Author name: OPEN Foundation

Matthew Johnson is part of the team at the Johns Hopkins University that conducts research with psilocybin in a growing number of areas, ranging from mystical experiences to the treatment of end-of-life anxiety and addictions. Matthew’s personal focus lies in addiction treatment, and his latest scientific article described his research using psilocybin for smoking cessation. He spoke with the OPEN Foundation about his studies and the future of psychedelic science.

How did you wind up in psychedelic research ? Was this an old dream of yours, or rather a chance event?

Well, it was both an old dream and a chance event. About 15 years ago when I was in graduate school, I was hoping to do research with psychedelic compounds, although I anticipated that it would take many decades before achieving that. But then I was fortunate enough to discover that my postdoctoral fellowship mentor, Roland Griffiths, had started research with psilocybin. I discovered this when I was on my postdoctoral interview, so I jumped in as much as I could, and I’ve stayed on the faculty here many years since.

What got you interested in the first place?

Well, the questions these psychedelics are associated with, these very broad, interesting, philosophical questions that really intrigued me. When I was about 19-20 years old, I became very interested in many of the readings on psychedelics and on the older research with them, the questions of mind-body connections, the nature of mind… we don’t have any definitive answers to those questions, but psychedelics seem to be a very good place to start when you’re interested in them.

Do you have any tips for those who would like to embrace the same career?

The biggest piece of advice is to receive training in some type of discipline that would allow you to conduct research: either receive an MD or receive a PhD to become a researcher in some area of neuroscience or psychology. I suggest picking an area that dovetails nicely with more mainstream interests. A researcher is not likely to find a position where they can exclusively focus on psychedelics. Take me for example, I study addiction generally, the acute effects of drugs, the nature of addiction and addiction treatment, and this dovetails very nicely with my interest in psychedelics in the treatment of addiction. So that other area of work is able to support my position even though the focus on psychedelics wouldn’t be able to do that by itself. So get into something mainstream that can intersect with your interest in psychedelics.

Getting to the research you’ve conducted, your latest article was about your smoking cessation study using psilocybin in combination with cognitive behavioral therapy. The results seem very promising, as the article reports an 80% success rate on the limited sample of the study. What could be the mechanism of action that helps people kick their addiction when treated with psychedelics?

So far, evidence suggests that there are psychological mechanisms of action at play. For example, people endorse that after the psilocybin sessions, it was easier for them to make decisions that were in their long-term best interest, and they were less likely to make decisions based on short-term, hedonistic desires. They also reported an increase in their self-efficacy, their confidence in their ability to remain quit. Many of the participants had what they considered spiritual or very meaningful experiences. All of these psychological aspects are consistent with addiction therapies. Certainly, there’s a long history of people reporting that spiritual experiences or insights have led them to overcome an addiction. We believe there are also biological mechanisms which we have not explored yet, we’re just beginning to in this next phase of the study. Ultimately, I believe the answer’s going to cover many aspects and reveal both psychological and biological mechanisms.

What about the 3 people (out of 15) who weren’t able to quit smoking? Do you have an idea why?

They tended to have less meaningful experiences in their psilocybin sessions. Our sample is relatively small, so we’re cautious in overstating our conclusions, but it appears that the trend is that those people who had less personally meaningful or spiritually significant session experiences were less likely to be successful in the long term. And that’s consistent with other data we collected in other psilocybin studies. The nature of the experience, particularly the positive, mystical-type nature of the experience, seems to be what’s predicting positive change in personality and long-term attributions of benefit.

If these interesting results could be confirmed on a larger scale, do you think this kind of therapy could become generally available, and if so, how long could it take?

Yes, I do believe so. I think it would be at least ten years, I’m hopeful that it wouldn’t be much longer than that. Research with psilocybin in the United States is further along in the treatment of cancer-related anxiety and depression. We would expect that in the US, initial FDA approval of psilocybin as a prescription medicine would likely be for cancer-related distress. But we would anticipate, if the data continue to look promising, that an addictions indication could come soon after that. I think it absolutely is possible, and that’s our hope, that this would be disseminated beyond research, into approved prescription use. We believe that this would be conducted in clinics, in a way similar to outpatient surgery. So it would not be, “take two of these and call me in the morning”, sending the patient home with psilocybin to use on their own. It would involve preparation, much like what is going on in our research. Screening, followed by a few preparatory meetings with professional staff, and then one or a few day-long experiences where the person would come in in the morning and leave at 5 or 6pm. They’d be released into the care of a friend or a loved one, very similarly to the way outpatient surgery procedures are performed.

