Real questions from real people exploring psychedelics because, while I’m not a doctor or scientist, “Ask April” is how meaningful dialogue begins.
What You’ll Learn in This Post
Why psychosis history is a real contraindication and what the emerging research is doing about it
How ibogaine differs from psilocybin and ayahuasca, and what the kratom data is showing
What psychedelic-assisted psychotherapy actually looks like across all three phases
Why expectation management is the most important safeguard for people with addiction histories
The honest state of psychedelic access for people with opioid use disorder experiencing homelessness
Below is the full Q&A from the Psychedelic Salon Psychedelics & Substance Use recorded live on March 5, 2026, with Dr. Sackett, addiction psychiatrist at the University of Washington and director of the Center for Novel Therapeutics. Rarely do we have time to do a deep dive into the questions at the Salon, so below is more context, more evidence, and more to consider on this emerging field of research. You can listen and watch the full live recording here.
If you live in Seattle and are in recovery, please reach out to me directly about the bi-weekly Psychedelics in Recovery meeting hosted on Capitol Hill. If you live outside of Seattle, check out the PiR website for chapter information.
The short answer is: we don’t know yet.
Psychosis exists on a spectrum. In its broadest definition, it describes a break from reality, disorganized thought, and disorganized speech. The more important clinical fact is that nearly all severe psychopathology, including depression, PTSD, and anxiety in extreme form, can end in a psychotic state. Trauma and psychosis aren’t always separate categories.
The concern with psychedelics is specific: people who carry a strong genetic load for schizophrenia or bipolar disorder may have that illness triggered by a psychedelic experience, or by any significant stressor. Because of that risk, most clinical trials have screened this population out entirely, which means the evidence base is thin, but that’s starting to change.
A handful of European research groups are now administering psychedelics to people with psychotic illness under controlled conditions, specifically to understand whether there’s any therapeutic role and what the risk profile actually looks like. While we don’t have those results, we do have a standard screening protocol that excludes personal or family history of psychosis, and the field is not yet ready to move beyond it.
If you carry that history and you’re curious about psychedelics, the conversation to have is with a psychiatrist who specializes in this area, rather than a facilitator who is not a clinician.
Integration protocols vary widely across research sites. Most phase-3 psilocybin trials report strong outcomes at six to twelve months, but what happens in integration sessions isn’t standardized the way the dosing protocol is. A group in Montreal is currently conducting comparative work on integration models to address exactly this question. These results aren’t yet conclusive.
Just as true of every intervention in psychiatry, with or without psychedelics, outcomes improve with a strong therapeutic relationship between clinician and participant. Dr. Sackett’s framing: psychedelics amplify therapeutic work when the container supports a powerful experience, so it is integrated into behavioral change.
It’s not dead, but the path forward is complicated in ways that matter for how we understand the whole field.
MAPS was very close to approval for MDMA-assisted therapy for PTSD. What derailed it was a combination of factors. Missing data and gaps in the trial data emerged during analysis. More significantly, boundary violations by several therapists in the trials, including at least one that became public in 2023, undermined the credibility of some of the studies. MDMA’s pharmacology produces deep openness and reduced fear response, a combination that makes patients in those sessions particularly vulnerable to therapist misconduct. The field has long known this was a design risk, but the trials didn’t build adequate safeguards proportionate to it.
The deeper structural problem is that the FDA regulates drugs and has no framework for evaluating therapy. MDMA-assisted therapy is a protocol: the compound plus a trained therapist across an eight-hour session, plus integration sessions before and after. When the agency found the molecule to be inseparable from a therapeutic container, it couldn’t assess the trial design and said no.
The result, as Dr. Sackett put it plainly, is that pharmaceutical companies are now incentivized to reduce the impact of the psychotherapy component, because that’s the only path to an approvable drug, even if the outcomes are not fully realized.
MAPS is currently running new trials, so there’s still potential for MDMA to become an approved treatment for PTSD. But anyone following this closely should understand that the version that eventually gets approved may look quite different from the protocol that produced the outcomes that made it compelling in the first place.
