- The Drop In by DoubleBlind
- Posts
- Tripping on High-Dose LSD Shows Promise for Depression Relief
Tripping on High-Dose LSD Shows Promise for Depression Relief
Plus DMT orgasms, effects of music on the tripping brain, and mushroom potency.
Good morning! Welcome back to The Drop In, DoubleBlind’s newsletter delivering independent journalism about psychedelics straight to your inbox.
Today’s lead news story is about a new study showing that macrodoses of LSD are more likely to reduce depression than low doses. We love this story because, in the move to funnel psychedelics down a path of medicalization (read: creating psychedelic pharmaceuticals), LSD has been largely left out of the conversation due to the reputation (or stigma) it gained in the ‘60s. Is this finally changing? We’ll see! You’ll have to read the story below to find out.
If you keep scrolling, you’ll find pieces on aeruginascin, DMT orgasms, and how bad music choices can trigger nightmare psychedelic experiences.
In community 🫶🏾,
Mary Carreón
Editor-In-Chief

Together With ENTHEO*
Take your next MDMA experience to the next level.
We consulted the experts to create a free guide for creating meaningful solo and partner journeys, including:
How to create a container and set intentions
Tips for working solo, with a partner, or with friends
Safety and dosing essentials
How to integrate your experience post-journey
Get the guide here, your heart will thank you!
Featured

High-Dose LSD Shows Stronger Antidepressant Effects in New Clinical Trial
A fresh wave of research reveals that higher doses of LSD may significantly ease depression symptoms, opening new doors for psychedelic therapy.
In Basel, Switzerland — the birthplace of LSD, where chemist Albert Hofmann first synthesized and self-administered the psychedelic in 1943 — a team of researchers has found that higher doses of LSD, paired with supportive therapy, may significantly reduce symptoms of major depression.
The results come from a randomized, double-blind, phase 2 trial conducted at the University of Basel’s Department of Psychiatry. Published in Med on June 6, 2025, the study compared the effects of high-dose versus low-dose LSD-assisted therapy in people diagnosed with moderate-to-severe major depressive disorder (MDD).
Participants were divided into two groups: One received 100 micrograms of LSD in the first session and 200 micrograms in the second, while the other group received two sessions of 25 micrograms. All participants underwent a structured course of supportive psychotherapy over 19 weeks. The researchers assessed changes in depressive symptoms at several time points: two weeks after the second dosing session, and again at weeks 5, 9, 13, and 19.
The main takeaway? Higher doses of LSD led to greater and more sustained reductions in depression scores. “High-dose-LSD-assisted therapy reduced depressive symptoms more than low-dose therapy,” wrote the study’s authors. “Improvements in depression scores persisted up to 12 weeks after treatment.”
The findings offer the most comprehensive modern evidence yet for LSD’s potential as an antidepressant — one that acts rapidly and endures well beyond a single trip. At the study’s primary endpoint, clinician-rated depression scores (IDS-C) dropped by nearly 13 points in the high-dose group compared to just 3.6 points in the low-dose group. The difference, statistically significant, had a moderate-to-large effect size. Self-rated scores followed the same trend.
However, the researchers noted that some of these findings lost statistical strength after controlling for baseline differences. Still, the overall picture remained consistent. “All secondary endpoints at all time points were in the same direction,” the authors wrote, suggesting a treatment effect that held steady across measures.
The trial enrolled 61 participants with an average of 17 years living with depression. Nearly all had tried psychotherapy and antidepressants before. The sample included individuals with comorbid anxiety disorders and prior hospitalizations, making it a notably representative clinical population.
Therapy sessions took place in cozy, living room-like spaces. Participants were encouraged to recline on couches, listen to music, and turn inward. Integration sessions followed each dosing day to help process the experience. Importantly, participants and therapists were blind to dosage, although both groups were fairly accurate in guessing assignments — a challenge common in psychedelic research. “Blinding was not effective in a considerable number of cases,” the researchers acknowledged.
Acute effects were notably more intense in the high-dose group, as expected. On a standard measure of altered states of consciousness (5D-ASC), participants reported nearly double the subjective effects compared to the low-dose group. Interestingly, even the 25 microgram dose — often labeled a “microdose” — produced noticeable alterations in consciousness, calling into question assumptions about its subtlety.
Safety was closely monitored. While both groups experienced adverse events, they were generally mild and similar in frequency. A few participants in the high-dose group dropped out after experiencing dysphoria or anxiety. One person who had withdrawn from the study months earlier later died by suicide — a tragic incident, though the authors emphasized it occurred well outside the study window and was judged unrelated to the treatment. Still, the risk underscores the need for caution and comprehensive screening.
“LSD could be used safely within the framework of this study,” the researchers concluded. They also highlighted one of LSD’s defining features: Its long duration of action. While this can be a therapeutic asset, it also demands more clinical time and resources compared to shorter-acting psychedelics like psilocybin.
Limitations of the trial include a modest sample size and issues with blinding. And yet, despite these caveats, the signal is strong: LSD-assisted therapy, particularly at higher doses, holds real potential for treating depression.
“The findings of this exploratory trial support further investigations of LSD as a treatment option for major depression in a larger phase 3 trial,” wrote the authors. Given the scale of unmet need in mental health care — and the limitations of existing antidepressants — it’s a path worth exploring.

