Psychedelics in End-of-Life Care

Many indigenous peoples around the world have developed traditional uses for psychedelic compounds. In Western medicine, these were mostly unknown until Albert Hoffmann synthesized LSD (lysergic acid diethylamide) in 1938. He later tried to figure out how it might be used after having an extraordinary personal experience. By the mid to late 1960s, psychedelic drugs like LSD or psilocybin had become a cultural phenomenon. By 1970, medical research on such drugs was essentially shut down.

What Scared the FDA and the NIH?

Even if a researcher wanted to perform research on psilocybin or LSD, the FDA was not supportive. Neither were funders such as the NIH. The memory of the 1960s with the slogan sex, drugs and rock and roll created a no fly zone for scientific investigation.

But over the last decade or so, there has been increasing interest in the use of such compounds to ease the anguish of post traumatic stress disorder, the existential crisis of a cancer diagnosis, drug dependency or even schizophrenia. But the hallucinatory potential of such drugs continues to discourage many researchers from studying such compounds.

Would You Consider LSD If There Were No Hallucinations?

Investigators at University of California, Davis have modified LSD so that it does not cause hallucinations. The new compound, called JRT, appears to have some therapeutic benefit, however. That’s because it increases neuroplasticity.

So far, the drug has only been tested in animals, but the initial responses appear promising. The hope is that JRT will have fast-acting antidepressant activity and may even be helpful against schizophrenia (Proceedings of the National Academy of Sciences, April 14, 2025).

The authors of this research point out that current treatments of schizophrenia leave a lot to be desired. They don’t work very well:

“…for addressing the negative and cognitive symptoms, and evidence suggests that they are unlikely to rescue morphological or synaptic deficits.”

One of the negative symptoms of schizophrenia often includes the term anhedonia, which is described as an inability to feel pleasure or joy. It is also characteristic of depression. Another negative symptom of schizophrenia is avolition. It means an inability to get motivated to participate in goal-directed activities. That’s psych talk for profoundly disturbing blahs. People just cannot mobilized to get going or stay going. Social activities are just overwhelming.

Then there are the “impairments in attention and working memory.” It is hard to function when you have brain fog, little to no motivation, and few, if any, feelings of joy or happiness.

JRT and Neuroplasticity:

The researchers who helped create the new compound called JRT suggest that this nonhallucinogenic compound promotes “neuroplasticity” in the brain. So does LSD. What is neuroplasticity you ask. It is, according to Wikipedia:

“…the ability of neural networks in the brainto change through growth and reorganization. Neuroplasticity refers to the brain’s ability to reorganize and rewire its neural connections, enabling it to adapt and function in ways that differ from its prior state. This process can occur in response to learning new skills, experiencing environmental changes, recovering from injuries, or adapting to sensory or cognitive deficits. Such adaptability highlights the dynamic and ever-evolving nature of the brain, even into adulthood.”

The researchers who helped create JRT note that:

“Effective treatments for complex neuropsychiatric diseases like depression, substance use disorders, and SCZ [schizophrenia] are likely to involve multiple targets rather than a single site of action. However, the polypharmacology of such agents must be carefully tuned to maximize benefit while minimizing unwanted side effects. The unique polypharmacology of (+)-JRT might endow it with specific advantages compared to compounds currently in use.”

“Despite its lower hallucinogenic potential, (+)-JRT has demonstrated profound therapeutic effects.”

It’s a long and winding road before JRT could become available as a medication to treat challenging conditions such as PTSD or schizophrenia. In the meantime, there is a lot of new and intriguing research involving drugs that do induce hallucinations.

Below you will learn about interviews we have done with some of the key players. You may even want to listen to the podcast. An easy way is to click on the arrow inside the green circle at the top of the page under the photo of Dr. Matthew Johnson.

Current Research on Psychedelic Drugs:

Over the past decade or so, investigators have been conducting research on the healing potential of psychedelic drugs. Dr. David Nichols, an international authority on these compounds, describes the history of this research. His son Charles Nichols, a pharmacologist, studies the molecular and behavioral effects of hallucinogens in animal models.

The Healing Potential of Mystical Experience:

Dr. Matthew Johnson, associate director of the Center for Psychedelic and Consciousness Research at Johns Hopkins School of Medicine, has conducted a number of clinical trials utilizing psilocybin. He and his colleagues have been exploring the possible uses of psychedelic drugs as medicines for people with life-threatening cancer. They have also examined the possible benefits of a single dose of psilocybin for smoking cessation and overcoming alcohol misuse. Their research was recently highlighted in an episode of the CBS television show “60 Minutes.”

How Psychedelic Drugs Affect Existential Crises:

When people are diagnosed with terminal cancer or other life-threatening conditions, many become extremely anxious or depressed. While this reaction may seem rational in the face of a frightening diagnosis and foreshortened life expectancy, it can interfere with people actually appreciating the days, weeks or months they have left. Dr. Johnson and other scientists have found that a session with psilocybin that results in a mystical experience can alter people’s lives dramatically. They have far less anxiety and depression and seem to find more purpose in their lives, along with other positive changes. How does this work? Dr. Johnson’s most recent publication (with colleagues) explores the nature of these mystical experiences (PLoS One, April 23, 2019).

This Week’s Guests:

David Nichols, PhD, is an adjunct professor at the Eshelman School of Pharmacy at the University of North Carolina, Chapel Hill.  David Nichols had an active research program at Purdue University for 38 years prior to his retirement in June 2012. His research interests focused in two areas: the study of hallucinogens (psychedelics), where he was recognized as an international authority, and also discovery of novel D1 dopamine receptor full agonists, which showed efficacy comparable to levodopa in both animal models of Parkinson’s disease, and in human Parkinson patients. In 1993 he founded the Heffter Research Institute, which has encouraged and supported modern clinical studies of the psychedelic agent psilocybin (from “magic mushrooms”) for treatment of depression, anxiety, and various addictions. His general interests continue in the medicinal chemistry and pharmacology of CNS-active agents.

Charles Nichols, PhD, is Professor of Pharmacology at Louisiana State University Health Sciences Center in New Orleans. As David Nichols’ son, he did not begin his career with the intention of studying hallucinogens. However, his current research interests include the molecular and behavioral effects of such compounds on the brain.

Matthew W. Johnson, PhD, is Associate Professor of Psychiatry and Associate Center Director of the Center for Psychedelic and Consciousness Research at Johns Hopkins School of Medicine. The photograph of Dr. Johnson is courtesy of Johns Hopkins Magazine. The website is https://hopkinspsychedelic.org

Listen to the Podcast:

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