Treating Cluster Headaches Using N,N-DMT and Other Tryptamines

by Quintin Frerichs
To extend this recent EA Forum Post, I wanted to share the results of Qualia Research Institute's research into using tryptamines to abort and prevent cluster headaches. While the quotes and statistics contained here can provide some notion of the pain experienced by cluster headache sufferers, I think it is truly unimaginable. This report contains specific interventions to be pursued in both a philanthropic and for-profit business capacity. While for-profit options are beyond our scope, those interested in supporting philanthropic interventions should consider donating to ClusterBusters (the most important nonprofit dedicated to researching treatments for cluster headaches), or QRI (which does foundational research on ways to reduce intense suffering).
Mission: Instantly and safely abort cluster headaches and treat migraines, the #2 and #10 (respectively) most painful medical conditions according to NHS. Emphasis is placed on chronic cluster headaches, which account for as much as 80% of all clusters and currently lack an effective treatment option.

I. Problem:

"Even child birth is 1/10th the pain of a cluster headache, seriously this name needs to change… call it ultra super migraine." (source)

A back of the envelope calculation indicates there are roughly 14 thousand people enduring a cluster headache right now.[1]
14.2% of US adults 18 or older reported having migraine or severe headache in the previous 3 months in the 2012 NHIS. The overall age-adjusted 3-month prevalence of migraine in females was 19.1% and in males 9.0%, but varied substantially depending on age. (source)
Current treatments are either ineffective, costly, unsafe, or some combination of the three. The most effective treatments available for cluster headaches include oxygen, which requires the patient to carry an oxygen tank with them at all times, and triptans, which can be used a maximum of three times daily (an issue for chronic sufferers especially) and have side effects from pain to heart attack and stroke. The most effective treatments for migraines include triptans and opioids (which have high addiction potential). Emgality, a more promising treatment for episodic cluster headaches, has recently entered the market, but its long-term risk profile and efficacy have not yet been established.
Bob Wold founded "Cluster Busters" in 2002 with the explicit purpose of trying to get psychedelics to be prescription medication (see his lecture Treating Cluster Headaches with Psychedelics). He tried over 75 different prescription medications and was at the end of the rope when he found psychedelics could be helpful:

As noted in this Qualia Computing article, the survey surfaced that about 83% of all cluster headaches are experienced by 20% of the sufferers, most of which are classified as 'chronic'. No existing medication has been approved for use to treat chronic cluster headaches. Vaporizing DMT could be the first such treatment, offering instant relief for cluster headaches as often as they arise in a (potentially large) percentage of sufferers.

II. Solution:
"One of the most incredible experiences of my life was when I first aborted a CH [cluster headache] with DMT. That feeling of going from a place of excruciating pain…and feeling the pain fizzle away and die in a matter of seconds" (source)
It is known by a majority of cluster headache sufferers that psychedelics can be highly effective treatments. Due to the legal status of psychedelics, no randomized controlled trial (RCT) has been conducted, but analysis has been done on online forum responses and anonymous surveys, and interviews have been recorded. Evidence from these reports points to a number of important factors: tryptamines (the class of psychedelics which includes compounds like N,N-DMT and psilocybin, the active chemical in 'magic mushrooms') seem especially effective, sub-psychoactive and non-psychedelic doses can be therapeutic, and psychedelics can also decrease the frequency of headaches on long time horizons. While smoking/vaporizing is the fastest method of administration available, information from a private correspondence suggests that the FDA may be averse to approving inhalants. Intramuscular administration, utilizing Rick Strassman's protocol, could be an alternative that would achieve rapid relief without the use of an inhalation device[2]. Since the pain being experienced is so severe, having a faster method of administration is critical.
From the relevant academic literature:

"The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications." (source)
"Also, for DMT, it was suggested that singular or infrequent dosage could have potential long-term beneficial effects on headache disorders: 'Even a single dose, or perhaps a couple, can be a lifelong benefit.'" (source)
"Of interest, an open-label study found that similar compounds (2-bromo-LSD) without psychedelic effect were promising for this purpose" (source)

From online surveys:

A survey of members of online cluster headache forums revealed that 68% of respondents who used tryptamines had a 4 or 5 out of 5 relief. 5 indicates "completely eliminated the cluster headaches".
This survey again suggests that the main barrier to use is lack of access and hallucinogenic effects. As we found in an interview with an anonymous sufferer (see below), hallucinogenic effects may be avoidable.

Difficulty getting. 0 – Extremely easy to acquire, 5 – Nearly impossible to acquire
Legal risk. 0 – Not concerned at all, 5 – Extremely concerned
Side effects. 0 – Not concerned at all, 5 – Extremely concerned
From interviews with cluster headache sufferers who have tried N,N-DMT:

"If I'm starting to experience a CH and I vaporize as little as 3mgs [of DMT, sub psychoactive] I feel the pain subside almost completely within 3 to 5 seconds, and it doesn't come back for a few days." – (full document; also: another interview with an anonymous cluster headache sufferer)

III. Philanthropic Opportunities
Due to the Schedule I status of psychedelics in the United States, pursuing this intervention in the US will not be feasible for a number of years (see Section IV for more information on pursuing FDA approval for DMT for cluster headaches/migraines).
A possible solution would be to create an online education campaign publicizing the results of this report to cluster headache sufferers, designated as 'information-only', and pursuing the use of psychedelics to treat cluster headaches and migraines in countries where tryptamines are legal, including Brazil, Jamaica and the Netherlands. In addition, given the gravity of the disorder, it could be cost-effective to fly patients to such countries for months at a time.
While we believe that traditional metrics such as the QALY do not accurately capture the suffering caused by a cluster headache (see upcoming post on the true pain/pleasure scale), a rough QALY calculation would be as follows (focusing on chronic cluster headache sufferers rather than average, since they compromise up to 83% of total headaches[3]):

Facebook AD campaign:

An estimated 370,000 Americans suffer from cluster headaches, 68% of whom are on Facebook[4] (=251,000). About 15% of these suffer from chronic cluster headaches (=37,740). According to Sprout Social, the average estimated cost per click of an ad campaign is $1.72. Assuming 1/10 who click are cluster headache sufferers, to reach all chronic sufferers would take (ballpark) $650,000.
Assuming about 30% of those who view the ad will pursue the treatment (rough estimate-those who put 2 or less on survey results for questions of legality, difficulty to acquire etc.) and that in 68% of cases it cured or nearly cured their clusters (based on survey results), then the resulting increase in QALYs would be (37,740 people * 0.3 * 0.68) * [0.760 (QALY coefficient) * 1 QALY – ( -0.429 (QALY coefficient)* (0.47QALY)) [5]] = $650,000/7, 404QALY = $87.70 per QALY.
These ads could also be targeted to users in countries where psilocybin and DMT are legal for use recreationally, increasing conversion rate. Further targeting could be done on Facebook groups (and other social media groups) which are associated with cluster headache treatment.

IV. For-profit Opportunities
The recent emergence of psychedelics in for-profit business settings also affords the opportunity for entrepreneurs to seek legal rescheduling of N,N-DMT in the US for the purpose of treating cluster headaches and/or migraines. Below is an outline of the process of navigating the FDA IND process, which could result in a change in legal status:
Market Size:
'Orphan disease' status:
There are two main classifications of cluster headaches, chronic and episodic. Episodic cluster headaches are characterized by periods of headaches (up to 8 times per day) of a week to a full year, which remit for periods from a month up to a year. Chronic cluster headaches, on the other hand, either last for longer than a year or have remittance periods of less than a month[6]. A meta-analysis from the NIH estimates that cluster headaches affect 124/100,000 in the U.S., meaning an estimated 370,000 people suffer from cluster headaches a year[7]. Of these, about 15%, or 60,000, suffer from chronic cluster headaches.
The FDA grants 'orphan disease' status to diseases which affect fewer than 200,000 persons in the U.S per year, and offers incentives to those pursuing treatments through the FDA's IND process for such diseases, such as longer periods of exclusivity (monopoly on drug manufacture and sale) for the treatment after approval.

The global market for migraine drugs (which encompasses cluster headache drugs) in 2017 was $1.7 billion.

Healthcare and lost productivity costs associated with migraine are estimated to be as high as $36 billion annually in the U.S. Current estimates of cluster headaches' annual cost in the U.S. is ~$3.5 billion.

Share of market

5 years after launch (with FDA approval, with a 5-year monopoly) – serve 20% of chronic migraine sufferers (800,000), serve 20% of cluster headache sufferers (40,000)

Platform's average annual revenue per patient (migraines): $452/patient/year

Tryptapens – $20
1g of DMT is ~$100, approximately 50 doses (although an anecdote indicate 3mg may be sufficient). Compare to triptans, at ~$115 per 9 doses. Assuming 20% markup:

Chronic migraines at 20mg doses: $120/g*0.02g/dose*15 doses/month *12 months = $432/patient/year.

Platform's average annual revenue per patient (cluster headache): $344/patient/year-low estimate, $6932/patient/year – high estimate

Tryptapen – $20
There is significant variance in frequency of cluster headaches: estimates range from [$120/g*0.02g/dose*30 doses/month *3 months = $324, $120/g*0.02g/dose*120 doses/month*12 months = $6912/patient/year].

