Dr. Manoj Doss
"How do you go from talking about history and Cleopatra to then mirroring that with strippers in Las Vegas?"
The question (more of a hypothetical, really) above is referring to Frank Ocean's song "Pyramids" from Channel Orange, and it's coming from Dr. Manoj Doss to me following a lengthy explanation of his affinity to, and appreciation for, hip hop. This was on a Tuesday night, a few minutes after 11 pm, after over two hours on the phone, and after Manoj had just returned to Baltimore from a five day stint in Austin, TX, where he presented a poster and had a talk at the College on Problems of Drug Dependence (CPDD) annual convention. Only after two hours of discussing his background, post-doctoral work at Johns Hopkins, psychedelics, psychology and neurocognitive research, was he ready to deep dive into hip hop's genre-benders.
I only wish I would've started the call earlier.
Needless to say, I had an absolute blast talking zen and the art of questioning subjective experiences with Dr. Doss. Follow him on Twitter at @ManojDoss where he offers his two cents on the latest publications in the fields of behavioral psychology, pharmacology and psychedelics. And before we begin: let's all pump the brakes on CBD.
The following interview took place on June 25, 2019, and was edited for brevity and clarity.
Where’d you grow up?
Texas and Tennessee. So I was born in Austin but we moved to Houston when I was two or three. We were in Houston until I was five and then we moved to Tennessee. Do you know the song Wagon Wheel?
Of course. I lived in Nashville.
Yeah, so, Johnson City. Then I moved to Dallas, and then back to Austin for undergrad.
What was the reason for all the moving around?
My dad's job. He got his PhD, too, and was a materials engineer. In Austin, I can't remember if he got laid off or a better offer to work from Nokia, which was in Dallas. Then he was working at Siemens, which they had a factory in Johnson City.
The thing is, he kept moving actually after that. There was a point in high school
where he was elsewhere, high School through college actually, where he was in Oregon and then in Washington.
Considering his background, did that translate to an early interest in science?
Kind of, yes. I remember he definitely, you know, implanted certain things in my head. He told me about atoms, electrons and protons from when I was in like kindergarten, and I guess I was interested in the idea of mixing things together and coming up with something new and I was definitely a bit of a nerd through like seventh grade.
But then there was there was definitely a period of time where I also just totally
ditched science. A part of me was ditching my culture, my heritage, of being Indian. So, I ditched being academic, especially in the sciences. I mean, I still was in AP classes in math and science in high school, and I started college as an engineering major, but then smacked my head really hard and couldn't retain much for a month.
Wait, really? What happened?
For sure. It was an extremely, you know, surreal moment. Later on, in a memory class, there were certain moments where I was like, oh my God, I think that's what happened to me!
So I skate, I'm an aggressive skater, and we were at JCPenney headquarters in
Plano, Texas, which is an amazing spot for skaters - they have the perfect stair rails. The funny thing is, when we'd go, we'd normally get kicked out in like 30 minutes, but not this time. I get a few tricks done, and then I try to jump this rail and it just went awfully wrong. I jumped in the wrong place, wasn't looking where I was going, and smacked my head on the ground.
Broke up a couple teeth, got some stitches. Apparently I was awake the whole
time. It was mostly my episodic memory that was impaired, episodic being your ability to like mentally time travel and encode new information, but there were also aspects of semantic memory, like factual information, that was gone. The EMTs asked me who the President was, and I said, "Fucking Bush." So I got that correct, but then they asked me if I had a brother or sister, and I said, "Brother." Which I don't, I have a sister.
The more interesting thing was, my friends snuck into the emergency room and
at some point, I realized something had happened, but I didn't know what so I asked. They tell me, and I was like, OK, but a few seconds later, I'd ask again, "What happened?" So I couldn't encode anything new. The next day, my friend, Keaton, calls me and tries to explain what happened, and it sounded so familiar because by that point I'd heard about it numerous times, but still nothing. After that, when I'd ask, my friends would just say, "Blueberry giraffe," and I'd be like, "Oh, OK."
