Psilocybin for depression, MDMA for PTSD: the future of mental health?

Around the world, people’s mental health is in trouble. Even before the pandemic hit, rates of depression and anxiety were rising globally. Now that we also have Covid-19 to contend with, the problem is even more glaring.

Studies show that all the virus-induced losses — of life, of jobs, of social connection — have come with serious upticks in mental illness worldwide. In the US, for example, the prevalence of depression is four times as high as it was in the second quarter of 2019.

The pandemic has highlighted the inadequacy of our existing tools for coping with these problems. It’s not just that a health crisis can easily disrupt access to mental health services, though we’ve definitely seen that to be true. It’s also that drugs like traditional antidepressants are, at best, only a partial solution. While their effectiveness has been hotly contested over the past decade, the evidence now shows that they are more effective than a placebo, but not that much more effective. (Once we account for the placebo response, the effect size of the drugs themselves is modest.) And for some folks who have treatment-resistant depression, the drugs don’t work at all.

So if you want to invest in the mental health of people around the world, making us all more resilient to future crises, what can you do?

The promise of psychedelics to treat depression and PTSD, explained

Believe it or not, your best bet might be to fund drug development for psychedelic-assisted mental health treatments. At least that’s the upshot of a new in-depth report by Founders Pledge, an organization that guides entrepreneurs committed to donating a portion of their proceeds to effective charities.

Psilocybin, the active ingredient in magic mushrooms, is being investigated as a potential treatment for depression. Over the past decade, a few studies have investigated the effectiveness of psilocybin for treating depression and end-of-life anxiety in cancer patients, and found that the psychedelic had a surprisingly large effect.

Meanwhile, the drug MDMA (also known as ecstasy) is being studied for use in people with post-traumatic stress disorder. MDMA, which affects serotonin, dopamine, and norepinephrine levels, is best known as a party drug. But research suggests it can also relieve depression and help users access and process memories of emotional trauma. The users in studies participate in psychotherapy sessions where a therapist helps them integrate what they experienced while taking MDMA — which often includes increased feelings of empathy and bonding — into daily life.

There’s some evidence to suggest that ingesting these substances, in a safe setting and under the supervision of trained therapists, can be more helpful with depression and PTSD than traditional drugs; in some studies, the reported effect sizes for psilocybin, say, are greater than the effect sizes of the current best treatments for depression (though these studies have limitations, so we would need more data to establish this with certainty). Psychedelics might also be helpful for anxiety, addiction, and other issues.

If this seems surprising, it’s worth noting that medical research into psychedelics has been going on since the late 1800s. In the 1940s and 1950s, psychiatrists used LSD to treat pain, anxiety, and depression. (There are promising preliminary results from studies of LSD for anxiety, though larger controlled studies are needed.) And in the 1970s and 1980s, psychotherapists and psychiatrists administered MDMA to thousands of patients. As psychedelics became popular for recreational use, though, MDMA was banned in 1985 in the US, and the research slowed in many countries.

As Michael Pollan detailed in How to Change Your Mind, research into the therapeutic potential of psychedelic drugs has been undergoing a renaissance over the past decade. These therapies are now gaining traction in some quarters. In Oregon, Measure 109 is on the ballot in November, and if passed, the state will be the first in the US to allow psilocybin therapy to be administered by licensed facilitators.

We still need a lot more research on these treatments, though — and one of the benefits of funding the drug development process is that that process will involve doing high-quality studies to prove efficacy and safety. We also need organizations willing to do the hard work of getting a drug approved for medical use nationwide.

The Usona Institute is one such organization that the Founders Pledge report highlights. It’s currently working on drug development for psilocybin as a depression treatment in the US, and it’s already got a preliminary Breakthrough Therapy Designation from the FDA. That’s an acknowledgment that the FDA thinks the early evidence shows psilocybin may have an advantage over available therapy, and it means the FDA offers Usona intensive guidance on its drug development so that it may gain expedited approval. Founders Pledge thinks Usona will put your dollars to better use than any other organization in this space. If interested, you can donate here.