Would doctors need a special license to practice this kind of thing?

Yes, they might need some specialized training, some certificate in the basics of conducting these kinds of sessions. The procedures that are at play in the current research studies with psilocybin are very effective, so it would essentially look like this, with similar safety mechanisms.

You’ve also conducted research on mystical experiences, in another study. Everything seems to indicate that those experiences induced by psychedelics cannot be distinguished from spontaneous or naturally occurring mystical experiences. What are the implications of this, and what does it mean for scientific research?

I think it opens up many avenues. It’s going to be a long time before we fully realize – perhaps we never will – the potential of this. The most interesting thing, perhaps, is what it may tell us about the biology of naturally occurring experiences. Even if those occur without the provocation of an external substance, it may be that something very similar is going on endogenously. One speculation that Dr. Rick Strassman has put forth is that naturally occurring dimethyltryptamine (DMT) could be responsible for extraordinary spontaneous experiences of this type. We don’t really know that to be the case, although it certainly sounds plausible at this point. But I think if we do find a similar biological basis to naturally occurring spiritual or mystical experiences and psychedelically mediated experiences, this would have profound philosophical implications for how we view human experience generally, the idea that there’s not this dualistic divide between biology and subjective experience. It would suggest that these are always two sides of the same coin.

What do you think we can gain or learn from mystical experiences? Could they be useful to society as a whole?

It’s been speculated that the world would be a better place in many ways if more people had such experiences. Perhaps it’s wishful thinking to think that these experiences, by themselves, would save the world. But it makes sense that if more people have genuine experiences of openness and connection with the rest of humanity, that can only help – whether this be from psychedelics or spontaneously occurring experiences, or through the use of other techniques. I’m interested in the speculation that these experiences can lead to prosocial behavior, which can be good for the world in general, although I’m a bit cautious. I certainly wouldn’t say that psychedelics are a panacea that is single-handedly going to save the world. But perhaps, if cautiously used under the right circumstances, they could be part of and contribute to an overall greater level of awareness. Ultimately, we’re all completely dependent on each other, we’re on this planet together, trying to figure out how to ultimately survive and thrive, and I think these profound mystical experiences, however they might be occasioned, can perhaps help point us in the right direction.

Several sources, including the scientific articles themselves, seemed to suggest that the subjects in the studies about mystical experiences were highly educated, high functioning, and prone to spiritual practice. Isn’t there a bias here that could prevent generalization towards the general population?

That’s an interesting question and a good point. Across the number of studies we’ve conducted, we’ve become less specialized in our target population. In the very first study that Roland conducted, these were people who already had an intense interest and an ongoing spiritual practice of some type. In subsequent studies, we have loosened our requirements of that nature, and now it’s getting closer to a general population. At baseline, before people enter the study, we collect measures of their lifetime experience of mystical-type effects, using the Hood mysticism scale. We found that people in our subsequent studies have a much lower score than in that initial study. In my smoking study of 15 individuals, these were very ‘normal’ people in that regard. Some had an interest in spirituality, but most of them didn’t have any particularly strong interest. Regarding education and level of functioning, the subjects are generally pretty high functioning, although it tends to get rather normative. In the smoking study, we had an elementary school teacher, we had a carpenter that fixed furniture, a child care worker, as well as a lawyer, for instance. So although some did, not all of them had intellectual occupations. Furthermore, we haven’t noticed any real difference in experience between highly intellectual individuals or people with high socioeconomic status and people who are more normative.

Are there any significant differences from one substance to another, or does everything revolve around having the psychedelic experience in and of itself, whatever the substance that triggers it?