It's the whole dichotomy of recollection versus familiarity. Something can feel
familiar, but you can't remember where you learned that information. It's known as the butcher on the bus phenomenon. If you see your butcher out of context, there'll be something familiar about them, but your recollection might not kick in at that point.
Did that event influence your turn to neuropsych?
Oh yeah. The whole thing was a strange experience, and certainly got me interested in psychology.
So you mentioned you turned away from science in high school. When did you get introduced to research science?
It was actually not until the end of college. I went abroad my sophomore year and had no idea what I wanted to do. So I went to Spain and I just thought, you know what, I like Spanish and worst-case scenario, I'll just teach Spanish one day or something. The whole experience of learning another language was also a weird psychological experience. You find yourself thinking in the language. I don't know if I had full out dreams, but certainly several phrases and words and things definitely creeped in.
After undergrad, I went to London for a semester and applied and was accepted to
a psych program at University College London. UT-Austin has a really weird policy where unless you're a psych student, it's really hard to take psych classes. I just decided I wasn't going to claim a major until I knew exactly what I wanted to study. So, at UCL, I took a mathematical cognition class, social psychology and a cognitive neuroscience class. It was hard. I didn't have the patience to sit through class. I was kind of notorious for falling asleep.
The way the classes worked is you don't do anything throughout the whole
semester besides go to lectures, and you should be prepping but you don't have to, and then you get a month to prepare for exams. It was during that prep time that I was like, holy shit, I really like this. There were a lot of cool topics, like schizophrenia, synesthesia, and episodic memory, and of course the methods, fMRI and EEG, are really interesting as well.
So I claimed my major and the summer before my last year, Alison Preston gave
me a research assistant position in her lab at UT-Austin. I think at the time she was relatively new to the faculty, still getting her lab up and running. One thing it showed me was how little I knew. I found that everyone in that lab was like a computer scientist/physicist/mathematician as well as like a neuroscientist psychologist. It was really tough to be honest.
And then you were at UC Davis, right?
Yep, in Charan Ranganath's lab, and that's where things really came together for me. I went back to doing intense memory research there. In my experience, the cog-neuro labs are where the best methods are developed whether you're talking about the tasks that people should be using for cognitive testing or how to probe the brain in ways that tell us more about general function as opposed to just memory. That was great because it gets you thinking like, how can some of these basic cognitive tasks be used in ways that tell us something about clinical pathology like mood disorders and what not. At the same time, something I also came to realize with clinical environments, and this isn't always true, but people in those environments don't have the best methods training whether it's statistics or knowing how to code or programming experiments.
So it was nice to have a background, a good mix of environments, and know how
to do those things myself. It gave me a good, cynical yet optimistic, view of my own science.
That seems like somewhat of a, not necessarily required, but important precursor for incoming graduate students. In my class, the most successful students had had prior research or work experience that they could draw from. They came in understanding on a deeper level the level of complexity in the problem they were approaching. It's easy to fall prey to some really encouraging preliminary data. That's a different learning curve to adjust to, safeguarding against the high highs and low lows.
Oh, I'd agree. I had massive bipolar swings. I don't tell anyone to go straight from undergrad to a PhD. I mean, some people can do it, but getting a good background is so important. You're taking a lot of classes your first couple years and it's really tough to do that and research.
Now there are automated experiment-making programs like E-Prime, but at the
end of the day they're slower than if you know how to code. If you know how to code, you can code something up. It's much faster to do that and tweak things on the fly. Then, as soon as I ran an experiment, my data were already analyzed so I could quickly move to writing up the paper. For that reason, I succeeded in grad school, and that wasn't the case for people who didn't have a coding background.
I tell everyone now, you should learn to code and learn statistics because those
are skills you can do anything with.
Yeah, I've asked a couple interviewees now, what aspect of their graduate school experience current grad students should be envious of, and most mention the opportunity to study basic science, like a single biochemical process or cellular protein implicated in disease, and how projects now are so multidisciplinary and require a comprehensive understanding of multiple fields.
