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We're excited to bring you an AMA with three people who have done a lot to increase the profile and prospects of psychedelic research. 

Effective altruism has a history of engaging with psychedelics (see these posts, for example) as a promising intervention for mental health issues — one which could sharply reduce the suffering of tens or hundreds of millions of people.

Between Tim, Michael, and Matt, we have many kinds of expertise here — nonprofit investing, journalism, medicine, and more. We hope the discussion is interesting, and useful for anyone who's thought about working or giving within this area.

We'll gather questions for a couple of days. Michael and Matt will answer questions on Sunday, May 16th. Tim will answer questions on Tuesday, May 18th (we've pushed his original date back by one day).

Author introductions

Tim Ferriss

Hi, everyone! I’m Tim Ferriss, and I’ll be doing an AMA here. More on me: I’m an author (The 4-Hour Workweek, Tools of Titans, etc.) and early-stage investor (Uber, Shopify, Duolingo, Alibaba, etc.).

Through my foundation and since circa 2015, I have committed at least $4-6 million to non-profit scientific research and clinical treatments of “intractable” psychiatric conditions such as treatment-resistant depression, opioid/opiate addiction, post-traumatic stress disorder (PTSD), and others. I believe (A) this research has the potential to revolutionize the treatment of mental health and addiction, which the data from studies thus far seem to support, and (B) I’m a case study. Psychedelics have saved my life several times over, including helping me to heal from childhood abuse.

Projects and institutions include the Centre for Psychedelic Research at Imperial College London (the first such center in the world); the Center for Psychedelic and Consciousness Research at Johns Hopkins University School of Medicine (the first such center in the US); MAPS (Phase 3 studies for MDMA-assisted psychotherapy); divisions and studies at UCSF (e.g., The Neuroscape Psychedelic Division); The University of Auckland (LSD microdosing); and others (e.g., pro bono launch of Trip of Compassion documentary on MDMA-assisted psychotherapy). 

I evaluate non-profit and scientific initiatives in the same way I evaluate for-profit startups, and I believe some bets in this nascent field represent high-leverage, low-cost opportunities to bend the arc of history, much as Katharine McCormick did for the first birth control pill. Here is one blog post with more elaboration.

I am happy to answer any questions through the AMA. Dr. Matthew Johnson is no doubt better qualified to answer the scientific (and more), and Michael Pollan is no doubt more qualified to answer the journalistic (and more), but I will do my best to be helpful!

Michael Pollan

I'm a journalist and author who focuses on ways that the human and natural worlds intersect — including within our minds. 

In 2015, I wrote a New Yorker article on psychotherapy, "The Trip Treatment", which profiled a number of cancer patients whose experiences with psilocybin had reduced or entirely banished their fear of death. This led me to embark on a two-year journey into the history of psychedelic policy and its potential for modern medicine, and to write a book: How to Change Your Mind: The New Science of Psychedelics. My forthcoming book, This is Your Mind on Plants, covers the strange contrast between the human experience with several plant drugs — opium, caffeine, and mescaline — and how we choose to define and regulate them.

I'd be glad to answer questions about anything I've written on the subject. Particular topics of interest:

  • The history of drug regulation, and the dynamics that lead to specific substances facing especially harsh regulatory regimes
  • The ways in which different cultures incorporate plant drugs, and how that might or might not map to cultures (e.g. in the United States) that have yet to legalize those substances
  • The potential of psychedelic therapy to alleviate the worldwide mental health crisis
  • My personal experience with psychedelic substances, and how it changed the way I think about my own mind

Dr. Matthew W. Johnson

I’m a Professor of Psychiatry at Johns Hopkins University School of Medicine. I’m an experimental psychologist who has conducted research with psychedelics since 2004, including studies of psilocybin and such topics as mystical experience, personality change, tobacco addiction treatment, cancer-related distress treatment, and depression treatment. I’ll soon start studies on the treatment of opioid addiction and PTSD among others. 

I’ve supervised hundreds of psychedelic sessions and have personally guided over a hundred people through psychedelic sessions with psilocybin and other psychedelic compounds. I’ve also conducted research on the nature and treatment of addiction with drugs such as cocaine, methamphetamine, opioids, alcohol, and tobacco.  

I’m looking forward to answering questions related to psychedelics, including those about therapeutic effects, risks, mechanisms, and opportunities. You can ask me anything!

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First of all, I'd like to say I've been excited about this topic for some time and have been following each of you, and your (excellent) work individually, so it's a very pleasant surprise to have you all here!

Question: what is your thinking on how cost-effective, from a donor perspective, additional resources are if put towards psychedelics compared to other problems, e.g. the GiveWell-style health and development interventions? 

Follow up: How valuable do you think additional detailed research on this would be (to you)? 

This is primarily for Tim, seeing as he's really putting his money where his mouth is!

Background: I run the Happier Lives Institute and I want us to take look, in the near-future, into funding psychedelics.* Psychedelics seems very promising, but it's unclear exactly how promising.

One generic issue is that it's hard to sensibly model the cost-effectiveness of systemic interventions, e.g psychedelics, to 'atomic' ones, e.g. handing out cash transfers to one person at a time, because you have to make so many assumptions about how funding one thing might impact an entire society. The best analysis currently is from  Founders Pledge, who compared funding... (read more)

Thank you very much for the thoughtful questions and kind words, Michael. I’m familiar with your writing and so a bit nervous to share much of this for the first time, but I hope it’s somehow helpful. I’m also open to improving my thinking, so please consider this all a rough draft! Please note that I use the words "invest" and "investment" to refer to non-profit donations, gifts, grants, etc. I think "investment" is the right way to think about how you place certain bets, whether for-profit or non-profit. To date, I have deliberately not made any for-profit investments in the psychedelic space.

My thoughts are inline below, I've bolded my replies, and apologies for any typos: 

Question: what is your thinking on how cost-effective, from a donor perspective, additional resources are if put towards psychedelics compared to other problems, e.g. the GiveWell-style health and development interventions? 

TIM: Broadly speaking, I’m both/and instead of either/or, as I view the nature of these “investments” as quite different. I’m a big fan of GiveWell. I view GiveWell and its recommended recipients as well-vetted “late-stage” options for donors, defined as such because so many varia... (read more)

Tim,

Thanks enormously for this very thorough write-up - shared despite your nervousness(!) - 
which was insightful, not just for your thinking about psychedelics, but also about non-profit and for-profit investing.

You said lots. I'm just going to focus on two things here.

1. (Dis)analogies between investing and donating

You drew the analogy that GiveWell-recommended charities - evidence-based 'micro-interventions' - are like index funds, whereas funding research is more like angel investing. I agree with you that the risk-return structure is similar, in the sense we think the former has lower variance and lower expected value and the latter has higher variance but also higher expected value. Crucially, 'value' here is being used ambiguously: for investing, we're interested in financial value; for philanthropy, in moral value. Because of this, the analogy isn't exact and it doesn't follow we should think about investing and philanthropy the same way.

