AMA: Tim Ferriss, Michael Pollan, and Dr. Matthew W. Johnson on psychedelics research and philanthropy

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 variables are well understood: inputs, outputs, various costs, longitudinal cross-comparisons, etc.. It’s like investing in a low-cost index fund with great historical data. There’s a great place for it in your non-profit portfolio, just as you might think of your portfolio of stocks or assets. Personally, I’m donating to and through GiveWell this year, and according to the dashboard GiveWell provided me, my listeners have donated $266,526 in immediate donations, with $104,440 in additional one-year value of recurring donations. Much of that came after my interview with Will, and I’m a believer.

That said, these types of late-stage/predictable options are not 100% of my portfolio. I view my donations in psychedelics—to be more specific, psychedelic-related scientific research—as “early-stage” investments, defined as such because much of the work is on the cutting edge, and the outcomes or mass implementation of findings are seldom clear at the outset. 

Sometimes, the intended clinical applications are tested from the beginning (e.g., psilocybin for major depressive disorder at Johns Hopkins), but other times, the research is exploratory and hoping to establish fundamentals (e.g., safety and fMRI studies of salvinorin A, a lesser-known psychedelic which acts on kappa opioid receptors). Will salvinorin A have therapeutic applications? It’s too early for scientists to say, but there are clear preliminaries (the first blinded study to show its psychoactive effects is outstanding) that help get us closer to answering that question. In the realm of scientific and medical research, many of the breakthroughs that have changed our world A) weren’t obviously breakthroughs in the beginning, and B) couldn’t have been intelligibly subjected to questions of cost-effectiveness until a much later stage of development. Since these bets tend to be less crowded, and I’m very comfortable with early-stage startup investing from the for-profit world (some examples of wins and losses here), I find my skill set and temperament well-suited to this playing field. I really enjoy it.

Furthermore, I believe the potential ROI of the early-stage investments to be much greater than the later-stage investments, but you can waste a lot of money unless you approach them with good rules and follow said rules consistently. A big component of this is thinking of all of your bets—and their interactions or synergies—as a portfolio, rather than as one-off silos. I’ll attempt to explain this more in another bullet. 

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

TIM: When such research can be meaningfully done with larger data sets, it would be incredibly valuable. MAPS has already done some cost-effectiveness analysis of MDMA-assisted psychotherapy versus the current standards of care, but these side-by-side comparisons will be most interesting ~2–⁠4 years from now when we have actual data for both instead of actual vs. hypothetical. As mentioned above, this doesn’t affect my enthusiasm for donating to early-stage projects, as I think the opportunities to make a disproportionate impact with small amounts of capital are generally correlated with more unknowns. This requires making more assumptions, of course, and therein lies the tradeoff.

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.

TIM: Of course, I’d certainly love to see the Happier Lives Institute jump in! Even though psychedelics entail many unknowns, there are some very significant knowns. Several of these knowns seem to point to entirely new paradigms for understanding and treating mental illnesses. Importantly, results have been replicated in a number of cases. 

One example: the Phase 2 and very recent Phase 3 trials of MDMA-assisted psychotherapy for PTSD. In MAPS’ completed Phase 2 trials with 107 participants, 56% no longer qualified for PTSD after treatment with MDMA-assisted psychotherapy, measured two months following treatment. At the 12-month follow-up, 68% no longer had PTSD. Most subjects received just 2–3 sessions of MDMA-assisted psychotherapy. All participants had chronic, treatment-resistant PTSD and had suffered from PTSD for an average of 17.8 years. On August 16, 2017, the FDA granted Breakthrough Therapy Designation to MDMA for the treatment of PTSD.

2–3 sessions and 68% are asymptomatic 12 months later… after an average of 17.8 years of suffering. This appears to be addressing the root causes of PTSD and not simply masking symptoms, as many maintenance drugs do. It’s actual processing instead of numbing.

The Phase 3 trials did just as well, and here are a few excerpts from recent NYT coverage:

“Two months after treatment, 67 percent of participants in the MDMA group no longer qualified for a diagnosis of PTSD, compared with 32 percent in the placebo group. [All had severe PTSD and had been diagnosed, on average, for more than 14 years.]

