Philip E. Wolfson is a psychiatrist and psychotherapist who used MDMA legally in his practice in the 1980’s. A founding member of Stanislav and Christina Grof’s Spiritual Emergence Network and of the Heffter Research Institute, he has held a long-time interest in the use of psychoactive substances as adjuncts to psychotherapy. Currently, he is working on the early stages of a MAPS clinical study on the use of MDMA to relieve anxiety in patients with life-threatening illness.

You were trained as a psychiatrist and therapist, and you worked in those capacities for most of your life. How did you cross over to psychedelic research?

There was no crossover, actually. The research that’s arisen comes out of the illegalisation of MDMA, in this case. I was doing clinical work with MDMA in the 1980’s, with a large group of other therapists, psychiatrists and psychologists, when it was suppressed in 1985 by making it illegal. People either went underground or stopped. But the promise of that research was so great that I stayed attuned to being able to do that. As organisations like MAPS and Heffter began to have mild success with the FDA, and were able to do research on a very small scale, I became involved again. Also, I had lost my oldest son to leukaemia, and I was very involved with people with cancer and life-threatening illnesses and their families. So it really wasn’t a crossover, it was a natural kind of confluence of various interests in my life.

You use another substance, ketamine, in your current practice as a treatment against depression. Has this always been legal? Do you need a licence to use it, or how does this work?

Unlike MDMA, which is a Schedule I drug, like LSD, ketamine is a dissociative anaesthetic, and it’s Schedule III. It’s been in widespread use as an anaesthetic and analgesic. In the 1970’s, the late Salvador Roquet, a Mexican psychiatrist of great consequence, began recognising that in the sub-anaesthetic realm – dosages that were less than what put people to sleep – ketamine caused major psychedelic phenomena. This was also occurring among surgical patients who, when they came out of anaesthesia, often had exit effects that were very perplexing and often disturbing. So this began to be explored and the potential of ketamine as a psychedelic agent became widely known. It’s even been banned in Russia because of street use and is a drug of widespread abuse in China. It has a spectrum of use from low-level, which causes a kind of sedative effect, to what’s called the “k-hole”, where for a period of time, say 45 minutes with a significant dose, people have truly deep and transformative psychedelic experiences.

To add to that, in the late 1990’s, some people at the National Institute of Mental Health (NIMH) began to explore ketamine in even lower dosages, trying to eliminate the psychoactive properties and retain what had been perceived to be an anti-depressant effect in some individuals. They developed what I call the intravenous drip method, in which they use 0.5mg/kg instilled over 40 minutes in a slow drip, so there’s not particularly much of a psychedelic effect. They began to claim, somewhat adventitiously, off another experience that was just by happenstance, that there was an antidepressant effect. Unfortunately, that antidepressant effect is very short-lived and doesn’t persist for most people.

So there were these two tracks, and the NIMH track began to develop a method which enabled off-label use for a different kind of indication, in this case what was called ‘treatment-resistant depression’. A body of literature emerged, which enabled people like myself to say: “Off-label use is not covered by malpractice insurance, if we’re going to do this, we’ll have to have very stringent protocols and informed consent methods, but we can begin to use it as an antidepressant and, more importantly, as a transformative experience.” That’s the kind of work I and quite a few others are doing more and more. Methods remain very variable, and because the anti-depressant effect tends to be short-lived, there are more and more sessions being added on to clinical practice – so, series of sessions over time. It is an evolving practice that needs a lot more information and clarity.

What’s also occurred in the United States is that there are an increasing number of anaesthesiologists involved in providing the intravenous treatment for depression, so it’s not even psychiatrically oriented. I see this as: “I can make some money, I’ll set up a ‘clinic’ and treat some people with low-dose IV for 45 minutes. They can walk out and maybe there’ll be a difference.” So it’s promising in some ways and it’s controversial in others. We don’t know enough yet, either about my methods or about the antidepressant IV methods to say definitively this is a great antidepressant. I don’t think so, I think like all things that are useful in this realm, it has to be embodied within a psychotherapy framework. It’s a different kind of psychotherapy, because people are really not present in an emotive contact way for periods of time until they come out of the influence of the drug.

