This follow-up survey to an open-label study (n=20) on psilocybin for treatment-resistant depression (TRD) found that connection (vs disconnection) and acceptance (vs avoidance) of emotions were the two main mechanisms through which the therapy was successful.
“Objective: To identify patients’ perceptions of the value of psilocybin as a treatment for depression.
Method: Twenty patients enrolled in an open-label trial of psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Thematic analysis was used to identify patients’ experiences of the treatment and how it compared with previous treatments.
Results: Two main change processes were identified in relation to the treatment. The first concerned change from disconnection (from self, others, and world) to connection, and the second concerned change from avoidance (of emotion) to acceptance. A third theme concerned comparison between psilocybin and conventional treatments. Patients reported that medications and some short-term talking therapies tended to reinforce their sense of disconnection and avoidance, whereas treatment with psilocybin encouraged connection and acceptance.
Conclusions: These results suggest that psilocybin treatment for depression may work via paradigmatically novel means, antithetical to antidepressant medications, and some short-term talking therapies.”
This is a follow-up to Carhart-Harris et al. (2016) which was an open-label study on ‘Psilocybin with psychological support for treatment-resistant depression’.
Twenty patients who had received treatment with psilocybin for treatment-resistant depression participated in a semistructured interview at 6-month follow-up. Two main change processes were identified: change from disconnection to connection and change from avoidance to acceptance.
Over the past 10 years, there has been a growing interest in using psychedelic substances as treatments in psychiatry. Recent clinical trials have found promising safety, tolerability, and efficacy.
Modern investigations into the therapeutic potential of psychedelics started in the mid-1990s with basic human psychology and neuroimaging research. Eight separate studies have been conducted by eight independent research teams since 2006, but there has been relatively little discussion of underlying psychological mechanisms.
Qualitative studies are an important adjunct to quantitative data in the development of psychedelic-based treatments in clinical practice. They can provide extra information on long-term progress.
Two recent clinical trials involving psychedelic-based treatments have included qualitative analyses of patient experiences. Themes relating to similar concepts were found in both analyses, although they were described and organized in different ways.
The current qualitative study involved interviewing patients from the first clinical trial of psilocybin for Treatment-Resistant Depression. The patients were allocated two experienced clinicians as the therapeutic “guides” who attended all visits.
The two dosing sessions involved patients reclined on a bed, wearing eyeshades, and listened to a specific music playlist. Guides provided support by checking-in with the patient every 30 to 60 minutes, and encouraged them to “surrender” to the drug effects without resistance.
Clinical outcomes in the first 12 subjects were exceptionally positive, with 15 of the 20 patients showing some degree of reduction in depressive symptoms at 6 months follow-up. The remaining three patients reported barely detectable drug effects but no discernible changes in their depression.
Current Study: Patients
Twenty patients with TRD were enrolled in a clinical trial of psilocybin for TRD conducted at Imperial College London. All 20 patients took part in the qualitative follow-up interview.
Procedures: Qualitative Interviews
Nineteen patients gave their informed consent to take part in an optional follow-up interview, which consisted of a series of questions tracking patient experience. The interviews lasted about an hour and were recorded and transcribed by the first author.
Thematic analysis was used to identify central themes for each patient. Respondent validity checks were carried out after the final themes were identified.
Table 1. (continued)
Patients described psychedelic treatment as rectifying their sense of disconnection from self, others, and the world, and helping them confront, process, and accept painful thoughts, feelings, and memories.
Patients did not differentiate between high-dose and low-dose sessions, and often did not remember which particular session they were referring to.
A.1. Depression is Disconnection
Patients described their experience of depression as being “trapped in their minds”. Some described feeling persecuted and besieged, while others described their minds feeling like computers that have been “switched off” or “shut down”.
Most patients described being disconnected from their senses, including a lack of response to music and reduced sense of touch and visual perception.
Patients described feeling disconnected from their “self” and from the things they used to enjoy. They described becoming a diminished form of who they once were or who they might become.
Disconnection from others was particularly distressing for all patients, and for some it had gone so far that they no longer felt able to be touched.
A. 2. Psilocybin Treatment as Bringing Connection
Regardless of the quality and valence of the drug experience, most patients who showed a clinically significant response to the treatment described feeling a sense of mental freedom after the treatment.
One patient described how going back to a clear and open state during a meditation retreat helped him escape from depression.
For the 17 patients who experienced a normal level of subjective drug effects, the dosing experiences were rich in sensory phenomena.
