In order to understand how fear affects our lives, we must consider that every day we face this emotion in different ways, becoming the reason to do or stop doing, a mobilizer or a paralyzer.
A large part of our decisions come to be conditioned by this emotion. These fears that lead us to do or avoid are often born from thoughts driven by limiting beliefs in our mind. They may be caused by some teaching or limitation in our childhood, as well as acquired in the course of our development.
It is a basic, universal and primary sensation, whose function is protection against risk situations. It acts as a regulator of our behavior, warning us of danger and possible threats; damage to the physical integrity, reputation, self-esteem, self-concept or security of the person1. The limbic system is a set of brain structures that, in a simplified way, we can say that it is the main person in charge of this sensation, within which we can highlight the amygdala.
Among the general functions of the amygdala we can mention: the perception of emotions, behavioral responses to fear, recognition of emotions (based on the facial expression of others) and responses to pleasure2. Given these characteristics, it has been observed that the amygdala is strongly related to the processing of fear signals and conditioning of this 3.
Fear, in turn, is related to the Autonomous Nervous System, which controls the involuntary functions of the body, resulting in a flight or fight response when faced with a threat. Today we talk about four responses: fight, flee, freeze or fawn. The latter has recently been added to the conversation about complex post-traumatic stress, where we find a response of flattery towards the threatening person as a protection strategy.
PTSD and Phobias
There are various psychological disorders and discomforts associated with fear, which share symptoms such as stress, anxiety, intrusive thoughts, muscle tension, among others.
An example of this is Post-Traumatic Stress Disorder (PTSD). A disorder that represents a global public health problem, which is directly related to our response to fear. After exposure to an event that puts the person’s physical and/or psychological integrity at risk, it is possible to develop this disorder, which is characterized by three main symptoms; hyperarousal (anxiety and hypervigilance), intrusive experiencing of traumatic experiences (memories, nightmares, flashbacks, ideas) and avoidance (avoiding stimuli that may remind us of the traumatic event)
On the other hand, we find phobias, also related to our response to fear. Phobias are a subtype of anxiety disorder, derived from the basic emotion of fear. When fear remains for a long time without the environment demanding it, anxiety occurs; When said fear that persists is linked to a specific object, animal or situation, it is called a phobia. Irrational fear in relation to the situation experienced, since one is not in real danger.
Regarding treatment, the three cognitive-behavioral orientation processes chosen for the clinical treatment of specific phobias are systematic desensitization, exposure techniques and virtual reality (VR)5. The advancement of technology in our time has allowed the creation of new tools such as VR, showing greater effectiveness in treatment, although its results are not sustained over time and more clinical trials and larger samples are needed to generalize its results. . These processes used within cognitive behavioral therapy aim to modify sensitivity to stimuli that cause us anxiety or fear.
Regarding pharmacological treatment, in recent decades the only drugs approved by the FDA for the treatment of PTSD were paroxetine and sertraline, showing limited effectiveness. Regarding the different types of psychotherapy for this problem (based on exposure), these have shown that a significant number of patients do not respond to treatment. This is when new forms of treatment begin to be tested, such as the incorporation of MDMA in the therapeutic process. MDMA is a psychoactive substance and an amphetamine derivative that promotes the release of at least three neurotransmitters: serotonin, dopamine and norepriphenine7,8.
Psychedelic therapy: MAPS and MDMA
In 1986 Rick Doblin founded the Multidisciplinary Association for Psychedelic Studies (MAPS), a year after the illegalization of MDMA (Pollan, 2018). His goal was the eventual approval of MDMA and other psychoactive substances as medicine by the Food and Drug Administration (FDA), the agency responsible for regulating food and drugs in the United States. Since graduating in 1987, Doblin has dedicated his life to try to change the opinion of the government and the American population on the subject of psychedelic drugs. This is why he completed a doctorate in Public Policy at Harvard, to be able to study the complexities of the approval process for substances such as psilocybin and MDMA. Since its founding, MAPS achieved approval and funding of important research with MDMA, psilocybin, cannabis, LSD, ibogaine and ayahuasca. In addition to MAPS, there are currently a large number of centers and associations involved in the development of psychedelic therapy9.
The inclusion of psychedelics in psychotherapeutic treatment aims to help catalyze this process and increase the capacity of cognitive and emotional processing, reducing fear, the level of activation and strengthening of the therapeutic alliance or pointing to the processes of extinction of fear and consolidation of the memory. Thus, since 2017, the FDA designated MDMA as an innovative therapy for PTSD, and it is currently expected to legalize and regulate its medical use in combination with psychological intervention. This request has priority review, where the action date has been established as August 11, 2024 8.
The justification for its application lies not only in the physiological effects of MDMA, but also in the interaction that it generates (medicine, participant and therapist). The administration of this medication produces an experience that appears to temporarily reduce fear, where at the same time it increases the range of positive emotions (about oneself and others) and increases interpersonal trust.
