Founders Pledge Report: Psychedelic-Assisted Mental Health Treatments

AidanGoth

Founders Pledge Report: Psychedelic-Assisted Mental Health Treatments

AidanGoth

5 min readSep 30, 2020

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Siebe

Great report! I have a two questions for you:

1. On the following:

There are already many ongoing and upcoming high-quality studies on psychedelic-assisted mental health treatments, and there are likely more of those to follow, given the new philanthropic funding that has recently come into the area. (p. 45-46)

Based on the report itself, my impression is that high-quality academic research into microdosing and into flow-through effects* of psychedelic use is much more funding-constrained. Have you considered those?

2. Did you consider more organisations than Usona and MAPS? It seems a little bit unlikely that these are the only two organisations lobbying for drug approval?

*The flow-through effects I'm most excited about are a reduction in meat consumption, creative problem solving, and an improvement in good judgment (esp. for high-impact individuals). Effects on long-term judgment seem very hard to research, though.

AidanGoth

Thanks for your questions, Siebe!

Based on the report itself, my impression is that high-quality academic research into microdosing and into flow-through effects* of psychedelic use is much more funding-constrained. Have you considered those?

Yes, but only relatively briefly. You're right that these kinds of research are more neglected than studies of mental health treatments but we think that the benefits are much smaller in expectation. That's not to say that there couldn't be large benefits from microdosing or flow-through effects, just that these are much more speculative.

Note that we think it's more likely than not (59%) that psilocybin will turn out to be less effective than existing treatments for depression (pg. 35). Even the mental health benefits are fairly uncertain and these other benefits you mention are even less likely to materialise. The kinds of research you suggest could be valuable but I think it makes sense to focus on the mental health treatments first.

On microdosing specifically, we mention our specific concerns (pg. 21):

Another psychedelics intervention that is often suggested as potentially promising is microdosing: taking psychedelics in very low doses. Here, however, the evidence is even sparser. We currently see no reason to think this will have benefits comparable to those of higher-dose psychedelic-assisted mental health treatments, as there is reason to believe that with classic psychedelics, the latter benefits are mediated by ‘mystical-type’ experiences, which microdosing doesn’t occasion. Furthermore, we don’t know much yet about the risks of prolonged microdosing, and from a legal perspective, making microdosing available for healthy people seems much further away than psychedelic-assisted mental health treatments.

I think the last point, about microdosing being further away than mental health treatments, applies to many flow-through effects. If, indeed, psychedelics could bring about wide-ranging benefits, then the best first step is probably to get them approved as mental health treatments anyway and so advancing this seems valuable. If approved, it will also be easier to carry out other kinds of research.

2. Did you consider more organisations than Usona and MAPS? It seems a little bit unlikely that these are the only two organisations lobbying for drug approval?

This is related to your other comment, so I'll answer both together.

I was confused about the usage of the term drug development as it sounds to me like it's about the discovery/creation of new drugs, which clearly does not seem to be the high-value aspect here.

Drug development can but need not involve the creation of new drugs. It's the process that has to happen in order for banned or new substances to be approved for medical use. It involves high-quality studies to prove efficacy and safety. Drug development is very expensive - it costs at least tens of millions of dollars (usually more) to go through the FDA approval process. So actually, there just aren't many organisations able to do this. Usona and MAPS aren't just lobbying for approval, they're conducting clinical research in order to approve psilocybin and MDMA for medical use.

Another org also doing drug development of psilocybin (but for treatment-resistant depression, rather than major depression) is Compass Pathways. Compass is for-profit though, so we didn't consider it as a funding opportunity here.

Milan Griffes

Thank you for all the work that went into this - I'm very happy that it exists!

---

A couple points from our correspondence that might be interesting to readers here as well -

From the report:

The evidence on increased prosocial attitudes and behaviours and improvements in subjective well-being is weak. We found only one experimental study that used direct subjective well-being measures before and after taking a psychedelic, and it found no statistically significant improvement.[51] That said, two studies—a prospective[52] and an unpublished[53] one—found improvements on a composite well-being scale and multiple studies found self-reported, self-attributed improvements of subjective well-being, i.e. participants stated that they think the psychedelic experience improved their well-being and prosocial behaviour and attitudes.

