Rethink Psychedelics

Guide: Impactful ways to help mental health and psychedelic scientific progress 🤕🍄🔬

The most impactful things you can do to progress psychedelic and MDMA science. This is written for you if you’re interested in mental health medical research, or psychedelic research for “healthy” people.

Table of contents

1. Summary
2. Background and safety
3. People interested in mental health should care about psychedelic science
4. “Healthy” people should care about psychedelic science
5. Impactful ways to help mental health and psychedelic science progress

Summary

Psychedelics have great therapeutic potential, and people interested in mental health should be interested in psychedelic science – both for “healthy” and “unhealthy” people.
The best ways to help are to help find large contributors to Phase 3 FDA trials for psilocybin and MDMA.

⛑ Background and safety

If you're looking for an overview of psychedelics, see here.
Feel free to skip the background if you don’t need it.

All drugs are not equal.
Caffeine causes relatively few deaths, perhaps in the realm of less than 5 per year of pure caffeine overdoses (James 2013).
Alcohol causes ~90,000 deaths per year in the US (NIAAA).
Cigarette smoking causes ~480,000 deaths per year in the US and “is the leading preventable cause of death in the United States” (CDC).

Drug overdoses are a big problem in the US — 52,000 people died due to overdoses in the US in 2015. About 33,000 of those were due to opioids — heroin, oxycodone, etc — with the other significant causes being benzodiazepines and cocaine (NIDA).

Unfortunately, some people’s perceptions of which drugs are most/least harmful are not based in fact (though this seems to be improving).
Nutt, King and Phillips (2010) did research to rank drugs by harm.
And don’t worry, the harm to users measure is not impacted by popularity: “The user harm rankings are likely to be largely insensitive to universal criminalisation or decriminalisation”.



Research indicates that psychedelic use is associated with reduced suicidality (Hendricks, Thorne, Clark, Coombs, & Johnson, 2015), and that psychedelics are “not linked to mental health problems or suicidal behavior” (Johansen and Krebs, 2015).

Are drugs addictive?
Proportion of users that become dependent:
Tobacco: 32-68%
Alcohol: 15-23%
Cannabis: 9% (30% of users with abuse or dependence)
Cocaine: 17-21%
Stimulants: 11%
Anxiolytics (includes benzodiazepines): 9%
Analgesics i.e. pain relievers: 8%
Psychedelics: 5%
Heroin: 23%
Anthony, Warner, Kessler, 1994; Lopez-Quintero, Pérez de los Cobos, Hasin, et al., 2011

MDMA is not the same as “Ecstasy” / “Molly”
“MDMA is not the same as "Ecstasy" or "molly." Substances sold on the street under these names may contain MDMA, but frequently also contain unknown and/or dangerous adulterants. In laboratory studies, pure MDMA has been proven sufficiently safe for human consumption when taken a limited number of times in moderate doses.” – MAPS.org

🤕 People interested in mental health should care about psychedelic science

Mental health diseases are really significant, and psychedelics show promise in mental health. Scientific research into mental health seems valuable.

Mental health diseases are significant.
According to the World Health Organization, unipolar depressive disorders are the 10th largest cost of disability-adjusted life years, with 75 million life years lost worldwide in 2011. For context, HIV/AIDS caused 95 million life years lost worldwide in 2011 (World Health Organization 2013).

Psychedelic medical research shows promise in mental health.
This placebo controlled trial from January 2017 found that ayahuasca had rapid antidepressant effects.
These two randomized double-blind trials from November 2016 (one, two) found that psilocybin, the active ingredient in magic mushrooms, produced “substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer”. These were the largest and most significant trials with psilocybin done so far.
Ketamine has shown extremely positive results for rapid depression symptom reduction. Although not considered a psychedelic by all, Ketamine is certainly caught up in the stigma against researching illegal drugs.
In November 2016, the FDA approved Phase 3 trials for MDMA for the treatment of PTSD after promising Phase 2 results.
Heffter notes that with the Usona Institute they expect to start the final FDA Phase 3 study in 2017 with psilocybin for cancer-related emotional distress.