From an investor's perspective, it does make sense to make both sorts of investments, but only because there are diminishing marginal returns to income on well-being. If there were no diminishing marginal returns to income on... (read more)

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Aaron Gertler 🔸
I basically agree with the model here — that there aren't diminishing returns on moral value. That said, a couple of notes on the specific situation: a) From the perspective of inspiring action, it would make sense to me if Tim saw his listeners as being somewhat risk-averse (as most people are!) and tried to recommend GiveWell in the expectation that this would raise more overall money than a higher-risk option. This approach might still be Tim's best way to maximize his impact as a fundraiser. (No idea whether this is something he actually tries to do.) b) Some of the opportunities Tim has supported (e.g. scientific studies by a particular lab) aren't necessarily in a position to accept small donations, and so wouldn't make sense to recommend for listeners. (That said, there are times when these opportunities have been available to small donors, and he's advertised them.)  From Open Phil's latest set of suggestions for individual donors: Funnily enough, this actually is an analogy to investing; you need a certain amount of capital to invest in certain hedge funds, startups, etc. What a wealthy person does with their portfolio isn't necessarily the same thing they can recommend to a broad audience. This also strikes me as valuable, though in light of point (b) above, you might want to select "best in class" funding opportunities for donors of different sizes (e.g. the best place to give if you plan to donate under $1000). That said, this is possibly worse than creating some kind of psychedelics fund that can combine many small donations into grants of a size that make sense for universities to process. (I wouldn't be surprised if this existed already and I wasn't aware of it.)
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MichaelPlant
Hello Aaron, Re (a), that would be a sufficient justification, I agree: you suggest the option that is less cost-effective in the expectation more people will do it and therefore its expectation value is higher nonetheless. My point was that, if you have a fixed total of resources then, as an investor, the lower-risk, lower ROI option can be better (due to diminishing marginal utility) but, as a donor, you just want to put the fixed total to the thing with higher ROI. I am not aware of this, but I have had a bit of discussion with Jonas Vollmer about setting up a new EA fund that could do this. This hypothetical 'human well-being fund' would be an alternative to the global health and development fund. While the latter would (continue to) basically back 'tried-and-tested' GiveWell recommendations (which are in global health and development), the former could, inter alia, engage in hits-based giving and take a wider view.
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BrianTan
I have so many thoughts and learnings from this writeup, so I'll break them up into two comments. Firstly, I didn't know that you're a big fan of and a believer in GiveWell. I know you've had them sponsor a podcast episode of yours before, and I was aware that your listeners had donated to them after your episode with Will, but it's great to hear you're a big fan of theirs! Having Elie Hassenfeld or Holden Karnofsky (co-founders of GiveWell) on your podcast could lead to a lot of donations to GiveWell, as well as inspire future non-profit entrepreneurs or thoughtful philanthropists. They also probably have lots of inspiring and interesting stories to tell from their journey of starting and growing GiveWell. Have you considered having either of them on your podcast?
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BrianTan
Secondly, it's refreshing and great to see you put your startup investing mindset to the world of philanthropy! I didn't know you had such a thoughtful mindset to your own giving, and others could be inspired to be as thoughtful as well by listening to you. I think you should seriously consider creating an episode on your podcast where you talk about this, or interview other philanthropists who are as thoughtful as you about their giving, i.e. Dustin Moskovitz.  Presumably, many people have become interested in angel investing in the past because of your episodes or blog posts in which you talk about your angel investing mindset and wins. In the same way, I think that if you share about your non-profit investing mindset and wins, more people would become more thoughtful with their giving, possibly becoming non-profit  or science "angel investors". I'd be curious to hear if you are considering talking about this on your podcast!

1) Where do you see untapped opportunities for nonprofit entrepreneurs in the space of mental health?

2) What role do you see entrepreneurs (vs. established organizations) play in this field, including incubation programs like CharityEntrepreneurship.com that has incubated mental health charities before?

3) How do you assess the potential of new mental health treatments for the Global South? Is this sufficiently prioritized and do you see particular roadblocks to rapid adoption?

What is the best case against psychedelics being an important area? 

I'll preface this by stating that I obviously believe psychedelics are an extremely important area.  I'll focus on challenges. One is that they are not FDA (or international equivalents) approved for treatment yet, so for therapeutics as a field we need to continue to follow the regulatory pathway with larger and more definitive studies.  Another is that at least as currently conducted this is a pretty expensive treatment due to professional time. However I think that is more than off set by the large success rates - it pays for itself in the long run so long to the degree that the payer is incentivized to care about long term costs. And more scalable and safe treatment models need to be explored in studies. Another challenge is that given that people often grapple with the "big questions" during psychedelic sessions, there is a potential that therapists coopt the patient experience (intentionally or unintentionally) toward the therapists' own metaphysical belief system.  At the extremes this can lead to cults, but the risks are present even short of the extremes. Another legitimate question and challenge is determining how many people would want and benefit from the... (read more)

How could psychedelics-assisted therapy be scaled up? Isn't this super hard because you need at least two trained professionals on multiple lengthy occasions? Where will those people come from? 

There's a lot of good work being done on this important question. Several new training programs have been started, but there is also research to see if there are other, more efficient models of therapy besides the traditional two facilitator model-- group therapy is one; designing treatment suites where one therapist can guide several patients at once, etc. But the Psychedelic Science Funding Collaborative estimates that 100,000 facilitators will be needed in the next decade, so this is a potential bottleneck to scaling psychedelic therapy.  It's also an opportunity for philanthropy.

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Dr. Matthew W. Johnson
There are already multiple training programs for people interested in professional psychedelic therapy. I expect such programs to grow and new, rigorous ones to be developed, but I generally don't think lack of of therapists will be a bottle neck. I think the challenges for scaling will be more in terms of paying for the treatment model by insurance, and governments programs such as Medicare and the VA. And as discussed in another response, I think cheaper treatment models need exploration, for example group therapy. 
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Rjsnarskis
Are there training programs you’d recommend for those who are wanting/ready to explore this field like myself? Any resources would be great!
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Pranab
You may be interested in looking at Fluence and Polaris for ketamine-assisted psychotherapy training and the MAPS MDMA-assisted psychotherapy trainings.

For everyone: What are your thoughts on the effective altruism movement? What do you like about it, and what do you not like about it?

Thanks for the question, Brian. I'm a big fan of the effective altruism movement and have tracked it for some time. That said, I am by no means an expert, so my answers are those of a casual observer. Caveat lector!

THINGS I LIKE:

*Keeping it simple: I like forums where people can stress-test their ideas, assumptions, and arguments in the service of pursing good. The more rational, evidence-based decision makers we have, the better off the world will be, whether in non-profit work or any other field. EA provides concepts and tools, as well as a community within which to test them. Last but not least, the EA movement encourages people to think deeply about their impact in and on the world. This is a wonderful thing.

THINGS I HAVE PONDERED:

*Does the EA community tend to overemphasize philanthropy? If so, why? If you look at the etymology of phil-anthropy, it is literally "man-loving." Many of the causes favored in the EA community seem to focus on the well-being of humans (and animals). While I strongly support causes that focus on human well-being -- psychedelic science is certainly an example --  I simultaneously believe that there are many worthwhile causes with measurable benef... (read more)

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BrianTan
Thanks for the thoughtful answers! Seems like you've pondered quite a bit on EA. Here are my comments and reactions, if you or others would like to read them: On "*Does the EA community tend to overemphasize philanthropy? If so, why?..." That's the first time I heard of the etymology for philanthropy. Anyway, I think what you meant here is that you think the EA community overemphasizes working on causes that mainly help humans and farm animals, at the expense of other causes that help other beneficiaries, i.e. wild animals or the environment. To some extent you are right, but maybe you're not aware that some people and organizations in the EA community are also doing important work for wild animals and the environment. There are two EA-aligned organizations working on wild animal welfare, which are Animal Ethics and Wild Animal Initative.   Wild Animal Initiative became a top charity of Animal Charity Evaluators last year, and they focus on helping scientists, grantmakers, and decision-makers investigate important and understudied questions about wild animal welfare. You might be interested to read their research or donate to them. They wrote this article on trophic interactions, which you might be interested in given that you mentioned trophic cascades in a separate answer.  For the environment, the EA-aligned organization Founders Pledge has done research into what are the highest-impact funding opportunities for climate change here. I'm not an expert here, but it's quite possible that these organizations may have a larger positive effect long-term for biodiversity and preventing further environmental damage than the Amazon Conservation Team, which you support. On "*Do some in EA inadvertently select non-profits that are the least likely to survive?" When you said "For me, an inability to raise funds effectively would be a disqualifier, not a qualifier", I think it's quite possible that the most evidence-based and effective charities are not the ones who ca

I suspect Tim would be the most relevant expert here given his role as a philanthropist. So, I can't really offer any critique. I can just say from my knowledge I love and admire the idea of being strategically and empirically informed as to how a given amount of philanthropy can improve the world.

