The Possibilities of Mind-Altering Compounds | Dr. Suresh Muthukumaraswamy | The Tim Ferriss Show

In a live Edmund Hillary Fellowship session, Tim Ferriss interviews Dr. Suresh Muthukumaraswamy about mind-altering compounds and mental health. They trace New Zealand's doubling of psychological distress over a decade and contrast how ketamine works (NMDA antagonism plus a very promiscuous receptor profile) against classical psychedelics like LSD and psilocybin (serotonin 2A receptor). A central theme is methodology: the durability of antidepressant effects, the role of psychotherapy wrapped around the drug, and the field's profound difficulty in blinding placebo controls. Suresh details how a legal loophole in New Zealand's Misuse of Drugs regulations let his team run a six-week LSD microdosing trial in 80 healthy volunteers. The conversation closes on funding, training pipelines, intellectual property battles, and the risk of a political backlash returning psychedelics to prohibition.

• New Zealand's adult psychological distress more than doubled in a decade, from 4.6% (2011-12) to about 9.6% (2020-21).
  00:04:38
• Suresh's scopolamine trial found NO antidepressant response; using an active placebo (glycopyrronium), they ascribed most of the apparent effect to placebo.
  00:08:46
• Ketamine's half-life is about 4 hours, so at 24 hours there's essentially no drug left in the body yet patients remain non-depressed, proving it flips a functional 'switch' in the brain.
  00:14:56
• Psilocybin therapy's long durability may be confounded by roughly 40 hours of wraparound psychotherapy per course, whereas ketamine is usually given as a bare one-hour infusion.
  00:19:40
• A loophole in New Zealand's 1977 Misuse of Drugs regulations legally allowed prescribing a Class A substance, enabling the LSD microdosing trial.
  00:25:59
• The completed trial gave 80 healthy volunteers a six-week LSD microdosing course: the first dose in the lab and 13 further doses taken at home with 100% video-recorded adherence.
  00:26:29
• Microdosing uniquely permits genuine placebo control because high-dose psychedelics are so obvious to subjects that blinding is nearly impossible.
  00:48:54
• Suresh warns the workforce-training pipeline is one of the most challenging issues of the next 5-10 years, risking a surge of gray- and black-market 'charlatans.'
  01:06:33

• Scopolamine is naturally occurring in psychoactive plants and is thought to produce amnesia while leaving the person functional.
  00:09:48
• Ketamine metabolizes into norketamine, which is itself neuroactive, and exists as separate R- and S-enantiomers with different receptor profiles, making it a 'dirty' or very rich drug.
  00:12:54
• Microdosing means roughly one-tenth of a recreational dose (about 10 micrograms of LSD versus 100-150), popularized by James Fadiman's 2011 book, typically taken every third day.
  00:23:54
• Johnson & Johnson's Spravato (esketamine nasal spray) is essentially a patenting/marketing exercise with no clear added efficacy over generic ketamine.
  00:38:57
• In New Zealand a vial of generic ketamine costs about $20 while Spravato runs $5,000-6,000.
  00:39:29
• In the LSD trial, around 10 micrograms was near the detection threshold in males, but sensitivity varied widely so some participants needed dose reductions.
  00:51:29
• Niacin makes a poor active placebo (its skin flushing tips subjects off) yet has been used since the 1960s; what matters is the participant's belief, not the compound.
  00:52:32
• Australia created a $15 million fund for breakthrough mental-health therapeutics while New Zealand's government takes a hands-off approach with no dedicated funding pathway.
  00:55:39
• LSD doses are measured in micrograms (millionths of a gram); Albert Hofmann's first famous trip happened on a bicycle after absorbing it through his fingers.
  01:00:18
• Suresh's group is beginning to sketch a Maori-led, Maori-researcher-run intervention project for methamphetamine or alcohol use.
  01:13:18

Books, products and media the guest or host genuinely endorsed here — with the buy link.

Affiliate link — we may earn a commission at no extra cost to you.