Annual revenue, 5 years after launch: $13.6M [low cluster headache estimate] – $344M [high cluster headache estimate]
 Annual revenue, 5 years after launch (migraines): $344M

The 5-year (or more, if 'orphan disease' status is gained) monopoly provided by the FDA would allow for further R&D, and as-yet undetermined projects. Some promising directions:

Depression treatment ($13.7B market)
DMT may be beneficial for tobacco cessation ($7.0B market).

Ayahuasca shows significant evidence for efficacy in treating addiction.
There is anecdotal evidence that vaporized DMT is also effective in this space.

Why now?

FDA on track to approve MDMA therapy in 2021, psilocybin therapy in 2022

FDA approval will catalyze a large increase in demand for psychedelic services
There is sufficient evidence to attempt bringing DMT for headaches through the FDA process as it becomes increasingly open to psychedelic interventions

Reasons to start before FDA approval of MDMA and psilocybin:

A "psychedelic renaissance" is underway: funding for psychedelic research has skyrocketed, and multiple psychedelic decriminalization initiatives (1, 2) have recently passed. Riding the current wave of activist and public support is advantageous to our efforts.
More time to build relationship with the FDA (important for seeking DMT clearance)
More time to build relationships with organizations currently seeking FDA approval for therapeutic uses of psychedelics (MAPS & Compass Pathways)

Challenges:
Regulatory:

Taking on the FDA IND process can be challenging and high risk from an investment standpoint. The average cost of successfully completing Phase 1-3 trials (after which the drug can be rescheduled and approved for medical use) is $100m, requires about 9-11 years and has a 6.7% success rate (private correspondence).

The Multidisciplinary Association for Psychedelic Studies (MAPS) has recently raised $26.7M for Phase 3 MDMA trials alone[8]. Total, MAPS has spent in the ballpark of $30M. If Phase 3 trials demonstrate statistically-significant results, MDMA could be selectively rescheduled for use in therapeutic settings, but would require subsequent Phase 4 trials.

The FDA is risk-averse and has incurred backlash from their last notable rescheduling of fentanyl in 1985[9]. Convincing the FDA to pursue rescheduling for treatment of a relatively rare disease with other available medications will likely be difficult.
The success or failure of MAPS in receiving approval for MDMA will be crucial for defining the regulatory landscape for other psychedelics. Should they fail, bringing another similar substance through the process may prove much more difficult.

Competition:

As discussed in Section I, most available migraine and cluster headache drugs are ineffective, expensive, and/or have heavy risk profiles. Emgality, a new migraine drug approved last month, has received FDA 'breakthrough therapy' status for its ability to decrease the frequency of episodic cluster headaches and has shown promise as a palliative for migraines as well[10]. Emgality has not been approved for use in treating chronic cluster headaches, however, and does not achieve the same rapidity of administration as the DMT vape pen (see Section III). Thus, our solution is still critical for relieving symptoms instantly, and maintains the advantage of being eligible to treat chronic cluster headaches, an 'orphan disease'.

Business model:

We would design studies to fulfill the three-step FDA drug review process:

Phase 1 studies (typically involve 20 to 80 people).
Phase 2 studies (typically involve a few dozen to about 300 people).
Phase 3 studies (typically involve several hundred to about 3,000 people).

Use of Funds

Expenses for research and operations staff

Technicians
Analysis consultants
Researchers with clinical experience
Legal counsel (paperwork)

Phase 1 FDA trial (our connections to expertise in the field would reduce the cost compared to average Phase 1 trials)

Data on Cost of Trials
The following information is from the MDMA/PTSD Trials led by MAPS. However, the treatment for PTSD involves: multiple therapy sessions and an MDMA-trained psychotherapist. Therapy sessions also last 6-8 hours. Presumably, some of these costs would not apply to a DMT/CH trial, so we expect trials for DMT/CH to be cheaper than the MDMA/PTSD Trials.
However, cluster headaches are not well suited to the therapeutic environment that is used to treat mental health conditions (they arise unpredictably, and require instant relief). This means there are likely significant cost-saving opportunities in the experimental design protocol.
Summary of costs for MAPS IND Process:

[1] Assume a world population of 7.7 billion people, and 53 out of 100,000 yearly prevalence suffering from this. Going by public health records, we see that the average number of cluster headache attacks that a sufferer experiences is about 30 a year (with a huge variance, where some people get only about 5 a year and some get them multiple times a day). Attacks last on average 1 hour (but range from 20 minutes to 3 hours). Hence, the number of people currently experiencing a CH is: 0.00053*7,700,000,000*(30/(24*365)) = 13,976.03 ~= 14 thousand
[2] Perspectives on DMT Research
[3] According to survey
[4] https://www.facebook.com/business/help/1461718327429941
[5]  For chronic sufferers, an average of between 1-8 CH per day, 1-4 hours per CH, for ~0.47 years/year having CH
[6] https://www.mayoclinic.org/diseases-conditions/cluster-headache/symptoms-causes/syc-20352080
[7] https://www.ncbi.nlm.nih.gov/pubmed/<PHONE>
[8] https://maps.org/research/mdma/ptsd/phase3/timeline
[9] https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf
[10] https://investor.lilly.com/news-releases/news-release-details/fda-approves-emgalityr-galcanezumab-gnlm-first-and-only


Realms as Interpretive Lenses

How people in different (Buddhist) realms interpret pain:
1) Heavenly Realm / God Realm: Pain is impermanent. It's a trick of the mind. A method to help us wake up and realize who we truly are. [said while peacefully unaware of actual pain due to the formidable amounts of pleasure and distractions on hand]
2) Asura Realm / Titan Realm: Pain is a tool to succeed. It is a challenge to be overcome at a personal level, and a weapon to be used against one's enemies. If I didn't suffer intensely for the things that I achieved, would they mean anything? [said while experiencing intense cravings for social recognition and the need to feel superbly significant]
3) Animal Realm: Pain is the separation from my pleasures of the day to day. My morning coffee, interrupted by a call. My conversations with a friend, when someone's bad luck is brought up. The annoying commercials in-between the chunks of TV I like. [said while snoozing the alarm for the 4th time in a row]
4) Hell Realm: Pain is reality in and of itself. Life is suffering. And if it isn't at the moment, that's just temporary good luck. Happiness is merely the absence of suffering; happiness is therefore as good as nonexistence. [said while waiting in the ER while experiencing a kidney stone]
5) Hungry Ghost Realm: Pain is realizing that only 10 out of the 15 people who RSVP'ed to my party showed up. It is the feeling of noticing that the Pringles are almost gone. The feeling that you get when you make out with someone and only get to 2nd base when you could have gotten to 3rd or 4th. [said while scrolling Reddit for the 3rd hour in a row].
6) Human Realm: Pain is a healthy signaling mechanism. When you look at it scientifically, it is just a negative reinforcement signal that propagates throughout your nervous system in order to prevent the chain of causes that led to the current state. It's nothing to worry about, just as you shouldn't worry about the weather or the shape of the solar system. [said while dispassionately reading a neuroscience textbook].

See also: Traps of the God Realm and The Penfield Mood Organ
Picture by Utheraptor

Realms as Interpretive Lenses


Cluster Headache Frequency Follows a Long-Tail Distribution

[Warning: Disturbing content ahead. Why talk about it? This is an ethically very serious topic and it deserves more attention. But please beware that thinking about this might be bad for one's mental health.]

One of the key insights that shows why Effective Altruism is so important is that the positive effect on the world that results from donating to various charities follows a long-tail distribution:
Cost-effectiveness of health interventions as found in the Disease Controls Priorities Project 2. See "The moral imperative towards cost-effectiveness in global health" by Toby Ord for more explanation. [Taken from: The world's biggest problems and why they're not what first comes to mind]
It is for this, among other, reasons why focusing on the best interventions really pays off. Where else can we expect long-tails to appear?

In Get-Out-Of-Hell-Free Necklace we discussed how introducing a new metric into the Effective Altruist ecosystem could shed light on neglected cost-effective interventions. We presented the Hell-Index:
A country's Hell-Index could be defined as the yearly total of people-seconds in pain and suffering that are at or above 20 in the McGill Pain Index (or equivalent)*. This index captures the intuition that intense suffering can be in some ways qualitatively different and more serious than lesser suffering in a way that isn't really captured by a linear pain scale.
In a future article we will discuss how the quality of suffering as a function of different medical and psychological conditions very likely follows a long-tail distribution. That is, some conditions such as Cluster Headaches (which affect about 1 in 1000 people worldwide) produce pain that is orders of magnitude worse than the pain experienced in other kinds of medical conditions, such as migraines (which are themselves already described as orders of magnitude worse than tension headaches). In other words, a 0-10 pain-scale is better thought of as a logarithmic compression of the true levels of pain rather than a linear scale. So concentrating on the worst conditions could really pay off for reducing suffering in bulk amounts.
Now: the long-tailed nature of suffering may extend beyond the quality of suffering, and show up also in its quantity. That is, the frequency with which people experience episodes of intense suffering, even among those who experience the same kind of suffering, is unlikely to be normally distributed.
Intuitively, one may think that how much suffering people endure on a given year follows a normal distribution. This intuition says that if the median number of hell-seconds people endure in a year is, say, 1,000, then people who are at the 90% percentile of hell-seconds experienced per year will be experiencing something like 1,500 or at most 2,000. If suffering follows a long-tail distribution, in reality the 90% percentile might be experiencing something more akin to 10,000 hell-seconds per year, the 99% percentile something akin to 100,000, and the 99.9% something akin to 1,000,000. If true, such a heavy skew of the distribution would suggest that we should concentrate our energies on addressing the problems of the people who are unlucky to be on the upper ranges, rather than be overly concerned with "the typical person"*.
Unfortunately, I come to share the bad news that suffering probably follows a very long-tail distribution:
It is generally acknowledged that Cluster Headaches are some of the most painful experiences that people endure. Having a single Cluster Headache, lasting anywhere between 15 minutes to 4 hours, is already an ethically unacceptable situation that should never happen to begin with. It is disheartening to know that 1 in 1,000 people experience such extreme pain. But the truth of the matter is yet much worse than we intuitively think…
We recently analyzed a survey** of Cluster Headache patients that was conducted with the intention of determining the reasons why sufferers do or do not use psychedelics to relieve their pain. As it turns out, LSD, psilocybin, and DMT all get rid of Cluster Headaches in a majority of sufferers. Given the safety profile of these agents, it is insane to think that there are millions of people suffering needlessly from this condition who could be nearly-instantly cured with something as simple as growing and eating some magic mushrooms.
We will get back to this in more depth in later articles, but for the time being what we want to highlight is the responses to the question "About how many cluster headaches do you get in a typical year?".
After cleaning the data***, we end up with 270 participants. We then ranked the values from smallest to largest, and visualize them:

