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Promising data that psilocybin may treat Anorexia*

by Greg Gilman | Psychedelic Spotlight | 5 May 2022​

There is currently no FDA-approved treatment for anorexia. Could psychedelics be the answer?​

Psilocybin has more mental health applications than treating depression, and Compass Pathways (Nasdaq: CMPS)recently shared promising study results that indicate its COMP360 psilocybin therapy may be beneficial for those suffering from anorexia.​

A 10-person trial conducted by Dr. Walter Kaye at the University of California San Diego School of Medicine found a single 25mg dose of the psychedelic drug led to 30 percent experiencing clinically significant reductions in eating disorder psychopathology at the 1-month follow up, and 40% experiencing clinically significant reductions at the 3-month follow-up. Overall, nine of the 10 subjects studied found the experience to be meaningful and therapeutic, and no serious adverse events were reported.

“The results provide promising preliminary evidence that COMP360 psilocybin therapy could help people living with anorexia nervosa,” says Dr. Guy Goodwin, Chief Medical Officer, COMPASS Pathways. Though, he adds, the company’s confidence in the potential to treat the condition “needs to be further investigated in larger scale clinical studies.”

The data was shared at the Society of Biological Psychiatry Annual Meeting in New Orleans last month, and it adds to a small but growing body of scientific inquiry into this particular application of psilocybin.

As Psychedelic Spotlight has previously reported, several leading research institutes including Johns Hopkins University and the Imperial College London are recruiting patients suffering from the condition for trials testing the efficacy of psilocybin to treat anorexia nervosa — an eating disorder characterized by an abnormally low body weight, an intense fear of gaining weight and a distorted perception of weight.

In her 2013 paper Perplexities of Treatment Resistance in Eating Disorders, psychiatrist Katherine A. Halmi states there isn’t a dramatically effective treatment for anorexia nervosa, which stems from the ego. “The core eating disorder psychopathology of anorexia nervosa becomes a coping mechanism likely via vulnerable neurobiological features and conditioned learning to deal with life events,” she wrote. “Thus it is reinforcing and ego syntonic resulting in resistance to treatment. The severity of core features such as preoccupations with body image, weight, eating and exercising predicts greater resistance to treatment.”

To date, there is no Food and Drug Administration (FDA) approved medical treatment for anorexia nervosa, but this new data and previous studies suggest the promise of psychedelics. A 2017 study examined people with eating disorders who took part in an ayahuasca ceremony. 11 of the participants claimed their symptoms improved as a result of the experience, and 14 felt the medicine improved their emotional regulation.

Like depression, eating disorders are deeply rooted in the mind, and psychedelics are a tool to untangle that knot of our self-conscious view of ourselves, so anorexia is on the growing list of health issues that psychedelic medicine may one day effectively treat. Meanwhile, Compass Pathways will continue to explore the effect of COMP360 on treatment-resistant depression with a Phase 3 clinical trial launching later this year.

*From the article here :
 



Psychedelics offer a new route to recovery from Eating Disorders*

Psychedelics can lead to a new sense of self and a release from rigid rules for people with anorexia, bulimia, and binge-eating disorder.

by Marianne Apostolides | NEO-LIFE | 3 Feb 2022

Taking MDMA was pivotal for me as I recovered from bulimia. Unlike the people in clinical trials currently assessing the effectiveness of psychedelic-assisted psychotherapy for eating disorders, I didn’t take the drug in a treatment room. Instead, I was at a rave, a lollipop in my mouth, dancing and running my hands through the buzz-cut hair of a friend’s girlfriend. I was also in a state of revelation, enthralled by what I felt in my body: not disgust or discomfort or revulsion, but utter okay-ness. That sounds like a small thing, but, for someone with an eating disorder, it was pure glory.

That was decades ago. Like many with serious and enduring eating disorders, I’ve cycled from one disorder to the other—anorexia, bulimia, binge-eating disorder, all accompanied by obsessive exercise. The behavior is part of my life, sometimes dominating, often kept in check, but never at rest: it’s always there, threatening to overtake me.

This experience is all too common, and often dangerous. Anorexia is the single most deadly psychiatric disorder, with mortality rates from suicide and cardiovascular complications estimated from 3–10 percent. Relapse rates for bulimia are upwards of 60 percent. And binge eating disorder—defined by out-of-control consumption without the purging that characterizes bulimia—is the most widespread of any eating disorder, affecting an estimated 2.8 million Americans.