I wish this discussion of Griffiths et al. 2006 (footnote [51]):

specified that only one aspect of subjective well-being (affective balance) was measured. Life satisfaction isn't measured by PANAS.
noted that community observers detected a positive change in participant behavior & attitudes (but not in control's behavior & attitudes) two months after the session (see the bottom of Table 4). A third-party observer report of behavior & attitudinal change seems much more objective than a participant self-report of such changes.

Also interesting here – individuals may rescale their assessments of subjective well-being over time. I speculate that the particulars of the psychedelic experience may drive rescaling like this in an intense way.

Siebe

I speculate that the particulars of the psychedelic experience may drive rescaling like this in an intense way.

I also think that the psychedelic experience, as well as things like meditation, affect well-being in ways that might not be captured easily. I'm not sure if it's rescaling per se. I feel that meditation has not made me happier in the hedonistic sense, but I strongly believe it's made optimize less for hedonistic wellbeing, and in addition given me more stability, resilience, better judgment, etc.

AidanGoth

Hi Milan, thanks very much for your comments (here and on drafts of the report)!

On 1, we don't intend to claim that psychedelics don't improve subjective well-being (SWB), just that the only study (we found) that measured SWB pre- and post-intervention found no effect. This is a (non-conclusive) reason to treat the findings that participants self-report improved well-being with some suspicion.

As I mentioned to you in our correspondence, we think that experiential measures, such as affective balance (e.g. as measured by Positive and Negative Affect Schedule (PANAS)), capture more of what we care about and less of what we don't care about, compared to evaluative measures, such as life satisfaction. But I take your point that PANAS doesn't encompass all of SWB.

On 2, behaviour change still hasn't been studied enough for there to be more than "weak evidence" but yeah, I agree that reports from third-parties are stronger evidence than self-reported changes.

Also interesting here – individuals may rescale their assessments of subjective well-being over time. I speculate that the particulars of the psychedelic experience may drive rescaling like this in an intense way.

Yeah, I don't think we understand this very well yet but it's an interesting thought :)

Milan Griffes

Further elaboration of the rescaling hypothesis and Griffiths et al. 2006 here: https://enthea.net/founders-pledge-report-psychedelics-and-subjective-wellbeing.html

Milan Griffes

Yeah, I don't think we understand this very well yet but it's an interesting thought :)

The rescaling hypothesis and the "no effect from psilocybin-assisted therapy" hypothesis both would explain the "no change in PANAS" result. It seems you're favoring the "no effect" hypothesis.

The rescaling hypothesis seems more concordant with other results from Griffiths et al. 2006:

Participants reported an increase in subjective well-being
Community observers noted an improvement in participant attitudes

Something like the rescaling hypothesis also fits better with my experience, fwiw.

Milan Griffes

As I mentioned to you in our correspondence, we think that experiential measures, such as affective balance (e.g. as measured by Positive and Negative Affect Schedule (PANAS)), capture more of what we care about and less of what we don't care about, compared to evaluative measures, such as life satisfaction. But I take your point that PANAS doesn't encompass all of SWB.

I wish this preference was more explicit in Founders Pledge's writing. It seems like a substantial value judgment, almost an aesthetic preference, and one that is unintuitive to me!

e.g. favoring affective balance over life satisfaction implies that having children is a bad decision in terms of one's subjective well-being. (If I recall correctly, on average having kids tends to make affective balance go down but life satisfaction go up; many people seem very happy to have had children.)

AidanGoth

I wish this preference was more explicit in Founders Pledge's writing. It seems like a substantial value judgment, almost an aesthetic preference, and one that is unintuitive to me!

We don't say much about this because none of our conclusions depends on it but we'll be sure to be more explicit about this if it's decision-relevant. In the particular passage you're interested in here, we were trying to get a sense of the broader SWB benefits of psychedelic use. We didn't find strong evidence for positive effects on experiential or evaluative measures of SWB. As you rightly note, just using PANAS leaves open the possibility that life satisfaction could have increased (the former is an experiential measure and the latter is an evaluative one). But there wasn't evidence for improvements in evaluative SWB either so that fact that we place more weight on experiential than evaluative measures didn't play a role here.