Yeah, but you can definitely still do like pure experimental psychology, but then obviously, yeah, later in my career I was doing more multidisciplinary work. Which again is why I highly recommend learning to code. It's funny because when I went to UC Davis, Charan had everybody coding and I kind of resisted it to some degree and I really wish I had learned more in that time and taken advantage of the resources. But I was 23 to 25 years old and just wanted to go have fun.
I wouldn't be here at Johns Hopkins if I didn't have that coding background.
That's literally why I was hired to do the brain imaging stuff here.
So what was it about the University of Chicago?
So there's like this secret society of memory researchers called the Memory
Disorders Research Society and they meet once a year and you're not allowed to go unless you're a member. But if it happens at a university you attend, you're allowed to go to it assuming you're a member of one of the member's labs, and it was at UC Davis while I was there. So I met Dave when I was walking through the arboretum to a little wine reception. Later on, when I applied, I found out that he was working with Harriet de Wit doing drug research. That collaboration was a huge part of why I wanted to go there as well as to keep studying memory distortion, which is related to this idea of re-consolidation where when you activate a memory, it might undergo a state that's labile, so you can either strengthen it, distort it, or maybe even delete that memory.
I wanted to do that and some drug manipulations and try to combine the two,
which I learned is a lot. There's not even enough work showing what drugs do to basic memory processes, so that's what I ended up doing mostly for my PhD.
But anyways, yeah, so after that meeting, Dave called Charan, and Charan's like,
Dave Gallo just called me and asked about you? So I told Charan what I was interested in studying, and he's like, do you know psychopharmacology? And I said, yeah, I did a Master's in it. I don't know what he told Dave, but Dave called me an hour later and we spoke for about an hour, mostly general memory stuff. It was great. I was fortunate because Charan really wanted his research assistants to flourish as well. We'd read and discuss lab papers for meetings, and he'd expect us to have done our research just like his grad students. It wasn't just like hey, go change the ink cartridges. It was more, here's a project for you, here are the things you'll be participating in, and at the same time, please also do change the ink cartridges and get the water jugs for the water coolers because those are things you do when you're new. So, Charan massively influenced my career and it was whatever nice things he told Dave about me and then Dave and I's conversation that got me to Chicago.
Tell us a little about your work at UChicago.
In my first year, I started with a four-experiment project where I collected like one hundred and forty subjects on top of a heavy class load, but then in the second year, I kind of had to prove to Dave that I could get shit done. So, he talked to Harriet and one of the drugs they'd never tested before was MDMA. I knew it was a rather rare drug to be testing. Actually, I think she's still probably the only person testing it experimentally, non-clinically, in the US.
We wanted to do a re-consolidation paradigm where we'd have people encode
things and then mess up their memories later, give them MDMA to see if we could delete things, which would have obvious implications for PTSD. But then we realized we don't really know what MDMA does to memory encoding, memory retrieval, emotional memory recollection and familiarity. So it was an opportunity for me to just try out my first experiment in a drug lab and see all the other things that go on in the process. There's a lot more that goes into a drug experiment other than just giving basic tasks to participants - how long you're going to be with them, how much interaction you'll have with them. Of course the drug testing and really important details like collecting heart rates and blood pressures, making sure nothing bad's happening. All these things I didn't really realize went into drug work even though I'd done a cannabidiol study, but that's cannabidiol - it doesn't really do anything so it didn't really feel like a study.
But anyways, it was because of applying this model that I learned at UC Davis,
like we wouldn't have found anything if it wasn't for that model. It was then, I think, Dave realized that only a memory researcher would have done the experiment the way I did. There's actually a finding from that MDMA study that I didn't quite believe because there was an impairment of one memory process and an enhancement of another. I just didn't believe it because, like, taking MDMA doesn't enhance memory of any sort, but recently we found a similar sort of effect with psilocybin, effective largest at a really high dose. Psilocybin and MDMA have some similar pharmacology, they both bind to the serotonin 2A receptor, so I think it might be a real effect.
That's really interesting.