A close runner-up is the Multidisciplinary Association for Psychedelic Studies, which is carrying out drug development for MDMA-assisted psychotherapy for PTSD in the US, Canada, Israel, and soon Europe. If interested, you can donate here. This treatment is already in phase 3 trials, which means approval of MDMA as a therapy could be granted in these countries in a few years.

But the large-scale rollout of new drugs takes a long time. Founders Pledge estimates that for MDMA, it’ll take six to nine years, while for psilocybin the timeline will be more like eight to 11 years.

What if you want to improve mental health right now, during the pandemic?

Investing in causes that may have a big positive impact in the long term is a wise thing to do. But during a pandemic, some people will want to relieve the suffering they see happening right now.

“The psychedelics drug development won’t be done for years. So in terms of having an impact now, that’s not the way to go,” Aidan Goth, who co-wrote the Founders Pledge report, told me.

He emphasized, though, that investing in global mental health during the pandemic is a worthy cause. Mental illness can feed into physical illness, and in itself may cause as much suffering as physical illness in some cases. It can also harm people’s ability to hold a job or care for their dependents. Plus, we should not fall prey to the misconception that mental health is a so-called first-world problem.

“We’ve looked at the burden of mental health globally, and it is a really, really big problem in lower- and middle-income countries as well. It’s not true that it’s just affecting people in high-income countries,” Goth said.

If you’re itching to improve people’s mental health while the pandemic is in full swing, you’d do well to invest in a project that gives you an immediate return on your investment. For that purpose, Founders Pledge recommends a couple of organizations: StrongMinds and Action for Happiness.

There’s a serious lack of mental health professionals in many developing countries in Africa. StrongMinds, a Uganda-based organization, understood that in order to treat the millions of African women suffering from depression, it would have to train laypeople.

Since its founding in 2013, it’s scaled up pretty quickly. Lay facilitators have led group talk therapy sessions reaching a total of 70,000 women. Over a 12-week period, the women learn to identify the triggers of their depression and devise strategies to overcome them.

As demonstrated in two randomized controlled trials, this is a powerful and cost-effective intervention, Founders Pledge researchers say. They estimate that StrongMinds prevents the equivalent of one year of severe major depressive disorder for a woman at a cost of around $248 — a pretty good deal, especially when you consider this helps the woman as well as her dependents.

StrongMinds says it is “uniquely positioned” to meet the demand for depression treatment in sub-Saharan Africa during the pandemic. It’s offering teletherapy, a chatbot, and other treatment approaches in line with social distancing requirements.

Like StrongMinds, Action for Happiness brings people together in small groups and it’s run by volunteers in each local community. But this one is a UK-based organization that mostly operates in Europe, though it’s also reached countries like the US and Australia.

Action for Happiness provides eight-week courses, called Exploring What Matters, where participants talk through strategies for crafting a happier life, such as developing a mindfulness practice. The course has been shown to improve subjective well-being, with reductions in depression and anxiety and increases in happiness and life satisfaction. Based on a randomized controlled trial, Founders Pledge found this program to be extremely cost-effective, with high potential for scale-up.

During the pandemic, Action for Happiness has gone from in-person courses to virtual ones, launching a free online coaching program to improve wellbeing.

Given that Founders Pledge evaluated StrongMinds and Action for Happiness before the pandemic, you might wonder whether these organizations are still helping people cost-effectively now that they’ve had to shift from an in-person to an online methodology.

Goth explained that when Founders Pledge researchers evaluate an organization, they examine not only the specific programs it’s running but also the organization as a whole — whether its leadership is strong and whether its management can be trusted to competently carry out its mission. So the researchers still believe in StrongMinds’ and Action for Happiness’s ability to serve people effectively now.

“We trust that they’re well-run and we think they’re doing good work given the circumstances,” Goth said. “They’re the best we’re aware of.”

If this cause speaks to you, you can donate to StrongMinds here or donate to Action for Happiness here.

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