Psychedelics may also help people with “mild unhappiness”, in addition to people with diagnosable depression or anxiety.
There's a separate argument that mental health can be looked as as a spectrum, and there are hundreds of millions more people that aren't diagnosable with depression or anxiety, but that don't have high “subjective well-being” — and psychedelics may have therapeutic value here, too, based on anecdotal reports and loose extrapolations from medical research.

🔬 “Healthy” people should care about psychedelic science

Relationship quality with friends, coworkers and your spouse may impact happiness, and MDMA may help with relationships.
Quality of close relationships and social support seem to significantly impact happiness and life satisfaction. MDMA was used in the 1980s for couples therapy (Greer & Tolbert 1986). If this was an approved therapeutic practice, this could boost relationship quality and therefore life quality for millions.

Research indicates MDMA helps PTSD, and millions more people may be undiagnosable “micro-PTSD”.
Hypothetically, millions more people have “micro-PTSD” or “micro psychological trauma” beyond those with PTSD. In early MDMA trials, MDMA psychotherapy was substantially more beneficial than psychotherapy alone (24% success with psychotherapy alone vs 83% success with MDMA psychotherapy).

If mental health is a spectrum, then psychedelics may help “healthy” people.
You may occasionally have “mild unhappiness” or “mild anxiety”. In a 2016 psilocybin for cancer-relationed emotional distress, >80% of participants endorsed “moderately or greater increased well-being/life satisfaction” — what if it provided a similar effect on “healthy” people?

Psychedelics may relate to IQ, creativity, self-efficacy and long-term thinking.
There was a problem-solving (no placebo group unfortunately) experiment done with LSD in the 60s with interesting results.
Psilocybin can increase the personality domain of openness and openness has a r=0.3 to 0.45 correlation with intelligence.
Self-efficacy refers to your belief that you will succeed at something, and has numerous positive applications — and the psilocybin for smoking addiction participants gained an increase in abstinence self-efficacy.
Psilocybin for smoking addiction participants endorsed “that after the psilocybin sessions, it was easier for them to make decisions that were in their long-term best interest”.

Billionaires and Nobel laureates are finding utility with psychedelics for creativity and other means.
There seem to be other interesting things with psychedelics, though we don't have research to say exactly what. Bestselling author and host of a podcast with 100 million downloads Tim Ferriss stated on CNN that “The billionaires I know, almost without exception, use hallucinogens on a regular basis.” Eric Weinstein, the manager of a billionaire's hedge fund, talked about “meeting some of the most intellectually gifted people in the sciences and beyond and I realized that [psychedelics were] sort of the open secret” of “billionaires or Nobel laureates or inventors.” The “hallucinogenic elite” were using “these agents either for creativity or to gain access to the things that are so difficult to get access to through therapy and other conventional means.”

Psychedelics may help with new forms of addiction that become more prevalent, e.g. social media dependence.
The 6-month success rates of conventional smoking addiction treatments are disappointingly low: individual counseling at 10% success, group counseling at 13% (Mottillo S, Filion KB, Bélisle P, et al., 2009). The best smoking addiction treatments have 6-month success rates of lower than 35%, with patch + inhaler at 32% (Cahill K, Stevens S, & Lancaster T, 2014).
In a 2014 trial psilocybin had an 80% success rate for smoking addiction at 6-month follow-up (Garcia-Romeu et al., 2014). More research is needed because it was an early stage study, but promising nonetheless.
It seems like addictions will be a large problem in the 21st century — digital addiction, food addiction, social media addiction, gaming addiction.

😃 Impactful ways to help mental health and psychedelic science progress

Summary
The most impactful thing that can be done to help psychedelic science progress is to help find large funders who are willing to publicly express interest in funding psychedelic scientific research, because this will help fund the FDA Phase 3 trials for psilocybin and MDMA, and it will give researchers the confidence they need to propose more research knowing that they’ll have a reliable source of funding over a few years.

What are the problems slowing psychedelic scientific progress?

More money is needed, because the patents for MDMA and psilocybin are expired and so research is donor funded.
MAPS needs to raise $15-20 million to “complete these Phase 3 trials and all associated toxicity and pharmacology studies over the next 5 years.”
Once approved, likely this year, psilocybin Phase 3 trial sponsors will need to raise money to fund the trials.