The only time that we've used SWB measures to evaluate a funding opportunity, we looked at both happiness (an experiential measure) and life satisfaction (an evaluative measure).

I wonder which of hedonistic and preference utilitarianism you're more sympathetic to, or which of hedonism and preference/desire theories of well-being you're more sympathetic to. The former tend to go with experiential SWB and the latter with evaluative or eudaimonic SWB (see Michael Plant's recent paper). I don't think it's a perfect mapping but my inclination towards hedonism is closely related to my earlier claim that

experiential measures, such as affective balance (e.g. as measured by Positive and Negative Affect Schedule (PANAS)), capture more of what we care about and less of what we don't care about, compared to evaluative measures, such as life satisfaction

This might explain our disagreement.

e.g. favoring affective balance over life satisfaction implies that having children is a bad decision in terms of one's subjective well-being. (If I recall correctly, on average having kids tends to make affective balance go down but life satisfaction go up; many people seem very happy to have had children.)

This is an interesting example, thanks for bringing it up. I don't have a strong view on whether having children increases or decreases hedonistic well-being (though it seems likely to increase well-being in desire/preference terms). So I'm not too sure what to make of it but here are a few thoughts:

1. This could well be a case in which life satisfaction captures something important that affect and happiness miss - I don't have a strong view on that.

2. The early years of parenting intuitively seem really hard and sleep-depriving but also fulfilling and satisfying in a broad sense. So it seems very plausible that they decrease affect/happiness but increase life satisfaction. I'd expect children to be a source of positive happiness as well, later in life though, so maybe having children increases affect/happiness overall anyway.

3. If having children decreases affect/happiness, I don't find it very surprising that lots of people want to have children and are satisfied by having children anyway. There are clearly strong evolutionary pressures to have strong preferences for having children but much less reason to think that having children would make people happier (arguably the reverse: having children results in parents having fewer resources for themselves!)

Milan Griffes

I don't have a strong view on whether having children increases or decreases hedonistic well-being (though it seems likely to increase well-being in desire/preference terms).

Yes, I haven't looked closely but it seems like a complicated topic.

Pollmann-Schult 2018 thinks that the having kids<>life satisfaction relationship depends a lot on the context:

There are, however, considerable cross-country variations in life satisfaction between parents and non-parents. Within Europe, parenthood is more positively associated with happiness in social democratic countries than in conservative, liberal, and Eastern European countries (Aassve et al. 2012).

Notably Swedish, Danish, and Norwegian parents are more satisfied with their lives than their childless counterparts (Kohler et al. 2005; Hansen et al. 2009; Daukantaite and Zukauskiene 2006). A positive association between parenthood and life satisfaction has also been found in Russia (Mikucka 2016).

Parents in the USA and continental European countries, in contrast, experience equal or lower levels of life satisfaction than childless individuals (Alesina et al. 2004; Umberson and Gove 1989; Keizer et al. 2010; Myrskylä and Margolis 2014; Pollmann-Schult 2014; Rizzi and Mikucka 2015).

Milan Griffes

I wonder which of hedonistic and preference utilitarianism you're more sympathetic to, or which of hedonism and preference/desire theories of well-being you're more sympathetic to. The former tend to go with experiential SWB and the latter with evaluative or eudaimonic SWB (see Michael Plant's recent paper).

As far as I can tell, experiential and eudaimonic well-being converge in the limit, but it's important to prioritize eudaimonic well-being along the way to avoid premature optimization.

e.g. Jhanic states are more hedonic than cocaine or Twitter, but also more difficult to access.

Siebe

I was confused about the usage of the term drug development as it sounds to me like it's about the discovery/creation of new drugs, which clearly does not seem to be the high-value aspect here. But from the report:

Drug development is a process that covers everything from the discovery of a brand new drug for treatment to this drug being approved for medical use.

AidanGoth

I've hopefully clarified this in my response to your first comment :)

Hauke Hillebrandt

Good Ventures, a major donor to Founders Pledge, also funds the two non-profits you recommend.