You were the editor of a recent thematic issue on ketamine of the International Journal of Transpersonal Studies. In one of your articles, you expressed the view that the antidepressant effect of ketamine is correlated with the intensity of its psychedelic effect – or at least, that if you suppress the psychedelic effect, you’ll probably suppress the antidepressant effect as well.

Well that’s the controversy, you’ve put your finger on it. I don’t know if it’s correlated with actual dosage, because at some point you get anaesthesia. But yes, I think if you suppress the psychedelic experience, the antidepressant effect will vanish too. I think that’s really the controversy, and it remains to be shown both ways.

It seems that results with classical psychedelics are more long-lasting, while the effects of ketamine experiences seem to fade over time. Do you think there’s a real difference between ketamine and the so-called ‘classical’ psychedelics?

No, I don’t, and I don’t think it’s true that it fades more with ketamine than with LSD or psilocybin. I think what we see with, for instance, the Johns Hopkins work with psilocybin is that profound – often dosage-related – experiences that are peak or transformative experiences have a more lasting impact on us. Any of us who did LSD way back as a first drug, or MDMA for that matter, as an empathogenic first experience, had very important experiences from it. I don’t think that’s any different for ketamine. People have profound, transformative experiences that last, in terms of impact on soul, impact on imagination, and they discover how vast their minds are. I don’t think any of those substances are terribly different in that sense. I don’t think we can distinguish between them, like one is good and one is bad, or one more powerful than the other.

Ketamine is definitely not a classical psychedelic, though. What would you say are the differences in effects and nature?

Ketamine has a different mechanism of action, but I don’t think its effects are so different from classical psychedelics. You have to lie down, you go into an altered, deep space in which you’re journeying through the cosmos, and personal, psychological, mythic, transpersonal, cultural, philosophical experiences arise, generally unbidden. I think that applies as a taxonomy of experience across the psychedelic board with different amounts of different substances producing somewhat different effects as they have different effects within the brain. Anyway, there are so many hundreds of psychedelics out there, with new ones coming every day, so what’s classical and what’s not? We’re not going back to Mozart here, we’re going back to 1943…

You mentioned that it’s easier to use ketamine because it’s a Schedule III substance, unlike the others that are on Schedule I. What are some of its other advantages or disadvantages, like the fact that it’s short-acting, and most often injected instead of ingested, or others still?

I’m not so sure these differences are critical. The shortness of the peak experience, 35 minutes to an hour, with a trail-off of another hour or so, is not discouraging at all, because time dilation within that framework is so extreme…

What I meant is that the shortness of action is more practical for the therapist, who doesn’t have to spend the whole day.

You spend three to four hours, there’s just no way around it, because people have to recover. It’s not a simple walk to the convenience store. The IV method is convenience store, people don’t go that far, they can walk, they’re not really asleep, they’re always conscious. The IV format is easy, the intramuscular format is not so easy. And if you compare duration of action, DMT is 10 minutes and you’re walking, 5-MeO-DMT is 18 minutes, or 40 minutes, however you slice it, so ketamine is not that short-acting.

Regarding the route of administration, oral use of ketamine requires a lot of material and is unpredictable regarding absorption and timing. The nasal route is easy to use and is the main route for street use. There’s no reason to do medically based work using the intravenous method save for analgesia. For psychiatric work, it makes it very medical, and I think it’s an alienating kind of format. The intramuscular method is safe, the drug is relatively safe, so I don’t think that’s intimidating. And, yes, you have to stay with your people until they are safe and you have helped them to re-integrate.

You devised a study with ketamine in order to examine this NIMH protocol and its claim of antidepressant effects, but you enrolled non-depressive subjects who were experienced with ketamine.

