DISCOVER
What are psychedelics?
Psychedelics are substances that temporarily alter perception, thought, and emotion. The so-called classic psychedelics, such as psilocybin, LSD, and DMT, act mainly on the brain's serotonin 5-HT2A receptor. Their effects last from a few minutes to about 12 hours, depending on the substance and dose. Some, like ayahuasca or certain mushrooms, have been used by Indigenous peoples of the Americas for centuries.
Over the past two decades, universities and pharmaceutical companies have conducted controlled clinical trials suggesting benefits for depression, post-traumatic stress, and addiction, among other conditions. The evidence is promising but still limited: many studies are small, it's difficult to keep participants from knowing whether they received the substance or a placebo, and long-term effects are still being studied.
These substances also carry risks. They can trigger crises in people with a history of psychosis or bipolar disorder, cause intense distress during the experience, and raise blood pressure and heart rate. That's why, in clinical trials, they are administered only after a prior medical evaluation, in a controlled setting, and with professional support.
Last reviewed: September 2026.
Psilocybin
Psilocybin is the active compound in more than a hundred species of mushrooms, and is the psychedelic substance furthest along the regulatory path. Two phase 3 trials by the company Compass Pathways, with 839 participants in total, showed a reduction in symptoms among people with treatment-resistant depression, compared with placebo (COMP005) and compared with a very low dose (COMP006). These results come from company press releases and have yet to be published in scientific journals. The U.S. regulatory agency (FDA) is reviewing its application under priority review.
Other studies are evaluating it for major depression, alcoholism, and distress in cancer patients. In alcoholism, for example, a 2022 published trial found a significant reduction in heavy drinking days. Australia has allowed prescription by authorized psychiatrists since 2023, and Czechia legally authorized it starting in 2026, though treatment there is still being rolled out.
LSD
LSD (lysergic acid diethylamide) was synthesized in 1938 by Swiss chemist Albert Hofmann, who discovered its effects in 1943. It was widely studied in psychiatry in the 1950s and 60s before being banned. Today it's being researched again: a 2014 Swiss study found reduced anxiety in people with serious illnesses, a phase 2 trial published in JAMA in 2025 showed benefits for generalized anxiety disorder, and in 2026 the company Definium reported positive phase 3 results for that same indication. Its effects last between 8 and 12 hours, making sessions long and demanding.
DMT
DMT (dimethyltryptamine) is found in many plants and is the main psychedelic compound in ayahuasca. Smoked or injected, it produces a very intense experience lasting less than half an hour; taken orally, it's only active when combined with substances that block the MAO enzyme, as happens in ayahuasca. Therapeutic research is still early-stage: a phase 2a trial published in 2026 in Nature Medicine, with 34 participants, found a reduction in major depression symptoms compared with placebo after a single intravenous dose. A related compound, 5-MeO-DMT (mebufotenin), is in clinical development for treatment-resistant depression.
MDMA
MDMA is not a classic psychedelic: it releases serotonin, dopamine, and norepinephrine, and is often described as an entactogen. In two phase 3 trials, published in 2021 and 2023, MDMA-assisted psychotherapy reduced post-traumatic stress symptoms more than psychotherapy with placebo. However, in August 2024 the FDA rejected the approval application over concerns about study design and adverse event reporting, and in August 2026 the company, now called Resilient Pharmaceuticals, resubmitted it. Australia has allowed its prescription for post-traumatic stress since 2023.
MDMA can raise body temperature, blood pressure, and heart rate. In recreational use, adulterated pills are an additional major risk.
Ketamine
Ketamine is an anesthetic that has been used in medicine since the 1960s. Unlike classic psychedelics, it acts on the glutamate system. At low doses it has a rapid antidepressant effect, sometimes within hours, in people with treatment-resistant depression. In 2019 the FDA approved esketamine nasal spray for this use, always under medical supervision.
In Colombia, ketamine is a legal medication, and some clinics use it to treat depression. Its antidepressant effects tend to be temporary and require repeated sessions, and frequent use can cause dependence and bladder damage.
Ayahuasca
Ayahuasca, also known in Colombia as yagé, is a traditional beverage of Indigenous peoples of the Amazon. It is prepared with the Banisteriopsis caapi vine and the leaves of plants containing DMT, such as chacruna (Psychotria viridis) or chagropanga (Diplopterys cabrerana). Its effects last between four and six hours. Observational studies and a small clinical trial in Brazil, with 29 participants with treatment-resistant depression, suggest benefits, but the evidence is preliminary.
It carries specific risks: it can interact dangerously with antidepressants and other medications, and is not recommended for people with heart disease or a serious psychiatric history. For the peoples who use it, it is, above all, medicine and spiritual practice, and that traditional use deserves respect.
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WARNING
This information is for educational purposes only and does not constitute medical or legal advice, nor an invitation to use these substances. Fundación Polígonos does not offer therapies, and does not sell, supply, or facilitate access to psychoactive substances, nor does it recommend providers. Many of these substances are controlled in countries across the region. If you are going through a mental health crisis, seek professional help or contact your country's helpline.