Yeah. I mean, it's been one of the best experiences because Dave has kind of let me do whatever I want as far as basic memory research goes. I'd say, I have an idea, and he'd say, OK, and wouldn't necessarily agree with it, and most times he was right. Though there was one time where he didn't necessarily give his blessing for a study, and it turned into a Psychological Science paper, which for experimental psychology, is kind of like your Science or Nature, a lot of flashy titles, but a lot of good papers, too. I think our paper ("The Dark Side of Context: Context Reinstatement Can Distort Memory") had like 20 pages of supplemental material, a pretty intense review process. We replicated the experiment three and a half times, so yeah, I think it's 100 percent believable.
How has your day-to-day changed since starting at Johns Hopkins?
The funny thing is now, I just get the brain data and analyze it, and I've been reanalyzing a bunch of their other studies. But I do a lot less running of other things and dealing with money than I did in Harriet's lab. It's a really large operation here where I don't see a lot of things. With a recent salvia study, I actually ran those subjects, but my time is mostly spent analyzing the brain data and I mean, that's where my time is best spent.
If I wanted to sit with somebody for eight hours while tripping out then I would
just go to a festival -
There are plenty of very willing subjects available!
No, and I plan on being in one of these sessions at some point. But other than Fred (Frederick Barrett, PhD, Assistant Professor of Psychiatry), no one else knows how to analyze these data and they have three or four imaging studies that are still unpublished. So at the moment, I'm just trying to get this all out there.
But at some point, I'd like to be there when people lay on a couch with eye shades
on, listening to some track from a Bill Richards playlist created in the seventies, to see how different peoples' experiences are compared to being at a festival or at someone's house or something. I mean, I've seen a lot of drug use, I've seen people have their mystical experiences, but maybe it is different in the lab, especially under really high doses. I don't think that kids used to be taking as high of doses, or if they did, they had a bad time compared to what we're doing now.
Right. I mean, look at marijuana. Strains run up to like twenty-five percent THC. Wax and dabs can be eighty percent THC. I think about my humble beginnings and I can guarantee the first joint I smoked was like five percent, if that.
I used to definitely scoff at the idea of like people being addicted to weed, but now it's like oh shit, no, people can, and those lives are certainly worse off because they're doing it all the time. It's not as bad as an alcoholic, but yeah, I think it is a little scary.
I still think it should be legalized, and by the way, I don't speak for Johns Hopkins
or any of the people associated with me, but I do think the vast majority of drug scientists would want it decriminalized and legalized. I think it's certainly the best option at this point. I think the majority that use, including the cannabis scientists I know who do, are responsible cannabis users.
In a recent Vice article, "The Ethics of Taking the Drugs you Study", you argue that experience isn't a requirement for the psychedelic researcher and that powerful subjective experiences may result in biases and the loss of objectivity in one's work.
It made me think of other intra-field chasms like the beta-amyloid versus tau
debate in Alzheimer's research, and obviously they're unrelated, but is this a conversation that's often taking place between psychedelic researchers who feel strongly one way or the other?
I think you can see from the article there are some people who feel very strongly about it. But the irony is that they still couldn't articulate why it was necessary.
You can say, oh, well, if you're a therapist, you should be able to try it to know
what you're getting yourself into. What about therapists who treat patients with schizophrenia? Do they need to have schizophrenia to treat it? For that matter, do you need to take anti-psychotics in order to administer anti-psychotics to schizophrenic patients? You don't see men's health doctors having to take Viagra in order to treat their patients.
I just find that it's not a good argument. Maybe one day there will be one insight
that someone will have that came from that drug that no other therapist had ever thought of, that will help us better understand the drug or disorder, but I just don't see that.
In conversations I've had with those in the pro-camp, they won't argue back with
me, but yet they won't agree with my either. I think the loss of objectivity is a real problem. I haven't really seen anything novel come out of most psychedelic work. Maybe the closest thing is brain function, but even that, a lot of those studies are just brain images that deal in, "OK, here's a picture of the brain, let's try to reverse inference what's going on in the mind." That's a massive problem in fMRI in general. "Here's a picture of the amygdala, and it's activated therefore the patient is scared." Actually, the amygdala is activated for many reasons. The problem is a lot of drug researchers didn't start off as brain imaging people or psychologists as cognitive psychologists, which is maybe the best area of psychology in terms of interrogating brain data.
