Exposure therapy under psilocybin for general anxiety disorder and claustrophobia

doi:10.21203/rs.3.rs-2859973/v1

Download PDF

Case Report

Exposure therapy under psilocybin for general anxiety disorder and claustrophobia

https://doi.org/10.21203/rs.3.rs-2859973/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Case report of a patient with GAD and claustrophobia who underwent exposure therapy using psilocybin-assisted psychotherapy. The patient had failed to respond to conventional psychotherapeutic treatment. After three sessions of psilocybin-assisted psychotherapy, the patient experienced a reduction in anxiety and fear associated with closed spaces, elevators, and planes. The protocol included both an imaginary exposure exercise and a classic exposure therapy in an elevator during the psilocybin-assisted psychotherapy. the patient experienced a significant improvement in his score on the Beck Depression Inventory-II (BDI-II), the State-Trait Anxiety Inventory (STAI), and the Fear Questionnaire before and after therapy. He reported a generalization of the treatment effects, feeling more relaxed and having a greater willingness to confront fearful situations. He also described a shift in his perception of fearful stimuli, which may be explained as the development of new memory representations and a major disconfirmatory experience.

Exposure therapy is a psychotherapeutic intervention that involves gradually and systematically exposing individuals to their feared object or situation in a controlled and safe environment, in order to reduce their anxiety and fear. It is considered the gold standard treatment for specific phobias, and has been shown to be effective in reducing fear and anxiety in individuals with these types of phobias.

There are several theoretical models that have been proposed to explain the mechanism of action of exposure therapy, including the model of extinction learning (1, 2). According to this model, extinction is thought to result from the development of new memory representations that compete with, but do not erase, the original memory of fear. One of the main compound of extinction learning is to produce in patients a stronger as possible disconfirmatory experiences, meaning the expected feared outcomes are not happening (in claustrophobic fear, the patient might expect to die from a heart attack).

Some researchers have explored the use of medications, such as β-adrenergic receptor antagonists (3), in conjunction with exposure therapy to reduce the physical effects of feared stimuli and potentially reduce negative cognitions. Benzodiazepines have effects on anxiety and are evidence based treatments for (GAD) (4) but, as they reduce the fear reactions, they might not change the cognitions and emotions, and therefore might fail to induce new effective memories representations.

In contrast, psychedelics, such as LSD and psilocybin, have the potential to produce changes in emotions, cognitions, and physical sensations, and may be useful in creating new, effective memories (5). These substances have been shown to induce intense modulations of perception, such as synesthesia, ego dissolution, and insightfulness, and may be able to reduce fear responses and facilitate the formation of new experiences. In addition, psilocybin has been shown to increase brain network integration in patients treated for depression, which may facilitate the formation of new memories (6).

Human clinical trials have demonstrated the effectiveness of psychedelics in treating resistant depression (7, 8) and general anxiety symptoms (9). Animal studies have also shown that rats treated with 5-HT2A antagonists exhibit a reduction in fear without a reduction in exploration behaviors (10).

Based on these findings, the hypothesis can be put forward that exposure therapy under the effects of psychedelics may be effective in reducing fear and anxiety in individuals with phobias, by facilitating the formation of new, effective memory representations and reducing fear responses to feared stimuli. One of the main expected mechanism is to induce a strong disconfirmatory experience: the patient under psychedelic will experience altered emotions, perceptions and cognitions inducing a completely different outcome as their habitual strongly conditioned fear reaction.

A patient in his 40s, diagnosed with general anxiety disorder and a secondary depressive condition, has mainly claustrophobic and somatic anxiety, as well as a history of panic attacks. He reports no traumatic events or antecedents and has described a happy childhood and adolescence. He completed a university education and is currently employed. His anxiety gradually developed during early adulthood and became disabling, preventing him from traveling and being in closed spaces such as elevators. Conventional psychotherapeutic treatment and SSRI antidepressants have had moderate to no results, and benzodiazepines have had limited effect and the patient fears becoming dependent on them.

Given the unsuccessful psychotherapeutic treatment and the patient's fear of conventional antidepressants, as well as the favorable side effect profile of psilocybin, the decision was made to propose psychedelic assisted psychotherapy as a potential treatment option. The patient was interested in finding a way to overcome his fear and reduce his general anxiety.

After obtaining the necessary authorization from the Swiss Federal Office of Public Health (FOPH) to provide medical, limited use of psychedelics, the patient underwent three sessions of psychedelic assisted psychotherapy (PAP) using psilocybin. Psilocybin was chosen for its shorter duration of effects compared to LSD, but with similar psychedelic properties at the chosen dosage. The dosage of psilocybin used in this case was 25mg for the first two sessions and 35mg for the third session.

The classical PAP protocol includes preparatory sessions (in this case, three sessions) to explain the therapeutic process to the patient, followed by the psilocybin sessions, which take place in an outpatient setting. The patient takes the psilocybin under medical supervision after a psychiatric and physical evaluation, and is supervised by trained nurses during the whole session, which typically lasts 6-8 hours for psilocybin. During the session, the patient lies in a bed, wears a blindfold, and listens to music. The day after the session, the patient has an integration session with their therapist to debrief and work through any experiences or insights gained during the psychedelic session.

In this case, the treatment protocol included an exposure therapy component, both before and during the psychedelic treatment. The first PAP session involved an imaginary exposure exercise, in which the patient imagined himself in an elevator and on a plane. In the integration session, the patient reported that his perceptions were different and the normal bursts of anxiety associated with these thoughts were more tolerable. The second PAP session included a classic exposure therapy exercise in the clinic's elevator, with the patient exposing himself to the elevator (accompanied by a therapist and then alone) before taking the psilocybin. The patient reported an anxiety rating of 6/10, with bursts of 8/10 when alone.

