Everyone's Taking Psychedelics. Should You?

Every few weeks a new patient tells me a friend of theirs is microdosing mushrooms to "work on themselves," or that a cousin just got back from an ayahuasca retreat in Costa Rica, or that some executive at their company swears by a quarterly ketamine clinic day. The psychedelic boom is real. Whether any of it is right for you is a different question, and the answer depends more on your clinical picture than on what is trending in your social feed.

Here is what I tell patients when they ask.

What's real about the resurgence

Research suppression that held for fifty years has largely lifted. Johns Hopkins, NYU, UCSF, Yale, Imperial College London, and a long list of others now run psychedelic research programs. Psilocybin has breakthrough-therapy designation from the FDA for treatment-resistant depression. MDMA-assisted therapy for PTSD has gone through Phase 3 trials. Oregon and Colorado have legalized supervised psilocybin therapy. Several cities have decriminalized possession.

The science is progressing. The headlines are sometimes ahead of it, but the underlying work is serious, and for certain diagnoses (TRD, treatment-resistant PTSD, some addictions) the effect sizes from supervised trials are larger than anything in conventional psychiatry.

What I'm skeptical of

Microdosing. The body of evidence for sub-perceptual psilocybin or LSD as a routine wellness practice is mostly anecdotal. Randomized trials that control for expectancy (the placebo effect of thinking you are microdosing) have generally failed to find a meaningful signal. I am not saying it does nothing. I am saying I would not make clinical decisions on the basis of it yet, and I would not pay hundreds of dollars a month for mushroom capsules shipped from overseas.

Ayahuasca retreats. These range from genuinely therapeutic, well-screened programs run by experienced facilitators to effectively unregulated weekend trips that will hand you a cup of DMT brew regardless of what is on your medication list or your cardiac history. The dangerous version is more common than the retreat websites make it sound. Ayahuasca contains MAOIs that interact with SSRIs, SNRIs, some blood pressure medications, and a long list of other drugs in ways that are occasionally fatal. People have died on retreats. If you are considering one, get a cardiac workup and a medication review from a physician who is familiar with MAOI interactions, and do not assume the facilitators have done it for you.

The "quarterly clinic day" for optimization. Using psychedelics as a productivity tool without a therapeutic frame tends not to produce what people are hoping for. You can have a profound dissociative or psychedelic experience and then go back to your normal life on Monday morning and find that nothing has changed. Integration, the work you do in the weeks after, is where the actual change happens.

Where ketamine fits

Ketamine is grouped with classical psychedelics in the popular press, but clinically it sits somewhere adjacent. It is a dissociative, not a serotonergic psychedelic. It works through NMDA-receptor modulation and downstream BDNF release rather than through 5-HT2A activation. The subjective experience is typically shorter and less overtly "visionary" than psilocybin or ayahuasca. And it has one substantial clinical advantage over the classical psychedelics: it is already legal and prescribable, via both FDA-approved (Spravato nasal spray) and off-label (compounded sublingual, IV infusion) pathways.

For patients who have treatment-resistant depression, anxiety, or PTSD and want to pursue a dissociative or psychedelic-adjacent treatment under medical supervision, ketamine is almost always the right first call. The infrastructure exists, the dosing is well-characterized, and the safety profile in medical use is strong. Psilocybin may be a better fit clinically in two to five years once the FDA approves it for specific indications. Right now, in 2026, it is not generally the first option I reach for.

Who I refer out

I have referred patients to psilocybin clinical trials when they met entry criteria for a study I knew and trusted, when ketamine had not produced a durable response, and when the trial design included proper medical screening and integration support. These are rare situations, and I make the referral by name (to the specific investigator running the specific protocol) not to a retreat in the Amazon.

I have also referred patients away from psychedelics entirely. Personal or family history of schizophrenia or psychotic-spectrum illness is a hard stop. Active mania or bipolar I with recent episodes is a hard stop. Uncontrolled cardiovascular disease is a hard stop for substances that raise blood pressure acutely (which is most of them, including ketamine). Pregnancy. A current substance-use pattern that has not been addressed. If any of these apply, conventional psychiatric care is the right next step, not a retreat.

The question to ask yourself

If the thing pulling you toward psychedelics is curiosity about consciousness or a sense that you are "behind" culturally, I would pause. Those are reasons to read about it, not to put a Schedule I compound in your body without medical supervision. The foundational practices that actually move the needle on mental health for most people — sleep, exercise, mindfulness, nutrition — are still where I would start; we walk through them in our natural methods for mental health guide.

If the thing pulling you toward psychedelics is years of depression, anxiety, or PTSD that conventional treatment has not touched, that is a different conversation. Supervised ketamine is available right now. Supervised psilocybin is available in two states and in clinical trials. MDMA-assisted therapy for PTSD is close to approval. The options are real. The right one for you depends on your diagnosis, your medication list, and your medical history.

That is the question worth asking. Not is everyone doing it. What does my specific picture call for.

Next step

If you have been cycling through antidepressants without adequate response and want to know whether ketamine therapy is a reasonable next move, the five-minute eligibility check will tell you quickly. If the answer is no, I will refer you somewhere it is yes.

Frequently Asked Questions

Is microdosing safe?