Given the extent of the problem, and the recent wave of triumphs for psychedelic-assisted psychotherapy—success in treating PTSD, smoking addiction, end-of-life anxiety, major depressive disorder, social anxiety in autism-spectrum disorder, and more—I became curious: If the drugs alone could induce a profound change of perspective for me as a bulimic woman, how might that insight be transformed into therapeutic benefit with the guidance of therapists, in a therapeutic setting, with a mindset focused on the disorder and on health (which, in a way, is just a different kind of order)? I spoke with leaders in the field to find out.

The visceral understanding that comes with psilocybin

“We need to reframe the question,” says Meg Spriggs, who’s leading a clinical trial on psilocybin-assisted psychotherapy for anorexia at the Centre for Psychedelic Research, Imperial College London. “It’s not necessarily, ‘How do we treat anorexia,’” she says. Instead, the problem we need to address is, “How do we help people engage in the process of recovery?”

Spriggs’s reframing of the questions is actually quite radical, and consistent with the basic premise of psychedelic-assisted psychotherapy: The drug is a catalyst for treatment, not a treatment in itself. That approach runs counter to the model of antidepressants like SSRIs, which are meant to be taken daily, often for many years. With a psychedelics protocol, the drugs are taken only a few times, and are accompanied by two therapists’ guidance before, during, and after the dose session.

Psychedelics seem optimal for eating disorders because they improve “cognitive flexibility,” the ability to be more responsive to changing circumstances rather than to follow a predetermined pattern of behavior or thought. That’s particularly relevant for anorexia, a disease that’s characterized by the self-imposition of rigid rules to control caloric intake and govern exercise—combined with insurmountable anxiety when those rules are taken away. Anorexics feel compelled to cycle through stuttering thoughts, getting locked into actions determined by that rumination. "Psilocybin can 'break the pattern'” of those thoughts and maladaptive behavior," says Natalie Gukasyan, a psychiatrist at Johns Hopkins University who’s leading a clinical trial testing psilocybin-assisted psychotherapy for anorexia.

“A huge chunk of people receiving psilocybin reported long-term positive behavioral change,” Gukasyan says. That’s significant, she adds, because anorexia is a behavioral disorder. You behave your way into it, and you’ve got to behave your way out of it. That shift in behavior requires a tremendous amount of strength," she says, "allowing someone to overcome those very deeply ingrained emotional factors that get in the way of recovery.”

This strength can be increased by the demanding nature of a psilocybin session. “It’s not always easy to go through a psilocybin experience—to surrender to it and go where it takes you, potentially to very difficult places,” Spriggs says. That process, which is analogous to the recovery process from anorexia, can provide a sense of “inner courage and compassion,” helping the person remain with the recovery process.

Despite the solid rationale for testing psilocybin for anorexia, the early results from the Johns Hopkins study were puzzling. A few participants reported they felt little effect from the drug: no hallucinations, no dissolution of the ego, no sense of interconnectedness between the self and the world (the famed sense of “oneness”). Some asked whether they’d received a placebo.

The researchers aren’t certain why this is the case, although several plausible hypotheses have been put forward. Perhaps the serotonin receptor density in the brain is too low—either due to the effects of starvation or to factors inherent in anorexia itself—or perhaps the body can’t metabolize psilocybin efficiently, converting it into its usable form, psilocin. Either way, the researchers revised their protocol, allowing for up to four psilocybin sessions, spread over a 12-month period, with higher maximum doses. They’re also considering whether to admit people into the trial who are in partial remission from anorexia—those with a higher stabilized weight and less constrained eating, who are nonetheless terrified of being drawn back into the behavior. “That might be the perfect time to help people really solidify their progress,” Gukasyan says.

As the researchers learn more and adjust their treatment protocol, they’re seeing positive results, with data to be published later this year. Still, Gukasyan says, “It is very different from other studies I’ve been involved in,” with benefits taking longer to develop.

“It’s a really common misconception that this treatment is a magic bullet—you step in, you step out, it’s all fixed,” Spriggs says. “But it’s not like that.” Unlike other disorders like depression and PTSD, where psychedelics have been shown to provide immediate relief, the treatment for anorexia can make people feel worse. That’s because progress often induces anxiety as the protective mechanism of the disorder is threatened. “That’s a huge part of what keeps people from getting better,” Gukasyan says: "the ambivalence of giving up a disorder that’s made them feel safe and in control."

That ambivalence plays out in the conflict between knowing you have to eat but being afraid to navigate the day without the disorder’s strict rules. It isn’t logical. The behavior can’t be explained in rational terms, and efforts to provide rational reasons for its development seem incapable of changing the behavior.