Have you considered adding more disclosure statements wrt to those potential conflicts of interest to the FP research pages?

[anonymous]

Do you think it is a conflict of interest if FP recommends something that a donor of ours has funded in the past? This is a genuine question, and would be curious to hear what other people think

JP Addison🔸

If Alice funded you and Alice had a pet cause of X, I would find that information useful in evaluating your writeup of X.

However I wonder if this is due to the phrasing of "pet cause". If you get funding from the Gates Foundation and you recommend a global health intervention, I really don't think you need to put disclosures about that.

Which unfortunately leaves me without a principled distinction. In this case, with knowledge of the actors involved, I doubt it would affect your funding if you had/hadn't recommended these non-profits, so I don't feel like I would have needed the disclosure. But, yeah, unprincipled.

Hauke Hillebrandt

If Alice funded you and Alice had a pet cause of X, I would find that information useful in evaluating your writeup of X.

However I wonder if this is due to the phrasing of "pet cause". If you get funding from the Gates Foundation and you recommend a global health intervention, I really don't think you need to put disclosures about that.
Which unfortunately leaves me without a principled distinction. In this case, with knowledge of the actors involved, I doubt it would affect your funding if you had/hadn't recommended these non-profits, so I don't feel like I would have needed the disclosure. But, yeah, unprincipled.

I think there should generally be disclosure statements, especially when it comes to unbiased charity evaluation.

In science, it is now standard practise to disclose any funding (see for instance PLoS ONE's funding disclosure policies).

Even when it comes to uncontroversial causes such as global health, disclosure statements have their place:

For instance, the Gates foundation has funded research showing that additional spending in low-income countries from 2015-2030 will avert a death for $4,000-11,000 and that more aid should be spent on this cause. Yet, because the aid pie is somewhat fixed and global health might not be the most effective use of funds, the Gates foundation trying to advocate for and leverage funds for global health might have net negative side effects.

Within causes, disclosure statements might not be as important.

In this case here with psychedelics, there is legitimate worry about (real or perceived) conflicts of interest, especially because some prioritization is highlighted ("psilocybin for depression, is similarly as impactful as our recommendations in other areas") and given that the Good Ventures funding for these two non-profits that are singled out was very recent (one a year ago).

[anonymous]

Also, to clarify we don't recommend a donation to MAPS at this time given their funding situation

Comments

AidanGoth

Thanks for your questions, Siebe!

Based on the report itself, my impression is that high-quality academic research into microdosing and into flow-through effects* of psychedelic use is much more funding-constrained. Have you considered those?

On microdosing specifically, we mention our specific concerns (pg. 21):

Another psychedelics intervention that is often suggested as potentially promising is microdosing: taking psychedelics in very low doses. Here, however, the evidence is even sparser. We currently see no reason to think this will have benefits comparable to those of higher-dose psychedelic-assisted mental health treatments, as there is reason to believe that with classic psychedelics, the latter benefits are mediated by ‘mystical-type’ experiences, which microdosing doesn’t occasion. Furthermore, we don’t know much yet about the risks of prolonged microdosing, and from a legal perspective, making microdosing available for healthy people seems much further away than psychedelic-assisted mental health treatments.

2. Did you consider more organisations than Usona and MAPS? It seems a little bit unlikely that these are the only two organisations lobbying for drug approval?

This is related to your other comment, so I'll answer both together.

I was confused about the usage of the term drug development as it sounds to me like it's about the discovery/creation of new drugs, which clearly does not seem to be the high-value aspect here.

Executive summary

Psychedelic drugs have the potential to revolutionise how we treat mental health conditions, from depression and anxiety to post-traumatic stress disorder (PTSD). So, how should philanthropists go about funding psychedelic-assisted mental health treatments? In this report, we answer this question, detailing the best projects to fund in this unique and promising space. The purpose of this research was to identify high-impact funding opportunities for people especially interested in improving the wellbeing of the current generation.

