Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial

Summary & key facts

Researchers gave people with moderate to severe depression a placebo session and then, four weeks later, a controlled dose of psilocybin while they all took part in a structured psychotherapy program based on Acceptance and Commitment Therapy. After the psilocybin session, people showed bigger improvements in how flexible they were with their thoughts and feelings, in some parts of mindfulness, and in living according to their values. Those increases in psychological flexibility were linked to larger drops in depressive symptoms, and the improvements lasted through the 16-week study. The study is small and exploratory, so it does not prove cause, but it gives clinical evidence that changes in psychological flexibility may help explain why psilocybin-assisted therapy can reduce depression symptoms.

Key facts:

• This was an exploratory, placebo-controlled study where the same people first had a placebo session and then had psilocybin four weeks later.
• 19 people completed the placebo session and 15 people received psilocybin at a dose of 0.3 mg per kilogram of body weight.
• Dosing sessions were given inside a manualized psychotherapy program that used ideas from Acceptance and Commitment Therapy, which teaches flexible responding to thoughts and feelings.
• Researchers measured depression severity, psychological flexibility (the ability to notice and adapt to thoughts and feelings), mindfulness, and living according to personal values over 16 weeks.
• After the psilocybin session, psychological flexibility, several aspects of mindfulness, and values-congruent living improved, and those gains were still present at week 16 (about four months).
• Larger improvements in psychological flexibility and in accepting experiences were strongly linked to bigger reductions in depression symptoms after psilocybin.
• The study is small and used a fixed order (placebo then psilocybin), so the results are suggestive but not definitive proof that psilocybin causes these changes.
• These results add clinical support to earlier observational work suggesting that increasing psychological flexibility might be an important way psilocybin-assisted therapy helps people with depression.

Abstract

Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.

Topics

Chemical synthesis and alkaloids Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Acceptance and commitment therapy Alternative medicine Anxiety Clinical psychology Depression (economics) Economics Epistemology Experiential avoidance Flexibility (engineering) Hallucinogen Intervention (counseling) Macroeconomics Major depressive disorder Mathematics Mechanism (biology) Medicine Mindfulness Mood Pathology Philosophy Placebo Psilocybin Psychiatry Psychology Psychotherapist Statistics

Substances

Psilocybin

Conditions & symptoms

Anxiety Depression Sadness or low mood