I can’t count how many times I’ve been told, often under people’s breath, that my behavior is “bizarre.” This is not unknown to me. But the very bizarreness of the behavior—combined with the heedless drive to deny the body’s most basic need—lends itself to the surreal nature of a psilocybin experience. During the duration of a trip, a person doesn’t feel trapped in the cage of logic; she can slip into a different kind of understanding, where the dynamics underlying the disorder are made visceral and vivid. In my experience, those insights make more sense than any rational, word-based explanation.

All these benefits—acute insights combined with cognitive flexibility, compassion, and courage—contribute to a participant’s motivation to continue recovery. For both studies, motivation for change is one of the primary measurable outcomes. This goes back to Spriggs’ initial reframing of the question: Will psilocybin give people the fortitude to continue engaging with the recovery process—not giving up on themselves, or the goal of someday feeling free from the disorder?

“I remain cautiously optimistic,” Gukasyan says.

MDMA and the possibility of joy

Another psychedelic under evaluation for eating disorders is MDMA, the synthetic chemical prevalent in ecstasy, a recreational drug once associated with raves. Like psilocybin, MDMA increases neural plasticity, operating on the 5-HT2A receptors to induce the growth of dendrites, the branching part of the neuron that connects to other neurons throughout the brain. Despite binding to the same receptor as psilocybin, the drug produces a completely different experience.

MDMA is known as an “empathogen” because it creates a feeling of compassion—for yourself, your situation, as well as other people, which fosters social bonding and trust. These emotions seem to blossom because MDMA simultaneously reduces fear, allowing people to tolerate feelings that otherwise would’ve overwhelmed them, making them either numb or distraught.

“With MDMA, the fears people typically have around connecting with others in a vulnerable way—a more intimate way—are decreased,” says Adele Lafrance, a clinical psychologist running a trial for anorexia and binge-eating disorder, sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS). By facilitating a feeling of connection, MDMA can create a strong “therapeutic alliance” between participants and therapists, building a level of trust to help a person feel protected while engaging with intense emotions, memories, and thoughts. This is particularly advantageous for treating people with eating disorders, Lafrance says, since they often feel mistrustful in interpersonal relationships, uncertain whether the other person can fulfill—or even acknowledge—their emotional needs.

The sense of trust that flows to the therapists also gets directed inward, Lafrance says. “People start to trust their own internal processes, ranging from bodily sensations—including hunger cues—all the way to the experience of emotion, including anger and shame. When you put all that together, you have a beautiful opportunity.”

But that opportunity can also be treacherous. Given the level of openness during a dose session, a participant might feel overly exposed in the days afterward, as if the connection weren’t rooted in anything real. That’s why the preparatory therapy sessions are vital, says Michael Mithoefer, senior medical director for medical affairs, training and supervision at MAPS and the lead author of the training manual for therapists. Those prep sessions, held in the days prior to dosing, ground the therapeutic process in a relationship that’s not dependent on the drug’s effects. The sessions also familiarize the participant with the process that will unfold during dosing—which, in itself, creates a potential pitfall.

“People get really attached to getting better, having a breakthrough,” Mithoefer says. They therefore try to stay with their initial intention rather than following the emotions, recollections, or images that appear during the dose session. “The route to your intention may not be recognizable at the time,” Mithoefer says, “but you may realize it later. We see this so often, if you can let go and not get ahead of the medicine or your inner healing intelligence.”

That phrase, inner healing intelligence, is ubiquitous in the psychedelics community, even though its definition seems to elude many people. Whenever I sought an explanation, it was presented as either self-evident or ineffable, one of those beyond-the-bounds-of-language psychedelic things. Then Mithoefer explained it to me. He used an analogy from his days in emergency medicine, before he became a psychiatrist. He describes the process of helping patients who came to the ER with wounds. He could clean the wounds, get the gravel out, treat an infection—“but that wasn’t doing any healing,” he says. “That was just removing obstacles, creating favorable conditions to allow the healing process—which was innate—to go forward.” The inner healing intelligence, then, is the mind’s “complex and elegant organization” that drives toward wellness, if the obstacles to healing are removed and favorable conditions created.

The notion that MDMA elicits what’s already within us, there and waiting to emerge, can become a promise, like a secret we keep in ourselves. That’s what I felt on that night so many years ago, when I first tried MDMA. The fact that MDMA induces self-compassion can become a truism, but it will have depths of meaning for people with eating disorders because we understand the opposite of self-compassion: the relentless sense of repulsion toward their bodies and behavior. By giving me the ability to feel joyful in my body, MDMA changed the horizon of what was imaginable, and therefore what’s now possible. It must be possible, the drug seems to tell us, because you’ve already felt it: That joy is already yours.

