Discussion around the topic of psychedelic drugs tends to trip people up a lot, but with its increasing acceptance in the scientific and therapeutic field, there is more information than ever on the uses, dangers and apparent benefits of a mind-altering experience. Where before we feared what these substances could do to us, now various groups have been exploring what these substances can do for us and our fears. The research is ongoing, of course, and will be for a long time; the stigma of psychoactive drugs cannot be overturned easily. But, with the help of mouse models and human trials, can we make overcoming our deepest fears a little easier?

Arguably the most famous and successful research being undertaken at the moment is on the therapeutic use of MDMA with patients suffering from post-traumatic stress disorder (PTSD). This disorder is often characterised by the victims re-experiencing an event from the past vividly, as if it is occurring at that very moment. There is a deep, primal fear associated with such a memory, one that usually requires many years of conventional therapy to overcome. From initial trials of a psychedelic-assisted therapy technique, it appears that being on MDMA during a therapy session helps to relieve the fear in a participant more permanently than talking therapy alone. 

To answer the question of why this should happen, several studies have experimented on giving psilocybin based compounds to mice, which have been conditioned with a triggerable fear response. Without the dose of drug, the mice display typical fear-response behaviours. However, during and after the dosage, the mice display less to no fear-response behaviour when encountering the previously conditioned fear trigger. A similar response as seen in PTSD-sufferers. Further investigation reveals that a serotonergic receptor type 5-HT2A in the amygdala is blocked by the psychoactive molecule, which reduces the sensation of fear during the event, or in the case of PTSD, during the retrieval of the traumatic memory. But incredibly, this phenomenon doesn’t only occur during a trip, but is maintained even when the psychoactive substance has left the system. As a result, the mice in the trial no longer show as pronounced a fear-response behaviour to the trigger following the psychedelic event. 

Psilocybin and other hallucinogenic compounds have been shown to promote neurogenesis in the brain, with new dendritic spines forming from established neurons (more on this in the future); perhaps then it’s no surprise that they also influence the systems governing our memories and how we respond to them. Yet, does this mean that we should all be taking magic mushrooms to develop our brains and overcome our fears? Well, no. The main takeaway from these studies is that we are establishing a better understanding of the molecular and neurological responses in mice models, which in turn help us to understand what we see in assisted therapy trials. However, (and I cannot emphasise this enough) we aren’t mice, so further studies on human participants will be required to understand the brain chemistry. Moreover, psychedelic-assisted therapy is conducted in a safe environment where participants are made as relaxed as possible and are in the presence of licensed psychotherapists. Abusing these substances outside of a safe setting can be dangerous, especially when one has an underlying mental instability, such as forgotten traumas, strong anxiety, etc. 

Like with all good things, moderation is key, and if we can one day learn to apply a moderation of useful hallucinogenic experience to our therapies, maybe we can help to abate the fears that plague so many. 

Author: Thomas von Rein

References:

Byok, I. Taking Psychedelics Seriously. Journal of Palliative MEdicine. 21(4) (2018).

Daneluz, D.M., Sohn, J.M.B., Silveira, G.O. et al. Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation. Psychopharmacology 239, 3325–3336 (2022).

de la Fuente Revenga, M., Zhu, B., Guevara C.A. et al. Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice. Cell Reports. 37(3).(2021)

Pędzich, B.D., Rubens, S., Sekssaoui, M. et al. Effects of a psychedelic 5-HT2A receptor agonist on anxiety-related behavior and fear processing in mice. Neuropsychopharmacol. 47, 1304–1314 (2022).

Prouzeau, D., Conejero, I., Voyvodic, P.L. et al. Psilocybin Efficacy and Mechanisms of Action in Major Depressive Disorder: a Review. Curr Psychiatry Rep 24, 573–581 (2022).