Psychedelic-assisted mental health treatments

In 2017, mental health problems, including substance use disorders, accounted for roughly 7% of the global disease burden, up from 4% in 1990. Despite how much suffering they cause around the world, for many mental health problems, the best treatments available only have a limited effect. For example, for major depressive disorder (MDD), antidepressants and the most effective types of psychotherapy each have an estimated average standardised effect size of less than one third. This is equivalent to reducing patients’ Hamilton Depression Rating Scale scores by about 1.6 points on average, on a scale that ranges from 0 to 50.

Psychedelic-assisted mental health treatments have the potential to change this. They could one day help reduce the global mental health burden and tackle the lack of adequate treatment. They involve ingestion of a psychedelic substance such as psilocybin or MDMA in a safe setting, supervised by trained therapists, and are often combined with preparatory sessions prior to the active treatment sessions and integratory sessions in the weeks following the treatment. Integratory sessions are non-drug psychotherapy sessions, which aim to address any difficulties that arose during or following the psychoactive sessions and to integrate lessons and understanding gained from these sessions into daily life. Psychedelic-assisted treatments are currently being tested for a variety of mental health problems, including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD).

Intervention selection

Focusing on psychedelic-assisted mental health treatments, we identified three types of interventions to consider: direct treatment, academic research and drug development. Drug development is a process that covers everything from the discovery of a brand new drug for treatment to this drug being approved for medical use. Of the three interventions considered, drug development seemed the most promising. We focused on drug development in the United States, Canada, Israel, the European Economic Area and the United Kingdom, as we know of nonprofit organisations taking psychedelic-assisted mental health treatments through the approval process in these places.

Funding opportunity analysis

When investigating where philanthropists’ dollars could be put to best use, we considered funding opportunities at the two nonprofits currently working on drug development: Multidisciplinary Association for Psychedelic Studies (MAPS) and Usona Institute. We had detailed conversations with these organisations and other experts, and surveyed the research literature on the psychedelic-assisted treatments they are advancing. We then determined how cost-effective the two funding opportunities are.

Usona is currently working on drug development for psilocybin, the active ingredient in magic mushrooms, as a treatment for depression in the US. Meanwhile, MAPS is carrying out drug development for MDMA-assisted psychotherapy for PTSD in the US, Canada and Israel, and soon also in Europe.

MAPS recently announced its Capstone Campaign, with the aim of raising $30 million to make approval of MDMA-assisted psychotherapy a reality in the US, Canada and Israel and to start the commercialisation of this treatment. MAPS secured $10 million of initial funding and a $10 million matching pot to be unlocked if the remaining $10 million is secured. Soon after we evaluated this funding opportunity, its funding gap was filled, so we turned our attention to MAPS’s drug development programme in Europe.

Recommendation

We think Usona’s drug development programme is similarly as impactful as our recommendations in other areas in the mental health and subjective well-being spaces, such as Action for Happiness’ scale-up of their local community course and StrongMinds’ treatment of women with depression. So, if you are passionate about improving mental health, we recommend you give to Usona’s drug development programme alongside these other recommendations, especially if you are interested in ‘riskier’ interventions.

We came to the same conclusion about MAPS’s drug development programme and Capstone Campaign for the US, Canada and Israel but this funding opportunity has now been filled. We think that MAPS’s drug development programme in Europe is less cost-effective than the Capstone Campaign. This judgement is driven partly by our cost-effectiveness models, which suggest that the European campaign is around one quarter as cost-effective as the Capstone Campaign. Additionally, we expect the wider benefits of MAPS’s European drug development programme to be smaller than those of the Capstone Campaign as approval will come later in Europe and the first major approval will likely have the greatest wider benefits. Therefore, we think that the European programme presents a good funding opportunity for donors with a special interest in psychedelic-assisted mental health treatments but we would recommend it only in certain circumstances.

Funding opportunities vs nonprofits

To avoid confusion, especially when we are ranking funding opportunities in a particular cause area, we think it important to emphasise the difference between evaluating funding opportunities and nonprofits. 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.

In the case of this research project, our current best guess is that both MAPS and Usona are doing high-impact work. However, one reason why we do not recommend MAPS’s European drug development programme as highly as other funding opportunities in the mental health and subjective well-being space is that MAPS has an exceptional fundraising track record.