“This Is Something That Changed My Life”: A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders

Abstract

Background: The therapeutic benefits of ketamine have been demonstrated for a variety of psychiatric disorders. However, the role of ketamine induced psychoactive experiences in mediating the therapeutic effects is unclear. Despite the growing quantitative research on the efficacy of ketamine treatment, very few studies examined participant experiences of ketamine infusions in a treatment setting.Aims: The current study aimed to examine participant experiences of ketamine infusions and how these relate to therapeutic mechanisms in a clinical trial setting.Methods: We conducted semi-structured interviews with 12 participants who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II double blind, randomised controlled trial. The interviews explored participants' acute experiences of ketamine infusions, experiences of psychotherapy/education, and the lasting effects of the trial. The interviews were transcribed verbatim and analysed using thematic analysis.Results: Six key themes were identified. (1) Participants reported multifaceted motivations for trial participation. (2) The set and setting was found to be influential in determining acute ketamine experiences. The acute ketamine experiences included: (3) the inherent contradictions of the experience (e.g., dissociation vs feelings of connection), (4) rapidly fluctuating and changing experiences, (5) meaningful, mystical and spiritual experiences. Finally, the final theme (6) relates to the transformational effects of the infusions and the trial.Conclusion: Provided in a supportive and professional environment, ketamine treatment led to a significant change in relationship with alcohol. Ketamine induced ego dissolution and dissociation were reported to be related to the transformational effects on relationship with alcohol. The extent to which the acute psychoactive effects of ketamine mediate therapeutic effects on drinking outcomes remain to be investigated in the trial data. The acute effects of ketamine reported by our participants transcend its traditional conceptualisation as a “dissociative anaesthetic”; therefore, we suggest the development or use of new measures alongside ketamine infusions to fully capture the spectrum of these effects which may be crucial in its therapeutic and transformative effects.

A unified model of ketamine’s dissociative and psychedelic properties

“…Turning for the psychological experience in more detail, if we focus on the themes identified in psilocybin-assisted therapy for depression ( Watts et al, 2017 ) and search for them in the patient accounts of KAP for alcohol dependence ( Mollaahmetoglu et al, 2021 ), which is the controlled trial in which ketamine was embedded in a psychotherapeutic framework with more similarities to the PAP model, we are able to find some clear parallels. For example, in the first trial of psilocybin for depression, most patients reported how depression made them feel ‘trapped in their minds’, disconnected from themselves, their senses, others and the world and how psilocybin made them feel connected to their selves, senses, others, the world and to a spiritual principle ( Watts et al, 2017 ).…”

“…Results of qualitative interviews obtained during a RCT of KAP for alcohol dependence have also been published ( Mollaahmetoglu et al, 2021 ). Six key themes were identified: (1) multifaceted motivations to participate in the trial; (2) the influence of ‘set’ and ‘setting’ in the acute subjective experience; (3) the inherent contradictions of the ketamine experience; (4) rapidly fluctuating and changing experiences; (5) meaningful, spiritual and mystical experiences and (6) transformational effects of the infusions and the trial.…”

Psychedelics in the treatment of unipolar and bipolar depression

“…Indeed, investigations show that conscious phenomenological changes appear not to be a necessary condition for the antidepressant response to ketamine (Ballard and Zarate, 2020 ). However, also ketamine-induced psychedelic experiences might be of additional therapeutic value, when used in a psychedelic-assisted psychotherapy context (Mathai et al, 2020 , 2022 ; Mollaahmetoglu et al, 2021 ; Dore et al, 2019 ).…”

Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review

“…Ketamine can induce alterations in bodily perceptions, including feelings of lightness and floating [161,162]. Patients with AN tend to report high levels of cognitive control and cognitive rigidity [163,164].…”

“…Additionally, disconnection from the self, others and the world is core to AN [168][169][170]. It is possible that ketamine may have an additional therapeutic impact for patients with AN by promoting flexibility, ego dissolution, detachment from one's internal dialogue and openness to experiences [162]. Moreover, the mystical and spiritual experiences that often manifest during ketamine treatment [162] may enable patients to connect with their spirituality and alter their perceptions of both themselves in the context of the wider world and of the universe itself.…”