Really appreciate your taking the time to do this AMA — I badly want to see this cause area succeed, largely thanks to your writing (Michael), advocacy (Tim), and research (Matthew). Thanks for leading the way.

In a recent conversation with Tim, Hamilton Morris worries out loud about how the psychadelic pendulum has recently swung towards hype, with lots of trendy op-eds and new capital:

Well, what happens when that gets a little bit old, and what happens when, I don’t know, someone has a bad experience? Maybe a celebrity has a bad experience and they decide that mushrooms caused their psychosis. And then what?

How do you think about setting expectations here? Are you concerned about this resurgence in interest repeating some of the mistakes of the 60s? And, this time, what can we be doing to establish things for the much longer term?

I share Hamilton's concerns that psychedelic therapy can be over-hyped. Many of the researchers are sounding a more cautious note, but there's so much capital chasing so few good ideas right now, and the media is so positively disposed to psychedelics that a correct is bound to happen, and should. Some of these over-valued new companies will crash; there will be adverse events in the drug trials: if you trial hundreds of depressed patients, some of them are likely to commit suicide, and because the pre-existing narratives about psychedelics, this will be a big media story, even though suicides happen getting on and off SSRI's all the time. 

But in the end, it is the research that will determine whether psychedelic therapy earns a place in mental health treatment or not. I don't think we'll see a disabling backlash as we did in the 1960s. The need for new therapeutic tools is so desperate that the mental health establishment will embrace psychedelic therapy if the phase II trials are anywhere near as good as the phase II. 

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BrianTan
I think you have a typo here? :)
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Dr. Matthew W. Johnson
This is a concern, and perhaps the most important thing we can do about it is make sure the FDA require a solid REMS program (https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems) that mandates that treatments follow similar safety guidelines that are being used in clinical research (e.g., https://www.researchgate.net/publication/5259182_Human_Hallucinogen_Research_Guidelines_for_Safety ). Another thing we need to do it always acknowledge and address mitigation strategies for risks when interfacing with the public or other scientists. Many will not do this, so it is on us who recognize the risks and their implications for leveraging these treatments to help the greatest number of people to keep awareness of them in public discourse.

Hi, very cool that you're doing this, thanks! Here goes my question:

How likely is it that taking psychedelics makes patients weird? Scott Alexander wrote up some anecdotes about many early psychedelicists getting weird as they experimented with these substances. He emphasizes it's all very speculative and of course subjective. And it probably involved pretty high doses / frequencies. But my very superficial understanding is, that it's hard to find good studies on this sort of thing, precisely because of the regulatory environment. Is that accurate or am I missing something? So should patients seriously consider the risk that their personality, motivations and view of the world would be significantly altered in a way their current self wouldn't necessarily endorse? Would that be a bad thing?

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Dr. Matthew W. Johnson
There is a lot here. One is that at least some of this pattern is likely not causal but due to common predisposition. Those who are open enough to something outside of the mainstream and willing to consider topics that others consider beyond the pale, are likely to be interested in both psychedelics science and other fringe topics. Keep in mind a key issue is that we often (or ever) don't know ground truth, so there is a balance between being too closed and too open. For the statisticians this is the balance of type I and type II errors (false positives and false negatives). Another thing is that my impression is that at the extremes, there is a causal effect of psychedelics to cause negative personality problems (e.g., narcotism) and to adopt delusional beliefs. This is likely dose and frequency dependent but doesn't even show up for all folks who use high doses frequently. But for some, my guess is that yes, psychedelics can push people into these terrains. Of course, again, common predisposition is also at play, with those who are self-absorbed or into extreme conspiracy theories from the beginning also being attracted to psychedelics. I should say I have seen no evidence for any of this in either the older or modern sciences (including my own) with screened (for psychotic predisposition) participants with a limited number of sessions conducted with proper safety guidelines at play. Also, I wrote a receive piece that argues against the notion that as currently conducted, psychedelic therapy is likely to have substantial effect on political or religious affiliations ( https://www.scientificamerican.com/article/theres-no-good-evidence-that-psychedelics-can-change-your-politics-or-religion/ ).
1
Matt Putz
Very helpful, thanks!

How much evidence is there for microdosing having an effect significantly larger than placebo? From this conversation with James Fadiman I got the impression that it is more underwhelming than I thought. 

There have been 3 laboratory based double blind, placebo controlled studies of microdosing. None of them have shown evidence for any of the positive effects reported anecdotally, other than feeling just a tiny bit high (which could be considered potentially positive regarding potential antidepressant effects, but could also be considered  through the lens of abuse liability). Results range from no effect to slight impairment. It could have been that these studies did not measure the outcomes that would show an effect, or that some of them only looked at acute effects rather than a chronic dosing regiment such as those many endorse (e.g., taking it once every 3 or 4 days). Nonetheless, so far there is no evidence of benefit. I also think that the benefits anecdotally reported for microdosing are especially prone to placebo effects. Surely part of reported success is due to placebo effect, but that is true for most medical interventions. What you get in the real world is a combo of direct underlying efficacy (or whatever you wan to call it) and the placebo effect. The challenge is to see if any of the benefit is not due to the placebo effect. My best guess at this point is that ... (read more)

6
Michael Pollan
We haven't seen rigorous well-controlled trials of microdosing of psychedelic vs a placebo. One recent study, in which citizen scientists blinded themselves, strongly suggest a placebo effect. There is so much "magic" associated with psychedelics that that taking a tiny dose is likely to have an unusually strong placebo effect. But more research needs to be done.  It's important to understand that ALL the research done on psychedelics-- research that has already produced potentially revolutionary treatments for PTSD, depression, existential distress and addiction-- has been privately funded by philanthropists. This area is still too controversial for government funding.  I can't think of another case where philanthropy has achieved so much in twenty years.

MDMA-assisted couples therapy has been studied a bit. Could MDMA also be useful for interpersonal conflict resolution more generally, such as for enabling more constructive conversations between people with very different perspectives?

+1. I believe this to be well worth exploring.

I think the potential for using MDMA to solve conflicts is a rich area of exploration. I know Rick Doblin at MAPS has a longstanding interest in this. (In the 1980s he sent hundreds of doses of MDMA to the Russian leadership, hoping to advance arms negotiations!) I believe there are some projects along these lines underway or planned in Israel. 

I agree this is a worthwhile area for research.

For Tim: Have you considered having a page on your website as a public tracker with how much you intend to give per year, and/or how much was each donation you've made to each project? Why or why not? 

I think having a public tracker could help your audience know that you are a thoughtful and generous philanthropist, and it might encourage them to be public and thoughtful about their giving too.

Thanks for doing this!

For all three – how would you like to see EA participate in the psychedelic renaissance? What do you think a good marriage of the two communities would look like?

Hi Milan! It would be great to see increased discussion of the most attractive target projects related to psychedelics, as well as perhaps donation campaigns to reach critical mass for specific purposes. It's really remarkable how much can be done for how little at the moment. If there is interest, I might be able to help by drafting a blog post with some of the candidates I consider very high-leverage and worthwhile.

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DuncanP
This would be an invaluable resource.

For Tim: If for some reason you were unable to donate to scientific research and clinical treatments of "intractable" psychiatric conditions over the last few years (and in the future), what would you instead be donating that money on? I'd love to know about what other causes or projects you prioritize, whether they are mental health related or not.

Here are a few areas of interest:

  • Education. See tim.blog/causes for several examples. I also have some for-profit bets in EdTech, like NoRedInk.
  • Reintroduction of keystone species. Example: grey wolf. Related: read a bit on "trophic cascade."
  • Biodiverse land conservation, in combination with cultural preservation for stewards. Example: Amazon Conservation Team (ACT).

