Lysergic acid diethylamide (LSD), used under close supervision with a trained psychotherapist, may help ease anxiety in patients with terminal illness, preliminary research suggests.
Results from a small pilot study showed that the drug was safe and effective when used in combination with psychotherapy.
The study is the first controlled study of LSD-assisted psychotherapy in more than 40 years.
"These results indicate that when administered safely in methodologically rigorous, medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted," the investigators, led by Peter Gasser, MD, a physician in private practice in Solothurn, Switzerland, write.
The study was published in the Journal of Nervous and Mental Disease.
Dr. Gasser told Medscape Medical News that he and his team chose to investigate the therapeutic potential of LSD for 2 reasons.
"First, we wanted to reintroduce LSD in medical and psychotherapeutic research, and second, we wanted to honor the 100th birthday of Albert Hofmann, the Swiss chemist who discovered LSD in 1943."
Dr. Hofmann was working in the laboratories of Sandoz Ltd, in Basel, Switzerland, when he discovered LSD's psychoactive effects. It was named Delysid and was distributed by Sandoz as an investigational drug for psychiatric research and LSD-assisted psychotherapy. It was primarily explored for treating alcoholism, neurosis, and psychosomatic disorders.
Research into LSD-assisted psychotherapy came to a halt when it was made illegal in the United States in 1966 because of its association with nonmedical use. Since then, its use in research has been somewhat taboo, Dr. Gasser said.
However, some LSD-assisted psychotherapy continued in Czechoslovakia, the Netherlands, and Germany during the 1970s and in Switzerland from 1988 to 1993.
Recently, as reported by Medscape Medical News, the psychedelic drug psilocybin, the active ingredient in "magic mushrooms," showed therapeutic utility in terminal and nonterminal cancer patients.
In 1 study, conducted at New York University Tisch Hospital in New York City, 32 patients were treated with 0.3 mg/kg of psilocybin as well as psychotherapy prior to and after receiving the drug in 6- to 8-hour therapy sessions.
At the time, Stephen Ross, MD, principal investigator of this study, said the majority of the participants described having a sense of profound calmness and serenity, being in touch with sacred elements, having a sense of universal love, and having a sense of connectivity between their consciousness and the universe, or having mystical experiences.
For the new pilot study, Dr. Gasser and colleagues recruited 12 patients with anxiety associated with life-threatening diseases.
The participants were randomly assigned to receive 200 µg of LSD (8 patients) or an active placebo of 20 µg of LSD (4 patients).
The higher, or experimental, dose of LSD was a moderate amount that was expected to produce the full spectrum of a typical LSD experience without fully dissolving normal ego structures.
The smaller, or placebo, dose was chosen to produce short-lived mild and detectable LSD effects that would not substantially facilitate a therapeutic process, Dr. Gasser explained.
Participants were required to taper off of antidepressant and antianxiety medications and to avoid alcohol and recreational drugs 24 hours before receiving LSD. They were prohibited from driving for 24 hours afterward.
Before and after receiving LSD, participants had a total of 8 psychotherapeutic sessions.
After LSD was administered, they were instructed to focus their awareness and to follow their personal perceptions, emotions, and cognition, Dr. Gasser said.
"We discouraged lengthy discussions during the acute effects of the LSD," he said.
Most of the experimental sessions used music "to deepen self-awareness and facilitate emotional processing, and a third contained brief conversations," Dr. Gasser added.
The session ended after 8 hours, when the acute effects of LSD had subsided. Participants underwent 2 treatment sessions.
At 2-month follow-up, trait anxiety, as measured by the State-Trait Anxiety Inventory (STAI), was reduced (P = 0.033), with an effect size of 1.1, and state anxiety was significantly reduced (P = 0.02), with an effect size of 1.2.
Neither the experimental dose (200 µg) nor the active placebo dose (20 µg) produced any severe adverse events, panic reaction, suicidal crisis, or psychotic state. Further, there were no medical or psychiatric emergencies requiring hospitalization.
The positive treatment effects for the LSD persisted out to 12 months, Dr. Gasser said.
Safe and Effective
"I'm quite satisfied with the results because the most important thing after a stop of 35 years of research is that we could show that LSD is safe and effective. As this was the first pilot study, it was very important to show that LSD is a safe treatment," Dr. Gasser said.
However, he emphasized that patients were under constant supervision during treatment.
"They had to stay in the office for 24 hours. The active time with LSD is 6 to 8 hours, and all during this time they were guided and supervised by me and a female cotherapist, and then they had to stay overnight as well, just for safety reasons. They did not take the LSD at home; they took it in my office."
Several of the patients needed to be comforted, he added.
"This was not an unforeseen event, and we did not consider it to be an adverse event. You have to be with the patient. If they have to cry, that is ok. If they feel psychological pain, you have to be with them, you have to go through the process with them. It's not a kind of LSD that makes them happy, they have to go through an inner process," Dr. Gasser said.
The reduction in anxiety was sustained out to 12 months, he added.
At 12-month follow-up, participants were interviewed to assess anxiety symptoms, and according to Dr. Gasser, "anxiety levels remained down at 1 year."
"LSD is a medication with potential but also with risks, like any medicine. We have to go through the steps to discover and re-evaluate the medical potential for LSD," he said.
"It's not only a drug that hippies take, it's also a medicine. I would also say that it is more a psychotherapy rather than a drug therapy, so doctors who want to apply it should have special training," Dr. Gasser added.
Commenting on the study for Medscape Medical News, Valerie Tourjman, MD, medical director of the Mood and Anxiety Program at the Institut de Santé Mental de Montreal, Canada, said she was intrigued by Dr. Gasser's work.
She said she had some concerns about the effectiveness of ensuring that the study was double blind and also about the size of the study, with only 12 patients.
Despite these issues, giving so-called illegal substances to terminal patients is an ethical issue, Dr. Tourjman said.
"This brings us back to the whole issue of patients receiving substances which may be addictive in the terminal state of their illness. This has always seemed to me to be an ethical issue that has been mishandled, because the comfort of individuals in that situation seems to me to much outweigh any risk of addiction," she said.
Dr. Tourjman added that other "illegal" drugs might also be of benefit in reducing anxiety in such patients.
"We now have a substance that we are testing in depression, called ketamine. It's used as a street drug, also as an anesthetic, but we also know that it can also cause hallucinations in some people. Also, marijuana is another drug that could be used if it provides comfort to some patients."
Dr. Tourjman also voiced concern that LSD may heighten anxiety in some patients.
"I have nothing ethically against it in the sense that I think whatever can make end of life more comfortable is justifiable. But we have to first think of doing no harm.
"Addiction is not really a concern, but the concern is that we might be using a substance that might increase the fear or anxiety. Is LSD the best substance? It would be good to do this study in a larger population, but only if there was not a better alternative. I think that ketamine in small doses, which gives an immediate improvement of depressive states, would also be something to consider."
The study was sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS). Dr. Gasser and Dr. Tourjman report no relevant financial relationships.
J Nerv Ment Dis. Published online March, 2014. Abstract
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Cite this: LSD for Anxiety: Hallucinogen as Treatment Revisited - Medscape - Mar 14, 2014.