Psilocybin-assisted Therapy for Anorexia Nervosa

Overview: Anorexia nervosa is a severe mental health condition with limited effective treatments. A study investigated the safety and efficacy of psilocybin therapy in female individuals with anorexia nervosa. The study showed promising safety and tolerability outcomes, with participants reporting positive experiences and improvements in quality of life. However, the study had limitations including a small sample size, lack of a control group, and an exploratory design. While the findings offer hope, further research with larger, randomized controlled trials is necessary to establish the effectiveness of psilocybin therapy for anorexia nervosa definitively.

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What is Anorexia Nervosa?

Anorexia nervosa is a serious mental health condition marked by an intense fear of gaining weight, leading to extreme food restriction and unhealthy weight loss. It’s a deadly disorder, with high rates of morbidity and mortality, including an increased risk of suicide.

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Despite its severity, current treatments often fall short, leaving less than half of patients able to fully recover and with a high likelihood of relapse. Progress in finding effective treatments has been slow, leaving many searching for new solutions.

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One potential avenue of exploration is psilocybin-assisted therapy. In 2023, researchers conducted a study to explore the safety, tolerability, and potential benefits of using a single dose of psilocybin — the psychedelic drug found in magic mushrooms — alongside psychological support. This research offers hope for new approaches to tackling this challenging condition.

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Psilocybin for Anorexia Nervosa: Study Protocol and Procedure

In this study, researchers did what’s known as an open-label feasibility study, aiming to evaluate the safety, tolerability, and practicality of psilocybin-assisted therapy as a potential treatment for anorexia nervosa. The study enrolled ten adult female participants who met the criteria for either anorexia nervosa or partial remission. 

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Before participants were accepted into the study, they underwent a rigorous screening process. This process involved obtaining informed consent, conducting medical screenings including electrocardiograms (ECG), blood tests, and vital sign assessments, as well as reviewing past medical records.

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Additionally, psychiatric interviews and assessments were conducted to confirm a diagnosis of anorexia nervosa and to rule out other psychiatric disorders such as psychotic disorders, bipolar disorder, and substance use disorders within the past year. Screening also included assessments for imminent suicidality and borderline personality disorder. Participants who were taking serotonergic medications were gradually tapered off these medications during the screening period.

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Once successfully screened, participants received a single dose of 25 milligrams (mg) of psilocybin, administered in five capsules each containing 5 mg, along with psychological support. Throughout the psilocybin session, which lasted approximately 8 hours from ingestion, two psychologists were present to provide support and monitor safety (to learn more about the duration of psilocybin’s effects, see How Long Do Shrooms Last?)

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The setting for the psilocybin treatment of anorexia nervosa is carefully crafted to promote comfort and introspection, essential for the therapeutic process. The room usually has soft, natural lighting and soothing, neutral colors that create a calm and welcoming environment. To deepen the introspective experience, patients are provided with headphones playing music and eye shades to minimize external distractions and encourage inward focus.

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The day after the session, participants returned to the clinic for post-treatment assessments. They met with the psychologists for a safety assessment and engaged in a 60-90-minute integration session.

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Integration sessions are designed to help participants process their experiences during the psilocybin session, integrate insights gained, and address any lingering emotions or thoughts arising from the experience. These sessions play a crucial role in maximizing the therapeutic benefits of psilocybin-assisted therapy.

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Insights on Safety and Tolerability

In terms of safety and tolerability, this study yielded encouraging results. All adverse events reported during the study were classified as mild and transient, indicating that participants experienced no severe or long-lasting negative effects. 

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Specifically, there were no clinically significant changes observed in electrocardiograms (ECG), which measure the electrical activity of the heart. Vital signs, including blood pressure and heart rate, remained stable throughout the study period. Additionally, there were no indications of increased suicidality among participants following psilocybin administration.

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Two participants did experience asymptomatic hypoglycemia, a condition characterized by abnormally low blood sugar levels, on the day of dosing. However, these episodes resolved within 24 hours. It’s worth noting that both instances of hypoglycemia occurred in participants who had been given a standardized breakfast upon arrival at the clinic.