What do you think of drug policy reform more broadly, and where do you see your work on psychedelics fitting into that?

(Disclaimer/hopefully-acceptable-self-promotion: Peter Singer and I argued, in the New Statesman, in favour of full legalisation a couple of weeks ago. We didn't mention psychedelics specifically, but full legalisation would, amongst other things, make research into and the therapeutic use of psychedelics easier).

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Dr. Matthew W. Johnson
The public health science and related civil rights concerns are clear that we shouldn't be using the criminal justice system to address the real programs that can come from drug use. But that is true for all drugs, e.g., cocaine, meth, opioids, not just psychedelics. As I discussed with Lex Fridman, I like the language of regulation rather than legalization, as legalization is cloudy. Caffeine is sometimes illegal (e.g., an OTC mediation with more than the FDA allows), but I've done legal work giving meth and cocaine getting folks high, and these and other scheduled drugs have approved medical uses). The exception are things like impaired driving, where I do think the criminal justice system is very appropriate. We are a long ways from where we need to be, but I think decriminalization of drugs, meaning removal of felony and  misdemeanors, is appropriate as a step right now. The science behind safe injection sights is also strong and we is currently justified. We need regulation, and I would never want, to give an extreme example, minors to be able to buy cocaine at a convenience store, but we should be moving toward smart, science based regulation which is tailored for each drug and its own profile of risks. In terms of my own work of psychedelics, I am a little annoyed when psychedelic decriminalization efforts cite (even in the official ballot  initiatives or legislative bills) the work that my colleagues and I have done as the justification for decriminalization. If that is the standard, then we should follow the FDA path toward medical approval. Although we are well on our way, the science has not met that standard yet. But we should decriminalize for the reasons stated above. Psychedelics have real risks, like all drugs including caffeine, but the best way to realistically and effectively address them is not by giving criminal penalties that restrict employment and educational opportunities, separates families, etc.

How do you feel about people flying to e.g. Jamaica and going on psilocybin retreats? Is this a net positive or could it be a problem for changing the image of psychedelics towards a legal medicine? 

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Michael Pollan
I'm a bit of worrywart. Some of these retreat centers are well-run and legit, but others are sketchy, and when people start having bad experiences it will have consequences. The public is just learning about psychedelics, and negative stories are bound to shape their perceptions.  
2
Dr. Matthew W. Johnson
It is certainly a wild west, as Michael suggested. Question about net positive depends on - positive for what and who?  I have no doubt that some people are helped, so it can be a positive for them, but others are harmed. For the regulatory pathway, it is really independent so does not contributed to the positive path to medical approval. And as Michael said, if things aren't done well, the bad press could hurt the medical pathway. I'm not preaching to folks what to do or not do, but from my own position, all I can do is educated folks about relevant risks and safety factors (what separates more risky from less risky use), and remind the public and other scientists and regulators that what you see in these settings is not necessarily reflective of the risk/benefit profile at play with approved clinical treatment with our safety guidelines at play. 

I never thought I would see Tim Ferriss do an AMA on the EA Forum. I am such a fan. 

For Tim: 

  1. If you can share, have you been able to convince other donors (whether you personally know them or not) to donate more than $100k to psychedelic research? Is this something you've tried  or still try to do?
  2. Have you ever used your podcast and/or newsletter to fundraise for psychedelic research? If so, around how many donated, and how much were you able to raise?

Imagine, two or three decades from now, that all your hopes about psychadelic-assisted therapy materialise — it works at scale, and it becomes about as neglected and unhelpfully politicised as hip surgery and antibiotics.

What do you picture? How did these remarkable early studies scale to a system which fully lives up to their promise and reaches milions of people? And just how ubiquitous (in your more imaginative moments) do you see these treatments becoming?

4
Michael Pollan
Scaling psychedelic therapy is an enormous challenge-- it's so different from either the current models of pharmaceutical therapy -- a pill a day forever-- or talking psychotherapy -- a weekly session more or less forever or until the insurance runs out-- that it will take some genuine innovation to fit this square beg into these round holes. Yes, psychedelic therapy takes intensive preparation and integrations but only over a short period and with a small number of sessions. It actually cures many problems, so shouldn't need to be repeated constantly .  But when people say it's potentially revolutionary, they're thinking of these existing models. It needs to be said, however, that these existing models don't work very well for many, if not most, patients. If psychedelic therapy is proven to be superior, corporations and national health agencies (and potentially some public benefit corps like MAPS') will figure out the necessary new models. The success of the research is the key. 
3
Dr. Matthew W. Johnson
I discussed scaling in another response. In terms of how ubiquitous MIGHT it be, I think it has the potential to be a major portion of mental health treatment. We have to follow the data though.

More personal question: what reactions have you gotten from other people, such as your friends and family, when/if you've told them about your use of psychedelics? Was anyone shocked and appalled?

I was nervous about this. But the reactions I get are more curious than judgmental, even from my mother and son. In general I expect much more pushback --both personal and professional-- than I actually received. I've come to the conclusion this is one of those issues --like gay rights-- where it is vitally important for people to come out of the closet, discuss their experiences in an unsensational way, and when they do the public will listen and shift its views. This is how anything gets normalized-- by ordinary people telling their true stories. 

No one has been shocked and appalled by the fact that I've used psychedelics, and this was true even decades ago. As Michael said, the response is uniformly more curious than judgmental. For better and worse, you can't visit a yoga class or order a green juice these days without bumping into a rent-a-shaman, so it's all the more normalized. 

I struggled with IV heroin addiction for a decade and got clean, with psychedelics playing a major role. I went back to school and got a computer science bachelor’s, but realized I want to dedicate my life to helping both the psychedelic movement and others with addiction and/or mental illness. I am considering applying to med school in my 30s in the hopes of becoming a psychiatrist. Is this foolish? If so, how else can I contribute to the cause?

8
Agrippa
As a non-member of the AMA I apologize if this is unsolicited advice: To me it seems likely that you can help the psychedelics movement philanthropically as an engineer. Depending on your current earnings, its very plausible that by the time you become a practicing psychiatrist you could have instead donated $1M from continuing to earn to give as a software engineer. My guess would be that you can do more for the psychedelics movement w/ $1M, than with +1 psychiatrist.  I mention this because I think this is a common blindspot when people talk about going back to school.
4
Dr. Matthew W. Johnson
Ultimately this is a personal decision and it depends on countless factors that only you know. But I will say for the person with the right talents and dedication, this can be a realistic path. Thanks for sharing your experience. We will soon be conducing a study on psilocybin for opioid use disorder, and anecdotes like yours are one part of the reason for doing so.
4
Michael Pollan
Psychiatry is a long road, but we certainly will need more psychiatrist interested in psychedelic therapy. It's a good vantage from which to advance the field.

Should psychedelic researchers have personal experience with the substances? It could be a source of bias, but also help one design studies. 

5
Michael Pollan
I'd be curious to know what Matt Johnson thinks, but don't think it's necessary for the researchers to have the experience. However I do think it's useful and informative, and especially useful for the facilitators. This is one of the limitations of most current training programs-- the trainees can't legally have the experience they are administering.  The Berkeley Center for the Science of Psychedelics (full discloser: I am a co-founder) has an opportunity to offer the psilocybin experience to its trainees, since the Center will be working with "healthy normals" rather than volunteers with a clinical diagnosis. MAPS has gotten permission to do give MDMA to a limited   number of trainees. 
2
Dr. Matthew W. Johnson
It should never be a requirement as not all therapists would qualify per safety guidelines. It is complex. While I surely think that for some it can help to understand the treatment, other experiences can also help, and are probably all less important than personality and clinical rapport. And there are many folks who have taken plenty of psychedelics who would be horrible therapists. I wrote a letter of support for MAPS when they were trying to get approval for their therapist administration study (which is voluntary), stating that, per our Hopkins safety guidelines, a legal and safe experience could one way to experience the altered subjective states that we judged can be helpful for increasing empathy for the participant undergoing an experience. One final thing - just because somebody has had a psychedelic experience, or even 500 experiences, doesn't mean they have had the experience that THAT patient is having. So there is also a risk that a person falsely thinks their personal experience affords more insight than it really does. Humility is critical.