I think it's great to make these brain maps and we shouldn't try to over-interpret
them, especially on these super low N studies. I'm guilty of it, too. My salvia study only had twelve subjects, a lot of these fMRI studies have like fifteen, and now, the bare minimum is like twenty-five. I mean, it's challenging. The basic things we learn about the brain and these drugs, it's always like, take it with a grain of salt until there's more reliable data out there.
But as far as learning about new effects of the drugs on the mind, there's been
nothing new that's come out. To me, it's pretty clear that people are biased by their own experiences. One of the things Roland Griffiths (Professor of Psychiatry and Neuroscience at Johns Hopkins) did, there was a quantitative, but not qualitative, aspect that was novel in a mystical experience study where a bunch of people who had never done the drug, I think 70% of them had a "top 5" most mystical experiences of their life. But as far as like, people see things when their eyes are closed on these drugs, that's not new.
I want to learn more about the subjective experience alone. Like, take this MDMA
study example. It's a positive experience for most people, right? I think I've had maybe one subject who was a little anxious. But one thing I found was that people couldn't remember positive events or negative events. That was totally unexpected from the subjective experience alone or, for that matter, that certain aspects of memory are enhanced whereas others are impaired but in a non-stimulus-specific way. I'm sure you could give somebody a picture of their Mom and they'd remember that moment forever while they're on drugs, right? But with this study, there was a very specific memory process that involved very specific brain areas that appear to be enhanced by serotonin 2A drugs and it's now led to some other ideas I'd like to eventually test behaviorally.
One of my friends has suffered from depression most of his life. He's tried every anti-depressant, anti-psychotic, electric shock therapy - nothing's worked for him. He recently tried ketamine -
Did you know there's a clinic in Deerfield that offers ketamine with TMS (transcranial magnetic stimulation)?
Yeah, I actually can't believe they're allowed to do that.
Are you opposed?
No, not at all! I think it's something we should be trying more. TMS seems to work in some people. Ketamine seems to work in some people. What if we can enhance the longevity of ketamine via TMS or something? I don't know, I'm just making things up at this point. Sorry, go ahead.
Haha. Right, so it was a six-course regimen. And it was interesting to talk with him about his experience throughout the course of the program because he's not necessarily the most, I guess, susceptible or open-minded person to the idea of these "meeting God" psychedelic experiences. The way that he described these treatments, it really was like talking to a new person. He had a relapse, but even three or four months later, he's encouraged. For him, it was the first treatment that ever worked in the sense that there was a sustained positive effect.
My question to you: which psychedelic holds the greatest therapeutic promise for
the most amount of people?
Starting with ketamine, I think it's great that it's officially a medicine. Hopefully, you know, insurance companies will start paying for these things. I looked it up once and I think it was something like seven hundred dollars for an infusion of ketamine, which makes it a rich people anti-depressant. But now they have the intranasal form, it's just the S enantiomer which is why they call it esketamine and they put an "e" in front of it to be cute. Also, kind of absurd because the S enantiomer has been tested in people. I think there's an fMRI study from the 1990s where they tested the R versus the S, and the S produced more psychomimetic effects.
Regardless, what I find ridiculous is that they patented it and it's now really
expensive. Like, oh, when there was a way to patent it, that's when it finally was approved as a treatment.
There is something to be said about it only lasting a week - at the same time, that's
only 52 doses a year versus 365 which is your typical anti-depressant.
But as far as most promising, obviously depends on disorder. I know there's been a
little bit of fear around trying classic psychedelics with PTSD because of a fear of, for example, flashbacks becoming more intense whereas full-on hallucinations on MDMA are much more rare. It's hard to say, really. One thing that is interesting is combinations.
So is there no hope?