The idea was that a group of experienced users of ketamine – very intelligent, thoughtful people, some of them psychiatrists – could not understand how the NIMH protocol had any meaningful impact on anyone, because the intramuscular use is so much more profound. What we were reading and learning about the NIMH protocol was not. We didn’t have a group of particularly depressed people, we weren’t really measuring depression. We tried to have a set of experiences with the NIMH IV method that would give us some sense of comparison. In fact, knowing people over many years with longitudinal experiences, I’m not clear that ketamine is a great antidepressant, but I’m not clear that any psychedelic is a great antidepressant. The motivation of the study was to see what our own experience might tell us about what was being purported to be this great new breakthrough, which had been touted on Science magazine’s front page. And basically what people found was a very innocuous, not particularly meaningful experience.

We couldn’t really comment on depression, as you pointed out correctly, because the group was not composed of depressed people. So it’s theoretically aimed at what the effect on depression would be. The question is: what are the psychological mechanisms of action of ketamine? If you have just a mild kind of swoon, a kind of light taking yourself out of time as in the intravenous method, you have little highlights of psychedelic, but you don’t have much of an experience, so what does it mean? Why would that be helpful, as a 45-minute experience of being lightly anaesthetised, with a mild change in sensory modalities? Why would that do anything? And I don’t think it does, but there are reports – and I can’t debunk them completely – that say that doing that, people get an antidepressant effect if you do it enough times. Single dosage doesn’t seem to have much impact, it’s very short-lived – minutes, hours, a few people have days. So, it has been evolving into many consecutive IV sessions over weeks’ to months’ time with boosters to keep the effect going – if it occurs. Each time, it is a mild interruption of consciousness.

The larger argument is: why do the psychedelic effects of ketamine have an antidepressant or peak experience effect – when they do? You can look at it through a few aspects. One is of course set and setting. If you do it in a good setting you tend to have a better result than if you don’t. If you interrupt ordinary consciousness sufficiently, and you’re taking a break from the obsessional nature of the things that keep you going with depression, anxiety or confusion, there’s an interruption, and ketamine is certainly a very significant interruption of consciousness at the dosages that we’re using. This also goes towards electro-convulsive therapy, and the traditional therapies of interrupting consciousness. If you add to that the kind of brain scramble of a psychedelic experience which ketamine and others provide, this new mind-manifestation kind of experience, what we mean really by ‘psychedelic’, that people are having new experiences, that brain and mind are reorganising, then I think you have the capacity for both a change in mood and a change in consciousness. These two particular aspects, interruption of consciousness and new formation of consciousness, or reformation of ordinary consciousness, bring the possibility for real change.

It doesn’t happen all the time, though, people are very tough. Many people have done hundreds of acid trips, and seem pretty much the same. Our character re-exerts itself, so I think that’s one of the great riddles: why do we stay the same? I don’t have a clear answer, but we have definite strong pathways laid down in mind and brain that keep us humming in the same direction. Psychoactive treatment, I hope, is disruptive of that, in a good way. That’s why I think a therapy setting is important, because the disruption also has to be integrated, it has to be put back into a life stream, into a context, a community, integrated in the values that people hold, which are critical to any change. If you do a trip and all you see are lights and colours, and you come back and say, “Those were beautiful lights and colours, I really like that, I’ll do more lights and colours,” it’s not quite the same as saying, “What’s my attitude towards violence, or towards women, or racism, or what’s my being in the world, with nature, how do I perform and make my own character better?” That’s why I think a therapy that’s addressed to that – and not all therapies do that – is an imperative if we want to create a world of sharing, love and connection.

You’ve started conducting this new study with MDMA for people with anxiety related to life-threatening illness. You seem to consider MDMA as a genuine psychedelic as well. What differences and similarities would you point out with ‘classical’ ones?

I think MDMA is classical, it arose in the 1970’s. It all depends on how you define classical. The only real classical is nitrous oxide, right? It’s from the 1790’s, the second would be morphine, then mescaline with Arthur Heffter in 1897, etc.

Yes, but many people label it an empathogen or entactogen, and won’t consider it a psychedelic. What’s your opinion on that?

