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The Science

The Science Of Psychedelic-Assisted Therapy
 

DISCLAIMER: Any mention of specific substances on this webpage and the research presented here, are intended solely for reference and educational purposes, and should not be considered as a promotion of a particular substance or as a replacement for seeking professional guidance from a qualified healthcare practitioner. Please be aware that EQNMT adheres to all local laws and regulations of the countries it operates in. EQNMT promotes a comprehensive, evidence-based approach to mental health. While we acknowledge the effectiveness of different medicines, medications and treatment modalities, we recognise that psychedelic-assisted therapy may not be suitable to every individual. 


Overview & Mechanism Of Action
PSILOCYBIN
 
Psilocybin is a non-specific 5HT2A agonist. This means that it catalyses the release of serotonin across all regions of the brain. By releasing high doses of this neuro-hormone, emotional and percpetual functions of the mind become hyperactive. This allows for deep emotional processing of life experiences,  and alteration of perception that facilitates adopting new perspectives. By pairing this state with appropriate therapeutic inputs, we are afforded an opportunity to reconnect, rediscover and reinvent ourselves in profound ways within relatively short spaces of time.
 
KETAMINE
 

Ketamine works primarily by blocking the NMDA receptors in the brain. This allows for the balancing of two key brain chemicals or ‘neurotransmitters’ called Glutamate and GABA. Glutamate is our main excitatory neurotransmitter –  the ‘gas pedal’ of the brain. It plays a key role in motivation, learning and memory. GABA is the main inhibitory neurotransmitter – the ‘brake pedal’ of the brain. It reduces excitability and activity in the nervous system, allowing us to feel calm.
 

When optimal balance or ‘homeostasis’ is achieved between these two key neurotransmitters, the brain releases an important protein called Brain Derived Neurotrophic Factor (BDNF). BDNF has been likened to ‘fertilizer in the soil of the brain.’ It promotes the growth of new neural pathways (known as ‘neurogenesis’) and increased connectivity between existing pathways (known as ‘synaptogenesis’).
 

Neuroscience suggests a relationship between conditions like depression, anxiety, addiction, PTSD and OCD and reduced density, connectivity and communication between key neural pathways, resulting in low mood, excessive and repetitive worry, rumination and unhealthy habits.
 

However, through this process of neurogenesis and synaptogenesis, new and different brain regions are allowed to activate, connect and communicate. In this state of heightened connectivity, we experience fundamental shifts in our perceptions of ourselves and reality. These deep perceptual shifts allow us to process trauma and loss, resolve inner conflict, release suppressed emotion, gain self-insight and transform core beliefs and behaviors that may no longer serve us. Combining psychedelic medicine with therapy – hence the discipline of psychedelic-assisted therapy – allows us to deepen and sustain the profound benefits of psychedelic medicine.
 

A welcome analogy is to imagine the brain as a block of clay. Traditional therapies attempt to ‘chip away’ at this clay over time, shaping the mind into a more adaptive form. Psychedelic-assisted therapy ‘heats up the clay,’ making the brain malleable and remoldable in a remarkably short space of time. Hence, under the right conditions, psychedelic-assisted therapy has been likened to ‘undergoing years of therapy in the space of a few hours.’

 

Psychedelic-Assisted Therapy
 

2022 on combining ACT therapy with [psychedelics].

Mathai, D. S., Mora, V., & Garcia-Romeu, A. (2022). Toward Synergies of [Psychedelics] and Psychotherapy. Frontiers in Psychology, 1203.
 

2022 systematic narrative review of [psychedelic]-assisted psychotherapy.

Drozdz, S. J., Goel, A., McGarr, M. W., Katz, J., Ritvo, P., Mattina, G. F., … & Ladha, K. S. (2022). [Psychedelic] Assisted Psychotherapy: A Systematic Narrative Review of the Literature. Journal of Pain Research, 15, 1691.
 

2022 therapy augments effects of [psychedelics] for alcohol use disorder.

Grabski, M., McAndrew, A., Lawn, W., Marsh, B., Raymen, L., Stevens, T., … & Morgan, C. J. A. (2022). Adjunctive [Psychedelics] With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder. The American Journal of Psychiatry, appiajp202121030277-appiajp202121030277.
 

2022 optimizing [Psychedelic] treatment with trauma-informed psychotherapy.

Muscat, S. A., Hartelius, G., Crouch, C. R., & Morin, K. W. (2022). Optimized Clinical Strategies for Treatment-Resistant Depression: Integrating [Psychedelic] Protocols with Trauma-and Attachment-Informed Psychotherapy. Psych, 4(1), 119-141.
 

2021 therapy enhances durability of treatment effect.

Wilkinson, Samuel T., et al. “Cognitive behavioral therapy to sustain the antidepressant effects of [psychedelics] in treatment-resistant depression: a randomized clinical trial.” Psychotherapy and psychosomatics 90.5 (2021): 318-327.
 

2019 mindfulness-based therapy enhances positive effects with cocaine dependence.

Dakwar, Elias, et al. “A single [psychedelic] infusion combined with mindfulness-based behavioral modification to treat cocaine dependence: a randomized clinical trial.” American Journal of Psychiatry.

 

Psychedelics And Depression
 

2021 narrative review of [Psychedelics] for depression.

Jelen, Luke A., and James M. Stone. “[Psychedelics] for depression.” International Review of Psychiatry 33.3 (2021): 207-228.
 

2021 international expert opinion.

