; Schedule IV examples mentioned include benzodiazepines and sleeping aids
Diagnostic categories, the default mode network, and a call for paradigm shift in psychiatry
Robin critiques overly crisp psychiatric diagnostic silos and argues rising prescription rates haven’t solved the broader mental health burden. He describes psychedelic therapy as a hybrid approach—drug plus context—then explains the default mode network as a candidate substrate of self-related narrative and how psychedelics temporarily disrupt it, potentially enabling a broader perspective.
- •Robin says diagnostic categories are clinician aids but can misleadingly imply crisp biological distinctions
- •He argues the biomedical “magic bullet” model hasn’t delivered enough progress given worsening outcomes
- •He frames psychedelic therapy as context-managed treatment that leverages increased mental suppleness
- •He describes the default mode network as tied to self-narrative and notes psychedelics temporarily disrupt it, sometimes yielding a “bigger picture” perspective
From “over-the-counter” to supported care: decriminalization visions, Netherlands example, and safe vs unsafe trips
Christian argues that for many psychedelics, the guide and setting are crucial, so they should be medicalized but not over-the-counter. Ayelet agrees and sketches a “psychedelic spa” model with preparation and aftercare; Christian points to the Netherlands as an example where legal access alone hasn’t solved mental health issues. Tim reframes “good vs bad trip” as “safe vs unsafe trip,” emphasizing that difficult experiences can still be beneficial with proper support.
- •Christian argues professional support and context matter and cautions against unsupervised use, especially in depression
- •Ayelet describes an idealized supported setting model involving trained staff plus preparation and integration
- •Christian cites the Netherlands as evidence (in his view) that simple availability doesn’t resolve the mental health crisis
- •Tim suggests focusing on safety rather than labeling trips as good or bad, since challenging experiences can reveal uncomfortable truths
Sustainable business models, rescheduling realities, and closing hopes for the field
Tim asks how to build sustainable business models around treatments that may not require frequent dosing. Christian argues the need is massive and includes service models (clinics/spas), while acknowledging dosing frequency is still an open empirical question. Tim and Matthew then address why psychedelics landed in Schedule I, what it takes to move out of it (FDA-approved indication), and which indications have the strongest published evidence so far; Ayelet closes with a vision of medicalization and law change driven by investment and pressure.
- •Christian says biotech investing can be impact-driven and argues the market is large even if dosing is infrequent; service models may matter
- •He says optimal dosing frequency is not yet known and needs research to determine
- •Matthew attributes Schedule I placement largely to late-1960s/early-1970s cultural backlash and notes that “accepted medical use” has come to mean FDA approval
- •Matthew lists leading researched indications with published results (including cancer-related distress, smoking cessation, alcoholism, and depression outside cancer), and Ayelet forecasts a medicalized shift similar to state-by-state marijuana changes

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