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- A 2024 study of many research papers found that the antidepressant effects of psychedelics seem smaller in studies that better control for placebo effects.
- Psilocybin and MDMA seem to work only in studies where it was easy for people to guess if they got the drug or not, or where there was no comparison group.
- What people expect and how a study is set up really change the results in psychedelic therapy research.
- How well ayahuasca and LSD worked as antidepressants changed a lot between studies because the studies included only a few people.
- It's hard to say for sure if psychedelic research results apply to most people because it's hard to hide whether someone got a psychedelic or not in studies, and studies often involve small groups of people.
Do Psychedelics Really Help with Depression?
Recently, there's been a lot of interest in psychedelics and depression. This comes from early studies that looked promising, stories of big improvements, and a growing push for different ways to treat mental health. But are these substances truly revolutionary, or is the excitement bigger than what the science actually shows? To really know if psychedelics can help with depression, we need to look at how these studies are done, what the results are for different substances, and why the context of these treatments is as important as the drugs themselves.
What Are Psychedelics?
Psychedelics are strong substances that change how people think, feel, and see the world. Unlike typical medications that change brain chemicals without changing awareness, psychedelics often cause strong visual or emotional experiences. People often describe these experiences as deeply meaningful or introspective.
Common Psychedelic Compounds
Here are some of the most common psychedelic substances studied
- Psilocybin: This is in over 200 kinds of mushrooms. In the body, it turns into psilocin, which affects serotonin receptors in the brain. It's being studied a lot in current clinical trials.
- LSD (Lysergic Acid Diethylamide): Made from a type of fungus, LSD has been well-known for a long time and is famous for its strong and long-lasting effects on perception.
- MDMA (3,4-Methylenedioxymethamphetamine): While not a typical psychedelic, MDMA makes people feel more open and empathetic. This makes it interesting for treating trauma and depression.
- Ayahuasca: This is a traditional brew from the Amazon that has DMT and MAO inhibitors. It's known for causing intense emotional and visual experiences and is often used in ceremonies.
- DMT (Dimethyltryptamine): This psychedelic is powerful but doesn't last long. It's found in ayahuasca or can be smoked in a concentrated form.
These substances are different in their makeup and how they make people feel, but most of them affect the serotonin system in some way—especially a part called the 5-HT2A receptor. This part of the brain is linked to mood. This is one reason why researchers started to check if they could help with depression.
Psychedelic Therapy is Popular Again
Psychedelic therapy is becoming popular again in culture and science, shown in documentaries, wellness blogs, and new clinics. After being banned for decades after the 1960s, these substances are back as possible new treatments for mental health.
Why the Excitement About Psychedelics?
The renewed interest comes from
- People saying they've had deep personal healing after using psychedelics in a guided setting.
- Retreat centers that offer guided psychedelic experiences in groups.
- Online groups and regular people who are interested in self-discovery and new therapies.
- Scientific studies that seem to show really good results at first glance.
But how much of this excitement turns into real, scientifically proven antidepressant effects? And how much do things like what patients expect, how involved the therapist is, and expectations about placebos change the improvements seen?
Looking Closely at the Science: The 2024 Study Review
To find out what's real and what's just hype, researchers are carefully examining how psychedelic therapy studies are actually done. A recent study that looked at many past studies, published in the Journal of Affective Disorders, by Jia-Ru Li and others, gives us new information. It looked at 21 clinical trials that checked how psychedelics—like psilocybin, LSD, MDMA, and ayahuasca—affect depression.
What the Study Wanted to Find Out
- To see if psychedelics consistently help with depression.
- To check if how a study is designed—especially what kind of placebo or control is used—changes the results.
- To see how reliable these effects are for different substances and study methods.
What the study discovered was surprising: when studies were designed better, the therapeutic effects of psychedelics seemed less strong.
Study Design is Very Important
One of the most important things this study showed is that how you do a study changes what you find. In other words, how a psychedelic trial is set up greatly affects the antidepressant effects that are seen. When placebos were used in a more careful way, the benefits were smaller.
Types of Study Designs Looked At
- Non-active placebo: This is a placebo like a sugar pill or vitamin that doesn't have any noticeable effects. It's easy for people to guess if they are getting the real drug or not if they are supposed to be "tripping."
- Active placebo: This uses a small dose or a drug that causes some minor effects. This helps to make it harder for people to know if they got the placebo or the real drug.
- Pre-post design: This measures people before and after treatment, but doesn't have a control group to compare to.
- Waitlist control: A control group is told they will get the treatment later but have to wait.
- Fixed-order design: People get both a placebo and the drug, in a specific order (usually placebo first). This lets researchers compare the effects within the same person.
The Problem with Keeping People Blinded
A big challenge in psychedelic research is blinding—making sure that people in the study and the researchers don't know who is getting the psychedelic and who isn't. Because the experience is so strong and obvious, people can almost always tell if they got the real treatment. This can make people expect to get better, and this expectation, not the drug itself, might be why they report improvements.
What Did the Study Review Show?
The results of this study show something important when we look at psychedelic therapy: when studies are stricter, the effects seen are weaker. When studies were more careful to reduce bias by better blinding and controls, the big improvements often disappeared.
Summary of Results for Each Substance
- Psilocybin and MDMA seemed to have strong antidepressant effects in less strict studies (like those with non-active placebos or pre-post designs). But these findings were not statistically significant when tested in studies with active placebos that controlled for expectations better.
- Ayahuasca seemed to have consistently positive results, but these were usually from small studies with less control.
