The effects of acute tryptophan depletion on instrumental reward learning in anorexia nervosa – an fMRI study

Steding, Julius; Ritschel, Franziska; Boehm, Ilka; Geisler, Daniel; King, Joseph A.; Roessner, Veit; Smolka, Michael N.; Zepf, Florian Daniel

doi:10.1017/s0033291721005493

“…Unlike other serotonergic medications requiring repeated administrations, a single dose of psilocybin may lead to rapid and enduring synaptic adaptations that have the potential to improve AN symptoms 10 . However, the role of 5-HT dysfunction in AN and related affective states associated with restriction remains poorly understood with mixed findings 11 , 12 .…”

Section: Mainmentioning

confidence: 99%

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study

Peck,

Shao,

Gruen

et al. 2023

Nat Med

View full text Add to dashboard Cite

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m−2; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants’ qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement.

show abstract

“…The same group reported that, despite the reduction of TRP/LNAA ratio, there was no difference in anxiety and mood between recovered AN ( n = 22) and healthy controls ( n = 25) exposed to TRP depletion [ 91 ]. Finally, based on functional magnetic resonance imaging, acute TRP depletion was shown to normalize the reward-related neural responses in recovered AN ( n = 22) compared to controls ( n = 25) [ 92 ].…”

Section: Dietary Interventionsmentioning

confidence: 99%

New Perspective on Anorexia Nervosa: Tryptophan-Kynurenine Pathway Hypothesis

Alberts

¹

,

Owe-Larsson

²

,

Urbańska

³

2023

Nutrients

0

View full text Add to dashboard Cite

Anorexia nervosa (AN), affecting up to 4% of all females and 0.3% of all males globally, remains the neuropsychiatric disorder with the highest mortality rate. However, the response to the current therapeutic options is rarely satisfactory. Considering the devastating prognosis of survival among patients with AN, further research aimed at developing novel, more effective therapies for AN is essential. Brain and serum tryptophan is mostly converted along the kynurenine pathway into multiple neuroactive derivatives, whereas only 1–2% is used for the synthesis of serotonin. This narrative review provides an update on the experimental and clinical research data concerning the metabolism of tryptophan along the kynurenine pathway in anorexia nervosa based on the available literature. We propose that in AN, lower levels of L-kynurenine and kynurenic acid result in diminished stimulation of the aryl hydrocarbon receptor, which could contribute to abnormally low body weight. The impact of L-kynurenine supplementation on anorexia in animal models and the effects of changes in tryptophan and downstream kynurenines on the clinical progression of AN require further investigation. Moreover, prospective clinical studies on larger cohorts of restrictive and binge-eating/purging AN patients and assessing the potential benefit of L-kynurenine as an add-on therapeutic agent, should follow.

show abstract

Psilocybin Therapy for Females With Anorexia Nervosa: A Phase 1, Open-Label Feasibility Study

Peck,

Shao,

Gruen

et al. 2024

FOC

0

View full text Add to dashboard Cite

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m −2 ; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514.Anorexia nervosa (AN) is a costly and deadly mental illness, which is notoriously difficult to treat 1 . It is associated with substantial morbidity and mortality, including an elevated suicide rate and an 18-fold increase in mortality 2,3 . Despite its seriousness, there are no proven treatments for adult AN that reverse core symptoms and no approved pharmacological interventions 1 . As a result, estimates suggest that less than half of patients achieve recovery; relapse rates approach 50%; and approximately 20% of those with AN will develop a chronic course 3 . There have been minimal advancements in novel treatment strategies and stagnant outcomes over the past several decades, resulting in a 'crisis in care' 4,5 . Novel and innovative treatments methods are urgently needed to improve treatment engagement and outcomes. One such avenue may be psilocybin therapy.Psilocybin is a psychedelic molecule whose mechanism of action is thought to be mediated by serotonin 2A (5-HT 2A ) 6 and is the main psychoactive compound in the Psilocybe genus of mushrooms 7 . Considerable evidence suggests that individuals with AN have altered brain serotonin (5-HT) function, altered function of the 5-HT 2A receptor and

show abstract

The effects of acute tryptophan depletion on instrumental reward learning in anorexia nervosa – an fMRI study

Cited by 3 publications

References 93 publications

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study

New Perspective on Anorexia Nervosa: Tryptophan-Kynurenine Pathway Hypothesis

Psilocybin Therapy for Females With Anorexia Nervosa: A Phase 1, Open-Label Feasibility Study

Contact Info

Product

Resources

About