Honestly I am a bit suspicious of the very top numbers (I do not know how you can fit 25,000 Cluster Headaches in a year, so perhaps the participant interpreted the question as "lifetime number of Cluster Headaches"). So, just to be safe, we cut the top 20 highest numbers and visualize the bottom 250 values:

This is clearly a long-tail distribution. And since many people online do claim to have 3 or more Cluster Headaches a day, I am inclined to believe this curve. To zoom in on some parts of the distribution, here are some additional histograms that focus on the lower percentiles:

If we take the logarithm of the number of yearly Cluster Headaches, the distribution looks remarkably normal:
Natural log of the responses to the question "About how many cluster headaches do you get in a typical year?"
Using a Shapiro-Wilk normalcy test does not rule out a Gaussian distribution (p >0.05). Although this in no way shows that that the distribution is log-normal (which would require more specialized statistical analysis), it is at least suggestive of it.
I should also point out that the distribution is really close to the 80/20 Pareto principle – we see that the top 20% of the participants contain about 83% of the CH incidents per year. Below you will find the percent of the total number of incidents accounted for by the bottom x% of the respondents:

The bottom 10% accounts for .06% of incidents
The bottom 20% accounts for 0.36% of incidents
The bottom 30% accounts for .95% of incidents
The bottom 40% accounts for 1.82% of incidents
The bottom 50% accounts for 3.17% of incidents
The bottom 60% accounts for 5.54% of incidents
The bottom 70% accounts for 9.56% of incidents
The bottom 80% accounts for 17% of incidents
The bottom 90% accounts for 30% of incidents
The bottom 95% accounts for 43% of incidents

Below we also include the number of yearly Cluster Headaches experiences at different percentiles:

10% percentile experiences 5 CH/year
20% percentile experiences 17 CH/year
30% percentile experiences 30 CH/year
40% percentile experiences 45 CH/year
50% percentile experiences 70 CH/year
60% percentile experiences 105 CH/year
70% percentile experiences 200 CH/year
80% percentile experiences 365 CH/year
90% percentile experiences 730 CH/year
95% percentile experiences 1095 CH/year
98% percentile experiences 2190 CH/year

I believe that this information is crucial to consider when assessing cost-effective interventions to help people who endure intense suffering.

Here are some additional results from the survey.

The following graphs are about the beliefs and attitudes of Cluster Headache sufferers who do not use tryptamines (LSD, psilocybin, DMT, etc.) to treat their condition:

I think it is fair to say that the survey shows that one of the biggest barriers preventing CH patients from using tryptamines to treat their condition is simply the difficulty of acquiring them. Since a number of interviews we've conducted have shown that even sub-hallucinogenic doses of DMT can abort cluster headaches (writeup coming soon), more education could easily address the barrier of being concerned about hallucinogenic side effects. The social stigma seems like a minor problem, and the legal implications (the hardest to change, perhaps), are a big concern to about half of the participants (ratings of 4 or 5/5). Hence the importance of passing new laws allowing people with this condition to use them without repercussions.
Do CH sufferers who do not use tryptamines think they would work?

And do they work? Here is what the CH sufferers who do use them say:
Effectiveness
Tryptamines used
If we interpret a 2 or 3 in the 0 to 5 scale as an equivalent to a "maybe", and a 4 or 5 as a "yes" to the question "do they work?" we see a big difference between non-users beliefs in their effectiveness and their reported effectiveness by users. 24% of people who use tryptamines to treat their CHs report that "They have completely eliminated the cluster headaches" and in total 68% mark it as either a 4 or a 5 in the scale (which we can interpret as "working" even if not "completely eliminating them"). This is compared to only 30% of non-users who believe the tryptamines would work. This large discrepancy also suggests that outreach and education could help sufferers give this approach a try.
Finally, we also looked at whether the users and non-users had different number of incidents per year (reasoning that perhaps those who experience more incidents would be more desperate to try legally and socially risky treatments). We notices that there is a very slight difference in the mean (and mean-log) for the number of CH incidents a year between the 20% of sufferers who treat their CHs with tryptamines and those who don't. I won't report the difference in the mean because the skew of the distribution makes such a metric deceptive, but the log-mean of yearly incidents of tryptamine users is 4.73 whereas for all the rest it is 4.10 (which reaches statistical significance of p < 0.05 based on a t-test). That said, we don't think this is a very practically relevant difference. The distributions look roughly the same:

The similarity between these two distributions also suggests that there is a long way to go to make sure that those who are the worse off get prompt access to tryptamines.
The End.

See also https://clusterbusters.org/, which is an organization that aims to make psychedelics legally available to people who suffer from this condition. Please consider donating to them to help this very important cause. Also consider donating to MAPS which is championing the use of psychedelics for mental health applications. Finally, consider also donating to organizations that care and strategize about how to reduce intense suffering, such as: QRI, FRI, OPIS, and The Neuroethics Foundation.

*There are instrumental considerations here – if experiencing more than, say, 5,000 hell-seconds in a year is very likely to make you depressed and ineffective, then it might pay-off to also spend resources on keeping as many people as possible below that level. In particular, to be an effective Effective Altruist it pays off not to be heavily depressed and nihilistic.
**Thanks to Harlan Stewart for taking the initiative to conduct this survey. He advertised it on the Facebook groups and subreddits of Cluster Headache sufferers and got 371 responses.
***Some people provided numerical answers, which we used directly. Some other people provided ranges, in which case we used the middle point between the values provided (e.g. "200 to 300" was coded as "250"). Some people provided lower bounds, in which case we simply used such lower bound (e.g. "500+" was coded as "500"). We discarded the data of people who didn't provide an answer in any of those formats – which left 270 participants. A more strict analysis that uses *only* the numerical responses results in the same observations listed above (e.g. the distribution is equally long-tailed and it appears to be log-normal).

[Cross-posted in Effective Altruism Forum]


In brief, LSD…

A quick attempt at highlighting some of LSD's most important attributes:

It increases the amount of qualia experienced per "moment of consciousness" (this manifests as changes in the intensity, brightness, complexity, layering, etc. of the experience. cf. tracers).
It increases the number of symmetries you can use to organize said qualia (this gives rise to unusual geometry on high doses, as well as exotic phenomenal time).
It increases the range of possible valence (the distribution of valence per moment of consciousness on psychedelics follows a long-tail distribution, where some of the most intense moments of bliss are literally orders of magnitude bigger and more energetic than the median amount of bliss on the state or sober. I am convinced that this is a real thing, and that this fact will be shown scientifically in the future. It will require us to be able to generalize valence measurements to exotic brain states, but it will be done).
It increases the range of qualia varieties and values which form the building blocks of one's world-simulation (for instance, one may experience novel qualia that has some resemblance to smell and some resemblance to a certain kind of touch, but which is not just a synesthetic mix of the two, but which belongs to a genuinely new category of qualia. Presumably such qualia was not recruited for information-processing purposes by natural selection, but that does not mean that it couldn't find some applications for qualia computing and post-Darwinian  aesthetics).

Of the above, the most ethically relevant attribute is (3) – which is also the most profound when considered in light of what humans care about.
I really think that the majority of sensible people who happen to experience a- let's say- sense of bliss and wholeness that would score a 113 out of 10* in a happiness scale, and which crams 4 or 5 times "more qualia" within each moment of experience, should understandably realize at that point that "there is more, much more, to reality than we usually believe". The experience is a proof-of-concept of what reality is capable of consciousness-wise; and evidence that we live in vastly sub-optimal configurations of qualia relative to the love and beauty that we could live with instead.
Now, which precise intentional content gets annealed as a consequence of a high-valence experience is a matter of the tripper's ability to make sense of the experience, along with the power of the conceptual tools at his or her disposal. Independently of the specific things that LSD makes people believe in, I emphasize that one should not forget the key revelation. The key fact to never forget is that valence can go way, way, up. Valence can reach values way above the upper region of one's everyday experiences. This insight is both true and agnostic about the semantic content of the specific revelations people experience.

