The Heffter Research Institute: Past and Hopeful Future

This essay describes the history and the development of the Heffter Research Institute, in their ongoing efforts to supply psilocybin for the purposes of fundamental and applied clinical research, with a prospective outlook that psilocybin will one day be recognized to have legitimate medical value and integrated within a specialized therapeutic practice.

Abstract

“This essay describes the founding of the Heffter Research Institute in 1993 and its development up to the present. The Institute is the only scientific research organization dedicated to scientific research into the medical value of psychedelics, and it has particularly focused on the use of psilocybin. The first clinical treatment study was of the value of psilocybin in obsessive-compulsive disorder. Next was a UCLA study of psilocybin to treat end-of-life distress in end-stage cancer patients. While that study was ongoing, a trial was started at Johns Hopkins University (JHU) to study the efficacy of psilocybin in treating anxiety and depression resulting from a cancer diagnosis. Following the successful completion of the UCLA project, a larger study was started at New York University, which is near completion. A pilot study of the value of psilocybin in treating alcoholism at the University of New Mexico also is nearing completion, with a larger two-site study being planned. Other studies underway involve the use of psilocybin in a smoking cessation program and a study of the effects of psilocybin in long-term meditators, both at JHU. The institute is now planning for a Phase 3 clinical trial of psilocybin to treat distress in end-stage cancer patients.”

Author: David E. Nichols

Summary

The author entered graduate school in 1969 with a Ph.D. thesis project to study the structure-activity relationships of what were then called “psychotomimetics”, also known as hallucinogens or psychedelics.

After obtaining an academic appointment as an Assistant Professor at Purdue University, I secured funding from the National Institute on Drug Abuse to continue research on psychedelics. I met numerous colleagues who were interested in the study of psychedelics, but realized that research in this field was controversial and had little chance of receiving funding. I suggested that a private fund of $1 million might be sufficient to start a research institute.

In 1984, I was invited to a meeting at the Esalen Institute in Big Sur, California, where people discussed the potential value and benefits of MDMA, a drug that was still legal for medical use.

I met many people at the meeting, including Stan Grof, George Greer, Oscar Janiger, Dennis McKenna, Ralph Metzner, Claudio Naranjo, Sasha Shulgin, Leo Zeff, and many others, who sincerely believed that psychedelics held great promise as medicines for healing.

Everyone at the conference seemed pessimistic about the possibility of doing clinical studies with psychedelics, and Oscar Janiger replied that he had stopped because he “just didn’t understand how badly we were burned”.

Rick Strassman, an M.D. with good credentials in an academic psychiatry department, and I struck up a conversation at a second conference at Esalen in late spring of 1985. We kept up our dialogue after the conference was over, including strategy meetings with Daniel Freedman.

Rick Doblin, an undergraduate at New College of Florida who had reactivated a not-for-profit organization named Earth Metabolic Design Laboratories, was intensely focused on how MDMA could be made into a prescription drug. After obtaining quotes from commercial synthesis laboratories, he realized that the cost was simply prohibitive for him, so he asked whether I could make it in my laboratory. I made about two kilograms of high-purity MDMA hydrochloride at the very low cost of $4,000!

MDMA, including the first FDA-approved clinical study of MDMA, is stable at ambient temperature in the dark for more than 25 years.

Rick Strassman was able to obtain all the approvals necessary to administer intravenous DMT to human subjects, but couldn’t find any clinically acceptable DMT. I prepared the DMT for Rick, and he was the first psychiatrist in a generation to carry out clinical research.

Rick’s study was approved by the FDA because Curtis Wright convinced others that a study with psychedelics could be done properly. Rick’s tenacity was the other piece of the picture necessary for success.

In 1992, the National Institute on Drug Abuse and the FDA organized meetings to discuss psychedelic research. Both organizations recommended that clinical research be resumed, subject to the same regulations as other drugs.

I told a scientific meeting that clinical research with psychedelics could be done, but that private funding would be needed. I decided to do something about it.

I had met many physicians who were interested in joining a research institute to study psychedelics. I contacted Rick Strassman, Charlie Grob, Phil Wolfson, Dennis McKenna, Mark Geyer, and Jerry Patchen.

We incorporated in New Mexico as an IRS 501(c)3 not-for-profit organization in 1993, with George Greer as the point person for the legal details. We had our first board meeting near Los Angeles, at a Zen retreat on Mount Baldy.

