Motivation and emotion/Book/2023/Psilocybin assisted therapy and anxiety

Psilocybin assisted therapy and anxiety:
How can psilocybin assisted therapy help to treat anxiety?

Overview

Case Study

Empowering anxiety patients: Psilocybin therapy insights

Belser et al. (2017) conducted a quantitative psilocybin assisted therapy double-blinded study with 13 patients diagnosed with varying forms of anxiety related to cancer. All 13 participants experienced deep and meaningful encounters with loved ones, with some perceiving their loved ones as spiritual guides within their sessions. Participants described a range of profound experiences, including feelings of love, and joy, enhanced embodiment and increased interoceptive awareness, the discovery and exploration of their emotional depth, vivid close-eyed visuals, and lasting improvements in their overall quality of life. Every one of these experiences held profound significance for every participant, unique to their individual perspective and personal journeys. In this study, 7 participants initially faced struggles and distress ^[when?] but these were transient stages which led them into a deeper state of acceptance, surrender, love, and interconnectedness that expanded far beyond just themselves. Each participant also expressed their willingness and desire to experience psilocybin treatment again (Belser et al., 2017).

Known as Teonanacatl, "Flesh of the Gods," or simply magic mushrooms; psilocybin mushrooms, a serotonergic psychedelic substance, boasts a rich and extensive history. This entheogenic substance has been used throughout history as a medicinal remedy and a spiritual or shamanic tool (Stamets, 1996). Recent studies utilising psilocybin have shown promising results for effectively treating anxiety disorders and a number of other mental health conditions (Poulie et al., 2019). Psilocybin-assisted therapy has demonstrated its capacity to induce powerful emotional experiences that can lead to lasting changes in perception, emotion regulation, and behaviour (Yaden et al., 2021).

Focus questions:

What is the main theoretical framework behind psilocybin-assisted therapy for anxiety?
What are the specific mechanisms of action within the brain and how do these contribute to the therapeutic benefits for anxiety treatment?
What are the main components of a psilocybin-assisted therapy session for the treatment of anxiety?

Mechanisms of action: How psilocybin affects anxiety

Anxiety, particularly Generalised Anxiety Disorder (GAD), represents a more severe and enduring form of the common emotional state of anxiety. Anxiety disorders are often an agonizing subjective experience characterised by a persistent sense of fear, excessive worrying, tension, hypervigilance, and somatic symptoms lasting for 6 months or more (Hofmann & Hay, 2018; Wittchen, 2002). Comorbidity is prevalent among anxiety disorders, with many sufferers of the illness never fully recovering from symptoms (Wittchen, 2002). Recent studies reveal the profound effects and therapeutic advantages of psilocybin-assisted therapy as a promising and non-addictive approach for the enduring treatment of anxiety and its co-occurring psychiatric and physical conditions (Goldberg et al., 2020).

Serotonin receptor activation and neuroplasticity

Psilocybin is a tryptamine alkaloid found in certain fungi like Psilocybe cubensis (see Figure 2) and Psilocybe subaeruginosa (see Figure 1). Psilocybin rapidly metabolizes into its active form psilocin after ingestion. Possessing high hydrophilicity, it easily crosses the blood-brain barrier, entering the central nervous system, reaching the brain and influencing its function and activity (Ziff et al., 2022). The pharmacokinetics (how the body processes this substance) of psilocybin when taken orally in dosages ranging from 0.3 to 0.6 milligrams, show its effects follow a consistent and predictable pattern (de Vos et al., 2021).