Probably physically safe at the doses people use (typically 1/10 to 1/20 of a recreational dose), but the case for benefit is much weaker than the case for safety. The largest placebo-controlled trial to date (Szigeti 2021 in eLife, n=191 self-blinded participants) found that microdosers and placebo controls both improved on psychological outcomes, with no significant between-group differences. The findings suggest much of the reported benefit is expectancy. Most clinical psychedelic researchers I know are cautious about microdosing as a routine wellness practice; there's not yet enough data either way to recommend it confidently.

Are ayahuasca retreats legal?

In most US states, no. Ayahuasca contains DMT, a Schedule I substance under federal law. A small number of religious organizations (notably União do Vegetal and Santo Daime) have specific religious-use exemptions through the courts. Most retreats operate in countries where ayahuasca is unregulated or specifically permitted (Peru, Costa Rica, Brazil, Netherlands, Portugal). Returning to the US with material, or hosting ceremonies on US soil outside of those exemptions, is illegal.

How is ketamine different from psilocybin or MDMA?

Different mechanism, different profile, different legal status. Ketamine works through NMDA-receptor antagonism (glutamate system) and produces dissociative effects, with sessions typically 45-90 minutes. Psilocybin works through 5-HT2A serotonin receptor agonism and produces classical psychedelic effects with sessions typically 4-6 hours. MDMA works through serotonin/dopamine release and produces empathogenic effects with sessions typically 4-6 hours. Ketamine is the only one currently legal and widely available outside trials.

When will psilocybin be FDA-approved?

The most likely timeline is 2027-2029. The Compass Pathways and Usona Institute Phase 3 trials are running; results would inform FDA submission. Even after approval, access will initially be through a REMS program in certified clinics (similar to Spravato), not at-home prescribing. Psilocybin is already legal for supervised therapeutic use in Oregon (since 2023) and Colorado (rolling out 2024-2026) under state-level frameworks separate from FDA approval.

Can I combine psychedelics with my SSRI?

For ketamine: yes, generally compatible with SSRIs (different mechanism). For classical psychedelics (psilocybin, LSD): SSRIs blunt the experience by occupying 5-HT2A receptors, and most clinical trials require a 2-6 week SSRI taper before participation. For MDMA: SSRIs significantly reduce MDMA's effect AND increase serotonin syndrome risk; MDMA trials require a longer taper. For ayahuasca: SSRIs combined with ayahuasca's MAOI content can be life-threatening. The medication review is one of the most important parts of any psychedelic treatment workup. See our deep-dive on combining ketamine with SSRIs.

Should I try ayahuasca instead of ketamine?

For most patients with depression, anxiety, or PTSD: no. Ketamine is legal, prescribable, supervised by a physician, has a known safety profile, and can be initiated quickly. Ayahuasca requires international travel, has a much higher risk profile (cardiovascular, MAOI interactions, variable facilitator quality), and produces a much more intense experience that some patients find traumatic rather than therapeutic. Ayahuasca has its place for some patients with specific situations, but it's rarely the right first call when supervised ketamine is available.

What's the difference between supervised psychedelic therapy and a recreational trip?

Set, setting, screening, dose, and integration. Supervised therapy involves medical screening (cardiovascular, psychiatric, medication review), a controlled setting designed to reduce anxiety, dosing calibrated to therapeutic rather than recreational effect, the presence of trained guides, and structured integration sessions in the days following. Recreational use skips most of these. The difference in outcome between the two is large, even with the same molecule.

If I'm just curious about consciousness, what should I read?

Reading is a much better use of curiosity than putting a Schedule I compound in your body without medical supervision. Strong starting points: Michael Pollan's How to Change Your Mind, Ross Ellenhorn's How We Change, James Fadiman's The Psychedelic Explorer's Guide, and the Johns Hopkins Center for Psychedelic and Consciousness Research's published papers. If after reading you still want a supervised experience, ketamine is the legal current option; psilocybin in Oregon or Colorado is the next.

References

1. Szigeti B, Kartner L, Blemings A, et al. Self-blinding citizen science to explore psychedelic microdosing. eLife. 2021;10:e62878. PubMed: 33648632 · Free full text The largest placebo-controlled microdosing trial to date (n=191 self-blinded participants from Imperial College London's Centre for Psychedelic Research). Both microdose and placebo groups improved on psychological outcomes; no significant between-group differences. Source for the body's claim that randomized trials controlling for expectancy have failed to find a meaningful microdosing signal.

2. Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033. PubMed: 33972795 MAPP1, the first Phase 3 trial of MDMA-assisted therapy for severe PTSD. Source for the body's claim that "MDMA-assisted therapy for PTSD has gone through Phase 3 trials" and underpins the "close to approval" framing.

3. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856-864. PubMed: 16894061 Foundational NIMH ketamine trial. Mechanistic basis for the body's discussion of ketamine working through NMDA modulation and downstream BDNF release rather than through 5-HT2A activation.

Disclaimer: Compounded ketamine for anxiety, depression, PTSD, and chronic pain is not FDA approved. Discreet Ketamine provides at-home ketamine therapy to residents of Florida and New Jersey. All treatments are supervised by Dr. Ben Soffer, a board-certified physician.