After enjoying an explosion of popularity in the 60s, psychedelic use declined with the emerging “War on Drugs,” and research was completely halted for 20 years starting in 1972. Fast forward to today, and we’re now seeing some form of psychedelic renaissance, with growing interest in their ability to “change minds” for the average person and to potentially help people with a variety of ailments. For those of us who are keen to minimize the risk of entering another psychedelic drought, and who have experience with launching nonprofit startups, what type of nonprofit psychedelic advocacy group do you think could do the most good? 

Many thanks for your important work, and for doing this AMA. 

7
Michael Pollan
I can't overestimate the value of public education as a way to inoculate the public against the inevitable negative stories-- business collapses, sexual abuse in the treatment room, suicides, scandal. The press, having treated psychedelics so positively in the last few years, will eventually turn, as the press always does sooner or later.  But the more solid information and true stories in the information ecosystem, the less of an effect this will have.
5
Dr. Matthew W. Johnson
I second the points Michael made on this. Another point is that I think there is a role for nonprofits to play in monitoring and litigating the patent landscape. I support the appropriate use of IP, and when it works this incentivizes innovation that pushes advances that wouldn't have been made otherwise. But there is a need to make sure the system is not abused, and that patents are not awarded to ideas that truly don't meet the legal standards such as non-intuitiveness and originality. 

What's the current state of research into 'bad trips' and hallucinogen-persisting perception disorder

There seems to be this weird disconnect between people saying "but what about bad trips?" and psychedelic researchers basically shrugging their shoulders and replying "we actually don't see these in clinical trials". Is one explanation that clinical trials screen out certain people, eg those susceptible to schizophrenia, who are most liable to react badly to psychedelics?

In terms of bad trips, this is not an accurate reflection of the science. Many studies have reported bad trips (challenging experiences). We have done so many times at Hopkins. We have even developed a validated scale to assess them. They happen on about 1/3 of sessions at a high dose, which doesn't mean it lasts the whole session but that can happen too (although far more infrequently). However I call them challenging in this context because most folks report valuing these experiences and learning from them in the long run, and because with the safety guidelines in place, the really bad outcomes like harming themselves or others are substantially mitigated. We have done extensive survey work on bad trips in non-clinical use as well.  For example: https://pubmed.ncbi.nlm.nih.gov/27578767/ , https://pubmed.ncbi.nlm.nih.gov/28781400/ , https://pubmed.ncbi.nlm.nih.gov/27856683/ .   HPPD is a different topic. This is complex but the take homes are these. We have never seen this in the thousands of participants in either the modern era or older era (50s-early 70s) of clinical psychedelic research. So this very rare disorder likely has something to do with rare predisposition a... (read more)

Within the field of psychedelics, where do you think additional action is most urgent, and why?

5
Dr. Matthew W. Johnson
We need more research on the parameters of psychedelic therapy as my lab discussed in this paper: https://pubs.acs.org/doi/10.1021/acsptsci.0c00187 .  How are sessions best conducted (music, amount of prep, how much talking during session if any), what is the "afterglow" and if it is a time of increased flexibility how can we use it to maximize learning? Optimal number of sessions?  Optimal doses?  Combinations of compounds both within and across sessions? Combinations with empirically validated behavioral therapies? Which behavioral therapy combo works best for what disorder?  New psychiatric disorders to be explored, whether currently recognized by the DSM or not. And we have hundreds of psychedelic compounds that all need to be explored in clinical research. Do the multiplication regarding the interaction among these domains and there are likely more directions for research than there are stars in the universe. 
4
Michael Pollan
As mentioned earlier, training up facilitators is key. I also think we need more basic science to understand the brain mechanisms involved. Most research is focused on treating new disorders, which is important, but there's not much on HOW psychedelics work-- neuroplasticity,  neurogenesis, anti-inflammatory effects,  potential to re-open critical periods of development, etc. This work will lead to new treatment for new indications eventually. It will also shed light on what consciousness is.  There is a young generation of neuroscientists eager to do this work, but as yet, traditional funding sources are not available to study psychedelics, which is why private philanthropy can have an outsized effect here.

Thanks so much for doing this! I'm a massive fan of all of yours.

Michael, you've written that, as well as being used to treat mental health issues, psychedelics could be used for the 'betterment of well people'.

For anyone: currently, how much good evidence is there that psychedelic use can change healthy people in ways that are generally positive (by making them more open, empathetic, rational, etc.)? I'm never sure what to make of claims in this area.

2
Dr. Matthew W. Johnson
There is a great deal of evidences for positive psychology - improvements in people without disorders. I would say the evidence so far is strong in terms of showing benefit WHEN conducted with the appropriate safety guidelines in place. The openness finding, for example, has been shown by multiple labs. Some of that research on health people is reviewed here: https://pubmed.ncbi.nlm.nih.gov/30521880/ . We need continued research on this

 One of the other comments here says there might be some evidence of microdosing not doing much. One of my friends swears that a 'hero's journey' is orders of magnitude more impactful or effective than simply doing a normal dose. 1. Is there research being done on heavy one time usage? 2. If it turned out the most effective way to use psychedelics was to use a large amount at once, would this be politically feasible?

2
Michael Pollan
To say microdosing is "not doing much" is to underestimate the power of the placebo effect, especially when attached to a substance with as much psychological power as LSD. The doses being used in most of the current trials is quite high-- 25mg of psilocybin or about five grams of dried mushroom. This may nto quite be a heroic dose but it's close. Maybe Matt could weigh in on this.
1
Dr. Matthew W. Johnson
Sure. Most of the modern therapeutic research has in fact used a "heroic dose" of psilocybin, or close to it. Most of our high dose work at Hopkins has used 30 mg/70 kg (154 lbs) bodyweight of the person (e.g., a 200 lbs. person would get 39 mg). According to analysis of cultivated mushrooms, the classic "heroic dose" that Terrence McKenna would speak of (5 dried grams of psilocybe cubensis mushrooms) contains on average about 30 mg psilocybin. So our high dose is a "heroic dose" or even higher in some cases for heavier people. 5 grams is about half way between an eight and a quarter ounce of mushrooms (as a reference since ounces are the units of typical sale in the illicit market in the US).  For a typical recreational dose that one might take at a concert, for example, people might split a eight ounce between two or three people. So a heroic dose is indeed much higher than the dose many folks have used recreationally.  The entire history of the "psychedelic therapy" method of using psychedelics, dating back to the 1950s, rests upon using a very large (heroic) dose. For LSD this would be 300 micrograms or above, sometimes up to 800 micrograms or more.

What are your thoughts on chronic anxiety and DP/DR induced by psychedelics? Do you have an idea of how common this kind of condition is and how best to treat or manage it?