We don’t know yet. Very much of the recent resurgence of interest in psychedelics has been research done with psilocybin. Our presumption with many of these research questions is that similar results would be obtained with LSD, mescaline and the other classic psychedelics. But that’s just an assumption. We certainly know that they have a common biological pathway. I think there’s potential for both possibilities. When we compare our research to the older research with LSD, and when you compare these psilocybin accounts to naturally occurring, non-drug occasioned experiences, you do see substantial commonality. But at the same time, we do know that these various psychedelics have shades of different effects, even though the classic psychedelics all have effects at the serotonin 2A receptor. We also know that they differ in their effects at a variety of other receptor sites, and this is likely to account for some of the more subtle differences in subjective effects that people will report. Sometimes those might be specific to the individual: some people will report that e.g. psilocybin is more psychologically gentle, and that LSD is more abrasive, and other people will report exactly the opposite. All of this is reporting from anecdotal or recreational use. All those questions should be examined in the laboratory under double blind conditions to really validate them. There’s a lot of excitement that, if there is any promise to psilocybin or one or a few of these psychedelic compounds, we have a whole library of hundreds of compounds waiting in the weeds, much of the work that Sasha Shulgin and David Nichols and others have done to create dozens of compounds that are derivatives of the tryptamine or the phenethylamine structure. It’s going to be really exciting to follow up this initial research with psilocybin with a wide variety of compounds. It could be that they are all very general, but – I’m just speculating here – perhaps one of these other substituted tryptamines might be as effective for cancer-related anxiety as psilocybin, but perhaps comes with less of a chance of difficult acute experiences, or perhaps it’s a shorter or longer duration, in a way that makes it more ideal for treatment. I think there’s a lot of potential, and we’re in our infancy in examining these things, so there’s a lot of exciting things to come ahead.

Do you have an idea why psilocybin is so prominent right now?

Yes, for our group at Johns Hopkins and for a number of other investigators that have reinitiated research in the last decade, I think there was a sense that politically, we wanted to stay away from LSD. With people who are going to have a hair-trigger sensationalistic reaction when hearing about the research, LSD might have been a bad place to start, because it would raise all of the concerns about Tim Leary and the counterculture of the sixties. In some sense, psilocybin was a little safer politically because it was not the prominent psychedelic used recreationally in the 60s – that was primarily LSD. We also know that, next to LSD and mescaline, psilocybin is one of the classic psychedelics that received the most research in that earlier era of research from the 50s to the 70s, so there was a nice background on the basic toxicology and pharmacology. If we were starting with a brand new compound that’s never been administered to humans, there are many basic safety studies that would need to be done on animals and in early studies with humans. So psilocybin fit the bill nicely, and also, its time course happens to be pretty convenient: five to six hours. It fits into a therapeutic workday a little easier than the 10-12 hour experiences one can have with LSD or mescaline.

There have been some recent calls for legislative change regarding psychedelics (Nature Reviews Neuroscience in June 2013, Scientific American in February 2014). Are there any concrete efforts made to move these substances down a schedule or two in order to facilitate research?

The most concrete effort would be moving into phase 3 trials for cancer-related anxiety and depression. This is something that a number of the research teams in the US have talked about, and we’re preparing to enter into phase 3 research after our phase 2 study and the one at NYU are completed. We’ve already completed all our participants, so that’s going to be soon. If phase 3 is successful in terms of showing safety and efficacy, that would lead to the possibility of a schedule change. That would be a way within the current system to see a scheduling change, very specifically for one compound and one indication. Now a lot of the editorials that you’ve referred to are also raising concerns more broadly, regardless of whether phase 3 research prompts the rescheduling of a particular compound. There is concern that placing so many of these compounds in Schedule I, and the heavy restrictions we have on Schedule I compounds, can limit their clinical development potential. One aspect of that is that no pharmaceutical companies are interested in developing these compounds at all, and one reason for that is because they’re on Schedule 2, so that it’s a very bad bet to invest millions of dollars in a compound therapeutically if it’s already at the highest level of restriction and if it doesn’t seem hopeful that’s going to change. It also makes research much more difficult having a substance in Schedule I versus other schedules. It’s ironic that it can be much more difficult doing research with psilocybin or with cannabis, which are Schedule I drugs in the USA, than with cocaine, methamphetamine and many of the opioids, because these are Schedule II or less restrictive schedules. So even if a particular compound hasn’t gone through all the steps to merit clinical approval, there is still this notion – and I agree with this – that the level of regulation is too burdensome, and the system is not encouraging enough of cautious scientific exploration of these different compounds. There is this general sense across psychiatry that we have to some degree reached our limit with many of the conventional treatment methods, and so we need to be more open, and have a more flexible system for conducting safe research with some of these currently heavily restricted compounds.