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Researchers hypothesized that this hypoglycemia was likely due to the prolonged fasting period on the dosing day, rather than a direct effect of the psilocybin itself. Given the state of malnutrition and low carbohydrate stores associated with anorexia nervosa, attention to blood glucose levels before and after psilocybin therapy may be warranted, as hypoglycemia can pose serious risks in this population.

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Considering the high prevalence of serious medical complications and physiological disturbances in individuals with anorexia nervosa, the absence of significant safety concerns in this study is promising. However, larger-scale studies are needed to further evaluate the safety profile of psilocybin-assisted therapy in this population and to confirm these findings.

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Psychological Changes and Treatment Response

In terms of changes in anorexia nervosa symptoms, the study revealed some notable findings. 

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Weight concerns among participants decreased significantly from baseline to the one-month follow-up assessment. Similarly, shape concerns also showed a significant decrease at the one-month follow-up, although this effect was no longer significant by the three-month follow-up.

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When the researchers measured specific aspects of eating behavior — specifically ‘eating concerns’ and ‘dietary restraint’ — the changes observed from the baseline to the follow-up period did not reach statistical significance. Statistical significance is a term used to determine if the results of a study are likely not due to chance. In this context, it suggests that the intervention or treatment tested did not conclusively alter these specific behaviors or attitudes in a way that could be definitively attributed to the psilocybin treatment.

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While the changes in eating concerns didn’t meet the statistical threshold to be considered significant, the data suggested a possible effect that could be close to becoming significant. This means the results showed some indication of improvement in eating concerns but were not strong enough to firmly conclude that the treatment was effective. 

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The study observed that while overall changes in eating concerns and dietary restraint due to the treatment weren't strong enough to be statistically significant, there was some indication that eating concerns might be improving, suggesting that there could be potential benefits that might become clearer with either a larger sample size, longer follow-up duration, or more sensitive measurement tools.

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Approximately 40% of the sample demonstrated Eating Disorder Examination (EDE) scores, a structured interview that assesses the range and severity of eating disorder behaviors and attitudes that decreased to within 1 standard deviation of community norms at the three-month follow-up. This means that these participants’ scores on the EDE were comparable to those of individuals in the general community. This is interpreted as clinically significant improvement in their symptoms.

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However, the effects of psilocybin treatment varied widely among participants, indicating a diverse range of responses to the therapy across the study sample.

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Delving Deeper: Secondary Outcome Measures Shed Light on Treatment Effects

Secondary outcome measures are additional assessments done in a study to gather more information about the effects of the treatment being investigated. In this study, researchers examined several secondary outcome measures in addition to the primary ones.

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On average, changes in body mass index (BMI), a measure of body weight relative to height, were not statistically significant. Although the changes in BMI were not significant on average, this does not mean the treatment was ineffective for all aspects or for all individuals. Some participants experienced meaningful improvements in their eating disorder symptoms, as measured by the Eating Disorder Examination Examination.

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However, changes in BMI were inconsistent among those who showed improvements in eating disorder symptoms. Furthermore, there was no consistent pattern linking the degree of improvement in eating disorder symptoms to specific changes in BMI. This suggests that while the treatment might help alleviate psychological symptoms of eating disorders, these benefits do not necessarily translate into weight changes, or that weight changes are not a reliable indicator of recovery in these cases.

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It’s worth noting that five participants experienced an increase in BMI at the three-month follow-up. This finding is significant because individuals with anorexia nervosa often face challenges with weight rehabilitation due to factors like hypermetabolism and high caloric requirements. These factors can make it difficult for them to gain weight despite efforts to improve their eating habits.

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These results suggest that targeted nutritional rehabilitation, as typically used in traditional treatments, may still be necessary even when significant improvements in eating disorder symptoms are observed.

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Regarding other secondary measures, participants, on average, showed significant reductions in:

• Trait body image anxiety
• Trait anxiety
• Preoccupations and rituals surrounding food, eating, and shape at the one-month follow-up.

