This randomized, double-blind, active placebo-controlled, crossover study (n=32) investigated the antidepressant efficacy of ketamine (31mg/70kg) by using quantitative and qualitative assessments of its long-term effects and acute psychedelic experience. Rapid improvements in depressive symptoms correlated with higher scores on the spirituality, experience of unity, and insight subscales of the altered states of consciousness questionnaire (11D-ASC), but were not sustained beyond two weeks. The authors classified subjective themes of the acute experience (e.g. change in perception, emotion, loss of control, questioning of existence or self) which highlight the psychedelic qualities of ketamine, and identify six additional themes of their long-term perspective (change in perspective, change in mood, change in emotion, time, expectations, attitude to future treatments) alluding to differences between treatment responders and non-responders that are not readily captured by the standardized symptom scores.
“Background: Ketamine is central to one of the most rapidly growing areas of neuroscientific research into novel treatments for depression. Limited research has indicated that the psychedelic properties of ketamine may play a role in its antidepressant effects.
Aim: The aim of the current study was to explore the psychedelic experiences and sustained impact of ketamine in major depressive disorder.
Methods: In the current study, ketamine (0.44 mg/kg) was administered to 32 volunteers with major depressive disorder in a crossover design with the active-placebo remifentanil, in a magnetic resonance imaging (MRI) environment. The 11-dimension altered states of consciousness questionnaire and individual qualitative interviews were used to capture the acute psychedelic experience. The Montgomery-Asberg Depression Rating Scale and further interviewing explored lasting effects. The second qualitative interview took place ⩾3 weeks post-ketamine.
Results: Greater antidepressant response (reduction in Montgomery-Asberg Depression Rating Scale at 24 h) correlated with the 11-dimension altered states of consciousness dimensions: spirituality, experience of unity, and insight. The first qualitative interview revealed that all participants experienced perceptual changes. Additional themes emerged including loss of control and emotional and mood changes. The final interview showed evidence of a psychedelic afterglow, and changes to perspective on life, people, and problems, as well as changes to how participants felt about their depression and treatments.
Conclusions: The current study provides preliminary evidence for a role of the psychedelic experience and afterglow in ketamine’s antidepressant properties. Reflexive thematic analysis provided a wealth of information on participants’ experience of the study and demonstrated the psychedelic properties of ketamine are not fully captured by commonly used questionnaires.”
Authors: Rachael L. Summers, Emme Chacko, Rebecca McMillan, Meg J. Spriggs, Christie Anderson, James Chen, Amelia French, SungHun Jung, Akshaya Rajan, Gemma Malpas, John Hay, Rhys Ponton, Suresh D. Muthukumaraswamy, Frederick Sundram
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Journal of Psychopharmacology
March 30, 2021
Placebo-Controlled Active Placebo Double-Blind Within-Subject Randomized