Well, it arose from Alexander Shulgin’s research, who was rediscovering phenethylamines, mescaline analogues. Before we ever coined the term ‘empathogen’, it had this quality of a different kind of experiential space that was very related to other psychedelics, particularly in those days LSD and mescaline, peyote and mushrooms. But it’s not psychedelic in the sense of ‘hallucinogenic’. So the differentiation is around ‘hallucinogenicism’, that is the ability to create mind manifestations that are hallucinogenic. The term ‘empathogenic’, which I prefer over the others because I think it’s accurate, is not unique to MDMA either. We call a bunch of other substances, even LSD, empathogenic, depending on dose. Otherwise, 2C-B for instance is considered to be an empathogen with mild hallucinatory properties.

The beauty of MDMA in the work we were doing from the late 1970’s on until 1985 was that it was fabulously helpful in making people feel an ability to reach out to others and themselves in compassionate ways, and to handle what had been otherwise fearsome negative experiences, so that there was a warming that you could feel with it, and that warming came to be called empathy for good reason. But empathy is more than a warming, it’s the ability to put yourself in others people’s shoes, or in your own shoes but in a better way. So it became very potent as a psychotherapeutic experience. It revolutionised therapy – although LSD therapy had been doing it as well – in that you had to be with people for three to six hours. No therapy of the psychoanalytic or psychotherapeutic sort, with their 45- to 50-minute hours, was doing that much time with people. So the contact point was huge, and the knowing of the person or persons you were sitting with was immensely different. And because it enabled the re-examination, the feeling examination of oneself and one’s relationships, its potency for a quicker, more breakthrough, less defended kind of therapy was manifested.

Compared to previous end-of-life studies with LSD and psilocybin, is your protocol roughly the same, or did you include significant differences?

We’re not doing end-of-life, it’s more similar to the psilocybin protocol done at Johns Hopkins, in the sense that we have excluded terminal illness. We’re placebo-controlled, we’re doing at least three MDMA sessions, and up to five overnight sessions. We’re doing them in my home, and I’m there with my co-therapist and partner Julane Andries. These are 6- to 8-hour sessions with 24 hours of contact that are very taxing. In fact the intensity of the therapy is so strong that we’re with people 17 or more times, including those 3 or 5 sessions. So it’s a very exacting protocol, and we couldn’t bring in people who might be actually facing death or major events in the time period of the study, because that would distort the effects of MDMA and the therapy. So we created a boundary, as Hopkins did, which was that there would be at least 9 months of life expectancy. In fact, we’re having people coming to the study who are either in maintenance therapy for cancer or other illnesses, or they’re free of cancer as far as they know, but facing the possibility of recurrence, relapse and potential death. We needed to have enough space and time so that we could do the work and the measurements, which couldn’t have happened if this was truly and end-of-life study with terminally ill people.

The protocol goes as follows. First there are two sessions, either both with MDMA or both with placebo, in a randomised double-blind setup. We just had an amazing surprise there by the way, where Julane and I thought the person was on MDMA, when in fact they were on placebo. I was absolutely certain, but it was actually the effects of set and setting and therapy, and they had a marvellous experience. They had less certainty about it. So that was a great humiliation of my ego there, and I loved that it meant I could be wrong about something and still have the experience of a very positive effect. After the two overnight sessions, the study moves to a primary endpoint where we compare MDMA and placebo over those 2 sessions. If people got the placebo, they can go on voluntarily to 3 more sessions with MDMA, so they go on to a total of 5 sessions. Those who received the active dose in the first two sessions end the process with a third MDMA session. We have a secondary endpoint where we examine the impact of all 3 MDMA sessions. Finally, we have a 6-month follow-up and a 12-month follow-up. Right now, we’ve completed one subject, we have six more going, and there will be a total of 18 subjects. The whole process will take us a year and a half, and the first results should be out in 2017.

You’ve had personal experience with the use of MDMA in situations of distress, both as a therapist and as a father faced with the life-threatening illness of his son. Did this play a role in the choice of substance and/or subject population?