During the peak of the subjective effects of psilocybin, the patient was again exposed to the elevator, both accompanied and alone. He did not experience any major visual or somatosensory disturbances, but rather a feeling of strength and a lack of anticipatory fear. When accompanied, the patient reported an anxiety rating of 1/10, and when alone, an anxiety rating of 2/10.

In the integration session, the patient described a shift in his mindset when entering the elevator, viewing it as a worthy challenge rather than a fearful task. He reported focusing on his anxiety level and experiencing quick bursts of anxiety, but noted that these bursts were different from his expected reactions in that they did not last and were not perceived as preventing him from completing the task.

The third PAP session, which involved a higher dosage of psilocybin, resulted in similar outcomes. The patient did not feel that exposure before treatment was necessary, and found that exposure during the psilocybin session reduced his anxiety to a rating of 1/10. In the third integration session, he reported that the higher dosage of psilocybin induced a sensation of going through a major challenge with intense thinking. He was unable to be more specific, but described the experience as ineffable (classically described as an effect of a psychedelic experience). He explained that going through this major experience (which he compared to an internal storm) had helped to relativize the fear he had previously experienced in elevators.

The patient underwent a total of three PAP sessions with psilocybin, spaced about six months apart, and the overall treatment lasted for about a year. In parallel with the psilocybin sessions, the patient also received traditional exposure-based cognitive-behavioral therapy (CBT) for a total of 10 sessions over the course of the year, and began taking the SSRI antidepressant fluvoxamine (100mg) two weeks after the first psilocybin session. He continued taking fluvoxamine (100mg) during the second and third psilocybin sessions, based on a study showing that healthy subjects taking citalopram do not experience any side effects or reduced psychedelic effects when using citalopram (11). This was confirmed using the Mystical Experience questionnaire (MEQ-30) (12), which showed scores of 92, 63, and 93 (out of a possible range of 0-150) for the first, second, and third sessions, respectively.

As seen in Figure 1, the patient experienced a significant improvement in his score on the Beck Depression Inventory-II (BDI-II), the State-Trait Anxiety Inventory (STAI), and the Fear Questionnaire before and after therapy. He reported a generalization of the treatment effects, feeling more relaxed and having a greater willingness to confront fearful situations. He also described a shift in his perception of fearful stimuli, which may be explained as the development of new memory representations and a major disconfirmatory experience. He now sees fearful stimuli as opportunities for growth rather than something to be avoided due to his psychiatric condition.

This is on our knowledge the first case report of exposure therapy under psychedelics. It shows that classical exposure therapy combined with psilocybin is feasible, safe, and well-tolerated. The very positive results are encouraging and suggest that further research should be conducted to compare exposure therapy with or without psychedelic psychotherapy, and/or psychedelic therapy with or without exposure therapy.

The patient's concurrent use of an SSRI and classical exposure therapy undoubtedly played an important role in his overall improvement. However, the patient felt that the psychedelic exposure therapy was a major factor in his recovery, suggesting that it may have helped him to engage with conventional treatments.

i. Ethical Approval and consent to participate :

The participant provided a written consent for the participation of this case report

ii. Consent to Publication

The participant provided a written consent for the publication of this case report

iii. Data Availability statement

Not applicable

iv. Conflict of interest

The authors have no conflicts of interest to declare

v. Funding

Not applicable

vi. Acknowledgment

Not applicable

vii. Author contribution

GT: conceptualisation, writing-original draft preparation, patient follow up. LP,FS,DZ: conceptualisation, writing-original draft preparation expert opinion, CM patient preparation and follow up, LF, SR, draft review, expert opinion.

viii. Author information (optional).

Not applicable

All data generated or analysed during this study are included in this published article.

Craske MG, Kircanski K, Zelikowsky M, Mystkowski J, Chowdhury N, Baker A. Optimizing inhibitory learning during exposure therapy. Behav Res Ther. 2008;46(1):5-27.
Craske MG, Treanor M, Conway CC, Zbozinek T, Vervliet B. Maximizing exposure therapy: An inhibitory learning approach. Behav Res Ther. 2014;58:10-23.
Boyce TG, Ballone NT, Certa KM, Becker MA. The Use of β-Adrenergic Receptor Antagonists in Psychiatry: A Review. Journal of the Academy of Consultation-Liaison Psychiatry. 2021;62(4):404-12.
Slee A, Nazareth I, Bondaronek P, Liu YF, Cheng ZH, Freemantle N. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019;393(10173):768-77.
Preller KH, Herdener M, Pokorny T, Planzer A, Kraehenmann R, Stampfli P, et al. The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation. Curr Biol. 2017;27(3):451-7.
Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, et al. Increased global integration in the brain after psilocybin therapy for depression. Nature medicine. 2022;28(4):844-51.
Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021;384(15):1402-11.
Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022;387(18):1637-48.
Holze F, Gasser P, Müller F, Dolder PC, Liechti ME. Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study. Biol Psychiatry. 2022.
Pędzich BD, Rubens S, Sekssaoui M, Pierre A, Van Schuerbeek A, Marin P, et al. Effects of a psychedelic 5-HT2A receptor agonist on anxiety-related behavior and fear processing in mice. Neuropsychopharmacology. 2022;47(7):1304-14.
Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, et al. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clinical pharmacology and therapeutics. 2022;111(4):886-95.
Barrett FS, Johnson MW, Griffiths RR. Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. Journal of psychopharmacology. 2015;29(11):1182-90.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Exposure therapy under psilocybin for general anxiety disorder and claustrophobia

Status:

Version 1

Abstract

Figures

BACKGROUND

CASE PRESENTATION

TREATMENT

OUTCOME AND FOLLOW-UP

DISCUSSION

Declarations

References

Additional Declarations

Status:

Version 1