A Shortcut to Mushrooms: The Power of Psychedelics for Treatment-Resistant Depression
Most of this article is going to deal with drugs that, until very recently, have been both recreational and illicit. Grannus does not, of course, recommend breaking any local, state, or federal laws. We’re just reporting on recent developments—and maybe providing useful pointers on the development of emerging treatments for those who are coping with serious mental illness and looking for new ways to feel a little more like yourself.
Here’s the super short version: controlled microdoses of certain psychedelic substances seem to be extraordinarily effective for treating depression, bipolar disorder, PTSD, and other mental illnesses—especially for people whose symptoms haven’t responded to more standard talk therapy and medication.
The five most-studied psychedelics are psilocybin, MDMA, LSD, DMT (consumed in the form of plant-based substances like sacramental ayahuasca), and mescaline (found in plants like peyote). The US has historically treated all of them as illegal drugs, thanks to a combination of backlash against the ‘60s counterculture and a lack of solid research.
That has been changing. First slowly, in the 2010s, and now much faster.
Resistant to Treatment
For people with “mood disorders”—meaning depression, anxiety, addiction, bipolar disorder, PTSD, and others—life can be unbelievably challenging. These are real, physical illnesses that take the form of neurological dysfunction, which is science jargon for “brain cells aren’t producing/absorbing the right chemicals, so basic stuff like thoughts and motivation just don’t happen. Or at least don’t happen the way they should.”
The standard treatments are psychotherapy, or “talk therapy,” and a suite of antidepressant and antipsychotic drugs that, while they can be phenomenally effective, vary widely (vary very widely) in how well they work for any one particular person. For some, they can completely fail to relieve the most severe symptoms, like traumatic flashbacks or utter hopelessness.
That’s where new “psychedelic-assisted therapies” come in. Basically, you take a moderate dose of one of these drugs—MDMA and psilocybin are the most common right now, possibly because they’re less likely to cause vivid hallucination—and then talk through the resulting experience with a therapist.
The results have been dramatic. Landmark studies using psilocybin to treat depression have found substantial improvements, and in some cases have gotten rid of symptoms almost entirely. Most importantly, in these early tests, they seem to be effective even for very severe symptoms.
How Do They Work?
To quote the American Association of Medical Colleges (AAMC),
Ask the top researchers how psychedelic drugs alleviate mental disorders, and you get answers like, “we don’t really know” and “it remains a mystery.”
What that actually means is that we know a lot about the actual mechanics of what psychedelics do in our brain, which receptors they bind with and which networks of cells they activate. But we know very little about why those changes are so helpful. One major study, for example, has a whole paragraph that amounts to “yeah this makes no sense.” (It’s the paragraph about 5-HT2AR agonism, if you’re looking.)
That doesn’t mean we have no promising ideas. In fact, the AAMC article goes on to give a nice concise version of the big-picture explanation that most scientists accept:
Some hypotheses suggest that psychedelics enhance neural plasticity and that they can disrupt normal patterns of brain activity. Those mechanisms might help to break down neurological loops that trap people in destructive patterns of thinking, like being stuck in a traffic circle with no exits. Think of someone who has developed a depression-and-reward cycle that compels them to drink alcohol, or who keeps reimagining a traumatic experience (such as a violent assault) and feeling the fear afresh each time.
“These [harmful] mental patterns involve repetition and rigidity,” notes Greg Fonzo, PhD, co-director of the Center for Psychedelic Research and Therapy at The University of Texas at Austin Dell Medical School. “People get stuck in these patterns. The hypothesis is that these drugs help shake people out of these repetitive mental patterns.”
(Here’s a way more in-depth exploration of these ideas, for those curious.)
So, is This Legal, or What?
Psychedelics are making slow progress toward acceptance. In 2019 states introduced just 5 bills to make psychedelics more accessible. By 2022, that number was 36, and the most common goal was to decriminalize MDMA and psilocybin.
Starting in January of 2023, Oregon took the leap with magic mushrooms, and FDA approval is on the way—maybe as soon as this year.
You can check a map like this one to follow the legal status of psychedelic medications in your state. It’s important to wait for reform, not just to avoid legal repercussions but to ensure that your local medical system has care providers who are trained in the use of psychedelic medicine.
New Evidence
To wrap up, we want to spotlight a recent study that made us even more optimistic about the future of psychedelic-assisted psychotherapy.
The researchers asked whether psilocybin might help out an under-served group of patients: people living with bipolar II disorder. Bipolar disorder in general means that patients experience both mania (hyperactivity) and depression. Bipolar I skews toward the highs of manic moods, bipolar II toward the lows of misery and lack of motivation.
They started with a group of bipolar II patients who had all been depressed for at least three straight months and who’d found at least two previous drug treatments to be unhelpful. Therapists trained to work with psychedelics did three talk therapy sessions with each patient, a single day of psilocybin treatment, and then three more therapy sessions over the following weeks.
80%, were no longer depressed when they followed up three months later.
The study only had 15 participants—there was a pretty narrow set of criteria, after all. But of that group, 12 people, or 80%, were no longer depressed when they followed up three months later.
That’s a remarkable result for a single moderate dose of synthetic psilocybin. These aren’t patients who dropped three tabs of acid and saw the faces of their forefathers etched on the vault of the heavens, or whatever. They entered a mildly altered state of consciousness for a few hours, talked to a therapist a handful of times, and got their lives back.
It’s not possible to extrapolate from small studies like this one. Even the relatively chilled-out psilocybin can be a high-risk drug and should not be used carelessly. But numbers like these are incredibly encouraging and point to the need for more and larger studies. Millions of people could look forward to a better future if these results prove to be reality.