**Figure 4.** The chemical structure of serotonin (5-HT).

Psilocybin and psilocin share a similar chemical structure to serotonin (see Figure 3 and Figure 4), a neurotransmitter that regulates mood and learning, and plays a key role in the modulation of anxiety (Zangrossi et al., 2020). Psilocin exhibits high affinity for various serotonin (5-hydroxytryptamine or 5-HT) receptors (SRs) in the brain, primarily occurring at the 5-hydroxytryptamine 2A receptor (5-HT2A-Receptor) (de Vos et al., 2021). These 5-HT2A-Receptors work like control switches in our brains, starting or stopping various cellular processes. Psilocin’s interaction with 5-HT2A-Receptors triggers a cascade of signalling pathways, influencing downregulation of SRs. This process influences neurotransmitter release into the prefrontal cortex (PFC), impacting emotional regulation. Simultaneously, the limbic system is affected, in particular the amygdala which is involved in emotional processing (Smausz et al., 2022; Ziff et al., 2022). In simpler terms, psilocin sets off a chain reaction in the brain regulating SRs and influencing the PFC and limbic system. Binding to the 5-HT2A-Receptor induces hallucinogenic effects, significant changes in human consciousness, emotions, and thinking, altering neural pathways and enhancing neuroplasticity (see Figure 5) (López-Giménez & González-Maeso, 2017).

DMN and emotional processing: Exploring 5-HT2A-Receptors

Understanding psilocybin’s interaction with 5-HT2A-Receptor involves acknowledging specific types of nerve cells in the cerebral cortex, known as Layer 5 pyramidal neurons which produce 5HT2A-receptors (Carhart-Harris et al., 2014). These receptors are situated in the Default Mode Network (DMN) (see Figure 6), particularly in the Posterior Cingulate Cortex (PCC). Psilocin’s activation of 5-HT2A-Receptors modulate the DMN’s functioning, crucial for emotional processing, introspection, and self-reflection. This interaction influences how individuals process and perceive themselves and their emotions during psilocybin experiences, fostering heightened self-awareness. This enables us to re-write narratives we have about ourselves which contribute to the profound psychological effects occurring during therapy (Carhart-Harris et al., 2014).

"We saw the default mode network disintegrating under the psilocybin. In breaking it down, you would be breaking down self. You think, “Well, that doesn’t sound that great. Brain sounds as though it goes into a chaotic state and everything’s kind of messy,” but there lies the opportunity to see things differently." - Dr Carhart-Harris (Adler & Pollan, 2022, 00:33:13).

Therapeutic impact

Psilocybin treatments induce temporary alterations in brain function, leading to increases in openness, changes within perceptions, emotions, and thoughts, facilitating a unique exploration and processing of anxiety (Griffiths et al., 2017). While the exact mechanisms remain not entirely understood (Ziff et al., 2022), the therapeutic benefits of a psilocybin session equate to many hours of traditional therapy[factual?]. This may be attributed to time dilation effects and the sensation of experiencing multiple lifetimes during the session (Carhart-Harris et al., 2014).

Theoretical framework

[Provide more detail]

Altered states of consciousness in therapy

The altered states of consciousness, or "mystical-type experiences" (Yaden et al., 2021) induced by psilocybin-assisted therapy offer deeply introspective experiences, altering perceptions of oneself and the many facets of their internal and external world. The 4-6-hour experiences within an altered state have profound effects on individuals and rely heavily upon dosage (ranging between 1mg-30mg) (Griffiths et al., 2017), set (mindset) and setting (location) (Phelps, 2017; King & Hammond, 2021; Ziff et al., 2022). Changes and shifts within one's awareness of their self can lead to what is known as ego dissolution or ego death, strongly associated with the PCC (Carhart-Harris et al., 2014). These states involve ineffable experiences including intricate visuals, changes in perceptions of time and space, synaesthesia (see Figure 7), universal love, empathetic unity, and a deep sense of connection extending beyond the physical body (Yaden et al., 2021). Often, these altered states have noetic qualities, and a sense of the experience feeling extremely real. This is an important part of the psychedelic experience, due to its profundity during their journey inward, after the experience people can alter their beliefs and make drastic changes in lifestyle (Yaden et al., 2021)[grammar?].