When MDMA is administered, there is a reduction in activity in the insular cortex and the right amygdala, a structure which is responsible for storing and acquiring memories that generate fear and which is correlated with feelings of anxiety and sadness. It has also been shown to increase the prefrontal cortex 11. By reducing this activity and increasing the release of serotonin, an increase in cognitive flexibility is created, allowing participants to remain emotionally involved while reliving the trauma. Patients can express and experience feelings such as fear, anger, grief, and shame without feeling overwhelmed or avoiding these emotions, which in turn strengthens the therapeutic bond. During the experience, feelings of empathy, love and deep appreciation also emerge, hand in hand with a clearer perspective of the traumatic event and greater awareness and security in the present 10.
The objective of these sessions with MDMA is to reduce the symptoms of PTSD, improve the patient’s functioning, well-being and overall quality of life. We hope to be able to work with this substance in the future, since the evidence towards its effectiveness and safety is very promising, thus being able to cause a great change in the lives of many people.
Unfortunately, the legalization and regularization process is long and complicated. In mid-August 2024, the FDA denied Lykos Therapeutics’ request to approve MDMA as a PTSD medication, asking the company for an additional study 12. Although Lykos has not disclosed the exact reasons why the FDA has requested this additional study, some of the most frequent criticisms are the following: the difficulty in having a true placebo group – most participants can guess whether they have received placebo or not; the pressure to report a positive response; and difficulty distinguishing between the effects of psychotherapy and medication. Regarding the latter, other companies are choosing to carry out studies without the accompanying therapeutic component. Although this is useful to isolate the effects of the medication, it is essential to continue conducting studies that combine these two factors, since we risk reducing the use of these medications to a biomedical use as seen with classic antidepressants.
Although it is obvious that there is still much work ahead for the use and regularization of MDMA in the medical and psychotherapeutic field, we must be grateful for the great advances made in the last decade, much of it through the work of MAPS. The quality and quantity of available evidence has increased significantly, and thanks to this, work and safety protocols have been developed for the use of MDMA that have already helped hundreds of people with PTSD to substantially improve their quality of life. We hope to continue seeing these advances in the coming years, so that this help can reach many more people.
Bibliography:
(1) (2) Herrera Aboytes, V. H. ., M. J. . Aboytes Zarazúa, L. V., Salvador Valerio, and C. P. . Rojas Tapia. “The Functional Implication of the Amygdala in Relation to Fear”. International Journal of Medical Science and Clinical Research Studies, vol. 2, no. 11, Nov. 2022, pp. 1270-5, doi:10.47191/ijmscrs/v2-i11-20.
(3) Adhikari A, Lerner T, Finkelstein J, Pak S, Jennings J, Davidson T. Basomedial amygdala mediates top-down control of anxiety and fear. Nature 2015; 527(7577):179-185
(4) Mithoefer, M. (2017). A Manual for MDMA-Assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder; Version 8.1. Recuperado de: https://www.maps.org/research/mdma/mdma-research-timeline/4887-amanual-for-mdma-assisted-psychotherapy-in-the-treatment-of-ptsd.
(5) Reyes, Andrés Camilo Delgado, and Jessica Valeria Sánchez López. “Miedo, fobias y sus tratamientos.” Revista electrónica de psicología Iztacala 22.2 (2019): 798-833.
(6) Capafons Bonet, J. I. «Tratamientos psicológicos Eficaces Para Las Fobias específicas». Psicothema, vol. 13, n.º Número 3, diciembre de 2001, pp. 447-52, https://reunido.uniovi.es/index.php/PST/article/view/7898.
(7) Feduccia, A. A., y Duvauchelle, C. L. (2008). Auditory stimuli enhance MDMA-conditioned reward and MDMA-induced nucleus accumbens dopamine, serotonin and locomotor responses. Brain research bulletin, 77(4), 189–196. https://doi.org/10.1016/j.brainresbull.2008.07.007
(8) Sessa, B., y Nutt, D. (2015). Making a medicine out of MDMA. The British journal of psychiatry : the journal of mental science, 206(1), 4–6. https://doi.org/10.1192/bjp.bp.114.152751
(9) Apud, I., Carrera, I., Scuro, J., y Montero, F. (2021). ¿Es posible desarrollar investigaciones clínicas utilizando sustancias psicodélicas en Uruguay? Revista de Psiquiatría del Uruguay, 85(1), 63-76. https://doi.org/10.46706/PSI/85.1.4
(10) Revisión de prioridades de la FDA. Disponible en: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review . Consultado en enero de 2024 .
(11) Gamma, A., Buck, A., Berthold, T., Liechti, M. E., & Vollenweider, F. X. (2000). 3,4-Methylenedioxymethamphetamine (MDMA) modulates cortical and limbic brain activity as measured by [H(2)(15)O]-PET in healthy humans. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 23(4), 388–395. https://doi.org/10.1016/S0893-133X(00)00130-5
(12) Reardon S. FDA rejects ecstasy as a therapy: what’s next for psychedelics? Nature [Internet]. 2024 [cited 2024 Aug 28]; Available from: https://www.nature.com/articles/d41586-024-02597-x