When scientifically proven, the realization that there is a long-tail distribution of suffering and wellbeing ought to revolutionize how we make utilitarian calculations. This will give rise a very generative view, which I call "long-tail ethics".
Just as Effective Altruism made us think about the long-tail nature of "lives saved per dollar", long-tail ethics, more broadly, will make us ponder the implications of the fact that the bulk of bliss and suffering are concentrated in high-energy states of consciousness. By first getting rid of the negative extreme, and then finding adaptive regions of the positive extreme, we will find -what feels like it anyhow- our true home. In a sense our true home is, and has always been, in the form of a peak-valence region of the state-space of consciousness.
Without this understanding, one is simply "missing the key to the plot of reality".

*Given a scale where 10 marks the maximum bliss a human can have without strong changes to brain chemistry.

In brief, LSD…


Ephemerisle: Health Homeostasis, Worldview Annealing, and the Long-Tails of Serious Fun

Idealism leads to realism if it is strictly thought out.
– Ludwig Wittgenstein (from Notebooks, <PHONE>)
I just came back from spending a week on the water at Mandeville Point (~18 kilometers from Stockton, California), at a yearly gathering called Ephemerisle. Below I will share some thoughts, insights, and takeaways from this experience.

Introduction
Ephemerisle is an event first conceived as a social experiment to investigate how the construction of autonomous floating nation-states could work in practice. The history of Ephemerisle is full of interesting lessons in how ideologies react when subjected to the acid bath of reality (cf. mini-documentary about the first iteration of the event). Over the years, this event has evolved from a wild, loosely organized libertarian congregation of like-minded individuals with no central planning, no rules, and no taxes, into a -somewhat- tamer, loosely organized libertarian congregation with central planning, rules, taxes, insurance, and heavy legal waivers that you need to sign when boarding islands and vessels. Despite the introduction of rules and legal waivers, the overall vibe of the place is one of freedom, intellectual intensity, and a spirit of giving.
To gain a sense of the scale of the event I'd recommend looking at drone footage over the years: 2015, 2016, 2017, 2018, and 2019. Compared to Burning Man, this is a relatively tiny event, with a crowd that reaches up to perhaps as many as 600 people throughout the week, the equivalent of only 1% of the population of Black Rock City. In absolute terms, however, it is certainly very impressive to see that many people organized into a superorganism capable of delivering the basic survival needs for hundreds of persons in such an inhospitable environment, along with the luxuries of dance floors, sound systems, massage bunks, and trippy art.
Ephemerisle 2019 – Credit: Sameer Halai
The captain of the ship in which I camped said that "the slogan of Ephemerisle should be 'Figure It Out'". Indeed, this event falls in the same category as Burning Man when it comes to the degree of self-reliance that it demands from each participant. Burning Man, as noted before, could very well be called "the annual meeting of the recreational logistics community". Ephemerisle takes all of the hassle and preparation needed for Burning Man, doubles it, adds an extra dose of uncertainty, and sprinkles it with a number of challenges unique to living on the water for a week.
Location of Ephemerisle 2019
Indeed, attending Ephemerisle is not a simple task. The starting section of the Ephemerisle survival guide reads:
The first thing to realize about Ephemerisle is that it is not a festival. There are no tickets, no gates, and no central authority whatsoever. But Ephemerisle is on the water, which makes attending a very non-trivial task.

You are responsible for getting yourself to and from the event site and for everything you'll need to live there and survive for your stay. There are few to no resources adjacent to the event site, and none on the water. Think carefully about what you'll need, and plan ahead!
So, given the time, effort, resources, knowhow, and social connections needed to be able to attend, who actually ends up going to Ephemerisle?
Participants
Like Burning Man, the people at Ephemerisle are not representative of the general population.
Stating the obvious, the mean conscientiousness, openness to experience, and general intelligence of participants are all significantly above the mean relative to the general population. I might add that, based on many conversations I had, it seemed that the following qualities are also significantly more common relative to the general population: graduate studies, social skills, physical fitness, cryptocurrency investments, and of course, number of yachts owned.
What stuck with me was not only the average intelligence of the participants, but also the high density of particularly brilliant people doing impressive work of their own in fields such as nanotechnology, computational biology, machine learning, cryonics, innovation in politics, and many other heavy-duty intellectual fields. I lost count of the number of serial entrepreneurs, people with PhDs in STEM fields from MIT, and advanced meditators working on developing transformative technologies.
I asked people who have been to many Ephemerisles how to explain this unusual density of spiky people, and the answer seems to be a mixture of self-selection and founder effects. First, it takes some degree of agency and determination to choose to attend this event and do all the things you need to do to make it happen. And second, a large number of people attend via invitation from well-established boats and islands, which in turn were seeded by very impressive persons from the late 2000s/early 2010s Bay Area super-cluster of people working on seasteading, longevity, AI safety, and transhumanism. Taken together, these two factors make Ephemerisle a natural Schelling point for energetic people doing cool things to find one another.
If I were to cluster the population of Ephemerisle this year, I'd intuitively estimate that 35% of people are in the broad people-cluster of scientists, libertarians, anarchists programmers, entrepreneurs, cryptocurrency developers, Bay Area rationalists, and psychedelic users. 30% are people in the broad cluster of artists, off-the-grid environmentalists, Oregon ecosystem-oriented hippies, and psychedelic users. 20% are people who live physically nearby, who own a boat, and for whom it is relatively convenient to attend. 10% are people with a festival-oriented lifestyle (to the point that their main activity is to go from festival to festival), and the remaining 5% are real-life hard-core sailors who help trouble-shoot the most difficult problems that (inevitably) arise during the event.
Ephemerisle 2015
But Why?
Why are people willing to spend so much time and energy into making an event like this happen? Why not stay at home or go to a club, where the chances of drowning, breaking bones, and getting sepsis from exposing open wounds to delta water are orders of magnitude lower? Why bother to learn knots, anchoring, and how to handle a fire on your boat when you could instead learn to use a remote control, watch TV, and order a pizza? Why the need to carry bucketloads of water to and from different boats for hours at a time when you could simply drink tap water from the comfort of a vacation timeshare apartment? And if you are attending to meet smart people working on cool projects, why not go to a conference or visit an academic department?
I would claim that the thirst for adventure, fear of missing out, and ideological excitement can only go so far in explaining over-the-top events like Ephemerisle. To bridge the explanatory gap here we will need something more. This is why I will offer two analytic angles for explaining high-effort events like Ephemerisle: (1) Health Homeostasis (condition-dependence-based fitness signaling), and (2) Worldview Annealing (as a cure to adultification and the regeneration of a positive internal mental representation of one's conception of humanity). Let me explain:
Health Homeostasis
This analytic angle comes from evolutionary psychology. In particular, genetic fitness signaling dynamics may explain why some people may have the urge to do wild and risky things when they are exceptionally smart and healthy. The concept of "condition-dependance" comes handy here:
Condition-dependence: A trait's sensitivity to an animal's health and energy level. For example, dance ability is condition-dependent because tired, sick animals can't dance very well. (Mating Mind by Geoffrey Miller, from Glossary, pg. 437)
From a gene's eye view, it makes no sense for genetically robust individuals to spend one's healthy years in relative security, for one would have no way to advertise one's good genes relative to average specimens in such conditions. In a sense, doing complex and risky activities is a hard-to-fake signal of fitness. Therefore, from the point of view of one's genes, self-interest might (metaphorically) reason: "I have all this health and energy laying around, better don't let it go to waste and use it to signal genetic fitness instead" (see: An Infinite Variety of Waste).
Ephemerisle 2009. Credit: Christopher Rasch
This could be summarized with a general principle I call Health Homeostasis, which posits that among sexually-reproducing species who engage in fitness displays, we can expect that individuals will have a "desired level of health". If they notice that they are below that level of health, they will increase the time and resources focused on regenerating health. And if they notice that they are above that level of health, they will instead reduce the time and resources focused on regenerating health, and engage in costly genetic fitness signaling displays. Perhaps events like Burning Man and Ephemerisle have an element of this going on. They are appealing to people who have too much health and for whom the standard ways of signaling fitness simply won't cut it. They need health-diminishing activities in bulk. They need challenges where they can display physical endurance while exercising their powers of creativity. And this is why, all considered, these events are so sexy.
I should add here that I am not suggesting that this explanation implies that participants are doing this consciously. Executing an adaption rarely involves conscious planning and strategizing. All it requires is following the gradient of what feels right and good.
Introspect, dear reader, about the times where you have felt the most alive. Have you, perhaps, not experienced them during risky situations? When you felt that "this could be a real danger to other people"? When by luck or grace you happened to be willing and able to do something few others could have done? This is what I am talking about. This feeling of reality and authenticity may very well be a good proxy for the process of down-regulating your health. And this is what it looks like for health homeostasis to be at play.
Worldview Annealing
This event was- to be open and real with you- quite moving to me. I struggle to give words to some of the feelings, intuitions, and thoughts that I experienced towards the end of my stay. The situations in which I found myself made me feel new sensations about the possibilities hidden in humanity and the unfolding of intelligence on this planet. It felt mystical and significant. It's as if we were glimpsing the birth of a new stage for humanity.
Something akin to this happened to me at Burning Man a few years ago (with a slightly different flavor). How do I explain it? Someone I met there shared the view that at Ephemerisle we are experiencing a certain kind of "chemistry of consciousness" that is unique to the space. That collectively, in a space of this sort, we all resonate with a set of ideals, conscious efforts, and love that makes the whole environment vibrate with a unique quality of consciousness tuning the participants to a new level.
Perhaps! We could very well throw the towel and declare victory to mysterianism at this point! Alas, this is not the path that Qualia Computing has ever taken before.
So how can we explain the deep emotional feelings induced by Ephemerisle and events akin?
Here is the big picture idea: There are elements about the experience there that give rise to "heightened states of consciousness" for many hours at a time. This can be explained largely due to the build-up of semantically-neutral energy thanks to the high-density of surprising stimuli (cf. free-energy principle, entropic disintegration, and neural annealing). Over the course of several days, such build-up of semantically neutral energy enables neural search processes that solve constraint satisfaction problems that have to incorporate the fact that hundreds of human volunteers can come together to peacefully construct a mini-world in a treacherous environment, all for the benefit and enjoyment of others. Integrating this experienced fact can lead to the felt-sense that the world could be better, much better. That we could create heaven-worlds for each other. That the future could be a place of loving-kindness energized with electrifying creativity and positive energy. By the end of the event, one's cynical internal representations of humanity have been replaced -to an extent anyhow- by optimistic and loving thought-forms. It is hard to see the creation of such a beautiful thing without shifting one's priors about the real world.
It is important to realize that changing one's deep representations of high-level concepts such as humanity and the world can have far-reaching ramifications. The emotional valence that is attached to our big-picture ideals can determine how we see the world. A somewhat far-fetched but ultimately accurate analogy could be made with Rubik's cubes: Imagine that a "perfect state of the world" is equivalent to a "completely solved Rubik's cube". In addition to the degree to which you are close to a fully-solved state, you also have preferences about the aesthetics of the colors of the cube. But ultimately, you care more about the cube being solved than you care about the cube having pretty stickers.