MDMA produced no serious adverse side effects. Some participants temporarily experienced mild symptoms like nausea and loss of appetite.

…

“An estimated 7 percent of the U.S. population will experience PTSD at some point in their life, and as many as 13 percent of combat veterans have the condition. In 2018, the U.S. Department of Veterans Affairs spent $17 billion on disability payments for over one million veterans with PTSD.
...

‘This is about as excited as I can get about a clinical trial,’ said Gul Dolen, a neuroscientist at Johns Hopkins University School of Medicine, who was not involved in the research. ‘There is nothing like this in clinical trial results for a neuropsychiatric disease.’”
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To that extent, I think the “how promising” is quite clear, at least on an individual (e.g., “I felt like I went through 15 years of psychological therapy in one night.”) and Phase 3 basis. The question of how to scale to millions isn’t fully solved, of course, but that’s to be expected, and many smart teams are working on related problems. The fact that later-stage questions can’t all be answered now doesn’t deter me from investing in interventions that defy the odds and that could redefine psychiatry. For me, this is just like investing in for-profit startups. In the beginning, you need a good car (intervention/tool), a good driver (team), and a good map (plan), but the actual course will evolve based on changing conditions (technological, regulatory, etc.). Even if you’re driving with headlights that only shine 100 feet in front of you, you can make it across the entire USA safely if you set the initial conditions well and adapt. This is the nature of picking very attractive bets without complete information. Not everyone will be comfortable with this approach, but it’s a learnable skill.

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 psychedelic research  (specifically, Usona's research into psilocybin as a treatment for depression) to funding psychotherapy for mental health (specifically, StrongMinds, which treats women for depression in Africa). This is probably the most straightforward comparison, as it's in terms of depression in both cases, and finds them about equally effective. However, the Founders Pledge analysis of psychedelics is arguably too sceptical of psychedelics because, for instance, it only considers the impact research would have in the US, rather than world.

TIM: Certainly, the more unknowns, the more assumptions one needs to make. I read the two above-linked articles but didn’t see the comparison, so I’ll speak more to your comments. I’ll try and tie two things together. One -- How do I think about funding targets like psychedelic science, when the long-term, large-scale impacts are far from certain (versus, say, the immediate impact of cash transfers to one person at a time)? And Two -- How might I think about the following that you wrote? “However, the Founders Pledge analysis of psychedelics is arguably too sceptical of psychedelics because, for instance, it only considers the impact research would have in the US, rather than world.”

Let’s first compare a few games. Putting capital into the late-stage or predictable bets with more complete information (i.e., the GiveWell example earlier) is like betting on chess. It’s a game of complete information. This might also apply to the cash transfers you mentioned. Betting on early-stage science or startups is much more like betting on blackjack or poker. These are games of incomplete information, but unlike, say, roulette, they are not games of pure chance. There are elements of skill, methods of playing, and methods of staking players that—over sufficient periods of time—have greater success rates than others. 

Next, I’m looking for asymmetrical upside potential. If I can put $100 into one startup or project with an 80% probability of $150 of impact (and, say, 20% chance of $80 of impact), that’s great, but if I can put four $25 bets into four startups or projects, each with a 20% chance of $5,000 of impact (and, say, 80% chance of $10 impact), I am more inclined to take the latter option. The mindsets and assumptions are different: the former might optimize for loss avoidance and semi-guaranteed individual returns, whereas the latter would optimize for finding bets that really swing for the fences, such that one win could “return the fund” or make other losses irrelevant. The key is doing this in a methodical rather than haphazard way.

So, how do we find $25 bets that have the potential to return $5,000? Or how have I done this in the past?