Processing and resolution

"One participant said he “experienced all the emotions I know how to experience,” and another said she felt, “all of them, all of them. Every possible emotion.” Six participants shed tears during the interview itself when revisiting their experiences." - Belser et al., 2017

The emotional range experienced through psilocybin-based experiences is like no other. Psilocybin-assisted therapy, guided typically by two trained therapists and induced by high dosages of psilocybin (10-30mg), leads individuals on a deep and personal journey inward, facilitating a deep emotional release. Emotional processing and resolution that occurs within psilocybin-assisted therapy is highly subjective, with every individual’s journey being unique, encompassing a wide range of emotional themes (Belser et al., 2017).

Those grappling with anxiety often resort to avoidance behaviours as a coping mechanism, navigating away from confronting their emotions and experiences. Conventional anxiety treatments, such as exposure therapy, cognitive-behavioural therapy (CBT) and dialectic-behavioural therapy (DBT), aim to address and alleviate avoidance patterns (Hofmann & Hay, 2018). Overcoming avoidance is a key aspect of therapy, crucial for breaking the cycle of anxiety perpetuation. Anti-anxiety medications are seen as ineffective long-term, and while exposure therapy, CBT and CBT can be effective, many patients are often left symptomatic, leading them to explore alternative treatment methods (Hofmann & Hay, 2018; Wolff et al., 2020).

In psilocybin-assisted therapy sessions, central themes of avoidance often arise as individuals initially attempt to 'control' or avoid distressing or fearful situations (Hofmann & Hay, 2018). However, these situations are typically transient and transform into states of acceptance, characterised by the patient surrendering or 'letting go', facing their fears, and initiating a form of negative reinforcement (Belser et al., 2017; Hofmann & Hay, 2018; Wolff et al., 2020). Confronting these situations allows patients to reach cathartic emotional breakthroughs by uncovering and releasing previously suppressed emotional burdens - a key element in psilocybin-assisted therapy for anxiety (Wolff et al., 2020). Psilocin’s interaction within the brain enables a ‘re-wiring’ action fostering communication between areas of the brain not normally interconnected (Ziff et al., 2022). This promotion of neuroplasticity enables patients to adapt, develop healthier emotional regulation and responses, and integrate newfound love, acceptance and meaning into their lives. This phenomenon, known as the relaxation of beliefs, induced by psilocybin, explains why acceptance can be conditioned in this manner (Wolff et al., 2020).

"I took away from the experience that I used to get angry about having anxiety, now I think I can have the anxiety, I can just feel it and it will go, I don't have to have the fear or run away." - Wolff et al., 2020

To facilitate this extremely personal and cathartic journey through emotional experiences, several crucial elements come into play. These include the establishment of a pre-existing rapport with the therapists, the carefully crafted therapeutic setting, ensuring patient safety throughout the sessions and the vital phase of post-session integration (Phelps, 2017; Wolff et al., 2020).

Therapeutic process

[Provide more detail]

Therapeutic setting

The therapeutic setting for psilocybin-assisted therapy involves both set and setting within a controlled space. Set refers to the mindset of both patient and therapists and involves pre-session discussions about the intention of the session, what the patient may expect to experience, motivational factors and how it is that the therapists will help to guide a patient through the psychedelic experience (Phelps, 2017). Patients are consulted on the types of experiences that may ensue, such as the experience of challenging situations and heightened anxiety, demonstrating the importance of having well-trained therapists helping to facilitate the session (Ziff et al., 2022). Setting involves the mental, emotional, physical, and therapeutic space in which the session will be held (Phelps, 2017). The setting involves creating a subjectively safe space for the patient such as a quiet room, the use of a blindfold (to encourage closed-eye visuals) the use of music, lighting, an aesthetically pleasing environment with the patient lying down on a comfortable surface such as a bed or couch (Phelps, 2017; Reiff et al., 2020). Emphasis on the importance of both these aspects (set and setting) is integral to the success of psilocybin-assisted therapy (Phelps, 2017). Many of the early studies that took place were often held in what would be considered an unsafe space; sterile laboratory rooms with little guidance or compassion from therapists (Ziff et al., 2022).