Now, let's say that we start with a completely scrambled state, which you feel very bad about. If you feel hopeless about being able to unscramble it, you can focus on improving the look of the stickers. The stickers could be more pretty and that will briefly make you feel good, but you will know that doing any surface modification still does not help in rearranging the entire cube so that it is in a solved state. The analogy here is: changing the look of the stickers is akin to many of the band-aid solutions we use in our life. We try to make ourselves feel better by doing superficial things like changing our cars, our appearance, and our job titles. But deep down, none of that addresses the deeper sources of dissatisfaction. The cube of our life remains in an unsolved- if more outwardly pretty- state.
There could also be uncertainty about how far you are from the perfectly solved state. Especially when you are unfamiliar with the algorithms that work for solving the cube, you will find that there are configurations that give the impression of high disorder that are in fact close to getting the cube solved. And then there are situations that seem close to the goal line of a completely solved cube that still require a lot more work to figure all out. The same could be with the state of our lives.
Now, what do I mean with a perfectly solved cube? I'm referring to a sense that "everything is as it should be". I would argue that for many people, the very idea that humanity cannot get its shit together is a deep source of discomfort. Changing jobs, romantic partners, living situations, and perhaps even political parties do little to address this deep problem. They could be thought of as akin to trying to make the Rubik's cube more pretty by decorating the stickers.
Experiences where one gets a sense that humanity, if properly focused, could indeed get its shit together might have a much deeper emotional effect on people than one might intuitively realize. All you may need is a proof of concept to create a glimmer of hope. All you need is someone showing you a video of speedcubing for you to realize that there is a short path from the state of your cube to a fully-solved state. And this can be exhilarating and deeply moving.
Now, for this to take place, we need to be on a flexible state of mind. Hence the importance of art, meditation, philosophy, and psychedelics in conjunction with the unfamiliar space. This is the recipe for annealing a big picture change of mind -a reframing of humanity, its possibilities, and one's place in it. It indeed requires multiple days of iterations of changes of one's mental representations. Here, meditation, art, psychedelics, and philosophy synergize with the scene in order to raise the brain's energy parameter. The scene adds a lot of novelty: confrontation with the necessities for survival, extended exposure to people who are smarter and more competent than you along multiple dimensions, high temperatures, new wildlife (spiders and wasps), large amounts of water, wobbly platforms and ships, odd shapes and weird objects abundant in the platforms, etc.
This all results in what we might call worldview annealing. That is, the high energy state repeatedly cooled and re-heated over several days enables the fast search over alternate representations of the world. Worldview annealing gives rise to novel ways of seeing the world and one's relationship with it.* And this is, perhaps, the underlying reason why people report having durable psychological benefits from doing things like attending Burning Man and similar events (see graphs below for statistics about transformative experiences at Burning Man; I intuit that Ephemerisle might be similar in this regard).
Click to view slideshow.
At the end of an event like this, you may very well feel exhausted and totally partied out, but if worldview annealing successfully took place, you will be able to tell that something deep and inward shifted in a good direction. You now have a felt-sense for what a different and better world could be like.
Can such an effect be scaleable? Hopefully many more people can experience it in the future. Perhaps we need to open-source the essential features of that kind of event so that others can take advantage of these key properties and export its benefits elsewhere. And thus we encounter the concept of "Serious Fun".
Serious Fun
In the last few years I've given a lot of thought to the concept of paradise engineering. This comes up a lot when contemplating the coming centuries in light of David Pearce's Hedonistic Imperative, which posits that humanity will ultimately get rid of suffering by tackling its genetic roots. Now, it is true that the bulk of what will make our posthuman paradise a paradise is to be found in the quality of experience of our descendants rather than in their external environment. But for our Darwinian minds to contemplate what paradise might look like we usually need to evoke images that give us good feelings in our current state. For example, images of people cooperating to generate incredible experiences! Indeed, saying "in the future we will all be genetically endowed with negligible mu-opioid receptor down-regulation" does not sound nearly as exciting as saying "we will all be incredibly sexy, live our lives in massive cuddle puddles, be on the brink of orgasm, and have mind-blowing levels of intelligence and loving-kindness" (note: the wise would be advised to choose the first option, for the second does not guarantee sustainable happiness while the first one does). To tickle our imagination and inspire motivation it is indeed a good idea to trigger visions that engage our current reward architecture (even if we know that we are responding to Darwinian triggers and that a true paradise has more to do with brain configurations than external conditions).
So let's think about wonderful external conditions to evoke a sense of paradise. I like to think of large groups of people engaged in serious planning and strategizing to create amazing experiences for even larger groups of people. Burning Man and Ephemerisle are a proof of concept of what could end up becoming super-fun events of civilizational proportions. And here is where we start wondering: what makes such events possible? What is the distribution of effort, time, resources, etc. contributed by each participant that is needed for Serious Fun to take place? My hunch is that to make this work in real life, the distribution needs to have a long-tail:
The Long-Tails of Serious Fun
It is interesting to ponder the idea that the distribution of the total contribution per participant in events like this has a long tail. In the most simplistic case the distribution could be a power law. As it turns out, many phenomena that are usually described with power laws don't really fit power laws when closely examined.** Now, whether the "true distribution" of the contribution per participant follows a log-normal, Zipf, Pareto distribution, or one of the general Lévy distributions is an open question. But for the time being, what I want to emphasize is the long-tailed nature of it. In particular, the fact that there seems to be a small cluster of individuals who contribute massively to the event, followed by a larger group that contributes a lot, followed by a large minority who contribute more than they consume, followed by a majority who come to the event and mostly enjoy what others brought with them. Nothing inherently wrong with this, for after all, the people who contribute the most tend to truly enjoy giving, believe in the ideals of the event, and earn the respect of others. That said, it should be noted that if the distribution is too skewed it may lead to burnout among the most active members, which does not bode well for the sustainability of the event.
Although statistics for Ephemerisle are lacking, we can again use as an example people's responses to the Burning Man Census:
Burning Man expenses (other than ticket cost). The exact wording of the question in the online survey was, "How much did you spend this year to go to Black Rock City and return, including fuel, camp dues, food, lodging, airfare, supplies, etc. (but not including your ticket to the event)? If you shared expenses with a group, only include the portion of expenses that you contributed. Give your best estimate in USD." (source)
(source)
The above results are represented with too few bins to really be able to tell what kind of long-tail distribution they follows. However, it is pretty clear that we are looking at a very skewed distribution that does not at all look like a normal/Gaussian distribution. I really wish they had included one more option (e.g. $20,000+) so that we could see the number of people who are really (economically) invested in the event. In addition, another key question that would shed light on the long-tailed nature of the event would be "How many hours did you spend preparing/building/helping others/driving/cooking for others/etc.?" Again, I'd expect a very skewed distribution in the responses to such a question.
As we begin to think about how we can plan the creation of heaven worlds (i.e. large-scale projects of fun) we should consider the long-tailed nature of the contribution distribution per participant. My hunch is that we can perhaps determine whether an event is even possible by estimating how skewed the distribution needs to be to make it happen. On one extreme we have events such as "a picnic at the local park" where the event can realistically take place even if most people do roughly the same amount of work (save for perhaps the organizer who post the event details online and coordinate setting up the chairs and coolers). On the other extreme, we could imagine an actual Seasteading event out in the open ocean, or a festival at the very cusp of Mount Diablo, or even something extreme like a party at the Lagrangian between the Earth and the moon, where we would need a group of people to come together and intensely collaborate for many months and spend millions of dollars on providing the basic infrastructure for the event. In-between these two extremes you could find events like community-led concerts, regional Burns, Ephemerisle, and Burning Man proper. Whether a pie-in-the-sky idea like Ephemerisle ever actually gets to happen may be a matter of the event having the right long-tail skew that makes it possible for actual humans to carry it out. In some sense, I suspect that Ephemerisle is right at the edge of impossibility, while Burning Man proper may have more slack and hence can afford to be substantially bigger.
Lagrangian party?
What other amazing events are there that are "just barely impossible"? And what events will become possible as soon as we discover new techniques, ideologies, and cultural norms to make the distribution needed to make them happen just barely less skewed than impossible? This might be a very generative question to ask if you want to invent "the next Burning Man".
A final thread to pull here concerns to allometric scaling properties of large events (cf. allometric analysis of Chinese cities). Due to economies of scale, there are thresholds for the number of participants at an event at which some utilities become rentable. Thus, there could also be many un-imagined crazy events that simply require a threshold number of participants to become possible. For example, perhaps a tunnel-based event at a beach is impossible with 100 participants but completely realistic with 500. Who knows! It's an interesting thing to wonder about.
Anyhow, I invite you to think more about these ideas… perhaps this way you will help us invent the next iteration of paradise on earth.
The End.
Ephemerisle 2009. Credit: Liz Henry

