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LSD to treat severe anxiety? Cleveland Clinic at forefront of psychedelic research

Story by Julie Washington,• Saturday

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CLEVELAND, Ohio — The Cleveland Clinic is in the vanguard of a new era of research into psychedelic medicine.

I think that we're going to see a fundamental shift in the way that psychiatry is practiced over the next five to 10 years, with psychedelics becoming a mainstay of treatment for many patients,” said Dr. Brian Barnett of the Cleveland Clinic. He is running the Clinic’s LSD study investigating the drug as a treatment for severe anxiety.

The Clinic is the only Ohio site participating in a national study looking at whether LSD, administered in a controlled setting, can help people with severe anxiety. The disorder is a risk factor for suicide.

If the results of the Clinic’s trial and others like it across the country are positive, LSD could be approved as a psychiatric treatment within the next five years, said Dr. Brian Barnett, a physician with the Center for Adult Behavioral Health at Cleveland Clinic – Lutheran Hospital. He is running the Clinic’s LSD study, and is co-director of the hospital’s Treatment-Resistant Depression Clinic.

Dr. Brian Barnett, a physician with the Center for Adult Behavioral Health at Cleveland Clinic – Lutheran Hospital, adjusts a monitor in the room where participants in an LSD study will receive doses of the drug, or a placebo. LSD may be able to help the large numbers of American adults diagnosed with a mental health disorder. The Cleveland Clinic is in the vanguard of a new era of research into psychedelic medicine. The Clinic is the only Ohio site participating in a national, multi-site study looking at whether LSD, administered in a controlled setting, can help people with severe anxiety. The disorder is a risk factor for suicide.© Julie E. Washiington/

“Psychedelics are the most powerful psychoactive drugs that we have,” Barnett said. “We believe that if LSD is used appropriately by trained personnel in a therapeutic setting, it can be extremely beneficial.”

Starting this month, study participants will go to Lutheran to receive a single dose of LSD or a placebo, as part of the randomized, placebo-controlled trial, while under observation, Barnett said. They may notice that colors look more intense or that they are able to hear music in more detail than normal.

Small doses of LSD loosen up the patient’s consciousness and make them more readily able to discuss unconscious thoughts. Larger doses induce what’s called a mystical experience, during which people feel connected with the universe and as if they have experienced the divine.

LSD may be able to help the large numbers of American adults diagnosed with a mental health disorder, said MindMed CEO Robert Barrow. MindMed, which is sponsoring the study at the Clinic and 19 other sites, investigates the therapeutic potential of psychedelic drugs for psychiatry, addiction, pain and neurology.

Psychedelic drugs have the unique ability to show clinical benefits quickly while also maintaining those benefits for up to a year after only a few doses, Barrow said.

“In a field that has seen little meaningful innovation in decades, this represents a potential revolution in the treatment landscape for the many patients suffering from conditions like generalized anxiety disorder,” Barrow said.

Those interested in joining the study can follow this link.

Discovered in 1943, LSD — or lysergic acid diethylamide — was the subject of numerous scientific studies into its psychiatric use during the 1950s and 1960s. But its association with drug culture, and eventual criminalization, slowed its use in research.

“That history included over 20 studies in hundreds of patients with anxiety, depression and other neurotic illness, with consistent remarkable treatment responses,” MindMed’s Barrow said.

“Fortunately, we have seen a resurgence of research with LSD and the psychedelic drug class over the past several years, and this modern research has confirmed those earlier findings,” Barrow said.

The Cleveland study is among one of the first industry-sponsored trials involving LSD in about 50 years, the Clinic’s Barnett said.

“There’s really just so much that we don’t know,” Barnett said. “Research has been shut down for so long that we’ve had to start at the beginning. But there are a lot of very positive signs from research decades ago.”

Comfortable room guides LSD experience

A cozy room — decorated with cushioned chairs, a rug and pillows in soothing blues and taupes — has been set up at Lutheran especially for people taking LSD as part of the trial.