Therapist's role: Guiding the session and safety

Therapeutic training of therapists is a key aspect of psilocybin therapy. Having professionally trained therapists can make or break the outcomes of the experience for the patient both before the session, during, and post-session integration from the experience (Phelps, 2017; Ziff et al., 2022). According to Phelps (2017), the first key aspect of well-trained psychedelic therapists is the presence of compassionate and enduring support throughout the session. Therapists must maintain a person-centered and unequivocally empathetic approach towards patients as they move through unfolding mystical moments, having an unwavering calmness during moments of distress, patience, mindfulness, active listening, and continual openness. Therapists must uphold these traits as they witness patients undergoing a transcendental and mystical experience. During such moments, patients' heightened senses make them susceptible to the tones of voice, moods, or feelings of those around them. Typically, there is little dialogue between the patient and therapists unless initiated by the patient. For many psychedelic therapists, the act of meditation through their patients’ experiences is beneficial; helping to hold space and create a point of grounding and stability for them. This allows patients to feel and explore what they need to without interruption by continually feeling a secure presence of safety and compassion (Phelps, 2017).

The second key aspect revolves around trust that is built between the patient and therapists. This is something that occurs before the psilocybin session and involves the patient knowing they are with reliable and trustworthy guides (rapport building) and helping the patient trust their ability and capacity to heal themselves (Phelps, 2017). Normalisation and reassurance that the unexpected and paradoxical moments that occur during sessions are part of the process and should be trusted as such.

Other key aspects for therapists that Phelps (2017) describes include spiritual intelligence, which implies the understanding that we are transcendental beings connected to one another, the earth, and higher spiritual and abstract realms beyond our physical bodies. Also, a knowledge of shamanism (both ancient and modern indigenous practices), neurobiology and individualised drug responses of their patient. Typically, it is best if the therapists themselves have knowledge, familiarity, and experiences of their own with psilocybin. Therapists should be self-aware of their motives, maintain integrity and boundaries between themselves and the patient, understand attachment theories and adhere to ethical codes specific to psilocybin therapy. Therapists must be trained professionals in clinical psychology, psychotherapy, psychiatry, and the like. Additionally, it is important that therapists have acquired a variety of techniques such as somatic practices and guided imagery to use throughout the varying stages of therapy (Phelps, 2017). It is also beneficial if the patient has experience with meditative practices themselves (Griffiths et al., 2017; Reiff et al., 2020). There are many specialised training programs to assist therapists in gaining a multidisciplinary skill set for conducting and becoming trained facilitators of psilocybin-assisted therapy, such as Innertrek, Grof Transpersonal Training, Fluence, American Psychedelic Practitioners Association, Mind Foundation and Mind Medicine Australia.

The therapist’s role is not to heal the patient but to allow space for the patient to heal themselves by upholding an empathetic presence, through unwavering trust between the patient and therapists, and through honouring the patient's personal and subjective experiences. Every patient deserves to know that they are safe and that the therapists are solely there for them as they make meaning of their lives, experiences, and emotions within a psilocybin-induced space.

Post-session integration

Post-session integration is just as vital to the success of the treatment as the session itself. The therapist’s responsibility is to engage in meaningful conversations with the patient, delving into their experiences during their session, exploring thoughts, emotions and insights that have surfaced. It is not a mere reflection of their time with psilocybin but a deliberate effort to harness the transformative power of their psychedelic journey (Johnson & Griffiths, 2017). The translation of their profound experiences into lasting changes in their behaviour and attitudes towards their anxiety is what accounts for the true changes in one’s life. The study undertaken by Ziff et al. (2022) reported that 80% of participants experienced a significant decrease in anxiety 6 months post-treatment, remaining consistent with findings by Reiff et al. (2020). The shifts in patients’ perspectives, belief systems and attitudes that arose during the session allow the patient and therapists to find ways of incorporating the positive changes into their everyday lives. This is a bridging process between their everyday life and the transcendental experiences that occurred through psilocybin-assisted therapy (Belser et al., 2017; Phelps, 2017).