* This can be used in order to treat the problems associated with psychological adultification. You see, most of the people alive today have some degree of psychological trauma associated with adultification. Acting free and childish is something that we can only really do in a context where we feel like we've earned the right to do so. So many highly conscientious people need to nearly kill themselves for the wellbeing of others to feel like they can deserve the right to feel care-free and innocent again. Guess what? Ephemerisle does not have a shortage of ways for you to do prodigious amounts of work to show how much you love others. Hence, perhaps, it is a place where some exceedingly responsible people can finally feel deserving of a relaxed, care-free, time.
** I am using here power laws to point at the general property of long-tailedness. In reality many other similar distributions tend to fit the data better than power laws, among which the log-normal distribution is commonly a superior fit (see: So You Think You Have a Power Law — Well Isn't That Special?).

Notes:

Featured image source.
I know that the sense of the words idealism and realism in the header quote by Wittgenstein are inappropriate here. I am just amused that the quote happens to be a great fit for this essay if the senses are interpreted within a different context. In true libertarian fashion: Deal with it.


Wada Test + Phenomenal Puzzles: Testing the Independent Consciousness of Individual Brain Hemispheres

One of the most pressing problems in philosophy of mind is solving the so-called 'problem of other minds', the difficulty of proving that agents outside oneself have qualia. A workable solution to the problem of other minds would endow us with the ability to define the moral patienthood of present-day biological entities, evade our solipsistic tendencies, and open the door to truly understanding future nonhuman intelligences, should they prove to be conscious. Even more strangely, it would allow us to evaluate whether dream characters or the products of dissociative identity disorder are separate consciousnesses. Irrevocably proving the existence of qualia in other biological life which lacks the capacity for language and higher-order thought is not, to my knowledge, even conceptually feasible at this time. In the case of two agents with the capacity to communicate and problem solve, however, this solution has been proposed, which requires the agent being tested to prove they have qualia by solving a "phenomenal puzzle". Crucially, the solution does not require that the two agents experience the same qualia, simply that there exists a mapping between their respective conscious states.
If an agent A wishes to prove the existence of qualia in agent B using the above procedure, then A and B must have the following:

A phenomenal bridge (e.g. a biological neural network that connects your brain to someone else's brain so that both brains now instantiate a single consciousness).
A qualia calibrator (a device that allows you to cycle through many combinations of qualia values quickly so that you can compare the sensory-qualia mappings in both brains and generate a shared vocabulary for qualia values).
A phenomenal puzzle (as described above).
The right set and setting: the use of a proper protocol.

I contend that there may already be a procedure which can be used to generate a reversible phenomenal bridge between two separate minds: a way to make two minds one and subsequently one mind two. Moving in each of these two directions has apparently been demonstrated; by craniopagus twins connected with a thalamic bridge and by corpus callosotomy separating the two cerebral hemispheres. There is tantalizing evidence in each case that consciousness is being fused or fissioned, respectively. In the case of the Hogan sisters, the apparently unitary mind  has access to sensory information from the sensory organs of each cranium. In the case of separating hemispheres there is some debate: alien hand syndrome has suggested the existence of dual consciousness, while other findings have cast doubt on the existence of two separate consciousnesses. While a surgical procedure for separating the hemispheres is as yet permanent, a chemically-induced separation of the hemispheres via the Wada test may provide new avenues for testing the problem of other minds. While some forms of communication (namely language, which is largely left-lateralized) are impaired by the Wada test, other forms such as singing can be left intact. Thus, I believe a combination of Gazzinaga's procedure and Gómez Emilsson's phenomenal puzzle approach, in conjunction with a working qualia calibrator, could demonstrate the existence or absence of dual consciousness in the human mind-brain. A version of the Wada test with higher specificity may also be required, to negate some of the characteristic symptoms of confusion, hemineglect, and loss of verbal comprehension.

The procedure (utilizing the state space of color, with agents L and R corresponding to the left and right hemispheres) would be as follows:
Note: a difficulty of utilizing the below outlined procedure is determining which hemisphere should serve as the benchmark. While often language ability is dominant in the left hemisphere (especially in right-handed individuals) and therefore eliminated when the left hemisphere is inactivated during the Wada test, this is not always the case. In cases where at least some language ability is preserved in each hemisphere, either can reliably serve as the point of comparison.

Design a phenomenal puzzle, such that the solution corresponds to reporting the number of just noticeable differences required to produce a linear mapping between two locations in the state space of color.
Separate the left and right visual fields (Gazzaniga).
Sodium amobarbital is administered to the left internal cardioid artery via the femoral artery and EEG confirms inactivation of the left hemisphere. In the LVF a consent checkbox for performing the experiment is given to the right hemisphere, Y/N checked using the left hand.
Similarly, sodium amobarbital is administered to the right internal cardioid artery via the femoral artery and EEG confirms inactivation of the right hemisphere. Consent can be verbally obtained from the left hemisphere.
With both hemispheres activated, qualia calibration on the state space of color is performed (see: A workable solution to the problem of other minds).
With R inactivated, the phenomenal puzzle is presented to L without enough time for L to solve the puzzle.
Both hemispheres are activated, and L tells the phenomenal puzzle to LR.
L is inactivated and R attempts to solve the puzzle on its own. When R claims to have solved the puzzle (in writing or song most likely), both hemispheres are again reactivated in order to produce LR. R shares its solution with LR.
R is inactivated, and L shares the solution to the phenomenal puzzle. If the solution is correct, then R is conscious!

Point-of-view characterization of above procedure (Under the assumption that both hemispheres are, in fact, conscious):

From the perspective of the left brain: A researcher asks "do you consent to the following procedure?" You answer 'yes', perhaps wondering if you've lost just a part of your computational resources, or created an entirely separate consciousness. A short period of darkness and sedation ensues while consent is obtained from the right brain. Suddenly, the amount of consciousness you're experiencing expands greatly and new memories are available. The computer screen in front of you rapidly cycles through a series of paired color values. The Qualia Calibrator confirms a match by waiting for consensus of the right motor cortex (in lieu of a button press) and from verbal confirmation of the left hemisphere. It feels like an eye exam at hyper speed: "Color one or color two? Color two or color three?", but for thousands of colors, many of which you don't have a name for. Then, you sleep, for some indeterminate amount of time. When you awaken, the researcher explains to you the puzzle to solve. Your consciousness is then expanded again, and you repeat the puzzle to yourself, with the strange feeling that "part of you didn't know about it". You go dark again. And when the lights are turn on again, things feel normal, but you have a prominent new memory, the solution to the puzzle. Quickly you check. Take this strange shade of cyan and change it once, twice, three times…yup! That's the mellow orange you were looking for, and in the same number of "just noticeable differences".
From the perspective of the right brain: You awaken to a scrollable consent form with a checkbox, and a left-handed mouse. Despite your state of relative confusion and lack of verbal fluency, you're able to understand the form and check the box. Suddenly, your conscious experience expands and your fluency erupts. The computer screen in front of you rapidly cycles through a series of paired color values. The Qualia Calibrator confirms a match by waiting for consensus of the right motor cortex (in lieu of a button press) and from verbal confirmation of the left hemisphere. It feels like an eye exam at hyper speed: "Color one or color two? Color two or color three?", but for thousands of colors, many of which you don't have a name for. Again you sleep, your consciousness is briefly expanded, and you learn of the puzzle you are to solve. How did you learn about it? It is weird, you started "repeating" the puzzle to yourself, with the strange feeling that "part of you already had heard it before". But either way, now you feel like you have heard it really well. Next, it feels like you took a strong sedative and a memory-loss drug at the same time. Now, in this highly impoverished cognitive state, you have to solve a complicated puzzle. To prove that you exist. Ugh. Fortunately, you have help, in the form of an AI which provides the linear mapping you need to discover, provided you answer how many just noticeable differences occur between each set of two points. Half man and machine collaborate to find the solution, and you commit it to memory. Reunited once more, you "share your findings to yourself". It turns out you're conscious. The world now knows: the right hemisphere is conscious on its own when the left one is unconscious. Hooray!