I tend to focus on selection of people over selection of projects, as I assume projects will have some incorrect assumptions and tons of problems. My bet is on someone or some team that can adapt and solve for this. One example in startups would be Luis Von Ahn, co-founder of Duolingo, who previously had two successful exits to Google. The nascent idea that his team could apply his learnings from reCAPTCHA to language learning represented a total paradigm shift, so I invested in their Series A in 2011, but it was a bet on Luis. It would either fail and my downside would be capped to a small investment, or it would win big and the likely return 100-1,000x over 5-10 years. Even though he and his team have run into obstacles and dramatically changed some of their plans and strategies, Duolingo has now become the most used language-learning software in the world (revenue has done well, too). 

But that bet might seem obvious; after all, the guy had sold two companies to Google. What if you're dealing with people who are unfamiliar?

To explore that, let’s look into the world of science, which is also more attractive in some respects. Even though science can seem to move in slo-mo, single studies often provide feedback much more quickly than startups (funding to exit). I assess scientific teams by publication record, reference checks, and by giving them a small amount of capital to see what they can do with clear deliverables and deadlines. I did this when I first gave neuroscientist Dr. Adam Gazzaley a small amount of funding for Gazzaley Lab at UCSF, where they were attempting a number of firsts. The ultimate product was the scientific equivalent of sweeping the Oscars. His study using custom video games to help reverse age-related cognitive decline ended up the cover story of Nature with the headline of “GAME CHANGER.” I got to know Adam over more than a decade, and we were in constant contact for a year leading up to his recent launch of the Psychedelics Division of Neuroscape, which I supported and which could reinvent how we think of customized “set and setting” for psychedelic treatments.

Of course, the bets and projects need to be almost absurdly ambitious for this early-stage approach (or, better put, part of the portfolio) to work over time. But ambitious projects alone are fantasy; they need excellent operators with a proven ability to execute under time pressure. Once again, my preference is to test teams with small amounts of seed capital and short deadlines. Even though I’m perhaps best known in psychedelics for helping raise the $17MM for the Johns Hopkins Center for Psychedelic and Consciousness Research, the first such dedicated research center in the US, I tested the Hopkins team years before with a much smaller amount of personal and crowdfunded capital (~$100-125K total), which I offered after meeting Dr. Roland Griffiths. Only after that was I comfortable committing $2MM+ of my own foundation’s capital. From the NYT coverage:

“Mr. Ferriss said he met Dr. Griffiths in 2015, became intrigued with the research, and began thinking about the Johns Hopkins group as he might an investment bet. He launched a crowdfunding campaign for a small depression study, to see how efficiently the Johns Hopkins team used the money. ‘Essentially it was a seed investment,’ Mr. Ferriss said. ‘I ran a beta test, and they really delivered.’”

That initial bet proved to me that the team was capital efficient and could overdeliver on a timeline. The crowdfunding also tested reputational risk and showed me that the negative blowback and PR was… zero. Eventually, when the study was published (“Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder”), it had a measurable impact on national and international media and discourse. Here’s the note I received from Roland:

"I am pleased to report that JAMA Psychiatry, often considered to be the most prestigious psychiatry journal in the United States, just released the notice below showing that our psilocybin depression study ranked #1 on their quantitative assessment of attention each scholarly article received in traditional and social media (Altmetric methodology). The relative score of 2416 is substantially greater than the other high-impact articles. This is even more impressive given that our study was published in November while other articles were published earlier in the year so had a longer time to get attention.”

Parallel with all the above, I look for ways to win over time, even if a given bet fails. This might be the most important part of this long answer.

For instance, what can I learn, or who can I get to know, even if this project doesn’t pan out as we hope? If there isn’t a way for me to win, even if I “lose,” I rarely commit. In other words, there need to be benefits that reliably transcend the project. Taking this approach has consistently resulted in outsized successes, even when preceded by a string of supposed failures. The ancillary benefits accrue like a snowball over time.

Some in the EA community might view this as squishy, as it doesn’t involve much quantification, but the thought process and results are concrete for me. I view this approach as my biggest hedge against individual project risk.