Assessing risks in psilocybin therapy

Before starting psilocybin-assisted therapy for anxiety, trained therapists should determine its suitability for their patients (Johnson & Griffiths, 2017). While the positive aspects of psilocybin-assisted therapy have been explored in this chapter it is important to acknowledge the potential negative effects, especially for those with a predisposition to mental disorders, like schizophrenia. Though many find the experience transformative, leading them through brief moments of psychosis to spaces of acceptance, love and meaning, for some, this is not a transient state and can bring forth a predisposition to psychotic states of mind (Reiff et al., 2020; Ziff et al., 2022). Although this is a smaller portion of patients within studies, the seriousness should be considered before undergoing treatment. However, in stating this, it is important to know that many studies stipulate that patients did not experience adverse side effects, none that lasted longer than the session. Such side effects may include nausea, increases in blood pressure and heart rate, challenging emotional (sadness, fear) and physical aspects such as tremors, dizziness, or weakness (Bogadi & Kaštelan, 2021; Ziff et al., 2022).

Quiz

Take this short quiz below to see what you have learned ↓

Conclusion

Psilocybin-assisted therapy for the treatment of anxiety is emerging as a beacon of hope for those grappling with the debilitating effects of anxiety disorders. The profound encounters and insights shared by participants in the study by Besler et al. (2017) paint a vivid picture of transformation – of love, connection, and a newfound depth in their emotional landscapes. It’s a journey that transcends the individual, touching the very core of existence itself and questioning who and why we are.

The theoretical framework of this treatment lies in the magic of altered states of consciousness – a realm we have begun to explore again as modern humans. With psilocybin as a guide and the empathetic support of trained therapists, the barriers of the mind can be dissolved and pave the way to a deep experience of introspection and self-discovery. It is a therapy that goes way beyond the ordinary scope of treatments. It is not merely about neurotransmitters and brain functions; it’s about confronting fears, breaking through avoidance, and rewriting the narratives we’ve created for ourselves. This extraordinary fungus has the capacity to unravel the threads of anxiety, allowing individuals to release, heal and emerge with a renewed perspective on life; less fearful and more accepting of the tumultuousness that life can bring. Decreases in anxiety, persisting even 6 months post-treatment is a testimony to psilocybin’s enduring impact and its promising outlook as an alternative treatment.

References

Adler, J. (Writer), & Pollan, M. (Author). (2022). Chapter 2: Psilocybin (Season 1, Episode 2). In J. Deeter (Local Producer), M. Kahn (Researcher), J. Marra (Development Producer), & R. Perello (Executive Producer), How To Change Your Mind. Netflix.

Belser, A. B., Agin-Liebes, G., Swift, T. C., Terrana, S., Devenot, N., Friedman, H. L., Guss, J., Bossis, A., & Ross, S. (2017). Patient experiences of psilocybin-assisted psychotherapy: An interpretative phenomenological analysis. Journal of Humanistic Psychology, 57(4), 354–388. https://doi.org/10.1177/0022167817706884

Bogadi, M., & Kaštelan, S. (2021). A potential effect of psilocybin on anxiety in neurotic personality structures in adolescents. Croatian Medical Journal, 62(5), 528–530. https://doi.org/10.3325/cmj.2021.62.528

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., & Nutt, D. (2014). The Entropic Brain: A Theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 8. https://doi.org/10.3389/fnhum.2014.00020

de Vos, C. M., Mason, N. L., & Kuypers, K. P. (2021). Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. Frontiers in Psychiatry, 12. https://doi.org/10.3389/fpsyt.2021.724606

Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L., & Hutson, P. R. (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. Psychiatry Research, 284, 112749. https://doi.org/10.1016/j.psychres.2020.112749

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., Jesse, R., MacLean, K. A., Barrett, F. S., Cosimano, M. P., & Klinedinst, M. A. (2017). Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. Journal of Psychopharmacology, 32(1), 49–69. https://doi.org/10.1177/0269881117731279