5-MeO-DMT Trip Report by Anonymous Reader

Dose: Two 7mg hits separated by about 15 minutes.
Context: The writer of this trip report suffers from anhedonia. One of the main motivations for trying 5-MeO-DMT was to see if it could help with such anhedonia.

Oh my god. The emotion. Pure intense pain. The situation was so moving. I knew I was in a state where I couldn't not empathize with the pain. Coming out of it I felt like I was being let in on the lesson. My social barriers weren't formed yet and I felt like we're all melded in one family of empathized minds. There was no hiding or not acknowledging the immensity of pain. The lesson was "This is what is possible. This is what is happening to someone. This is very serious." But it wasn't just that recognition. There was a social experience, almost like an induction.
The come up was physically pleasant but very fast and then became very negative and high intensity. I think if I had my normal connection to my body, I'd be gripping the chair arm in pain and grunting, possibly weeping, but one thing I noticed about the experience was that there was a lack of strength to any aversions or fears or rejections, let alone expressions thereof. In ordinary sober life, something that negative would lead me to react with aversion.
Unlike the (less) painful experience of eating habanero peppers, I regarded the experience very sincere and true. Ordinarily I'm very wary of fanaticism and sentimentalism and social pressures and tragedies of the commons etc… to the point of social and emotional non-participation in society. I realize this is pathological so I try to get past my social cynicism and inhibition. This experience definitely put me right into a state of embracing a social consensus and I had very little ability to squirm or object to whatever indoctrination I could have seen it as. From the outside a social experience looks like indoctrination, but from the inside it is genuine and true. Beneath fanaticism is genuine empathy and significance, and I realized this when coming out and crying and sighing and making other social expressions at the message I had just received, having the sense of empathy transcend all social transactions of which I'm cynical.
There was a sense of magnetism and attraction both to this blazing core of serious suffering in the peak of the experience and the beautiful blue drawing undercurrents of the high valence, lovely come down, which lasted a good 15 minutes. The content of the experience was very unified and simple. "General" is the word that I think best describes the content. It includes the ontologies normally attributed to specific concepts. It includes these but isn't reduced to them. Very general state of thinking. "Feeling" might be a good word for the general state underlying particular "thoughts." And perhaps it was this general freedom which added to the impression that it broke through my social cynicisms.
The part that stood out for me was the emotion. I've never experienced emotion that strong before and it was useful to be reminded of what emotions feel like. There are levels of intensity and depth of emotion that mustn't be forgotten. I dream of the life where I can tap into an infinite river of significance-rich, intense emotion. I felt in the trip an endlessly self-powering current of pure emotional energy blasting away (negative in the peak) and then undertows of deep oceanic bliss emotions of wellbeing and peace in the come down. Sometimes when I'm coming off a long, multi-day fast with a meal and my hormones and neurotransmitters are changing I feel emotional. Sometimes when I've gone a long time without hearing music and I play some great Bach cantata really loudly, I feel a bit of that moving emotional significance again. Interestingly I didn't really separate the intensity from the significance during the trip. They felt one and the same. All meaning and sense of echoes and ramifications and contexts seemed to simply be unified in that general unified blazing entity of pure undifferentiated intensity. Yet, it didn't feel insignificant, even though it lacked more specific content.
I think this might help with suffering because it does two things. One is that in my experience one has little choice to resist. Embracing an experience rather than struggling with it prevents unnecessary suffering. It also gives a state of pure, undifferentiated feeling which sort of envelops pain. This is good because it shows you the "unreality" of your thoughts. When you're in an emotional state there's a feeling behind the thoughts and different thoughts come in to support that feeling, but contending with them individually only multiplies them. It's easier to just address the entire feeling at once. It's hard to say how bad that experience was when all my aversion and struggling and resisting and fighting were disabled… I couldn't protest the experience—does that cause me to infer in my memories that it must not have been worthy of resistance and therefore dispose me to take more when really it would be suffering that I would otherwise resist and avoid in the future? All I can say was that coming out of it I was very grateful, and not grateful that it was over but grateful that I had seen such truth for the sake of truth, and then the comedown incidentally turned nice and quite pleasant.
The come-off felt very slow and beautiful. Imagine taffy hanging over a rotating disk, like a lazy Susan. It felt like I was this taffy and passing beneath me was this undertow and after a delay it would pull me under in a pulse of pleasure. Or say there's a car and a string tied to it and on the other end your tooth, and as soon as you'd have a thought the car would start running with that string and as the slack gets pulled with the car you might get distracted but then you'd eventually have your tooth pulled and you'd have your attention brought back to a string you might not have realized was there all the time. That's what the long delayed slow crescendo pleasantnesses of the comedown of it would do for all kinds of thoughts and images and experiential events. To find out after a long delay that all this time a thought you had several seconds ago is still going on is quite reassuring—well, in this case it was. And these tooth pulls were quite pleasurable for some reason. And along with it came the bodily sensation of being magnetically drawn toward this thing.

Since going on an SSRI in 2015 (which I discontinued after 10 months in 2015), I've suffered chronic anhedonia (note that this paragraph was written over a week after the experience, where most of the report was written the day after, such as the exclamatory first sentences "Oh my god. The emotion," which I was able to express because my body was still giving me a fresh enough memory of the experience from the night before. I've since lost emotional connection/recollection of the experience). I find I do suffer, but I lack any sense of it mattering. In particular, there's a lack of a coordination between my frontal lobes and my limbic system (and SSRI's can reduce the connectivity between the limbic system and the cortex… kind of like a mild chemical frontal lobotomy…), so any complex understanding of things like life situations or future plans or anything that takes the "high road" in the fear/emotional response through the cortex, get's processed by the cortex but not communicated to the limbic system. So I can suffer, and I can verbally understand I'm suffering, but I can't see why that matters or why I should do anything about it. I can't emotionally reason. I can't envision things that excite me. I can't come up with reasons to alleviate ongoing anxiety like I used to. Before the SSRI, I'd have a pessimistic or anxious or sad thought and then I'd intervene with reasoning and "take perspective" and realize why things are ok after all or why something IS worth doing. None of that thinking reasoning gets through now. It seems only very immediate physical things with little dependence on the cortex get a somewhat appropriate level of emotional arousal out of me, like a car accident or crudely apprehended social threats/stress. I also have lots of indecision and waste time in dull thought loops. My thoughts lack emotional potency and they fail to support decision making. The experience of 5-MeO-DMT reminded me that suffering does matter, that things do matter, there is emotional significance. Because of the state depends of memory, I can't really access that much, though in the days following the experience my body did find a certain posture that would trigger a strong recollection of the experience. It feels like I'm in flatland and this experience is in the third dimension, the dimension of emotional significance, and my frameworks presently don't allow me much access to these memories, but I am grateful for the experience and the long come down which allowed me to take into my cortex the verbal/generic memories of the fact emotional stuff is real, and is out there. It restored hope and reminded me of the goal of getting out of this anhedonia. It's better to live in hope and some optimism, even if success is futile. Just look at very old or obese people who still take care of their appearance with grooming.

See also: Trip reports by anonymous Qualia Computing readers for LSD, 2C-B, and 4-AcO-DMT.


Get-Out-Of-Hell-Free Necklace

An approach to doing good is to come up with a metric for what constitutes good or bad, and then trying to do things that will optimally increase or decrease such metric, as the case may be.
If you do this, you have to be careful about what metric you choose.
If you have an ontology where you measure good by "number of people who feel benefited by you", you might end up doing things like sending everyone you can a doughnut with a signed note. If instead your metric is "number of people classified as poor" you might do best to focus on interventions that get people just over the hump of poverty as defined by your scale. And so on.
Conscientious and systematic altruists tend to see problems with metrics like those above. They realize that "people impressed" and "being poor according to an economic metric" are not metrics that really carve nature at its joints.
Dissatisfied with misleading metrics, one then tends to look closer at the world and arrive at metrics that take into account the length of different lives, their quality, their instrumental effect in the world, how much are they exactly being benefited by the intervention relative to other cost-effective alternatives, and so on. And that's how you get things like Quality Adjusted Life-Years (QALY), micromorts, and the happiness index.
This is, I think, all moving in the right direction. Metrics that make an effort to carve nature at its joints can provide new lenses to see the world. And looking through those lenses tends to generate novel angles and approaches to do a lot of good.

This is why today I will suggest we consider a new metric: The Hell-Index.
A country's Hell-Index could be defined as the yearly total of people-seconds in pain and suffering that are at or above 20 in the McGill Pain Index (or equivalent)*. This index captures the intuition that intense suffering can be in some ways qualitatively different and more serious than lesser suffering in a way that isn't really captured by a linear pain scale.
What does this metric suggest we should do to make the world better? Here is an idea (told as if narrated from the future):

Between 2030 and 2050 it was very common for people to wear Get-Out-Of-Hell-Free Necklaces. People had an incredible variety of custom-fit aesthetic and practical additives to their necklaces. But in every single one of them, you could rest assured, you would find a couple of doses of each of these agents:

N,N-DMT (in case of Cluster Headaches)
Quetiapine (in case of severe acute psychosis)
Benzocaine + menthol (for very painful stings)
Ketamine (for severe suicidal feelings)
Microdosed Ibogaine + cocktail of partial mu-opioid agonists (for acute severe physical pain and panic attack, e.g.. kidney stones)

Some other people would get additional things like:

Beta blocker (to take right after a traumatic event)
Agmatine (to take in case you suspect of having being brainwashed recently), and
Caffeine (if you absolutely need to operate heavy machinery and you are sleep-deprived)

In all cases, the antidote needed would be administered as soon as requested by the wearer. And the wearer would request the antidote as indicated by a very short test done with an app to determine the need for it.
But why? What's this all about?
The Get-Out-Of-Hell-Free Necklace contents were chosen based on a cost-benefit analysis for how to reduce the world's Hell-Index as much as possible. Cluster-headaches, kidney stones, bad stings, severe psychotic episodes, suicidal depression, panic attacks, and many types of acute physical pain turned out to account for a surprisingly large percentage of each country's Hell-Index. And in many of these cases, a substantial amount of the suffering was experienced before medical help could be able to arrive to the scene and do anything about it. A lot of that intense suffering happened to be tightly concentrated in acute episodes rather than in chronic problems (save for some notable examples). And by incredible luck, it turned out that there were simple antidotes to most of these states of agony, all of them small enough to fit in a single light necklace. So it was determined that subsidizing Get-Out-Of-Hell-Free Necklaces was a no-brainer as a cost-effective altruistic intervention.