For instance, long ago circa 2008-2009, I became the first advisor to TaskRabbit, back when it was RunMyErrand and only based in Boston. They were one of the first movers in what would become known as the gig economy, and I wanted to immerse myself and learn through doing. Perhaps a year before and quite separately, I had become an advisor to StumbleUpon. StumbleUpon didn’t ultimately produce a profitable exit for me, but 1) it provided me with many opportunities to partner and drive significant traffic to my blog, which had great value to me, and 2) it offered the opportunity to work closely with the founder, Garrett Camp. When Garrett co-founded Uber shortly thereafter, he invited me to become an advisor, and I was perfectly positioned to learn from my exposure to TaskRabbit. Uber ended up being the bet that returned the fund. 

I’ve funded studies and projects that haven’t yet made headlines, but relationships from those teams have led me —as expected after doing diligence beforehand—to academics, lawyers, and policy makers who seem capable of helping shape intelligent regulation of psychedelics. So, are these bets failures until they each hit the finish line or implode trying? I would argue that these are already “successes” if I view them in the context of a portfolio of bets/donations that are assembled to work together towards macro objectives. Some of my macro objectives for the last several years have been: helping to derisk and galvanize the formation of multiple psychedelic research centers at top US universities (completed); putting safeguards in place to minimize bad behavior by for-profit actors (e.g., patent trolling); helping set conditions for federal funding and large agency grants for psychedelic research; and enrolling experts to help facilitate insurance reimbursement for eventual treatments. More often than not, at least 2-3 of my early-stage bets will be chosen thematically to coalesce around one of my macro objectives. 

So, can I perfectly predict what will happen in or to society due to a systemic intervention? Not a chance! But can I think probabilistically and place bets that get me base hits most of the time, which when combined seem to contribute to my macro objectives? Yes. Moreover, I do think you can reliably predict some version of the future if you look for converging trends (tech developments, emerging scientific areas, media coverage, etc.) and place bets in groups where you can actually introduce those trends to one another. Alan Kay famously said that "the best way to predict the future is to invent it," but sometimes you don’t need to invent; you just need to push the ball in the direction it’s already moving.

Fortunately for me, looking across my 100+ early-stage for-profit and non-profit investments, simple heuristics often beat overly complex algorithms. There's definitely a place for really technical analysis, but it's easy to get lost in the weeds and mistake noise for signal.

Now, let’s shift gears and revisit one of the lines from your question that is very helpful to unpack. You wrote: “However, the Founders Pledge analysis of psychedelics is arguably too sceptical of psychedelics because, for instance, it only considers the impact research would have in the US, rather than world.”

There are multiple ways in which the impact of psychedelics -- and the value of supporting related causes -- is dramatically underestimated, in my opinion. 

First, to your valid geographic point, here is one example: if you support Phase 3 trials for MDMA in the US, you are also ultimately helping with MDMA-assisted psychotherapy in Europe, as the EMA will accept a lot of data that has been accepted by the equivalent (FDA) in the US. In other words, by helping in the US, you are substantially decreasing the costs of later expansion in Europe and beyond, as the safety studies, etc. don’t need to be replicated. FDA and EMA approvals will generate approvals in most other countries of the world without additional research. This is significant.

Second, if you care about intelligent drug policy and criminal justice reform, I believe you should care about and support psychedelic science or access. Psychedelics offer a tremendous opportunity as the tip of the spear. Generally speaking, these are drugs with exceptionally low toxicity (with a few exceptions) and little to no addiction potential. Both MDMA and psilocybin currently have bipartisan political support because of sympathetic patient populations (e.g., veterans with PTSD, terminal cancer patients with depression) and widespread indications that affect people across all socio-economic classes (e.g., opioid addiction, alcoholism). Psychedelics can be used as the wedge in the door to advance many other issues. Politically speaking, they are excellent gateway drugs. If you want to talk to both Democrats and Republicans about drug and criminal justice reform, it’s a lot easier to start with psychedelics and have a Medal of Honor recipient on your side. This opens the door to many other conversations that would otherwise struggle to get off the starting line.