2
Dr. Matthew W. Johnson
We don't know the population rate of how often these happen, but we do know that they happen. We have published multiple survey studies on such enduring negative psychological effects, e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551678/ . This was survey work probing folks who claimed to have had a challenging experience, but among these there was a clear signal for some people to have long lasting disturbances. I've been approached by a many such folks.  I would note that we have not seen this in the modern or older eras of research when good screening and safety practices are in place.
2
Michael Pollan
I don't know what DP/DR is, sorry. Episodes of anxiety are not uncommon, and some people using psychedelics outside of clinical trials  have panic attacks; these are sometimes mis-diagnosed as psychotic breaks, because they can present similarly, but they usually pass.  I can't stress enough the differences between using psychedelics "free range" and in a therapeutic setting, where even "bad trips" can prove so useful and constructive that they're typically referred to not as "bad" but "challenging trips." An experienced facilitator can divert a patient from a frightening episode, often by advising the patient to "surrender" to what's happening in the mind. The dissolution of one's ego can be terrifying unless you've been prepared to let it go, in which case it can be ecstatic. Setting and setting is everything when it comes to psychedelics.
2
SiebeRozendal
I think it stands for "depersonalisation" and "derealisation"

For Michael (or others): Do you think there might be a connection between (responsible) Psychedelic use and altruism? And if so, do you think this is a promising research avenue or future application for psychedelics?

In  How to Change Your Mind,  you reference the sense of 'oneness' and global community that often follows a psychedelic experience. I imagine these same feelings motivate many altruists, so psychedelics' ability to dial them up could potentially lead to some inspiring ethical change; the change that has motivated many players in the... (read more)

4
Dr. Matthew W. Johnson
This is a fascinating question but it is an empirical question meaning we need to test it with data. My guess is that at least among some people psychedelics lead to increased altruism. But there are likely many cases where there is no change, and cases where altruism is decreased. And this likely depends on many factors other than the psychedelic. We did find claims of increased long terms altruism in high dose compared to trivial dose psilocybin under double blind conditions as part of a "spiritual practices" program backdrop ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772431/ ). However we need more work to see if this holds up to more behavioral evidence. I will say the picture on  effects on authoritarianism is inconclusive and so far this is not good evidence for this, as I described in this paper with David Yaden: https://www.scientificamerican.com/article/theres-no-good-evidence-that-psychedelics-can-change-your-politics-or-religion/ . 
3
Michael Pollan
I think we need more research on these questions. There is some preliminary indications that a single psilocybin experience increase measures of "nature connectedness" and decreases tolerance for authoritarianism. But I wonder about the samples-- people positively inclined in these directions already. We need to test the drugs on anti-environmentalists and authoritarians to see if they have a reall effect or just strengthen predispositions.  I would love to see a trial of healthy normals to see if it increases altruistic behavior -- how about a trial of two groups of philanthropists, one gets high dose psilocybin and the other not, and which group increases its giving over the following year? do I have any volunteers?

What do you think of the research chemicals scene (e.g. r/researchchemicals)?

1
Dr. Matthew W. Johnson
Feel free to be more specific as there are many topics within this area. I'm hoping many of these will move to clinical research once the appropriate toxicology is conducted.  Many appear to have fascinating effects with great potential. They are all slightly different biological probes with different receptor profiles, they the scientific potential from triangulating across compounds is enormous. For casual users, I certainly advise caution as many don't show the remarkable physiological profile of psilocybin, LSD, and DMT for health people. For many of these other compounds, you can't just take 5 or 10 times the dose and expect to live. So in that sense they are like most medications and even caffeine or alcohol. People need to realize that psilocybin, LSD, and DMT, and even mescaline, are pretty freakish in their relative physiological safety profile, and people shouldn't extrapolate that this will be true of other compounds. There have also been deaths from folks taking one compound and thinking it is another, and compounds drastically differ in their dose range. 

Hi! Thanks for doing this. I read How To Change Your Mind a few years ago and quite enjoyed it, which lead me to following this space since then. A few questions come to mind right now but I'll post them separately. Feel free to answer what is interesting and ignore what seems less important. 

First off: How do you see the regulatory environment around psychedelics changing in the next decade? IIRC from this podcast with Rick Doblin, it looks like MDMA could be decriminalized in the US in the next years and psilocybin might follow a few years after that. Is this correct? 

2
Michael Pollan
Yes, it looks likely that MDMA will be approved in the next two years, followed by psilocybin within five years. So far the FDA has been true to its word, treating these compounds as if they were any others, throwing up no special hurdles.

How do you balance your efforts between helping others and taking care of yourself? 

I've recently been feeling burnt out in a way that is making me less effective in both areas, and I think this is a somewhat common feeling in the EA community because there really is no limit to the amount of good you could do and how hard you could work for it. 

8
Sophia
It is probably totally inappropriate to respond to questions on an AMA for other people, but I thought I'd mention anyway that I loved a talk (linked below) that Hayden Wilkinson gave, which was very relevant to this.  Hayden pointed out that even if, theoretically, your only goal* was to help others as much as you can over your lifetime, you still need to take into account that you are human and what you do now changes what your future self is likely to want to do.  If you try and do an extreme amount now, with no plan to give yourself a break from this extreme amount when you need one, then your lifetime impact will probably be less than if you set yourself much less demanding targets. If you then find that the less demanding targets are easy to maintain and you think you really could do more, at that point you can rev up. Likewise, when what you are doing feels too much (even if theoretically, you think you should be doing even more), giving yourself permission to properly take care of yourself in the short-term might be the best way to increase your impact over your lifetime.   *For the record, I'd guess that for almost everyone within the EA community, doing as much as they can to help others isn't even their only goal in life, even if it is still a very high priority for them (and for almost all goals that a person might have, self-care for your long-term wellbeing seems really important). I have other goals (like having an enjoyable life) because I am not perfectly selfless,  but I think it is plausible that letting myself have other goals increases the chances that this goal (the goal of helping others as much as I can with a significant proportion of my time and money) will be a pretty high priority for me for the rest of my life. 
2
Harry Taussig
Thank you for sending this Sofia, I'm glad you decided to inappropriately answer my question!
2
Sophia
Yay! I'm glad :)
6
Dr. Matthew W. Johnson
I spend time with my family including my 4 year old and wife, play music, listen to music, read non-work material, garden, lift weights, do cardio, try to get healthy sleep, spend time in sunlight near sunset and sunrise, eat healthy, and try to be honest with people including when there is a problem. That's my formula for staying balanced. Not holding myself out as an example, but you asked.

Hello and thank you for doing this AMA! I am an aspiring PhD student working on "neurorights", which is a branch of human rights research trying to formulate the rights and liberties of the individual over its mind. It mainly look at recent developments in neurotechnologies but therapeutic and recreational uses of psychotropics are defenitely concerned. 
How do you see the legal landscape evolving in the coming years? Be it internationaly, in the UK or in the US ?
On a personal note, I would love to contribute to this body of research, and later partici... (read more)

Thank you for your work and doing AMA! I have two somewhat related questions:

  • Do you think that psychedelics have the potential to improve the lives/wellbeing of people not suffering from any mental illnesses? Very anecdotally and only in the context of non-assisted/recreational use, one person I know claims that taking LSD substantially improved their default mood and wellbeing. Where "substantially" means that the contrast between past and present is obvious, "x2" improvement in their own words. While the reports of most other users I know were much mo

... (read more)

Thanks to all of you for your work in this space, and for doing this AMA. 

Question for anyone. In the spirit of Effective Altruism — where are donations best placed in this space? Is it simply about giving to MAPS, USONA, JHU, Berkeley, Neuroscape, etc. and letting them use as they see fit? 

Or is there a taxonomy or framework of giving opportunities potential donors should consider such as monitoring and litigating potential abuse in the patent landscape; scaling training for facilitators; harm reduction; public education campaigns; funding specific research studies ? Does it depend on how big the donation is?

3
Michael Pollan
Great questions. There are two ways to think about this.  If you have a specific concern or focus, you can find an institution that shares it. Carey Turnbull has formed an inititive to deal with the patent issues, for instance (I don't recall the name of it).  If you're interest in delivering and scaling MDMA therapy for trauma, MAPS is the place to donate. If interested in the treatment of other indications check out Hopkins, NYU, Yale or Mass General-- they're all working on different ones and they al do great work.  If basic neuroscience or public education around psychedelics is important to you, consider the Berkeley Center (with which I'm affiliated).  The second approach to find an institution whose values accord with your own and make an unrestricted gift, allowing the institution to allocate funds as they see fit. This is incredibly valuable to an institution, as it allows them to cover vital but unglamorous things like overhead.