Haha! No, I wouldn't be doing this research if I didn't - I'm not here to just shit on other people's work and try to take down the psychedelic movement. No, I 100% do think they work for people. Just look at the massive changes in people's depression, like even if you said that 75% of the subjects were under placebo effect, you'd still have the efficacy of an anti-depressant.
So I do think something's there. I think there's something about the weirdness
perhaps of psilocybin that could be maybe better for people with depression. Maybe not something like LSD because it lasts too long, but something like 2-CB, which is right between MDMA and LSD.
The thing is everyone's co-morbid for everything. These diseases are on a
spectrum. I think it's pretty rare to find a pure addict who's not depressed and anxious. So there may be something to mixing the drugs. There's a group in Mexico that's looking at 5-MAO, DMT and ibogaine, I think.
One thing I would like to say is psilocybin and LSD are not like the end-all of drugs.
There are over 500 classic psychedelics out there, and there's got to be one, or even several, that are better for some people. We're exploring psilocybin and LSD because they're tolerated relatively well by the body, they're big in pop culture, but there are so many more out there.
Alert the media. Let's get the word out. There's one for everyone.
Yeah, I mean in some ways, if it wasn't for a bunch of people taking psychedelics, thinking they're amazing, we probably wouldn't be doing this research right now. But to think that this is the only way forward and that psychedelics are going to save all humanity and all mood disorders are going to be cured is just absurd. There's a study at UCSF using psilocybin to treat anorexia, and MDMA for autism, or like CBD - I've never seen one drug used for so many purposes!
What are the best books on the hard science of psychedelics?
I like PiHKAL by the Shulgins. It's a nicely told love story between him and his wife, but also, that's where part of my interest in all these other drugs came from. He talks about, I can't remember which one of the MDs is bad, but one of them he called more psychotomimetic than psychedelic, and surmised that the bad flavor might just be linked to the monoamine action. Like if you mix a stimulant with a psychedelic, you might end up with a weird schizophrenic-type behavior, but it could be something else entirely! And that's the beauty of these things, what makes these drugs really special. Anyways, I thought that book was interesting, super informative.
I went through a phase of reading a lot of trip lit, and honestly, think most of it's
bad. They don't say anything new. And the worst one is the Tim Leary one where he just essentially rewrites the Tibetan Book of the Dead.
Alright, last question: Beatles, Rolling Stones, Led Zeppelin or Pink Floyd?
Hip-hop! Frank Ocean.
I just didn't really grow up on that type of music. I think my Dad listened to the
Beatles, but to be honest, he never really put it on us, and so it's hard for me to like get behind these greatest bands of all time. Frankly, I think they're a little overrated.
So I'm a Phish fan, and Trey Anastasio was recently interviewed by the New York Times, and one of the questions had to do with whether Phish is the last of a dying breed, and Trey was diplomatic in his response, but he just didn't seem to have interest in the idea and was unsympathetic about the dying off of nostalgia acts. He mentioned Anderson Paak and Kendrick Lamar as performers moving forward. And I feel like a lot of musicians right now feel that way about hip-hop.
I'm not one of those who's like old hip-hop is the only hip-hop. I definitely respect a lot of stuff from the 90s. I mean, if you tell me to throw on a track, I'm going with "I got 5 on it" by Luniz or "Return of the Mack." '95 was a good year.
But I love what's going on with new hip-hop. Old Kanye, new Kanye, I mean I don't
know about the latest incarnation of him, but The Life of Pablo? Amazing. As a whole, what he does with that album, where it goes from church music positivity to pure, bottom of the pit depression and then the Frank Ocean interlude and then it just gets weird. Bringing in a lot of electronic music was great, doing the singing rap was great, I guess Kid Cudi kind of started that.
Frank Ocean. The guy is just so educated in the way he talks about things. "Chanel"
has so many entendres. Maybe I'm over-interpreting it, but clearly he's a bit more open now about his sexuality, so there's that, but also being a part of fucking hip-hop as a gay male. Just...amazing.
Learn more about Dr. Doss and his work here.
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