Patients whose depression affected their sensitivity to touch reported dramatic improvements during the dose. One participant described a mental orgasm, while another reported feeling no sensations in his body, but described a connection to senses that was long-lasting.
A number of different themes emerged, including a boost of self-worth, restarting previous hobbies, and engaging in new activities that reflected new values.
Nearly half of the sample had realizations of being a “good person” and feelings of self-worth and self-compassion. They felt more confident and able to take on anything.
All patients for whom the treatment was effective reported reconnecting with past activities. One participant described flying on a plane again after avoiding this for a long time, and another described driving a long distance to visit his extended family.
The patients reported experiencing spontaneous “lessons” about eating plants instead of animals and about being loved and perfect. They also reported improvements to diet, exercise and cutting down on drinking alcohol.
Many people started new activities after the treatment, such as going out more and getting new jobs.
A. 2.4. Connection to others
Patients who had not previously identified themselves as spiritual reported having spiritual-like experiences under the psilocybin: “connecting to all other souls”, “I wonder if this is how the pope feels!”
Some patients saw religious imagery and/or iconography during the dose, and some identified with a deity. Others described a sense of expanding connection, and some struggled to put it into words.
B.1. Depression as Avoidance of Emotion
Rumination narrows emotional repertoire. For some patients, constant rumination left little space for processing emotions, and they felt stuck in their heads and unable to feel.
Some male patients described how social norms around masculinity had restricted their emotional repertoires, and how they had learned to put their feelings in a box.
Many patients tried to disguise particular emotions for other emotions, leaving them either in constant battle with the negative thoughts or living inauthentically.
Patients were particularly focused on battling with trauma memories, and after these intense “cathartic” experiences, they described a feeling of openness to experiencing emotions that was often long-lasting.
The high-dose session was experienced as “overwhelming bliss” for one patient, who described feeling intense emotions such as joy, fear, terror, tragedy, humour and love.
People described that during the dose, they could not avoid or hide from negative emotion, and that they finally surrendered, the feelings diminished.
Some people reported revisiting childhood traumas during the dose, sometimes in fragments that did not make sense until afterward.
Some patients reported going back to a memory they didn’t realise was there, or seeing a pillow held over their face as an infant. This memory helped them understand some things about themselves.
Drug experiences were often interspersed with memories of love and trauma, which provided much-needed relief and sustenance. These memories included being safe in the womb, playing as children, happy times as teenagers, and performing heroic acts.
Many patients had powerful bouts of sobbing during the dosing session, which were described as a welcome, physical “purging” or “purification”.
For many patients, surrendering to emotion was an embodied experience. They reported specific physical sensations, which they interpreted as emotions that had manifested as somatic symptoms because they had not been expressed.
C. Comparison of Psychedelic Treatment to Previous Treatments
The patients in this trial were resistant to treatment, and only three had positive experiences of talking therapy. Two cases of psychodynamic psychotherapy and one case of CBT were described as having provided long-lasting benefits.
It was “here’s some tablets now go away.” (P1)
Some therapists were unwilling/unable to address traumatic experiences, and the short-term nature of therapy meant that some patients never had a chance to reveal information about their past that they felt was important or difficult to tell.
Some patients had taken therapy many years previously, and attentional biases may have increased the saliency of negative memories.
Therapy was seen as exacerbating depression in some patients. Community mental health team services were described as disappointing, and psychodynamic therapy was seen as exacerbating depression.
Most patients described taking antidepressants as the first line of treatment suggested by the general practitioner, but for some, the only treatment available.
Many patients reported negative reactions to antidepressants, including weight gain, excessive sedation and sleep, and suicidal ideation.
Psychedelic treatment enhances connection and acceptance of emotion. Patients appreciate the length of preparation, dosing, and integration sessions, which allows them to bring up issues that are hard to talk about.
Patients reported feeling safe to cry during the dosing session, but two would have liked more therapy sessions afterwards.
One patient reported feeling unsure about his experience after his session, and would have benefitted from additional integration work.
Patients were prepared for difficult experiences during dosing, and were given reassurance that this would not harm them, and could lead to good treatment outcomes. However, some patients reported high anxiety going into the dose, which did not seem to affect outcome or treatment effectiveness.
Many people said the hospital setting made them feel safe, but two patients said it was too clinical and cold.
The music facilitated change process two very powerfully, leading patients to surrender to and acceptance of painful emotions. The emotional tone of the music could lead to a surge of the same emotion, which could lead to memories of childhood.
Some patients felt that the darkness of some of the pieces of music was unbearable, and some wanted more freedom to change the music.