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However, like with the primary outcomes, these results varied among individuals, indicating that the effects of treatment were not uniform across the sample. 

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Positive Perceptions: Participant Experiences with Psilocybin in Anorexia Treatment 

Participants in the study reported overwhelmingly positive experiences with the psilocybin treatment. For many, the experience was not only meaningful but also transformative.

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80% of participants expressed feeling more positive about their life endeavors after undergoing the psilocybin treatment. Remarkably, 80% described the psilocybin experience as one of the top five most meaningful experiences of their entire lives. Additionally, 70% reported a notable shift in their personal identity and an overall improvement in their quality of life.

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These findings are encouraging indicators of the potential benefits of psilocybin-assisted therapy for individuals with anorexia nervosa, especially considering the challenges associated with treating this complex disorder. It’s particularly noteworthy that all participants remained engaged in the treatment, with no dropouts recorded. This high level of engagement suggests that the treatment was well-received and tolerated by the participants.

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The positive perceptions reported by participants are significant not only because they indicate the potential therapeutic value of psilocybin but also because they may suggest improvements in quality of life — a crucial aspect of managing a chronic and debilitating condition like anorexia nervosa. Unlike many other mental illnesses, anorexia nervosa presents unique physiological and physical recovery needs, further emphasizing the importance of exploring novel and effective treatment approaches.

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Interestingly, the majority of participants (90%) expressed the feeling that one dosing session was not sufficient to fully benefit from the treatment. This suggests that additional psilocybin experiences may be necessary or beneficial for maximizing the therapeutic effects of the treatment. This finding underscores the importance of further research into the optimal dosing regimen and treatment protocols for psilocybin-assisted therapy in the context of anorexia nervosa.

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Understanding Study Limitations: Implications for Interpretation

It’s important to acknowledge the limitations of this study to provide a balanced perspective and ensure that the findings are interpreted appropriately.

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Firstly, the small sample size is a limitation, as it reduces the generalizability of the findings to a broader population. Additionally, the lack of a control comparison group and the open-label design introduce the possibility of confounding variables and bias, which can affect the validity of the results.

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Moreover, because the study was exploratory in nature, power analysis or correction for multiple comparisons were not conducted. Power analysis helps determine the sample size needed to detect a significant effect, while correction for multiple comparisons helps minimize the risk of false-positive results when analyzing multiple outcomes. The absence of these analyses limits the robustness of the findings and increases the likelihood of chance findings.

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Furthermore, the self-referral of all participants may have introduced a selection bias, as individuals who chose to participate may differ systematically from those who did not. This could affect the representativeness of the sample and the generalizability of the results to the broader population of individuals with anorexia nervosa.

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It’s crucial to discuss these limitations to provide context for interpreting the study’s findings and to emphasize the need for further research with larger, more diverse samples and rigorous study designs. By acknowledging these limitations, we can ensure a more cautious and accurate understanding of the potential benefits and limitations of psilocybin-assisted therapy for anorexia nervosa.

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Psilocybin Therapy for Anorexia Nervosa: Promising Paths Forward

In conclusion, the findings from this study offer promising insights into the safety, tolerability, and potential efficacy of psilocybin therapy for female individuals with anorexia nervosa.

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Participant experiences suggest that psilocybin therapy may hold promise in addressing the physiological dangers associated with the disorder and improving treatment engagement. However, it's important to recognize the limitations of the study, including its small sample size, lack of a control group, and exploratory nature, which necessitate cautious interpretation of the results. 

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Nevertheless, the robust response observed in a subset of participants in this single-dose trial is notable, particularly considering the limited effectiveness of current treatments for adult anorexia nervosa. The researchers suggest that additional therapeutic methods or extended therapeutic time may be beneficial in facilitating further behavioral change and increasing specificity, as seen in other psilocybin studies.

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In summary, while this study provides valuable preliminary insights, more trials are needed to draw definitive conclusions about the safety and efficacy of psilocybin therapy for anorexia nervosa. Further research in this area has the potential to advance our understanding and treatment of this challenging and often life-threatening disorder.