Hi all, thank you for everything you have done in this area. 

Do you think it will be difficult for North American/European cultures (bit vague, sorry) to integrate the experiential aspect of these drugs? The clinical results are amazing and will speak for themselves but the black box that is the mystical-religious type experience with it's unitive consciousness, self transcendence, union with "God", entity interactions etc etc

I fear this aspect of the drugs (IMO the most interesting/profound aspect!) will be hard to integrate with wider culture. Do you have this fear? How have you thought about how this can be integrated and taken seriously and not dismissed as a delusion/hallucination ?

Regards

2
Dr. Matthew W. Johnson
Yes, I think it will definitely be difficult. I think the biggest difficulty will be folks in science, medicine, business, and in the culture in general to "fill in the blank" when it comes to defining the ultimate meaning of these experiences. There will be increasing numbers of gurus and religions built around these mysteries. But from where I sit my focus is to make sure science, clinical psychology, and medicine don't get warped. When we use these as therapeutics or research tools, we much guard against the temptation to interpret the metaphysical meaning for people. This is already happening too much. One can set the occasion to bring someone to the experience, and provide for close and caring personal support to help the person make their own meaning, but we must resist the temptation to provide a metaphysical interpretation for people. I wrote about these themes here: https://pubs.acs.org/doi/10.1021/acsptsci.0c00198
2
Michael Pollan
The kinds of big often spiritual experiences people have on psychedelics could be difficult for our highly instrumental capitalist culture to absorb; such experiences are threatening to many people. This might explain why so much work is being done to develop non-psychedelic psychedelic compounds-- drugs that offer the benefits without the "experience." This strikes me as mis-guided-- the experience may well be the "drug" not the compound, but we'll have to see....

I'm interested in your thoughts on the use of psychedelics for the treatment of Autism. I have an older brother (58), 1st child of my mother, who has worked most of his life as a service clerk at a grocery store.  I have felt if he could break free of the fearful loops of his default mode network, so much more could open up for him.  My mother was diagnosed as having toxemia during her pregnancy with my brother.  I feel my mother's fears may have also been conveyed to my brother during pregnancy.  Do you feel psilocybin or mdma could be useful to treat my brothers Autism, and are you aware of any trials looking for candidates?  Thank you, Patrick

2
Dr. Matthew W. Johnson
There was some limited research decades ago using LSD to treat autistic children. I really can't say if there is much potential here. I certainly don't advise that anyone try it outside of a trial, and I'm not aware of any trials. There was some research published by Danforth and Grob on MDMA in the treatment of social anxiety within people on the autism spectrum, and that looked promising.

Successful legalization of psychedelics simply cannot happen without commercialization - but advocacy for psychedelic-assisted therapy has gone from being driven largely by medical academics, philanthropists,  and various grassroots enthusiasts, to being dominated by entrepreneurs and investors.  Shareholders seem prone to accepting company press releases regarding ethical concerns rather than questioning the approaches being taken by the relevant pharma startups they are stakeholders in. What can supporters of psychedelic therapy effectively do to ensure that healing, safety and accessibility get prioritized over ROI and market control?

1
Dr. Matthew W. Johnson
Copying part of a response I made to another question:  Another point is that I think there is a role for nonprofits to play in monitoring and litigating the patent landscape. I support the appropriate use of IP, and when it works this incentivizes innovation that pushes advances that wouldn't have been made otherwise. But there is a need to make sure the system is not abused, and that patents are not awarded to ideas that truly don't meet the legal standards such as non-intuitiveness and originality.

Do you think harmala alkaloids alone have any potential in this developing field of psychedelic medicines?

1
Dr. Matthew W. Johnson
Not sure. Some say they are only benzodiazepine-like in their effect when taken alone. I'm all for safe and approved research but this wouldn't be on my short list.

What do you see as the best path toward mainstream adoption of psychedelics? Do you think that parts of the “psychedelic culture” (think: ritual, emphasis on hallucinatory experience, etc.) will be adopted into the mainstream, and do you think they should be? What do you all think about the idea of “non-hallucinogenic” psychedelics?

4
Dr. Matthew W. Johnson
I think psychedelics have already influenced culture but that they will continue to do so. A huge overall hope is that this research brings a psychological focus back to psychiatry and mental health in general, and that it brings greater attention to positive psychology and preventative mental health.
1
Dr. Matthew W. Johnson
I think it is reasonable to explore non-psychedelic analogues as early rodent research is promising. It shouldn't be viewed as heresy against psychedelic medicine. It is just a different treatment model. We need more tools than fewer. It would be a different model likely requiring regular (e.g., weekly) administration, rather than taking the substance 1 or a few times and seeing large  benefit a year later or more as we see will full high dose psychedelic therapy. 

Thanks for doing this to you three! Two questions:

  • Do you see any social dangers from psychedelic use and the associated insights becoming more widespread? I am thinking of for example new forms of religious sectarianism through psychedelic induced spiritual insights, less caring about one's own and other people's suffering through a complete transcendence of the self and the identification with conscious states, etc.
  • Do you see any potential medical use of DMT?
1
Dr. Matthew W. Johnson
Yes, I see a potential danger, and I've described it in at least of couple of previous posts here. But I think with the right framing we can minimize such harms and maximize benefits. And yes, I absolutely see therapeutic potential in DMT.  DMT will surely be developed into an approved medicine in my opinion, although we need to follow the data of course.

Hi Tim, Michael, and Matthew. Thank you for doing this.

My question: Has there been any research that looks at how a person's pre-existing belief structures might affect a psychedelic experience? I've heard some anecdotal evidence that an extremely rigid set of beliefs (religious fundamentalism, in particular) can be a substrate for a very bad trip, because of a refusal to accept a frightening encounter during the experience as anything but the presence of real evil. Of course a "bad trip" can be extremely useful regardless, and these experiences ("good" or... (read more)

1
Dr. Matthew W. Johnson
Yes there is some research on this. We found in survey research the personality trait of neuroticism is associated with more difficult psychedelic experiences: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540159/ The Vollenweider lab has found that the personality trait of absorption in lab research was associated with greater pleasant and mystical experiences, and emotional excitability was associated with unpleasant and anxious reactions.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281871/
1
Michael Pollan
Not that I know of, but it's a rich and fascinating research questions. This is exactly the sort of work that needs philanthropic support. Who else is going to support it?!

What’s the best way to get in touch with a trustworthy guide? Is there a community of reliable people who we can begin to explore with?

1
Dr. Matthew W. Johnson
I'm half joking, but the answer is by joining a study at Hopkins or another university.  Otherwise, I don't give advice regarding the underground.

I have a 57-year-old sister with treatment-resistant depression (since age 12). Esketamine provides limites relief. What is the best way to get her into a trial or program to try psilocybin? Or, the more generalized question, how does one go about finding practitioners of psychedelic-assisted treatment?

1
Dr. Matthew W. Johnson
You can go here and look up psilocybin for any study you are interested in: https://clinicaltrials.gov
1
Michael Pollan
Compass PAthways and Usona are running large trials of psilocybin for depression-- check their websites for how to participate. For underground guides, you might start by consulting the list of "integration therapists" MAPS keeps on its website. 

Long comment; TLDR at the bottom.

 

Thank you all for doing this AMA. You three have done incredible things for the world of psychedelics. Michael—I loved How to Change Your Mind  and I'm looking forward to getting my hands on This is Your Mind on Plants when it comes out. Tim—I love your podcast and have been listening to it almost daily for the past two months. Dr. Johnson—your podcast with Lex Fridman was incredible.  