Sneak Peak
A$AP Rocky Took LSD with a Psychedelic Scientist That Led to One of His Biggest Hits
This Friday, we’re heading to a luxury London hotel room in early 2018, where A$AP Rocky, UK rapper Skepta, and a neuroscientist named Dr. Leor Roseman were deep in a loop—literally. As “Praise the Lord” played on repeat, the trio tripped on acid, refining rhymes and tweaking beats in a surreal session that helped birth one of Rocky’s biggest hits.
The story traces the friendship between a Harvard-educated psychedelic researcher and the Harlem rap icon, unfolding across studio visits, psychedelic experiments, and a moment when art, science, and rap collided under one hypnotic flute riff.
This is a story you don’t want to miss. Upgrade here to read it Friday morning.
& More Must-Reads
🍄 Scientists are redesigning psychedelic mushrooms to promise euphoria without the risk of a bad trip—and the secret may lie in an obscure compound called aeruginascin. Read more here.
👅 Is the brain’s most powerful psychedelic hiding in your orgasm? Scientists are probing whether sexual ecstasy triggers a natural rush of DMT—and why no one’s dared to find out. Read more here.
🎵 Why has classical music been the soundtrack for psychedelic therapy for nearly 80 years—and could it be time to change the tune? New research is exploring whether droning overtones, global rhythms, or even silence might better guide the psychedelic mind. Read more here. Read more here.
🍄 Ever wondered how potent your magic mushrooms really are? Thanks to new at-home testing kits, measuring psilocybin levels is no longer just for scientists in a lab. Read more here.
🫣 Music can shape a psychedelic trip—but the wrong song might steer it straight into chaos. New research reveals how bad music choices could turn your journey into a nightmare instead of a revelation. Read more here.

DoubleBlind Digs
GRANT OPP: Healing Hearts, Changing Minds has launched “Walking Each Other Home,” a $500,000 grant initiative to support psychedelic-assisted end-of-life care, with funding for projects spanning palliative care, practitioner training, and more. Applications are open through August 22. Learn more and apply here.
TRAINING: The Integration Circle is hosting its seventh training and consultation group for psychedelic facilitators. This cohort, starting on 9/10, will focus on deeper understanding of what transference and counter transference looks like in psychedelic work, working with trauma and related shame and fear, and a Jungian and Somatic approach for in-depth integration work. Attend the 12 week live group starting 9/10-9/11. Email [email protected].
SEX & PSYCHEDELICS: Join Dr. Alex Dymock, senior lecturer at Goldsmiths, University of London, on Wednesday, July 2, for a compelling look at how psychedelics are transforming understandings of sexuality, power, and therapeutic ethics. Join Zoom here.
Together With ENTHEO*
Want to work with MDMA in a more conscious way?
This free guide shows you how to create the ideal space for your ceremony — whether you’re flying solo, connecting with a partner, or sitting in a circle with friends.
Designed for people who care about harm reduction, healing, and integrating the lessons of the journey, it’s a practical roadmap for working with MDMA as medicine for the soul.

Around the Web
Are billionaire space dreams less about saving humanity and more about distraction, inequality, and profit? Read about why space travel could be the new ayahuasca for the ultra-rich. Diggit Magazine.
Thailand is poised to reverse its cannabis legalization, throwing a booming $1 billion industry and countless businesses into uncertainty. Read more from Reuters.
Michigan lawmakers are pushing a bill to let people with PTSD legally use and grow psilocybin mushrooms, spotlighting veterans who say the psychedelic has done more for them than years of VA therapy. Read more from Filter.
How was today's Drop In? |
💌 If you loved this email, forward it to a psychonaut in your life.
Reply