By 2050 safe and cheap genetic vaccines against almost all of these unpleasant states of consciousness had been discovered. This, in turn, made the use of the Get-Out-Of-Hell-Free Necklaces unnecessary. But many who benefited from it- who had been unlucky enough to have needed it- kept it on for many years. The piece was thought of as a symbol to commemorate humanity's progress in the destruction of hell. An achievement certainly worth celebrating.

* Admittedly, a more refined index would also distinguish between the intensity of different types of pain/suffering above 20 in the McGill Pain Index (or equivalent). Such index would try to integrate a fair "total amount of hellish qualia" by adding up the pain of each state weighted by its most likely "true intensity" as determined by a model, and then do so for each model you have and weight the contribution of each model by its likelihood. E.g. do both a quadratic and an exponential conversion of values in the 0 to 10 visual analogue scale into dolors per second, and then do a likelihood-weighted average to combine those results into a final value.

Get-Out-Of-Hell-Free Necklace


Low-Dose Ibogaine + Opioids: A Possible Treatment for Chronic Pain, Schizophrenia, and Depression?

Excerpt from Ibogaine in the 21st Century: Boosters, Tune-ups and Maintenance by Ibogaine treatment experts Patrick K. Kroupa and Hattie Wells

"Dirty" Maintenance
For some, abstinence from narcotic analgesics is not a reality-based goal. Many chronic pain patients are really not going to cast off their crutches [sic], light up some medical marijuana and dance in the meadow, after ibogaine.
In addition to chronic-pain patients, there are many people who are using narcotic analgesics to self-medicate a variety of comorbid conditions. In some cases a "successful" detox from opiates means that somebody can look forward to a lifetime's worth of maintenance on neuroleptics.
Given the choice between opiates and neuroleptics, there is no simple answer, but the side-effects of current anti-psychotic medications can be devastating. When you compare the quality of someone's life when they are controlling schizophrenia, for example, through the use of opiates (which tend to have extremely mild side effects) vs. the qualify of life attained using sanctioned medicines (usually neuroleptics, with Cogentin to alleviate some of the side-effects anti-psychotics produce), it is entirely possible, even probable, that the person is happier with the opiates.
Ibogaine is remarkably effective in addressing one of the primary problems in any sort of opiate or opioid maintenance: tolerance. Over time, individuals find they must do extremely high doses of their medications in order to achieve any effect whatsoever.
WARNING: the following category should be considered highly experimental. There is a complete lack of published scientific data regarding the following examples. The difference between 50mg and 500mg is extremely significant and quite possibly fatal. Ibogaine potentiates the analgesic effect of opiates and opioids.
Individual 1: Male, mid-30's, in good health, who has experienced full-blown resets using ibogaine HCl in the past. His average daily intake was 20Mgs oxycodone and 4–6Mgs hydromorphone (Dilaudid), which he is prescribed for pain management.
By using a very low-dose regimen of 25–50Mgs of ibogaine HCl on a daily basis, he was able to taper down to a point at which 3.75Mg of oxycodone is subjectively providing him with identical pain relief.
He began by taking 25Mg ibogaine HCl per day, and was able to immediately halve his intake of narcotic analgesics with no withdrawal symptoms or discomfort whatsoever. After 6 days he increased the ibogaine HCl to 40Mg, and at week two, he went up to 50Mg a day of ibogaine HCl. After 22 days of ibogaine maintenance, he took a ten day break, before returning to 50Mg which he presently takes every other day. His intake of oxycodone has remained consistent at 3.75Mg/day.
In his own words, "The goal with adding ibogaine to the oxycodone is to minimize if not end the need for it [oxycodone] for pain management. The HCl seems to help with the pain, or at least gives me awareness to take better care of my body by stretching, drinking more water and to get outside for exercise and sunshine."
"Most importantly the HCl has given me a feeling of well being and feeling comfortable in my place in the universe, allowing me to process through a depression I have been suffering from. I feel GREAT. The darkness has lifted, the impending doom is cast away! The low dose regimen has also been extremely helpful in musical inspiration; songs I had half-written are coming to completion and new songs are being created. There is a distinct connection between ibo and rhythm/melody, and further underscores for me the important aspect of music in the Bwiti ceremonies."
Individual 2: Female, early 40s, overall good health but suffering from anorexia, has been physically dependent on narcotic analgesics for 19 years. Her use started with heroin and eventually shifted to methadone maintenance and finally hydromorphone (Dilaudid). She has extreme fear and dislike of "tripping" and has repeatedly refused to take a full-blown ibogaine reset.
Her average daily intake was 28Mg of hydromorphone which she "cold-shakes" (breaks down the pills in a cooker so they can be injected) and IVs.
She began by doing 35Mg of ibogaine HCl and was immediately able to stop injecting the hydromorphone and obtained similar analgesia from 24Mg of Dilaudid. Over a period of five days she maintained on 35Mg of ibogaine HCl while continuously decreasing the hydromorphone, which she was taking orally, as prescribed. After five days she was on 16Mg of hydromorphone.
At the start of day 8 she began attending psychotherapy. Over the next two weeks she gradually increased her intake of ibogaine HCl to 50Mg/day, and decreased hydromorphone to 6Mg. On day 19, she took a 10 day break from ibogaine HCl, and her hydromorphone intake rose back to 12Mg/daily (oral), before tapering back down to 6Mg/day within hours of restarting ibogaine maintenance at 35Mg.
At six months out, this cycle appears to be consistent. She takes a break from ibogaine maintenance every 20 days. Slowly drifts from 6Mg/day of hydromorphone, up to 12Mg, before restarting ibogaine at 35Mg/day, at which point she drops back to 6Mg—which appears to be her comfort zone—while gradually increasing ibogaine HCl to 50Mg/day.
She has plans to try a 500Mg dose of ibogaine HCl, and attempt complete cessation of narcotic analgesics.

See also: Low-Dose Ibogaine for Hedonic Tone Augmentation, Anti-Tolerance Drugs, and On Hitting the Actual Target of Hedonic Tone for more up-to-date information.


Coffee Saves Lives

[July 18 2019 addendum: This assumes that coffee has a causal- rather than merely correlational- influence on longevity. See comment section for more details.]

The T-shirt in the featured image was probably designed as a joke, but I take it very seriously.
Indeed, I think there is a strong case to be made that subsidizing coffee could be seen as an Effective Altruist priority. You see, you can save a life with coffee for as little as $50k. This makes coffee an intervention that is on par with some of the top charities in the world, and it is an outlier when it comes to the cost-benefit ratio of medical interventions. Consider how, e.g. this article on QALY states that:
"The UK's recommendations, for example, are about £20,000 to £30,000 ($30,000 to $45,000) for each additional year of good health, once it has been adjusted to take into account the quality of life. So a drug that achieved 0.5 on the QALY measure would only merit £10,000-15,000 ($15,000 to $22,500)."
Assuming a QALY-adjusted average life-span of about 60 years per person, coffee is about 30 to 50 times more cost-effective than the types of medical interventions the UK is willing to subsidize to extend people's lives. And that's not even considering what people themselves are willing to pay to extend their own lives, which is, of course, a lot more than what a government would.
Relative to GiveWell's top charities this is still not the best intervention out there (with some of the ultra-effective charities saving a life for about 2,000 dollars). I would nonetheless point out that the ultra-effective charities out there are all effective because they address populations where very basic human needs are not typically met. In Malaria-ridden, war-torn areas, a little can go a long way. But what's different about coffee is that it is as effective everywhere in the world. Sure, you can save a life with $50k in many African countries. But can you do so in Sweden?! With coffee you can!
…
Anyhow, how did I arrive at these numbers? Well consider that you can get about 380 doses of coffee for as little as 10 dollars.*
So this means you can have a cup of coffee for as little as 2.63 cents(!). In turn, we know from a lot of research that each cup of coffee up to 4 cups a day prevents about 1/2 micromorts (interestingly, it is just as cost-effective to encourage people who don't drink coffee to drink 1 cup as it would be to encourage people who drink 3 to go ahead and drink 4).
Given those numbers, we have that the cost of a full life-span worth of micromorts is about $52,631.58.
Why are we not funding this?!

*With: Example 48 oz brand. (we could do even better buying in bulk – I reached out to a delivery company to get a quota and will update when I know more).

Coffee Saves Lives