Almost certainly yes, and Dr. Sackett elaborated on how this may play out. MDMA is particularly well-suited to PTSD because one of the hallmark effects of PTSD is a loss of access to joy and pleasure, what clinicians call anhedonia. MDMA’s mechanism restores the full emotional range, including positive affect, in a way that may be uniquely useful for that specific condition. Psilocybin, by contrast, shows its strongest evidence base for depression, particularly ruminative depression, the kind that loops and sticks. Different mechanisms act on different presentations.
What Dr. Sackett described is a range of compounds matched to specific indications and combined with various proven psychotherapeutic approaches, peer-based models, group work, and more. Although the clinical infrastructure doesn’t exist yet at scale, the logic of differentiated treatment is already being validated in the trial data.
These three compounds are often grouped together under “psychedelics,” but their pharmacology, origins, and therapeutic profiles are distinct enough that the grouping obscures more than it clarifies.
Psilocybin is derived from mushrooms and acts primarily on serotonin 5-HT2A receptors, producing downstream effects on mood, perception, and the default mode network. Sessions typically run four to six hours. The research base is the most developed of the three, with clinical trials across depression, addiction, end-of-life distress, and eating disorders.
Ayahuasca is an Amazonian brew that works through a specific botanical synergy between two plants. The ayahuasca vine (Banisteriopsis caapi) contains beta-carboline alkaloids, including harmine and harmaline, that function as monoamine oxidase inhibitors (MAOIs). Those compounds temporarily deactivate the stomach enzymes that would otherwise break down DMT before it could reach the brain. The second plant, most commonly Chacruna (Psychotria viridis), though some indigenous traditions use Chagropanga (Diplopterys cabrerana), supplies DMT. Neither plant produces psychedelic effects on its own. Together, they enable oral DMT absorption and produce a session lasting four to eight hours, often with intense visionary content. DMT is structurally related to psilocybin, and the experiential terrain of the two medicines overlaps in some ways, but the duration, intensity, and cultural container are quite different.
Ibogaine is in a different category. It is an alkaloid derived from a West African shrub, and its pharmacology is still being mapped. It does not appear to act primarily on serotonin receptors, which distinguishes it from every other compound labeled “psychedelic.” The mechanism of action responsible for its remarkable record in treating opioid withdrawal hasn’t been identified, but Nathan Sackett’s team at the University of Washington is currently analyzing data on ibogaine from Mexico-based clinics like Beond to design future clinical trials.
Psychedelic-assisted psychotherapy has three phases. The first is preparatory: multiple weekly sessions with the therapist to build rapport, discuss goals, and establish trust. The second is the medicine session itself, during which the participant lies down with an eye mask and headphones while the therapist (in clinical trials, two therapists) is present but largely hands-off. There is not a lot of active therapeutic dialogue during psilocybin sessions specifically. The participant is going inward. The therapist is there to ensure safety and to be present, and there may be meaningful exchange toward the end of the session. The third phase is integration therapy: the extended work of making sense of what transpired while in an altered state of consciousness induced by the medicine and translating it into behavioral change.
Dr. Sackett’s description of what the medicine session creates: having an overwhelming, sometimes terrifying, sometimes transcendent experience with your therapist in the room, emerging from it together, and then doing the relational work of integration afterward. That shared experience creates a bond that changes what’s possible in the therapy that follows.
The dominant therapeutic model in clinical trials is low-directive, non-prescriptive, and driven by what arises for the participant rather than by a structured protocol. There is active debate in the field about whether that’s the optimal approach across conditions. Refer to this earlier post (also linked below) to understand the non-directive approach mandated in Oregon’s psilocybin program versus Colorado’s.
Q: How do I find a psychedelic guide?
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Jun 12
How do I find a licensed psilocybin facilitator? Start with the state licensee directories above, then cross-reference vetted third-party directories. Narrow your list by location (proximity to the airport), setting (access to the outdoors), credentials, and specialization (sexual trauma, PTSD, mindfulness).