Study participants lie on a couch, don eyeshades and listen to a curated music playlist after ingesting LSD or a placebo. It is a double-blinded trial, which means that neither the caregivers nor the patient know who is receiving a drug or a placebo.

Participants can get 20 micrograms, 50 micrograms, 100 micrograms, 200 micrograms or a placebo.

Some people experience anxiety in the first hour after taking LSD. Facilitators use breathing exercises and guided imagery to help bring them back to a therapeutic response, Barnett said.

Study participants currently taking medications such as antidepressants must be willing to taper off those medications over a few weeks as part of the trial, he said. This allows researchers to evaluate the effectiveness of LSD without the assistance of other psychiatric medications.

Study participants also need healthy hearts, because psychedelics raise blood pressure and heart rates.

Very rarely, psychedelic drugs can unmask bipolar or schizophrenia in patients who have a family history of those disorders, but who have not yet had symptoms. People with family histories of bipolar disorder or schizophrenia are excluded from the study, Barnett said.

After receiving LSD or a placebo, study participants stay at Lutheran for at least 12 hours under observation, he said. Patients have nine visits to Lutheran total for the study, including the one-time LSD dosing session. There are six follow-up visits after the dosing session to evaluate the patients’ anxiety. These occur weekly to every four weeks, with the last one occurring 12 to 17 weeks after the dosing session.

“We think that LSD will be shown to be able to be safely administered in a supportive setting in a hospital environment,” Barnett said.

LSD: ‘three scary letters’ or beneficial drug?

There was a time when LSD was part of normal psychiatric treatment, especially on the East and West coasts, Barnett said.

Some LSD studies suggested that it helped patients with alcohol use disorder by helping them achieve a new self-image and willpower, according to a 2015 article published in the Canadian Medical Association Journal.

Another study published during this era, suggested that anxiety related to a recent cancer diagnosis decreased in patients who were treated with LSD.

But as LSD became linked with 1960s counterculture and drug abuse — although most experts say it is not addictive — the drug was made illegal.

“When I was growing up, LSD were probably the three scariest letters in the English language,” the Clinic’s Barnett said.

Currently, LSD is classified as a Schedule 1 substance, MindMed’s Barrow said. This means it is considered to have a high potential for abuse and no currently accepted medical use.

But attitudes toward LSD are changing. Oregon became the first U.S. state to decriminalize the possession of small amounts of LSD in 2020.

MindMed is conducting other trials to test LSD’s safety and effectiveness in treating attention deficit hyperactivity disorder. Other investigators are looking into the use of psilocybin, or magic mushrooms, to treat patients who are in hospice.

“The best way to get a drug rescheduled from Schedule 1 is to provide evidence of an accepted medical use,” MindMed’s Barrow said. If LSD is approved for patient use, it would probably be delivered in a clinical setting under supervision, Barrow said.

Because LSD is illegal, the Clinic had to meet Drug Enforcement Agency regulations before it could join the study. The drug is stored in a locked refrigerator that’s bolted to the floor, in a room monitored by surveillance cameras. Staff underwent background checks.

“It took us more than a year working behind the scenes with the company, the FDA and the Drug Enforcement Agency to get this off the ground,” the Clinic’s Barnett said.

These regulations are well intentioned, but they also make psychedelic research hard to do, Barnett said. Advocacy groups are working with Congress to reduce these bureaucratic barriers to further research.

“Having to go through months — even years — of paperwork is really what slows down the efforts by companies to bring these drugs to market as medications,” Barnett said.

The Clinic began recruiting for the MindMed study in February, with plans to treat its first study participants this month. The hospital system hopes to enroll at least 10 participants in the phase 2 study.

The Clinic’s Barnett hopes this study leads to the creation of a larger psychedelic therapy research community in Cleveland.

“I think this is a valuable opportunity for the scientific community (in Cleveland) to really catch up and participate in the psychedelic renaissance,” he said. “I think there’s going to be some significant opportunities to develop new treatments that could be potentially life-changing for patients.”


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