Third, it’s not just about the drugs and therapeutics. As famed psychiatrist Stan Grof has said, “Psychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is for biology and medicine or the telescope is for astronomy.” Recent studies, and the associated outcomes that defy conventional explanations, are already raising questions that could reshape how we think about mind, identity/ego, and even consciousness itself. This is a big deal. It’s not an accident that the center at Hopkins is named the Johns Hopkins Center for Psychedelic and Consciousness Research.

A particular issue is that psychedelics now seems to be getting increasingly more attention, so one might wonder if all the best projects will get funded anyway, and donors seeking the biggest impact should go elsewhere. 

TIM: I can tell you with 100% certainty that the best scientific and non-profit projects I see are still having trouble getting fully funded. There is a hype-cycle gold rush on the for-profit startup side, but the best research is still uncrowded and incredibly appealing. I think this is largely because of the due diligence required. Suffice to say, I have looked at a lot of causes and consider this area to have some of the best bang-for-the-buck value I've ever seen in my life.

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 these treatments. I think in terms of safety exclusions, it will be the large majority of adults, although more work needs to be done to understand the proportion in more detail. In terms of interest, I think it will never be everybody, but I think the number is already large enough to help a lot of people if approved by the medical agencies, but that the interest will also grow greatly if initial success is seen in the larger population once approved. For more info, I discuss some of these challenges here: https://pubs.acs.org/doi/10.1021/acsptsci.0c00198 

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.

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. 

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 benefits that don't have humans as the sole or primary beneficiary. This is why I always refer to my non-profit work as "non-profit work" and never as philanthropy. I dislike humankind a good portion of every week. We've made a fantastic mess of things.

*Do some in EA inadvertently select non-profits that are the least likely to survive? This could be a total misread, but I have come across a few passages like the below from FoundersPledge, and bolding is mine. I should note that I agree with much of their other writing: 

Our research conclusions do not imply that one nonprofit does more important work than another, or that a particular cause is more worthy of support than another. They instead reflect our overall view of which funding opportunities at nonprofits could currently use extra funds most effectively.

This is because we aim to recommend to our members funding opportunities with a maximum counterfactual impact. That is, our goal is to recommend opportunities where extra funding by our members would make the largest difference compared to if they provided no extra funding. Paradoxically, this implies that if a nonprofit does high-impact work but is in addition very successful at raising funds for that work, we should not recommend any funding opportunities at that nonprofit.

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In the for-profit startup world, if you invest in the seed round of a company and the startup can't raise a subsequent Series A, they are toast and the value of your investment goes to zero. No one passes Go.

In my experience, cash flow and donations are also the lifeblood of 99.9% of non-profits. I've seen multiple non-profit projects fail because they were ineffective at raising funds. It's fundamental.

In some cases, it's not a total red flag. Example: difficulty in raising funds is due to systemic or technical issues  (e.g., a scientist is asked by the administration to raise his/her own funds for a complex scientific study within a small university department). If, on the other hand, a non-profit has someone in "development" (fundraising) and they still can't raise funds, they are simply bad at raising money. 

For me, an inability to raise funds effectively would be a disqualifier, not a qualifier. It doesn't matter how good someone's project is, if it requires two years to reach fruition and they run out of cash six months after taking your donation, it's a failure IMHO. Furthermore, it's been my experience that the non-profits that are worst at fundraising are never the most effective at using funds.

*Is it possible that some in EA over-fetishize measurement? I am all for quantification, but I think there are some risks of worshipping the gods of many decimal points, or immediately scoffing at variables that are harder to peg numbers onto. A few thoughts:

• Probabilistic thinking and making predictions/bets with incomplete information is an incredible power worth developing. Think poker or blackjack versus chess. I'm not sure this gets enough attention within the EA community, and 2020 plus COVID certainly showed us that the majority of humans fail in this department. I haven't read it, but I've heard good things about Annie Duke's book, Thinking in Bets: Making Smarter Decisions When You Don't Have All the Facts.
• It's easy to fake important with precision. For example, let's say someone hands out 100 surveys to strangers to assess anxiety levels before and after eating free frozen yogurt. There are a few possible design problems already, but their abstract later includes something like "Administration of the frygrt270 intervention [frozen yogurt] decreased mean self-reported anxiety by 23.742% with a standard deviation of..." Never mind that people weren't given guidance on how to rate themselves, they got more free yogurt if they showed "good results," etc. It's easy to dress up sloppiness with numbers, even if the math checks out. Well quantified does not mean well reasoned or well done.

