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The High Guide Podcast: Psychedelics & Addiction: What the Research Actually Says


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126. Psychedelics & Addiction: What the Research Shows

Addiction psychiatrist Dr. Nathan Sackett on psilocybin, ibogaine, MDMA, ketamine, and what psychedelic-assisted therapy can and cannot do for substance use disorder.

Episode Summary

The conversation about psychedelics as addiction treatment is moving faster than the research. Dr. Nathan Sackett is trying to close that gap. Founding director of the Center for Novel Therapeutics at the University of Washington, Sackett is an addiction psychiatrist who still sees patients — which matters, because every study his center runs is rooted in clinical reality, not advocacy optics. In this live recording from the Psychedelic Salon at Town Hall Seattle, we cover what the evidence actually supports, what compounds carry genuine risk, and why the most important variable in treatment outcomes may not be the drug at all. If you've been following psychedelic news and want a clearer picture of what's real, this is the conversation.

🔵 Key Takeaways

Psilocybin works as an accelerant, not a cure. It amplifies therapeutic work already in progress — which means the therapeutic work has to be there first.

Ibogaine's cardiac risk is real and cannot be fully predicted even in pre-screened patients. Clinical monitoring with a cardiologist present is not optional — it is the protocol.

Ketamine is habit-forming in a way classic psychedelics are not. Since the pandemic, Dr. Sackett has seen a meaningful rise in ketamine use disorder in his clinical practice.

The variation in long-term outcomes across psilocybin trials may have more to do with integration therapy than with the drug. The field does not yet have standardized integration protocols.

Kratom is available at corner stores and gas stations nationwide and contains a compound with opiate-like properties roughly ten times more potent than morphine. It is undersupported in the research literature and underrecognized as a dependence risk.

🔵 Timestamps

[00:00] Welcome and standard disclaimer

[00:00] Intro: Dr. Sackett's origin story — clinical disillusionment, a patient who'd been to a retreat, and how that led to building UW's Center for Novel Therapeutics

[00:04] Why the center's name doesn't include the word "psychedelic" — and why that was a deliberate political and scientific choice

[00:05] The study no pharma company would fund: psilocybin for co-occurring PTSD and alcohol use disorder

[00:07] Why psilocybin over ketamine — metacognition, intensity, and the diversity of themes that come up during the experience

[00:08] April's bridge: metacognition, the default mode network, and the practice of cultivating the witness

[00:09] Ketamine: legal, widely available, genuinely useful for some — and increasingly implicated in use disorder since the pandemic

[00:11] The Psychedelic Education and Harm Reduction Clinic at UW: what a risk triage consult actually looks like

[00:13] Benzos and alcohol use disorder since the pandemic — and why women are prescribed benzos at twice the rate of men

[00:14] April's bridge: benzo pharmacology, cognitive risk in older women, the Ashton Manual, and who to contact before tapering

[00:14] Ibogaine: mechanism, cardiac risk, and the ethics of risk tolerance when the disease itself is fatal

[00:18] April's bridge: QTc interval, torsades de pointes, and why cardiac screening is the difference between a high-risk intervention with oversight and a dangerous one without it

[00:19] Ayahuasca and polysubstance use — why DMT's unusual craving-reduction profile makes it a candidate for trans-diagnostic research

[00:20] Cannabis as a case study: what legalization revealed about the gap between adoption and safety data, and whether psychedelics are on the same trajectory

[00:25] State psilocybin programs: Oregon's safety data, New Mexico's prescribed access model, and what happens to state programs once FDA approval arrives

[00:28] Synthetic psilocybin vs. whole-plant extraction — and why onset, duration, and clinical experience may differ between the two

[00:29] April's bridge: the entourage effect, Filament Health, and what we still don't know about whole-plant vs. isolated compound delivery

[00:30] The current UW trial: veterans and first responders with PTSD and alcohol use disorder, a single dose, and what the results look like so far

[00:32] The real cost of running a psychedelic trial: $2.5 million, 1,000 people screened for 12 participants, and the funding crisis threatening to stop this research before it reaches the people who need it

[00:34] Psychosis and psychedelics: screening practices, genetic load, and why European researchers are beginning to study this in populations previously excluded from trials

[00:36] Integration variability: whether differences in long-term outcomes across trials reflect the drug or the therapy model

[00:37] MDMA and the FDA: what actually happened, why the boundary violations mattered, and why the agency's hesitation was not irrational

[00:40] Which psychedelics for which disorders — and why MDMA and psilocybin may be suited for meaningfully different indications

[00:41] Psilocybin vs. ayahuasca vs. ibogaine: mechanism, receptor profile, and experiential differences explained for a general audience

[00:42] What psychedelic-assisted psychotherapy actually looks like: prep sessions, the medicine session, integration, and the role of the therapist

[00:44] Psilocybin for ADHD and depression: where the pipeline stands and what "mainstream" means when FDA approval is roughly 18 months away

[00:46] Safeguards for people in recovery: expectation management, the role of abstinence-based traditions, and why psychedelics are not a way to sidestep behavioral work

[00:47] Seattle NTC clinical trial site — open for enrollment; link in show notes

[00:48] Fentanyl, street-level opiate use, and what it would take to bring these interventions to people without housing or stable income

[00:49] Integrating psychedelic therapy into abstinence-based recovery culture — and why pitting the two against each other serves no one

[00:50] Kratom use disorder, ibogaine for kratom withdrawal, and the opiate pharmacology of a plant you can buy at any gas station right now

[00:52] April on kratom: what she's observed since 2007 and what the popular podcast conversation gets wrong

[00:52] Kratom and serotonin syndrome: what trusted sources exist, what Erowid covers, and where the drug interaction literature actually runs out

[00:54] MDMA for relational trauma: why Dr. Sackett is drawn to psilocybin for the PTSD-alcohol intersection and where MDMA research goes from here

[00:55] Outro: accelerant, not cure — what that distinction requires of us, of the field, and of the funding structures keeping this research alive

🔵 Guest

Dr. Nathan Sackett is an addiction psychiatrist and the founding director of the Center for Novel Therapeutics at the University of Washington, where he leads clinical research at the intersection of psychedelic-assisted therapy, trauma, and substance use disorder. He sees patients in both an addictions clinic and UW's Psychedelic Education and Harm Reduction Clinic.

Dr. Sackett on LinkedIn

Center for Novel Therapeutics, University of Washington

🔵 Resources

#46 Cultivating the Witness with Natasha Lannerd — on metacognition, integration, and the internal observer that makes psychedelic work stick

#117 Ibogaine Treatment at Beond — a conversation with the co-founders of the Mexico-based clinic whose cardiac data Dr. Sackett is currently studying

Ask April: Q: Does the president's executive order legalize psychedelics? — on the executive order, fast-tracked FDA review, and what access will actually cost patients

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