 

The question:

 

What are your thoughts on someone with Bipolar 1 taking psychedelics for non-therapeutic purposes? ... (read more)

2
Dr. Matthew W. Johnson
I'll start out saying I never encourage anyone to use psychedelics, and I don't give individual medical advice.  As you know and as Michael stated, modern studies exclude such folks. That said, there are those with anecdotal reports of psychedelics helping with bipolar disorder ( e.g., https://icpr2020.net/poster-presenters/benjamin-mudge/ ). Also, all else being equal, having another competent and sober person present is going to be less risky, relatively speaking, than being by oneself.  And all else being equal, lower doses will be less risky than higher doses. I'll end by saying there is definitely some risk that a psychedelic experience can exacerbate mania, and some of the anecdotal reports  of prolonged adverse reactions look like mania rather than psychotic episodes.
2
Michael Pollan
I'm not qualified to offer advice. In general people with bi-polar are excluded from the current trials.

Most folks who receive psychadelic-assisted therapy do so now because of a known and often severe issue — like depression, PTSD, or a form of addiction. Can either of you speak to an experience (personal or otherwise) of first realising or appreciating some issue through the use of psychadelics, in a way which helped resolve that issue?

More generally, how do you think about using psychadelics for treating the 'well'?

3
Michael Pollan
Psychedelics can have great value for people who are not clinically mentally ill and I look forward to a time when they will be available to such people in the same way  we make psychotherapy available to people who don't have a DSM diagnosis of mental illness. People seek therapy who are sad or anxious, who have relationship problems, career questions, etc etc. We're all on a spectrum at the far end of which is clinical depression or anxiety or obsession or addiction, so we stand to benefit from medicines that alleviate these symptoms. Watch the experiment on Oregon, which has legalized psilocybin therapy for any adult who wants it, beginning in two years or so. 
2
Dr. Matthew W. Johnson
We have conducted extensive research on healthy people (without disorders) at Johns Hopkins. Yes, sometimes these are extremely therapeutic for issues that didn't have anything to do with why they volunteers. Several instances of past trauma being relieved and processed, for example.

If you reran U.S. history from (say) 1960 to the present day, how likely does it feel to you that drug laws shake out in the way they did? Is there something about the way psychadelics ended up getting regulated that feels inevitable, or could the story easily have turned out differently? What could that tell us about hopes for influencing sensible regulation that lasts for > a decade?

2
Dr. Matthew W. Johnson
I love this hypothetical question on the probability of the factual and counterfactual if history was resampled. I'd say it would be 70% likely that things would end up pretty much as they are now. But that leaves 30% for something different.  
2
Michael Pollan
I think the history could have turned out differently. President Nixon got fixed on LSD as a critical element of the anti-war movement --why young boys were refusing to fight a war, which seldom happens. However it seems to me the researchers should have fought harder to maintain their ability to conduct research. It was never prohibited but scientists felt the government animosity and funding dried up. I can imagine a scenario where LSD was made illegal but the research continued and psychedelics were put on schedule 2 o3 3 rather than 1. This is purely hypothetical, of course.

What is especially neglected but promising within psychedelic science? 

2
Dr. Matthew W. Johnson
Copying and pasting a response I made before since it is the same: We need more research on the parameters of psychedelic therapy as my lab discussed in this paper: https://pubs.acs.org/doi/10.1021/acsptsci.0c00187 .  How are sessions best conducted (music, amount of prep, how much talking during session if any), what is the "afterglow" and if it is a time of increased flexibility how can we use it to maximize learning? Optimal number of sessions?  Optimal doses?  Combinations of compounds both within and across sessions? Combinations with empirically validated behavioral therapies? Which behavioral therapy combo works best for what disorder?  New psychiatric disorders to be explored, whether currently recognized by the DSM or not. And we have hundreds of psychedelic compounds that all need to be explored in clinical research. Do the multiplication regarding the interaction among these domains and there are likely more directions for research than there are stars in the universe. 

 Dr. Johnson

Question: For an 18yr old with treatment resistant depression, how do you stack psilocybin assisted treatment (or others you are actively researching) against current standards of treatment with respect to risks/side effects?  If this were your child, would you consider this and where would you point a parent for more resources?

Additional context: My son who turns 18 this month has been struggling with treatment resistant depression (3 different ssri’s, snri’s) and some social anxiety triggered and  exacerbated by covid realities... (read more)

What new psychedelic drugs are being invented, or are in planning stages? What would be the characteristics of the "perfect" psychedelic drug (regarding duration, intensity, etc). How might new, as-yet unheard of substances change the potential for psychedelic therapy? 

1
Dr. Matthew W. Johnson
We need to test all the variations. Shorter or longer lasting compounds could be better, and for different purposes. And work may move into the direction of tailoring duration, like the older work that Gouzoulis-Mayfrank did with continuously infused intravenous DMT, in which the duration and intensity can be adjusted. There may be compounds that have less chance of a particularly difficult experience. It is another question whether this would improve treatment. It would certainly  make it more attractive to a broader array of patients. Shulgin was particularly interested in 4-OH-DIPT as a therapeutic, as a somewhat shorter acting psilocybin-like compound. Lots to explore!

Thanks for doing this, guys, and for all the great work you’re doing in this field. As someone who is in serious need of these therapies, I’d like to submit that there is a huge piece of the puzzle that seems to have been ignored to this point. When it comes to treating TRD with psilocybin, has there been research done on the most effective method for transitioning patients off of their existing antidepressants and the implications of doing so? I, like many others, have tried and failed numerous times to get off of SSRI’s/SNRI’s. It’s a serious problem (se... (read more)

2
Dr. Matthew W. Johnson
There is no research on this with regard to psilocybin. Our approach has been to tapper, as this is the general consensus for getting off these drugs in general, regardless of psychedelics. 

Is the renewed interest in psychedelic research & psychedelic-assisted therapy happening only in Western countries? Are other countries more worried about these substances for some reason(s)?

2
Dr. Matthew W. Johnson
The only research that I'm aware of is going on in North American, Europe, and South America.  I'm assuming stigma is the reason it is not more broadly studied.

What would you say to journalists who may (or may not) be:

  1. willing to do accurate reporting on these topics
  2. too time-pressured (or otherwise unable) to read the original research
  3. strongly incentivized to sensationalize these topics? 
2
Michael Pollan
I teach journalism, and specifically teach science journalists how to read a scientific paper, which many of them are not equipped to do. I stress the importance of fact-checking and why journalists should not be afraid of ambiguous information, ie, no need to be all positive or all negative. It comes down to personal integrity and journalistic ethics, and is no different in psychedelic coverage than coverage of any other issue.

Which treatment type do you expect to see approved first? Do you think it will open doors for additional treatment types?

2
Dr. Matthew W. Johnson
MDMA for PTSD. Then psilocybin for depression. Then psilocybin for tobacco and alcohol use disorder (they are on a similar timeline). 
2
Michael Pollan
MDMA is farthest along and will probably be approved first, followed by psilocybin,. LSD< DMT, etc are many years away.

What's your stance on veganism since emission/deforestation caused by animal agriculuture/fishing are among the most destructive  anthropological forces going on right now? 

Hey all, thank you so much for your time. I think the implications of psychedelic research could revolutionize mental health care.

My question for you involves the use of psychedelic therapy for prisoners and those who find themselves on the wrong side of the law. Our current system of punishment and incarceration does very little to help actually rehabilitate those who commit crimes, which creates a vicious cycle of recidivism. I am wondering if the three of you share similar hopes as me for the creation of a more compassionate form of law enforcement whic... (read more)

Tim - I'd love to know which aspects of set and setting you're most interested in seeing researched via the forthcoming work at Adam Gazzaley's lab? 

What changes would need to happen to interest for-profit entities to invest in this field?

If you could get a influential US senator to introduce a bill targeted at changing the legal landscape within which psychedelics use happens, how would such a bill look like?