What's the ideal ratio of analysis to action? When should people be held accountable to some form of action? There are always more spectators than people on the field, and that's OK. But I think it's worth being aware of incentives that might keep people off of the field. In the EA community, people appear to be rewarded for well-worded debate and argument. There is social reinforcement when one engages well with the community. Could it be that overly engaging makes one less likely to be an effective altruist in the real world? For example, is the guy constantly racking up karma online within EA really being more "effective" than the woman who just helps one old lady across the street per day? Put another way, is mildly -- or massively -- ineffective altruism in practice better than effective altruism in theory? The word play and semantic jousting is fun, but it's the real-world results that matter at the end of the day. I think it's worth asking (and perhaps it's been asked and figured out already!) how the community can hold members accountable in some fashion, to ensure that those talking about effective altruism are actually putting skin the game in the wider world. That would really do a lot of good.

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.

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. 

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.

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/ ).

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 there is some direct non-placebo effect, and I am more compelled by the anecdotes on mood and depression treatment. After all, we have known for 70+ years that chronically augmenting serotonin transmission in various ways can be effective to treat depression (although there is certainly lots of room for improvement), so an effect of chronic 5-HT2a agonism on depression wouldn't be that surprising. It could be that some of the other reported effects (e.g., cognitive enhancement, creativity) are indirectly mediated by this improvement in mood.

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.

+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.

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.

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).

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.

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.  

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. 

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. 

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.

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. 

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.

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.

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.

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. 

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.

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.

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. 

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 and polysubstance use frequent among illicit use. My best guess is that HPPD is not unique to psychedelics at all, but that is a rare neurological condition that is also precipitated by other drugs (like alcohol, benzos, tobacco, etc.) or even no drug at all, but that psychedelics have gotten the historical attribution due to their sensational nature. See: https://pubmed.ncbi.nlm.nih.gov/27822679/ .  I'll also note that in illicit use (although  not in clinical research) it is not infrequent for folks to report visual effects one or a few days after a psychedelic, but these go away and are typically not distressing, and these are not the same as HPPD, which is a chronic and very distressing disorder. Other things sometimes referred to as "flashbacks" is likely an instance of state dependent learning, where meditation, cannabis, a warm relaxing bath, etc., and start to elicit a strong reminder of the earlier psychedelics effects. Again, this is not the same as HPPD. 

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. 

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.

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

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/ . 

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?

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.

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.

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.

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. 

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.

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. 

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.

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.

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

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....

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.

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.

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.

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.

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. 

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.

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/

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?!

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.

You can go here and look up psilocybin for any study you are interested in:

https://clinicaltrials.gov

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. 

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.

I'm not qualified to offer advice. In general people with bi-polar are excluded from the current trials.

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. 

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.

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.  

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.

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. 

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!

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. 

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.

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.

MDMA for PTSD. Then psilocybin for depression. Then psilocybin for tobacco and alcohol use disorder (they are on a similar timeline). 

MDMA is farthest along and will probably be approved first, followed by psilocybin,. LSD< DMT, etc are many years away.

Redemption: How Psilocybin, LSD, and MDMA Became Approved Medicines Across the Globe.

To serve an organizational role that you describe, you would not necessarily need to be trained in science, psychology, or medicine, but you would need to work very closely with such folks.

I have no concerns about this at all - it is independent from the other concerns you mentioned. There is good evidence that nature exposure is psychology healthy, which is not surprising at all. I am work on something that involves this now so stay tuned.

Our largest published psilocybin study was on just such themes. The study didn't have the ability to tease out each individual factor, and we took more of a kitchen sink approach, but we did find generally the psilocybin and these practices had additive effects for prosocial behavior: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772431/

I can answer part of this. For scientific research, the need for money in the field is the largest constraint. Plenty of talent is out there, and they will jump in when the job opportunities are right. Colleagues are still leaving psychedelic science for lack of funding. It's a huge issue.

