LSD: The Bad and Potentially Good Sides

LSD was first synthesized by Swiss chemist Albert Hofmann in 1938. He discovered its powerful psychoactive effects in 1943 after accidentally ingesting a small amount and experiencing vivid hallucinations and consciousness shifts.

On April 19, 1943, Hofmann intentionally took a larger dose, riding a bicycle home while “tripping.” The date is still marked as Bicycle Day by LSD fans.

Recognizing its potential, Sandoz marketed LSD in 1947 as Delysid, promoting it for treating schizophrenia and depression, as well as as a tool for exploring consciousness.

Rise of Recreational Use

Researchers were interested in LSD, thinking they might understand Schizophrenia or at least hallucinations by understanding what it did in the brain. George Aghajanian pioneered much of this work, from his lab to work with volunteers. George's first experiments on the potent psychedelic drug LSD were in the summer of 1957. From his earliest days at Yale, his mentor, Danny X. Freedman, saw this work as essential to biological psychiatry, theories of mental illness, and hopes for new treatments. Serotonin neurons had LSD silenced characteristic rhythmic firing that George showed. As George would later discover, this inhibition left the psychedelic hallucinogen free to orchestrate its actions through a subset of serotonin’s typical receptor targets. By the mid-1960s, LSD had gained popularity outside the research and clinical settings, becoming a symbol of the countercultural movement. Figures like Harvard psychologist Timothy Leary promoted its use for personal enlightenment but came under fire for unscientific and unethical experiments. The unregulated and often irresponsible drug usage attracted negative attention from governments and the media, associating LSD with dangerous behavior and social upheaval.

In the 1960s and 1970s, many musicians experimented with LSD and other psychedelics, including the Grateful Dead, Pink Floyd, and the Beatles, often integrating the experience into their music. The Beatles’ “Lucy in the Sky with Diamonds” is one iconic track inspired by the psychedelic experience, though the group denied it was directly about LSD. Jerry Garcia of the Grateful Dead was an advocate of the drug and a close friend of Owsley Stanley, the Dead's sound engineer, and a notorious clandestine LSD chemist.

In 1967, Paul McCartney became one of the first public figures to openly admit to using LSD, causing a media stir. Pink Floyd’s original frontman, Syd Barrett, used LSD extensively, which many believe led to his mental health deterioration and departure from the band. His struggle became a cautionary tale of the dangers of excessive psychedelic use.

In 1968, the federal government classified LSD as a Schedule I illegal substance, dramatically limiting legal access.

A Modern Resurgence of Recreational Use

By 2023 an incredible 9% of adults ages 19 to 30 and 4% of adults aged 35 to 50 had used hallucinogens at least once— LSD, mescaline, peyote, shrooms, or psilocybin. Among high school seniors, more than 8% used LSD at least once, and 21.5% of 12th graders said it was “fairly easy” or “very easy” to obtain LSD.

“We have seen that people at different stages of adulthood are trending toward use of drugs like cannabis and psychedelics and away from tobacco cigarettes,” says Nora D. Volkow, M.D., director of NIH’s National Institute on Drug Abuse (NIDA). Increased use of psychedelics is an important new trend, observes Dr. David Courtwright, Presidential Professor Emeritus at the University of North Florida. “But in a world awash with cheap fentanyl and methamphetamine, and with the cannabis industry spending promotional money like crazy, hallucinogens are not at the top of my worry list.”

Using LSD to Treat Generalized Anxiety Disorder (GAD)

After a clinical trial of LSD showed encouraging results in the treatment of generalized anxiety disorder, the U.S. Food and Drug Administration granted an LSD formulation "breakthrough therapy" status because the agent has the potential to solve a serious problem.

A new 2025 study published in the Journal of Affective Disorders of U.S. military veterans suffering from severe treatment-resistant depression found that a single dose of psilocybin was associated with significant reductions in depressive symptoms that lasted up to 12 months. The antidepressant effects began to wane after 9 months. Six months after the LSD dose, 50% were in remission, and 80% showed a clinically meaningful response. This study did not include a control group; participants were aware they were receiving psilocybin, which raises the possibility of expectancy effects or placebo responses.

The standard of care for generalized anxiety disorder (GAD) is a combination of cognitive behavioral therapy and medication. But medications, if they work at all, take time to produce any effect; experimentation with various doses is often required. In clinical trials, a single dose of LSD appeared to be significantly better.

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“LSD is difficult to manufacture with high purity and tends to degrade quickly in the presence of light and water,” MindMed's CMO Daniel Karlin, M.D., explained. “We’re manufacturing it to pharmaceutical industry standards, a highly pure version that is also shelf-stable.”Compared with LSD purchased illegally on the street, the study used a much purer grade of drug, which did not appear to induce “bad trips,” Karlin noted.

MindMed’s psychedelic protocols are distinguished by the use of safety “monitors” rather than clinical therapists as a way to test whether the benefit of anxiety relief stems directly from the drug itself or the therapist. The pharmacologic effects of LSD last up to 12 hours, and careful monitoring is part of the FDA guidance.

LSD Risks

Recreational use of LSD carries multiple medical and psychiatric risks, particularly with frequent or high doses. LSD can trigger or exacerbate underlying psychiatric disorders, leading to psychosis, schizophrenia, or long-term hallucinations. Uncontrollable visual disturbances can occur even after the drug has worn off.

In addition, bad trips or intense, negative LSD experiences may prompt emergency room visits, calls to poison center hotlines, acute anxiety, paranoia, and even panic attacks requiring medical intervention.

Flashbacks also pose a significant risk. Unexpected re-experiences of an LSD trip long after the drug’s effects have faded, flashbacks can occur unpredictably days, weeks, or even years later. Altered perceptions caused by LSD can impair a person’s sense of reality, leading to self-harm or accidents, especially in unsafe environments.

LSD may also increase blood pressure and heart rate, posing risks for individuals with preexisting heart conditions or hypertension. Severe dehydration and hyperthermia have been reported when LSD causes users to lose touch with bodily needs, like hydration, particularly at festivals or other events.

Combining LSD with other drugs that increase serotonin levels, such as MDMA (ecstasy), may lead to serotonin syndrome, a potentially life-threatening condition caused by excessively high levels of serotonin in the blood.

Current Status and Future Directions

Today, LSD is viewed by many researchers and some regulatory bodies as a potential tool in the mental health treatment arsenal. While still classified as a Schedule I drug, there is a push to re-evaluate LSD’s status and expand research access. For years, there has been a movement to microdose or take tiny amounts of psychedelics to support well-being. New research shows that microdose benefits for depression are attributable to a placebo effect.

With the approval of the ketamine-related medication Spravato for treatment-resistant depression, an FDA roadmap for hallucinogenic approval with safety monitoring already exists. Early LSD data for generalized anxiety disorder (GAD) is promising. Aghajanian's lab and work have formed the basis for understanding LSD, ketamine, and other promising treatments.

The future of LSD as a medication depends on Phase-3 clinical trials and their outcomes, as well as on changing attitudes towards psychedelics in the medical and public domains. In the meantime, recreational use likely will increase, and, sadly, so too will reports of dangerous outcomes.