After those phase 3 trials are completed, and if they’re successful, do you fear a renewed resistance, which would be more psychological or political in nature, from society and policymakers?

I do think there will be some resistance, and I think the only thing we can do is rely on data, and to conduct this research responsibly. The concerns about psychedelics are really related to the uncontrolled recreational use. They’re really very addressable when it comes to conducting research or approved clinical use. To draw an analogy, we know that drugs like heroin come with incredible toxicity and are associated with high death rates – that’s unquestionable. But heroin is virtually identical to the drugs that we use in medical settings, and those are indispensible to the practice of medicine. So mentally we draw a distinction between the uncontrolled hazardous use of heroin and other opioids on the street versus the careful use of morphine and other drugs in that same class in the clinic. As an example there, when under careful medical screening, people don’t stop breathing because of opioids, because that’s readily detectable and reversible if it happens in a medical setting, whereas people stop breathing unfortunately all too often in the recreational abuse of intravenous heroin. So in the same way, yes, with psychedelics, occasionally, even though it’s relatively infrequent, people will have panic attacks and hurt themselves, they’ll respond erratically, they’ll run across the highway, they’ll accidently fall from a height. They’ll do things that people do with many other drugs, such as alcohol, at a much higher rate. But those things are very addressable in a research or therapeutic context. They don’t happen in carefully controlled research contexts, because we just have all the safeguards in place. So the more we’re presenting cautious research and conveying the way this clinical intervention is done, the more we’re able to address those political concerns.

How badly are psychedelic researchers such as yourself considered mavericks within the scientific field, for studying such things as drugs and mystical experiences? Is this an obstacle to eventual implementation of results in society at large?

Not too much, I think. There’s a little bit of that, but I think it’s changing fast. It’s funny, sometimes media journalists want to highlight the controversy and they’ll find a clinician who really disagrees with this, often someone who runs a drug clinic or something, who will just say: oh, this sounds dangerous. But really, in the scientific field of those who study addiction and the harms of drug abuse, there’s not much in the way of controversy. It ranges from people who think this is very promising and are happy this kind of research is happening once again, to people who think this might be a bit weird and wouldn’t bet their money on it, but who agree that it is appropriate to conduct cautious research. No-one is credibly saying that this isn’t a legitimate scientific, medical inquiry. It’s really not so controversial, and I think the longer we and others are conducting the research, the more people respect the data. They can see for themselves that this mystical nature of experience is repeatedly predictive of long-term therapeutic outcome, so they recognize this is a meaningful scientific construct. These are also constructs that are known and respected in other areas of psychology as mechanisms of change. So I think this stuff is more and more becoming mainstream, and I guess it’s not much of an obstacle. I’d say to me it’s been more of a benefit, in terms of people saying: wow, that’s really interesting! How good of you to cautiously explore something that’s outside of the box and that needs attention!

Do you think there may be obstacles other than scientific that might bring psychedelic research to a halt all over again, like it happened before? Or do you think it will go on to evolve into standard practice?

I think it will move on and won’t be halted the way it was in previous decades. I don’t know definitively, but that’s what my gut tells me. As a society, we’re doing this in a much more mature way now. Also, in the 1960s, psychedelics were combined with so many other societal changes that it ultimately was a little traumatic for society. Psychedelics probably got too much of the blame for that, even though there were some individual harms caused. But much of it was just impression. There was a reason people were protesting the Vietnam war, fighting for civil rights, women’s rights, etc., completely outside of the fact that there were psychedelics. Today society has changed in many ways, and I think this research can be compartmentalized and can be seen for what it is: an interesting avenue that might be helpful in that it might address intriguing questions about the mind and biology, and there may be therapeutic outcomes. But I’m hopeful that if some rogue researcher comes around and does something very dangerous, it would be clearer now that things would go wrong because that researcher is dangerous and does his thing in an inappropriate way. Just like if someone were to apply morphine at a dangerous dose and not monitor the patient’s breathing in a hospital setting. That would be viewed more as an individual problem rather than as a reason to stop using opioid analgesics. I’m hopeful that that’s the point where we’re at with psychedelics.