Patients described good rapport with their guides, felt well looked after, and felt bonded to them after the dose. They valued the integration sessions after dosing, which helped them weave a story of what happened.
Psilocybin helped people access an “inner voice” that felt immensely powerful and motivating. They recalled this “inner voice” more vividly than the things their guides had said to them.
Some patients commented on how the 6-month follow-up interview helped them reconnect with how they had felt during their dosing days.
Psychedelic treatment was considered preferable to other treatments for depression. All 20 patients said they would like to experience it again and suggested that they would probably require at least one booster dose.
Four patients were formally in remission, 10 were depressed again at the time of the follow-up interview, but maintained that the psilocybin treatment had been a positive experience for them.
The trial team felt they could not condone patients seeking psychedelic therapy elsewhere, even if the therapy was legal. Two patients reported benefits, while another reported a less positive response.
A qualitative, thematic analysis of 6-month follow-up interview data in a recently completed clinical trial of psilocybin for TRD generated two major themes: patients described the treatment as having driven a change from disconnection to connection, and from emotional avoidance to acceptance.
Regarding the first change process, the experience of psilocybin treatment was described as a sense of the world getting bigger, and the mind “rebooted”.
Alongside the expansion outward, an “inner” expansion also seemed to have taken place, with patients reporting a range of intense emotions. This was consistent with previous findings of sustained increases in trait Openness in healthy volunteers after high dose psilocybin sessions.
Recent neuroimaging and pharmacological studies of psychedelics have suggested that the brain enters a hyperplastic state under psychedelics that may facilitate learning and change. However, psychological priming and environmental factors are essential determiners of the quality of responses.
The processes of connection and acceptance have parallels to ideas from depth psychology, such as Jungian notions of the collective unconscious.
Initiatives to systematically examine the relative merits of different therapeutic approaches and environmental components are currently being considered. This work should lead to a standardization of the therapeutic approach for psychedelic therapy.
Acceptance and commitment therapy (ACT) may be particularly complementary to the specific character of the psychedelic experience, as it aims to improve psychological flexibility via six key processes, all of which resonate with the themes generated by patients in this study.
Patients in this study reported feeling disenchanted with traditional treatments for depression. They valued the opportunity the present treatment afforded them to access their emotional pain, which brought tears of relief and reports of feeling lighter and more open afterwards.
Psychedelic therapy is novel and potentially antithetical to conventional talking and pharmacological therapies. However, future studies may examine the possibility of using psychedelic therapy as a catalyst of and/or supplement to conventional treatments.
The high level of care and attention patients received from the research team may have enhanced transference relationships and the implicit desire of the patients to get well for their therapists, which may have biased treatment outcomes.
Regarding other biases, it is likely that patients self-selected for this trial because they believed it would be effective for them. Moreover, they had negative views about their previous unsuccessful treatments, which may have biased their outcome.
The present article focuses on positive outcomes, but the data show that most patients had positive experiences. A few patients criticized the way the therapists delivered the treatment, but there were no serious adverse events.
Regarding specific cases, Patient 14 reported a “reliving” of a childhood trauma, while Patient 15 became uncommunicative for a prolonged period during the peak drug effects. The therapy team felt it unwise to offer a judgment on whether this was a real memory or fantasy.
In the current study, participants reported experiencing psychedelics in a way that deschematized and viewed experiences in another perspective, facilitated access to emotions and catharsis, and had no negative aspects of the treatment.
Psychedelic treatment has been found to help a wide range of conditions, such as posttraumatic stress disorder, addictions, obsessive-compulsive disorder, depression, smoking cessation, and end-of-life anxiety. Perhaps psychedelics have an impact on certain fundamental processes that underlie many psychiatric conditions.
In the present study, patients reported that months after the psilocybin treatment, they still felt better than before the treatment, and that they had greater meaning in their lives. This suggests that improved measures of psychological well-being may be needed.
Thematic analysis of structured interviews performed 6 months after psilocybin for treatment-resistant depression in 20 patients revealed two major themes: a change from disconnection to connection and a change from avoidance of difficult emotions and memories to acceptance.
Before you heard about the study, can you briefly describe what your experience of depression was like? How did you hear about the study and what made you decide to take part?
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Authors associated with this publication with profiles on BlossomDavid Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.
Rosalind Watts is a clinical psychologist and clinical lead at the Psychedelics Research Group at Imperial College London. She is also known for developing the 'Accept, Connect, Embody' psychedelic therapy model.
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.
Institutes associated with this publicationImperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.
The psychedelics given at which dose and how many timesPlacebo 10 - 25
mg | 2x
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