How do Psychedelics Actually Work and What Potential Do They Hold to Treat Psychiatric Illness?

The History of Psychedelics

Plant-derived psychedelics have been used for centuries by different cultures for healing purposes and continue to be used in traditional practises to this day (Carhart-Harris & Goodwin, 2017). Research by psychologists and psychiatrists in the 1950s noted the great healing potential that psychedelics may have for psychiatric conditions, yet the war on drugs led to strict legislation and a five-decade hiatus in research (Costandi, 2014). Psychedelic drugs are a family of chemical compounds famously known to alter consciousness, which have experienced a massive resurgence in pharmaceutical research for treating psychiatric conditions. Psilocybin is one psychedelic compound that has experienced a great revival in clinical trials, which is being investigated alongside psychotherapy to treat psychiatric illnesses including treatment resistant depression (BBC, 2021). Psilocybin is the psychedelic compound found in ‘magic mushrooms’, typically ingested through the mouth either in original fungi form or via a pill, which then metabolises to become psilocin in the body.

Psilocin in the Brain

It is thought that psilocin targets serotonin neurotransmitters and specifically activates the 5-HT2A receptor (Nutt et al., 2020). The binding of this receptor has been thought to induce mystical experiences felt, which are meaningful experiences that induce feelings of euphoria inspiring a sense of spiritual mystery and awe (Kelmendi et al., 2022). The binding of psilocin to the serotonin receptors activates increased cell signalling within the brain, which is thought to improve global brain connectivity and is associated with the promotion of new communication networks within the brain (Nutt et al., 2020).  This process is thought to promote new ways of thinking. Furthermore, increased density of serotonin receptors is produced by psilocin which is thought to have an antidepressant effect similar to selective serotonin reuptake inhibitors (SSRIs; Carhart-Harris et al., 2021). The 5-HT2A receptor activation has furthermore been implicated to drive neuroplasticity, which is the natural ability of the brain to change in structure and connectivity over time and has been linked to the easing of symptoms for psychiatric conditions (Calvey & Howells, 2018; Ly, 2018). Psilocin also causes a reduction in activity in the default mode network which is most active when one is daydreaming or relaxing. A decrease of activity in this region has also been associated with mystical experiences. While non-serotonin receptors and multi-receptors may also be involved in the effects of psychedelics, there is limited research investigating this (Kelmendi et al., 2022).

Psilocybin and SSRI’s

Psilocybin shares some clear similarities with SSRIs in the altered perception of environment and the heightened sensitivity to the external world in the psychedelic state (Carhart-Harris & Goodwin, 2017). However, the antidepressant action of SSRIs induces emotional dampening or numbing, which contrasts to the induced emotional reaction of the patient prompted by psilocin. It is thought this difference in emotional experience is due to the activation of different types of serotonin receptors in the brain (Carhart-Harris & Goodwin, 2017). Therefore, psilocybin may act as an improved antidepressant to traditionally used SSRIs due to increased emotional integration. Unlike typical SSRI antidepressants, psychedelic compounds are known to have an almost instant anti-depressant and anti-addictive effect (Calvey & Howells, 2018). It is hypothesised that the therapeutic advantage is facilitated by the 5-HT2A receptor and neuroplasticity, but this research is yet to be established in humans (Nutt et al., 2020). Past studies investigating psilocybin have been dominated by studies on other animals, constrained by ethical issues and the classified nature of psilocybin.

Therapeutic Benefits of Psilocybin

The improved openness and acceptance that is associated with psilocybin has been implicated to enhance the effects of psychotherapy. A recent documentary followed a study investigating the therapeutic potential of psilocybin alongside psychotherapy on patients with treatment resistant depression (BBC, 2021), which demonstrated dramatic improvements in depressive symptoms of those who participated. Acceptance and willingness of participants to address their trauma and negative emotions was highlighted to catalyse recovery. This reflected another study which investigated subjects with treatment resistant depression and their value of psilocybin as a treatment, which found patients to feel reconnected and more accepting of emotion six months after the initial assisted dose (Watts et al., 2017). Therefore, patients feel more willing to discuss their problems, trauma and process negative emotion when receiving a dose of psilocybin as compared to traditional psychotherapy. However, these studies both involved small sample sizes and targeted individuals with only treatment resistant depression and no other mental health issue. Recent research emphasises the presence of a psychotherapist during psilocybin treatment for psychiatric conditions, as the increased sensitivity induced by the drug can also lead to negative experiences of psychosis. However, the presence and assistance of psychotherapists during psilocybin treatment has costly implications.

Hopes for Future Research

Overall, psychedelics show great promise for understanding serotonin neurotransmitters in the brain. They also hold the potential to better inform us of areas and mechanisms of the brain which may invoke or repel symptoms of poor mental health and may drive forward improved treatments for psychiatric conditions. The increased neuroplasticity and activation of serotonin receptors that psilocybin facilitates suggests that people may develop new neural pathways to disrupt their previous negative thought patterns and process their emotions and trauma more effectively. Psilocybin shows great promise for treating poor mental health when patients are paired with a psychotherapist especially, as the compound has been found to help them express their emotions and work through their trauma with an open and accepting frame of mind which may not always be possible in traditional psychotherapy. Caution should be taken when investigating micro dosing as a treatment for psychiatric conditions, as there is limited research to validate this claim and it is largely based on anecdotal information. Future research should investigate the impact that psychotherapy has when psilocybin is micro dosed or taken as a full dose compared with a controlled-placebo or SSRI to uncover whether micro dosing has an impact when psychotherapy processes are facilitated.