Hofmann, S. G., & Hay, A. C. (2018). Rethinking avoidance: Toward a balanced approach to avoidance in treating anxiety disorders. Journal of Anxiety Disorders, 55, 14–21. https://doi.org/10.1016/j.janxdis.2018.03.004

Johnson, M. W., & Griffiths, R. R. (2017). Potential therapeutic effects of psilocybin. Neurotherapeutics, 14(3), 734–740. https://doi.org/10.1007/s13311-017-0542-y

King, F., & Hammond, R. (2021). Psychedelics as reemerging treatments for anxiety disorders: Possibilities and challenges in a nascent field. FOCUS, 19(2), 190–196. https://doi.org/10.1176/appi.focus.20200047

López-Giménez, J. F., & González-Maeso, J. (2017). Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. Behavioral Neurobiology of Psychedelic Drugs, 45–73. https://doi.org/10.1007/7854_2017_478

Phelps, J. (2017). Developing guidelines and competencies for the training of psychedelic therapists. Journal of Humanistic Psychology, 57(5), 450–487. https://doi.org/10.1177/0022167817711304

Poulie, C. B., Jensen, A. A., Halberstadt, A. L., & Kristensen, J. L. (2019). Dark classics in chemical neuroscience: Nbomes. ACS Chemical Neuroscience, 11(23), 3860–3869. https://doi.org/10.1021/acschemneuro.9b00528

Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodriguez, C. I., Kalin, N. H., & McDonald, W. M. (2020). Psychedelics and psychedelic-assisted psychotherapy. American Journal of Psychiatry, 177(5), 391–410. https://doi.org/10.1176/appi.ajp.2019.19010035

Roy-Byrne, P. (2015). Treatment-refractory anxiety; definition, risk factors, and treatment challenges. Dialogues in Clinical Neuroscience, 17(2), 191–206. https://doi.org/10.31887/dcns.2015.17.2/proybyrne

Smausz, R., Neill, J., & Gigg, J. (2022). Neural mechanisms underlying psilocybin’s therapeutic potential – the need for preclinical in vivo electrophysiology. Journal of Psychopharmacology, 36(7), 781–793. https://doi.org/10.1177/02698811221092508

Stamets, P. (1996). Psilocybes from a Historical Perspective. In Psilocybin mushrooms of the World: An Identification Guide (pp. 11–15). essay, Ten Speed Press.

Wittchen, H.-U. (2002). Generalized anxiety disorder: prevalence, burden, and cost to society. Depression and Anxiety, 16(4), 162–171. https://doi.org/10.1002/da.10065

Wolff, M., Evens, R., Mertens, L. J., Koslowski, M., Betzler, F., Gründer, G., & Jungaberle, H. (2020). Learning to let go: A cognitive-behavioral model of how psychedelic therapy promotes acceptance. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.00005

Yaden, D. B., Johnson, M. W., Griffiths, R. R., Doss, M. K., Garcia-Romeu, A., Nayak, S., Gukasyan, N., Mathur, B. N., & Barrett, F. S. (2021). Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities. International Journal of Neuropsychopharmacology, 24(8), 615–623. https://doi.org/10.1093/ijnp/pyab026

Zangrossi, H., Del Ben, C. M., Graeff, F. G., & Guimarães, F. S. (2020). Serotonin in panic and anxiety disorders. Handbook of Behavioral Neuroscience, 611–633. https://doi.org/10.1016/b978-0-444-64125-0.00036-0

Ziff, S., Stern, B., Lewis, G., Majeed, M., & Gorantla, V. R. (2022). Analysis of psilocybin-assisted therapy in Medicine: A Narrative Review. Cureus. https://doi.org/10.7759/cureus.21944

External links

Fantastic Fungi (Website and movie)
Psychedelics Research and Psilocybin Therapy (John's Hopkins Medicine)
How to change your mind – Michale Pollan (Podcast interview)

	True
	False