VUE Magazine, November 2011 Special Feature

Dr. John H. Halpern

Interview The chief medical officer of Entheogen Corp. and professor of psychiatry at Harvard Medical School talks about his investigations into the medical benefits of hallucinogenic drugs and his discovery of an LSD derivative with the potential to eradicate the agonizing affliction of cluster headaches.

David Hamburg

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John Halpern, can you tell us how you became interested in the area of hallucinogenic drugs and their use in remedial applications?

Actually, when I was in med school, I thought I’d go into surgery. But I also felt that I could connect closely to patients with mental illnesses, and it bothered me that there were not enough bright young doctors going into that field.

I felt there was a calling for me. I wanted to help people dealing with drug and alcohol abuse. This is how it all started. Then I began thinking that maybe some uses of psychedelic drugs had simply been overlooked as potential treatments for addictive disorders.

I did a sub-internship with Dr. Rick Strassman, who had approval to give subjects dimethyltryptamine, a naturally occurring psychedelic compound. By the time that I did my residency at Harvard, I knew I was on to something unique that had been overlooked. There weren’t any studies in this field. The use of peyote is a very potent and effective treatment used by Native Americans, and yet no one has ever done modern studies on that. So I worked hard to excel in my residency, won all types of awards, and had the opportunity to stay on with a research fellowship at McLean Hospital, which is affiliated with Harvard.

In fact, my fellowship with Harvard was for my work on Native Americans, on the health consequences of taking peyote as part of the religious practice of their church, the Native American Church. That work was published in 2005 in a major psychiatric journal, and it showed that these people were essentially healthy; there was no cognitive harm from the peyote. I wondered at how we reviled the use of that drug, while it was revered for ages by shamans for its healing powers. Is it really harmful for them when they take it in their sacramental space? And these types of natural drugs are used sacramentally by many other indigenous peoples around the world. Meanwhile I’ve never had a heroin addict tell me that using heroin had changed his or her life for the better. But many people who have used psychedelics have told me that they have learned something about themselves. Well, what is that? Maybe there are some medicines that can be captured from that?

So this has become the niche that I have carved out for myself while still practising general psychiatry. I have an academic appointment at Harvard and am the director of my own laboratory at McLean Hospital, where I study this niche. Maybe this work can ultimately help many more people than I could ever do practising clinical medicine.

Interesting work. Sounds like you’re part medical researcher, part anthropologist.

That’s true; I’ve actually lectured to anthropology undergrads. At times I feel like I’m a cultural wishbone,

getting pulled apart by two sets of obligations and responsibilities. Part of being a good psychiatrist is being very curious. Along the way, I’ve had to learn a lot about anthropology.

Consider this from a pharmaceutical perspective: I’ve spoken with many indigenous shamans from around the world – shamans who have reps from major pharma companies asking if they have plants that will cure cancer.

When a shaman tells them that they have to drink iowaska, the pharma prospector will say, “No that’s not good, because it’s a hallucinogen.” They totally miss it, because of their ethnocentrism. For the shaman, iowaska is a tool for identifying what they need to find, but pharma doesn’t want to know from it. So they have sent a message that they are not really trying to learn from these people who have very sophisticated understandings of the plant kingdom, and consequently they don’t get what they came for.

Understand that the indigenous medicine men are very bright people; they study their craft for many years. Just because they don’t have a written language doesn’t mean that they aren’t really sophisticated in their learning. Maybe the iowaska they drink gives them the vision of the plant that they must find to cure a particular ailment.

We want to have these black-and-white understandings of things: this drug is good, that one is bad. My job is to deepen our understandings about what these drugs do so that we can make better-informed and safer choices. If we don’t have an historical context (from shamans) in which to place these substances, we lump them all together as bad.

This simply is not true, though. Each drug has its own potential risks and benefits; it’s just that there is something about them that has been misunderstood. Maybe it’s due to how they were introduced to our society. But enough research has been done to show that hallucinogens have a medical benefit.

Tell us about your Entheogen Corp., the company you founded. How did you determine that a variation of LSD could cure massive headaches?

That’s an incredible story. Actually, the patients came to me with this finding. Massive headaches are awful; it’s been reported that it feels like having an ice pick jabbed into your eyeballs. It is searing and horribly painful. In fact, it’s the only form of headache that people will commit suicide to escape. It probably affects as many as one in a thousand people. Unfortunately, many of these headaches are misdiagnosed as migraines, and while the usual triptane medication prescribed in those cases can be effective on a single attack basis, they don’t stop the massive headaches from reoccurring. There are also lots of horrible side effects – for the heart – from those drugs. Interestingly, if you take vue November 2011

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enough of these triptanes, they induce hallucinogenic side effects.