Phase 3 trials might take 5 years, or they may take 10.
This depends in large part on the medical school partners (e.g. how quickly they recruit and process patients).
The best next step here is perhaps if you have experience running FDA Phase 3 trials to reach out to the psychedelic research sponsors and offer help.

There are currently no large funders that have expressed interest in funding psychedelic scientific research.
This is bad because researchers are funding constrained, and will often not pursue areas unless they believe they will be able to get it funded. It would probably be very valuable to psychedelic science if a philanthropic funder expressed interest in receiving research proposals. This post by The Open Philanthropy Project talks more about the benefit of expressed interest.
The best next step here is probably to contact people you know or find people who do philanthropic work and may be interested.

Government mental health medical research agencies haven't put funding into psychedelic medical research.
The NIH spends ~$30 billion/year on medical research. Even more specifically, the National Institute of Mental Health has a $1.5 billion/year budget, the National Institute on Drug Abuse (NIDA) has an annual budget of $1 billion/year, and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has an annual budget of ~$450 million/year. It's a real bummer for people with depression, alcoholism and tobacco addiction that these agencies haven't funded psychedelic research for mental health diseases.
The best next step here might be some kind of campaign organizing well-respected PhD and professors from top schools like Harvard and Stanford to write into these organizations and support more research. The other next steps would be 1) more private funding into psychedelic research particularly on tobacco and alcohol dependence so there's more data for the agencies to see 2) patient group advocacy campaigns — e.g. someone to organize people with alcoholism who want to see the psilocybin research for alcoholism get fully funded as fast as possible to ask NIDA and NIAAA to consider supporting the work.

Some universities make it difficult to do psychedelic research.
A few universities worry that psychedelic research will impact their reputation, and so approval processes for research at these schools can be slow or never succeed.
This is a small problem relative to availability of funding. If there were “sources of funds for psychedelic research that could ensure stability of funding over several years” then the main barrier is addressed. Addressing the perception and regulatory hurdles would also help, but there are researchers who want to study these things willing to go through the hurdles that don't have funding access or certainty.
The best next step is more funding availability for the reasons above.

There is currently stigma against mental health in general.
More people are working on this problem relative to the other problems — there are some philanthropic foundations funding work against mental health stigma.

Some people stigmatize psychedelics.
The best next step here would be well done storytelling/videos/articles with participants from the research so far sharing their stories. It may also be interesting to amass a list of highly respected people who sign an open letter indicating that they wish to see more psychedelic research funding.

Is it more important to fund Phase 3 trials, or earlier stage research?
Address Phase 3 gaps first, and then earlier stage research.
The first indication of a treatment is the most important — once a substance is approved for one use, it can be prescribed off-label for other conditions where there is good evidence it will be helpful. Additionally, once approved for Phase 3, we can expect the amount of government provided funding into the substance to increase, reducing the burden on private sources.

Things to avoid in working on progressing research:
Avoid an us vs them narrative. It needs to be framed as the medical benefit being good for both “sides”, which is reality.
We don't want people to be harmed trying these on their own — either don't promote use, or promote harm reduction for those that will use anyway.

What about drug policy work?
Updated: I’ve done more research, and I now believe all-drug decriminalization ballot initiatives in progressive countries and states to be a highly promising and impactul area.

What about medical ballots like marijuana?
Direct medicalization via policy has a higher risk of backlash which could further inhibit the already constrained medical research.

What about lobbying to reschedule these drugs for easier research?
Only very marginally helpful — not worth focusing on this.
Lack of funding is a much bigger problem.

List of supporters and allies in psychedelic mental health research
Tim Ferriss, angel investor

List of supporters and allies in mental health

List of supporters and allies specifically for psychedelic science

Please send this to one person you know who may find it interesting, likely someone who cares about mental health medical research and/or psychedelic scientific research.

Did this guide lead you to take a new path? Please email us so we know what impact we’ve caused.

If you need help: Are you working on progressing mental health or psychedelic scientific progress, and do you have ideas of where you may find volunteers useful (other than already mentioned areas)? If so, send us an email – we’d love to help you find volunteers.

Request for help: Do you know of other high impact people interested in mental health or psychedelic scientific research (e.g. tech executives, investors)? Please email us to let us know – we won’t list them publicly unless they’ve already talked publicly or they ask that we list them.