- LSD had mixed results—it only seemed to help in studies with non-active placebos and where it was easy to guess who got the drug.
Main Point
The better a study was at blinding people and reducing bias from expectations, the less strong the antidepressant effect appeared to be. This makes it harder to say for sure if psychedelics really work for depression, unless more research is done in better, more controlled studies.
Looking Closer at the Placebo Problem
One of the main problems in psychedelic therapy research is the placebo puzzle: how do you make a fake psychedelic experience that feels real enough?
Why This is Important
- If people know they've been given a psychedelic, it can really change how they understand, react to, and describe the experience.
- Expectations can make even small side effects seem like big breakthroughs, especially when it happens in a therapy setting.
- This isn't just a problem with psychedelics—placebo effects are strong in antidepressant trials in general—but because psychedelics have such strong and unique effects, it's even harder to deal with.
In studies that use active placebos, like small doses that cause mild physical effects (such as tingling, feeling sick, or changes in pupil size), people are less likely to know which group they are in. This gives a slightly better comparison. Interestingly, it's in these kinds of studies that the antidepressant benefits often get smaller or even disappear.
Psilocybin: The Most Talked About Psychedelic Therapy
Psilocybin has gotten more attention than any other psychedelic, both in science and in popular culture. It's been the focus of many clinical trials, pushes to make it legal, and use outside of formal settings.
Why Psilocybin is Special
- It comes from nature (magic mushrooms), which makes it appealing for wellness and for people who want to grow their own.
- It has a history of being relatively safe, with low risk of harm.
- It can cause deep emotional and introspective states, which can be helpful for therapy.
Research vs. Personal Use
In careful research studies, psilocybin is used with therapy from professionals, counseling before and after sessions, and safety monitoring. When antidepressant effects are seen in these situations, it's hard to know if it's the drug itself or the therapy around it that's helping.
People who grow psilocybin or use it on their own should keep this in mind. Growing mushrooms may have benefits for you personally, but don't expect the same kind of results as in a clinical study without the structured support that goes with psychedelic therapy.
What About Other Psychedelics?
While psilocybin is talked about the most, other substances are also becoming more interesting. Here’s a closer look at what the science says about them
Ayahuasca
- Traditionally used in Indigenous Amazonian cultures.
- Linked to emotional releases and spiritual visions that can be very intense.
- Studies are usually small, not controlled, and done in ceremonial settings. This makes it hard to compare results and say if they apply to most people.
- People often report strong antidepressant effects—but there aren't many large studies.
LSD
- Known for its long-lasting and wide range of mental effects.
- Surprisingly, there haven't been many modern clinical trials with LSD because of its history and rules around it.
- In the few studies in the review, only one showed clear benefit, and it wasn't a very strong study.
MDMA
- Becoming more popular for treating PTSD than depression.
- Works differently from typical psychedelics; it's more of an empathogen—it increases feelings of trust and connection.
- Shows some early promise for depression, but again, better studies show less of an effect.
Why Study Results Are Hard to Understand
Research on psychedelics is complicated for several reasons
- Hard to keep people blinded: Strong effects make it obvious when someone has taken a psychedelic.
- Mental health is subjective: Depression is complex and different for everyone.
- Context matters: A person's mindset and environment greatly change the experience.
- Studies are small: Most psychedelic trials have fewer than 50 people, which makes it harder to get clear results.
- High hopes: People who want to have spiritual or emotional breakthroughs may make results look better just because they expect to improve.
All of these things make studying psychedelics different from testing other medical treatments where, for example, you can easily measure if blood pressure goes down.
Why Do People Still Say They Feel Better?
Many people believe that psychedelics help with depression—even if they haven't been in a study. Are they wrong?
Not necessarily. These positive stories probably show real emotional benefits even if they aren't just clinical results. People might
- See their past traumas in a new way.
- Have important emotional or spiritual moments.
- Start to think better about themselves.
- Feel more connected to life or people they care about for a while.
But in research, we need ways to measure these effects reliably over time, and that's still being developed.
Advice for People Interested in Psychedelics and Mushroom Growers
If you grow mushrooms or are thinking about using psychedelics for your mental health, here are some important points based on the latest science:
- Don’t confuse personal benefits with effects that are proven for everyone.
- Have clear goals for your experience.
- Therapy context is important—try to include it if you can.
- Understand that real change takes time and effort after the experience, not just taking the substance.
- Keep learning and be careful; research is changing quickly.
Also, growing psilocybin mushrooms can be more than just a way to get a substance—it can be a hobby that helps you be mindful, patient, and feel purpose, all of which can improve your emotional well-being.
Moving Forward: Balancing Hope and Science
So, are psychedelics a breakthrough for treating depression?
They could be—but we're still working on getting solid proof, and some early studies might have made them look better than they are because of study problems or people's strong expectations. Psychedelic therapy is promising, but we need to be excited but also think critically.
For now, it’s important to respect both the science and your own beliefs. Whether you're growing mushrooms or thinking about guided psychedelic therapy, staying realistic, careful, and informed will make the experience better, safer, and possibly more helpful.
Citations
- Li, J.-R., Chiang, K.-T., Kao, Y.-C., Yu, C.-L., Yang, F.-C., Liang, C.-S., & Hsu, T.-W. (2024). The association between study design and antidepressant effects in psychedelic-assisted therapy: A meta-analysis. Journal of Affective Disorders, 350, 71–78. https://doi.org/10.1016/j.jad.2024.10.016