So where’s the line between what’s legal and illegal, what’s appropriate and inappropriate? We shouldn’t determine, on the backs of our patients, what drugs are okay to take. We need to find a way to allow patients to have the drugs that are effective for them. Even thalidomide, which has horrible side effects, is once again legal, because it controls leprosy and heals stomach ulcers the way no other medication does.

So now there are controls set in place for thalidomide to prevent it from getting prescribed to pregnant women. The point is that we’ve learned how to manage the drug’s risks without preventing its benefits.

This brings us back to cluster headaches. There was a group of cluster headache sufferers who discovered at college that the only time they were pain-free was when they ingested LSD or psilocybin. They organized themselves and called their group the Cluster Busters. They sought out neurologists who were interested, but the neurologists didn’t want to get involved with a taboo drug like LSD. Then these people came to me, because of my medical experience studying drug abuse. The first thing that we did was publish, in the medical journal Neurology in 2006, a very large case study of cluster headache sufferers and their use of LSD and psilocybin to treat the attacks.

There was no way I was going to publish a study on a trial use of LSD when there is nothing in the literature on it’s possibly being helpful. I’m a doctor; I’m not trying to promote drug use, and this is about medicine. I started thinking that the treatment effects of LSD and psilocybin had nothing to do with its psychoactive properties. I discussed this situation with my colleague in Germany, Dr. Torsten Passie, who has a lab similar to my own at Hannover Medical School; together we had written the only peer reviewed paper on the pharmacology of LSD. There are a number of derivatives of LSD that are not psychoactive – in particular, 2-bromo-LSD, which had been given in huge doses to hundreds of people as a placebo in the ’50s and ’60s, but nobody had ever used it to treat cluster headaches, and it’s never been approved for anything or patented for anything. Anyhow, we were able to run some trials in Germany, which allows for this type of testing in certain cases termed “compassionate,” and the results were extremely positive. For example, we had one patient who went from forty attacks a week for three years to no attacks for over a year. All this from just three doses – on day 0, day 5, and day 10 – with no major side effects. We published the data on the first five patients, in September 2010 in the journal Cephalalgia, and recently published a poster abstract on two more patients, which was presented at the International Headache Congress in Germany.

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This discovery later got profiled on the National Geographic Channel’s Explorer series; it was called “Inside LSD.” I patented the drug, bromo-LSD, with Dr. Passie, and thought pharma would come by, because this could potentially be quite disruptive to the headache market, especially since it works so well for migraine. It could be a blockbuster. Yet despite all of the major attention we received, no one called. So, along with a financier friend of mine and Dr. Passie’s, we decided to do it ourselves, and so we formed Entheogen Corp. Our motto is “To create the divine within,” because I believe that something which can heal you has spiritual significance.

Meanwhile we are still in this really long phase where we are trying to raise funds to license the patent from the institutions that our affiliated hospitals own. It’s very hard to get everything you need in order to get FDA approval for drug development. That said, I’m happy to say that we are in final-stage negotiations with some venture capitalists who have notified us that they intend to give us a term sheet. If only the economy weren’t so tough these days and so many bio-tech companies had gone bust. People are afraid and just want to develop copycat applications. Of course, I understand that this is the nature of the entrepreneurial experience.

Still, I’m optimistic that we will be successful. We believe in our results. Understand that we may have discovered the most important treatment for this condition that we know of. Imagine if we can move on, after this, to working on a migraine treatment.

John, the story of how your mission and curiosity have led you on a journey to potentially eradicate a horrible affliction like cluster headaches is inspirational. I wish you well.

Not bad for a son whose father and uncle were the first brothers to graduate in the same class from the University of Toronto medical school.

A Canadian connection that makes us proud. Thanks for your time, John. It’s certainly been a thoughtprovoking experience.

Dr. John Halpern, MD, co-founder and chief medical officer of Entheogen Corp., is assistant professor of psychiatry at Harvard Medical School and director of the Laboratory for Integrative Psychiatry, Division of Alcohol and Drug Abuse, at McLean Hospital. He has direct clinical research experience administering controlled substances, including leading MDMA-assisted experimental psychotherapy sessions. Dr. Halpern and his work have been featured in leading publications such as Newsweek, National Geographic, Wired, Discover magazine, The New York Times, and numerous medical journals.