McIntyre, Roger S., et al. “Synthesizing the evidence for [Psychedelics] in treatment-resistant depression: an international expert opinion on the available evidence and implementation.” American Journal of Psychiatry 178.5 (2021): 383-399.
 

2021 systematic review of 83 trials.

Walsh, Zach, et al. “[Psychedelics] for the treatment of mental health and substance use disorders: comprehensive systematic review.” BJPsych Open 8.1 (2022).
 

2021 systematic review and meta-analysis.

Bahji, Anees, Gustavo H. Vazquez, and Carlos A. Zarate Jr. “Comparative efficacy of racemic [Psychedelics] for depression: a systematic review and meta-analysis.” Journal of affective disorders 278 (2021): 542-555.
 

2019 review.

Krystal, John H., et al. “[Psychedelics]: a paradigm shift for depression research and treatment.” Neuron 101.5 (2019): 774-778.
 

2017 consensus from the American Psychiatric Association.

Sanacora, Gerard, et al. “A consensus statement on the use of [Psychedelics] in the treatment of mood disorders.” JAMA psychiatry 74.4 (2017): 399-405.

 

Anxiety, PTSD And OCD

2021 RCT for PTSD.

Feder, Adriana, et al. “A randomized controlled trial of repeated [Psychedelics] administration for chronic posttraumatic stress disorder.” American Journal of Psychiatry 178.2 (2021): 193-202.
 

2021 review of [Psychedelics] for PTSD and putative mechanisms.

Asim, Muhammad, et al. “[Psychedelics] For Post-Traumatic Stress Disorders And It’s Possible Therapeutic Mechanism.” Neurochemistry International (2021): 105044.
 

2021 review for addiction, OCD and eating disorders.

Martinotti, Giovanni, et al. “Therapeutic Potentials of [Psychedelics] in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature.” Brain Sciences 11.7 (2021): 856.
 

2020 review for the treatment of anxiety disorders.

Banov, Michael D., et al. “Efficacy and safety of [Psychedelics] in the management of anxiety and anxiety spectrum disorders: a review of the literature.” CNS spectrums 25.3 (2020): 331-342.
 

2020 review of [Psychedelics] for PTSD

Feder, Adriana, et al. “The emergence of [Psychedelics] as a novel treatment for posttraumatic stress disorder.” Advances in Pharmacology 89 (2020): 261-286.
 

2020 review for the treatment of OCD.

Sharma, Lavanya P., et al. “Clinical utility of repeated intravenous [Psychedelics] treatment for resistant obsessive-compulsive disorder.” Asian journal of psychiatry 52 (2020): 102183.

 

Psychedelics And Addiction
 

2022 systematic review of 83 trials.

Walsh, Zach, et al. “[Psychedelics] for the treatment of mental health and substance use disorders: comprehensive systematic review.” BJPsych Open 8.1 (2022).
 

2021 review for alcohol use disorder.

Worrell, Stephen D., and Thomas J. Gould. “Therapeutic Potential of [Psychedelics] for Alcohol Use Disorder.” Neuroscience & Biobehavioral Reviews (2021).
 

2021 review for addiction, OCD and eating disorders.

Martinotti, Giovanni, et al. “Therapeutic Potentials of [Psychedelics] in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature.” Brain Sciences 11.7 (2021): 856.
 

2021 [Psychedelics] for cannabis use disorder.

Azhari, Nour, et al. “[Psychedelics]-facilitated behavioral treatment for cannabis use disorder: a proof of concept study.” The American journal of drug and alcohol abuse 47.1 (2021): 92-97.
 

2019 RCT for cocaine dependence.

Dakwar, Elias, et al. “A single [Psychedelics] infusion combined with mindfulness-based behavioral modification to treat cocaine dependence: a randomized clinical trial.” American Journal of Psychiatry 176.11 (2019): 923-930.
 

2019 RCT for cocaine use disorder.

Dakwar, E., et al. “Cocaine self-administration disrupted by the N-methyl-D-aspartate receptor antagonist [Psychedelics]: a randomized, crossover trial.” Molecular psychiatry 22.1 (2017): 76-81.
 

2018 systematic review of [Psychedelics] for substance use disorders.

Jones, Jennifer L., et al. “Efficacy of [Psychedelics] in the treatment of substance use disorders: a systematic review.” Frontiers in psychiatry 9 (2018): 277.

 

Clinical Trials
 

2022 systematic review of 83 trials.

Walsh, Zach, et al. “[Psychedelics] for the treatment of mental health and substance use disorders: comprehensive systematic review.” BJPsych Open 8.1 (2022).
 

2021 review of neurobiological mechanisms.

Kohtala, Samuel. “[Psychedelics]—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms.” Pharmacological Reports (2021): 1-23.
 

2020 safety review of 6630 patients.

Feifel, David, David Dadiomov, and Kelly C Lee. “Safety of repeated administration of parenteral [Psychedelics] for depression.” Pharmaceuticals 13.7 (2020): 151.
 

2018 blood pressure safety review.

Riva-Posse, Patricio, et al. “Blood pressure safety of subanesthetic [Psychedelics] for depression: a report on 684 infusions.” Journal of affective disorders 236 (2018): 291-297.
 

2017 review on ethics and safety.

Singh, I., Morgan, C., Curran, V., Nutt, D., Schlag, A., & McShane, R. (2017). [Psychedelics] treatment for depression: opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry, 4(5), 419-426.

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