There are movements in many places to decriminalize plant medicines and to legalize drugs. Check out Decriminalize Nature and also Drug Policy Action-- both highly respectable campaigns. Philanthropic monies are flowing into policy work-- Dr Bronner's, for example, contributed quite a bit to the recent Oregon ballot initiative. 

Yes, I believe there are several groups working on preparing trials. We at Johns Hopkins are one of them. I think it is worth investigation for sure.

All the existing evidence is for higher doses. But who know?

I do think we will find a way to fold these powerful substances into our society. Do I think they could help change consciousness at scale? In my hopeful moments, yes-- they do seem to nudge people in the direction of altruism, ego-lessness, connection to nature, and to valuing nature, interconnectedness and love. Is this inevitable? Probably not-- some people emerge from their experiences of ego death with a worrying ego inflation.  There is also the question of how do you administer a drug to a whole society? You can't put psychedelics in the water like flouride. We have no other precedents, so we're really in uncharted territory here. But good research could help us decide if our hopes and aspirations for psychedelics are grounded in reality or dreams.

#1 if you mean regulated, non-research use, for healthy people without disorders, I'm not sure but I think a decent chance within your lifetime. Treatment for suffering (mental disorders) is the priority in my opinion. But society may move quickly. 

#2 No. I certainly don't think psychedelics are necessary for humans to survive and flourish. Hopefully they can help. But if psychedelics never existed, I still think there would be hope for us. 

We are running a trial now for psilocybin and early stage Alzheimer's disease.  https://hopkinspsychedelic.org/alzheimers

The distinctions between legal and illegal drugs are largely arbitrary. Alcohol  and tobacco do much more damage to society and individual than most illicit drugs.  A genuine risk/benefit analysis would lead to a complete overhaul of the federal schedule of illegal drugs, which cannot be justified on public health or scientific grounds. Politics and history have played a  much bigger role than science.

I think LSD might have even greater potential for therapeutics, but this is untested. I will be doing upcoming research with LSD in treating chronic pain with an eye for reducing or stopping opioid use. Some people say LSD is more likely to bring attention to one's personal issues. It is also a longer experience which might help as there is a variability to experiences and not all of the experience is going to be meaningful. Sometimes the meaningful part of a psilocybin experience only starts 4 or 5 hours in, leaving little time. That would be less of an issue with LSD. 

For the blinding question, I think we need to examine a broader range of active comparators. Oral THC would be a more credible comparator in terms of fooling folks that they got psilocybin. Amphetamine is a good comparator for MDMA. We also need to do a better job reporting on how well the blind works or not.

This is important work that remains to be done. The Oregon initiative represents one good-faith effort to design a regime under which people (in Oregon) will have regulated access to psilocybin therapy. There are surely other experiments that will be tried. But the FDA drug approval process is only one path. There will also be a religious/spiritual path, in which new churches that use psychedelics as sacraments will seek, and probably win, constitutional protection, as the Native American Church and two ayahuasca churches already have. This is an exciting time for policy and legal innovation in this area.

Sounds like a fascinating thing to try but I would not want anybody to hang their PhD work up on it. I tell folks to get their degree as soon as possible and not languish. If there is another path you might want to consider crowdsourcing future research with psychedelics.  You'll find that many PhD programs  have funding available through either research or teaching assistantships. 

I think there are many frontiers. One is neurological, of which headaches are only a subset. There are compelling reports of athletes with repetitive impact head injuries who claim the psychedelics have helped restore cognitive function. That will be fascinating to study, as it could potentially build a bridge between the neuroplastic effects seen in nonhuman research and human therapeutic effects. Ultimately one thing I'd like to study is treating people convicted of antisocial crimes. Essentially picking up on Leary's Concord prison study which was rather flawed in execution and analysis. I'm not saying it will work, and it will take more than the drug, but this would be absolutely fascinating.