Ketamine and the potential for reordering

As psilocybin and MDMA proceed toward FDA approval through clinical trials, ketamine is already there: An intranasal derivative of the drug was approved for treatment-resistant depression in 2019. Until now, though, the research on ketamine for eating disorders has been limited to case studies, most of which describe the effects of the drug on its own, without accompanying psychotherapy. This is now changing. Johanna Keeler, a PhD candidate at King’s College, London, is at the forefront of a new wave of scholarship in the field. With her research on the neurobiology of anorexia—specifically, how the brain changes through the duration of the illness—Keeler sees a good fit for ketamine, whose properties could potentially counteract some of the changes caused by starvation.

But this focus on neurobiology doesn’t discount the experiential component, Keeler says, noting that the drug can “expand the mind,” allowing therapeutic insight and better integration of those insights into daily life.

Ketamine, which is primarily used as an anaesthetic, is often said to be “dissociative,” meaning a person feels disconnected from parts of their body: a hand has its own animus, not attached to the mind that sees it. Although some in the field label the dissociative effects of ketamine as “adverse,” Keeler thinks they could be important for achieving a therapeutic benefit.

In interviewing people who’d taken ketamine for alcohol addiction, Keeler found that people “had profound hallucinations and vivid memories, helping them make sense of past traumas and past events” which in turn led to “drastic changes in their life for their well-being,” including abstinence from alcohol for some. Keeler is currently developing a randomized-controlled trial to test whether these effects are translatable to anorexia.

In some ways, ketamine is the inverse of MDMA: It doesn’t show us what we’d want, but shows that what we’ve got isn’t intractable or even solidly real. Our reality is changeable, and that very changeability is a source of hope. A person’s reality—for me, the reality that I must follow strict rules to control my eating and exercise, and thereby stabilize my world—is not the only way to organize the world’s dynamics and how they interact with me. Those types of insights arise not only because of ketamine’s dissociative effects, in which the relations among objects decohere. It’s also the quickness with which those relations come back to coherence—a speed far faster than psilocybin—that allow a reshaping of what’s possible.

The body’s fundamental appetites

All of these treatments will likely be available to people with anorexia, bulimia, and binge-eating disorders in the next 18 months, experts predict. That seems impossibly soon, since these trials are still in their early stages. But the most likely scenario is that people with eating disorders will benefit from other ongoing trials examining psychedelic-assisted psychotherapy for PTSD.

Given the advanced stage of those clinical trials, psilocybin and MDMA will likely be approved by the FDA for PTSD in 2023. Ketamine is already available for treatment-resistant depression. Because many people with eating disorders also have PTSD or depression, they would be eligible for treatment. For those who aren’t, they could still get the treatment if the drugs are prescribed for “off-label use,” meaning they’re given for conditions beyond the ones listed by the FDA. This is a common practice, with nearly one-third of antidepressant prescriptions currently off-label.

That’s why the data from these studies will be especially crucial for therapists and patients trying to determine whether these treatments are worth the expense and emotional effort. It’s also why bulimia needs to be studied: If the drugs are effective for anorexia and binge-eating disorder, they could also be effective for bulimia, given the underlying similarities of these conditions. But safety needs to be established regarding the physical effects of purging.

Despite these caveats, I, like Natalie Gukasyan, have become cautiously optimistic. That caution veers toward unbridled optimism when the treatments are reframed, as Meg Spriggs suggests—particularly if we clearly say we’re engaging not just with the “process of recovery,” but also with the process of being alive to our bodies, desires, emotions, and relationships, despite the presence of the disorder.

Interestingly, and somewhat disconcertingly, no one I spoke to mentioned appetite—not for sex, or food, or love. From my perspective, that’s central to all eating disorders: the need to control desire. We can talk about rumination, cognitive inflexibility, inability to process emotions. But what is felt, in the body, is the brutality of denying the body’s fundamental appetites.

With that in mind, I wonder whether our discussion around eating disorders is too theorized, too removed from the basic, primal nature of hunger, feasting, and eating. Psychedelics, too, usher us into the primal. This link is not made in scientific discourse, but that doesn’t discount its validity—at least not for people who will walk into that treatment room, with all their hurt and want and hope. I plan to be among them.

*From the article here :
 
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