As for the name of the Institute, I had long been aware that the first psychedelic to be isolated and chemically identified was mescaline, which was discovered in the late 1890s by a German scientist, Dr. Arthur Heffter.

A group of scientists and clinicians with no experience in business tried to envision how they might move forward by encouraging and supporting scientific research of the highest quality, done at top institutions, and having a peer-review process for vetting studies that they wished to support.

The first serious obstacle we encountered was how to get the funds to support the Institute. Most research institutes are started by wealthy donors who give millions of dollars to start the institute.

The Institute’s earliest funds came from the board members themselves, as well as a few small donors. However, the Institute’s principal supporter for many years was Bob Wallace, who had been the ninth employee of Microsoft Corporation and had a good chunk of Microsoft stock that had appreciated significantly.

At about the same time as Heffter was getting under-way, Rick Doblin was also trying to raise money to make MDMA into a prescription drug. Rick and I had many useful exchanges as to the best way to support our respective organizations.

Bob Wallace’s largesse allowed us to do a few important things in our early years, including attracting numerous highly respected scientists to serve on our Scientific Advisory Board and support several graduate students with stipends.

We supported Dr. Franz Vollenweider’s laboratory at the Psychiatric University Hospital in Zürich, Switzerland, and eventually helped him create a Heffter Research Center there. The HRI Center Zürich is where we continue to support basic brain research focused on the actions of psychedelics and other psychoactive drugs. Franz Heffter is the world’s top researcher in the area of basic clinical neuroscience studies of psychedelics.

After Bob Wallace’s death in 2002, new donors helped fund the first U.S. clinical studies using psychedelics, including Dr. Francisco Moreno’s investigation of the value of psilocybin in treating patients with obsessive-compulsive disorder.

As our donor base grew, we considered what kind of research we might support. We decided to support a clinical trial using LSD to treat dying cancer patients, as the approach to death can be extremely distressing and as a society we deal very poorly with dying.

The next question we addressed was which psychedelic we should use. We debated this topic extensively at several board meetings, and ultimately decided against using LSD because of the “social baggage” it carried.

Another psychedelic, mescaline, was known to have effects similar to LSD, but it caused nausea and vomiting in some users, thereby ruling it out for terminal patients.

Dr. Charles Grob had originally planned to use MDMA to treat terminal cancer patients, but decided to use psilocybin instead because it had none of the social baggage of LSD, was short-acting, did not cause nausea, and had no effect on the cardiovascular system.

Although psilocybin and LSD are classic hallucinogens thought to work by a similar pharmacological mechanism, psilocybin has a more complex psychopharmacology.

The decision was made to move forward with psilocybin in a clinical trial at Harbor-UCLA Medical Center. The results were very promising.

In 2008, Dr. Roland Griffiths initiated a study of psilocybin in cancer patients at Johns Hopkins University. The study was successful, and a larger study was started at New York University.

In my earlier collaboration with Rick Strassman, I had improved the synthesis of psilocybin by using a safer reagent. This made psilocybin more accessible, albeit somewhat expensive, and has been the medicine of choice in all of our subsequent clinical studies.

We funded a study at the University of New Mexico, Albuquerque, using psilocybin to treat alcoholism. The results thus far indicate excellent outcomes with the psilocybin-based therapy, and we have approved a larger two-site study to follow up on these initial, very encouraging findings.

We are supporting research related to addiction, including a study on the effect of psilocybin on helping long-time smokers quit smoking, and a study on the acute and persisting effects of psilocybin in long-term meditators who are expert observers of the mind.

Although we are supporting other studies, our main focus is to move psilocybin treatment forward toward FDA approval for end-of-life distress. We plan to finish the Phase 2 studies in 2014 and then meet with the FDA to discuss a larger, multi-site Phase 3 clinical trial.

After we complete the Phase 3 study of psilocybin in cancer patients, if it shows the kind of efficacy we have observed so far in our Phase 2 studies, the FDA will approve psilocybin for end-of-life distress. If it is safe for use under medical supervision, it will be reclassified into Schedule II.

Psilocybin will be moved into Schedule II, which means that psychiatrists will no longer be able to prescribe it as they wish. A training program has already been created for psychiatrists.

Study details

Topics studied
Anxiety

Study characteristics
Commentary