Dr. Sackett framed psychedelics as an accelerant, amplifying therapeutic work–not a replacement for it.
The safeguard he advocates for most strongly is expectation management. People with addiction histories are often drawn to psychedelics by the logic that a drug got me into this, so a drug might get me out. While that logic isn’t irrational, it can set people up to skip the ongoing behavioral work that has been shown to contribute to the optimal outcomes in addiction recovery. Addiction is a behavioral syndrome that evolves over years, so changing it takes time. Rather than serving as a shortcut, psychedelics can increase motivation and deepen engagement with recovery work.
Dr. Sackett was honest that this is far beyond where the field currently is.
The clinical infrastructure for psychedelic-assisted therapy is expensive, time-intensive, and requires sustained engagement. Designing that infrastructure to reach people whose lives are organized around housing instability, poverty, and active opioid dependence is a different problem than running a clinical trial at a university. Dr. Sackett hopes that the field will eventually build toward research and care that’s accessible to a wider range of people, but warns that we’re nowhere near that yet.
This was one of the more pointed questions of the night, and Dr. Sackett was explicit: Proponents of psychedelics use the failures of the existing treatment system as their primary argument for why these emerging therapeutic compounds should replace currently approved/accepted/adopted interventions. His position is that psychedelics need to be integrated into broader treatment paradigms, not positioned against them. What that looks like in practice will vary by culture, by individual, and by the specific recovery tradition involved because there isn’t a single answer. He stressed that clinicians have a responsibility to work with what’s already keeping people alive.
Abstinence-based recovery works for a lot of people, but not everyone. The more treatment options available, the more potential for successful outcomes.
First, a quick background on kratom.
Kratom is a plant from Southeast Asia that contains a compound called 7-hydroxymitragynine, an opioid with a potency roughly ten times that of morphine. It’s legal, unregulated, and available at gas stations. Kratom’s accessibility and powerful withdrawal make recovery especially difficult, and Dr. Sackett is seeing more kratom use disorder than ever.
Dr. Sackett’s team is currently analyzing data on using ibogaine for kratom use disorder. Early findings suggest ibogaine helps with the acute withdrawal phase, consistent with its broader opioid mechanism. Long-term recovery requires support structures that address the accessibility problem, not just the acute pharmacology.
On drug interactions between kratom and ibogaine specifically: the evidence base is thin, and Dr. Sackett confirmed there are no rigorous drug-interaction studies on kratom combinations.
Q: Is concentrated kratom more addictive than the leaf?
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October 21, 2025
Additiveness of concentrated kratom vs. the leaf? It’s a question stirring debate among users, scientists, and regulators alike. Kratom, a Southeast Asian plant long used for pain relief and energy, has found new life—and controversy—in Western markets. But while traditional kratom leaf offers mild, short-lived effects, today’s concentrated extracts can be far more potent, altering brain chemistry and increasing addiction risk.
Dr. Sackett was candid that the choice was partly pragmatic and partly about where the evidence gaps were largest.
MDMA is widely understood to be a relational medicine. Its mechanism, which promotes emotional openness, trust, and a reduction in fear response, is particularly well-suited to trauma that lives in the body and in relationships. The psilocybin-for-PTSD path was less traveled. A study of roughly twenty patients receiving psilocybin for PTSD was just published at the time of the Salon, the first of its kind. Dr. Sackett was drawn to the specific overlap between alcohol use disorder and PTSD, where the evidence for psilocybin in alcohol use disorder is strong, and wanted to understand whether that extended to the comorbid condition.
His interest in MDMA hasn’t gone away. His answer for why he ended up here: “I find myself more drawn to psilocybin, ayahuasca, and ibogaine.” Notice that these are plants that naturally provide psychedelic compounds.
The Psychedelic Salon on Substance Use covered all these questions and so much more. You can watch or listen to the full live recording on Substack, YouTube, or wherever you listen to podcasts.
Take care,
April
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