The psychedelic renaissance : the next trip for psychiatry ?
J. R. Kelly, A. Baker, M. Babiker, L. Burke, C. Brennan and V. O’Keane
Irish Journal of Psychological Medicine, 2019, 1 – 5
doi : 10.1017/ipm.2019.39
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
Keywords : Depression, psilocybin, psychedelics, treatment-resistant depression.
Four thousandmetres above sea level, in LípezAltiplano, Bolivia, a recent discovery of ancient artefacts, provided further evidence of the ever-present human desire for self-transcendence. Chemical residues of psychoactive plants, including psilocin, the active metabolite of psilocybin, were found on paraphernalia, dating back 1000 years (Miller et al. 2019). The altered states of consciousness evoked by these psychoactive plants in the brains of our ancestors were likely to have given them a different perspective on their relationship with themselves and their environment. Brain research is now throwing light on the processes involved in such altered states of consciousness.
What has also emerged is that psilocybin may be a potential therapeutic intervention for major depressive disorder. Following three decades of a psychedelic research embargo, Roland Griffiths at John Hopkins, and others, have conducted several double-blind placebo-controlled trials, using psilocybin in a supportive therapeutic setting. These studies have predominantly focused on healthy controls and those with anxiety related to cancer. In the group diagnosed with cancer, the psilocybin experience reduced anxiety (including death anxiety), improved mood, optimism and imbued a sense of meaning (Grob et al. 2011; Griffiths et al. 2016). Moreover, these effects were sustained at 6-month follow-up in 80% of the participants (Grob et al. 2011; Griffiths et al. 2016).
The findings in terminally ill cancer patients have been reproduced by other research groups (Ross et al. 2016; Reiche et al. 2018). Griffiths and colleagues reported that, in healthy hallucinogen-naive adults, psilocybin led to profound experiences of personal ‘meaning’ and ‘spiritual’ significance (Griffiths et al. 2006). These subjective experiences generally related to feelings of greater interconnectivity with the environment and with others (Erritzoe et al. 2018).
Other research groups have utilized the altered perspective induced by psychedelic-assisted psychotherapy to help people overcome tobacco (Johnson et al. 2014; Johnson et al. 2017) and alcohol addiction (Krebs and Johansen, 2012; Bogenschutz et al. 2015; Dyck and Farrell, 2018; Garcia-Romeu et al. 2019). Preliminary evidence also suggests that obsessive– compulsive disorder may also benefit from psilocybin administered in a controlled environment (Moreno et al. 2006).
A ground-breaking study from Carhart-Harris and colleagues at Imperial College London has once again
compelled psychiatry to re-appraise its ambiguous relationship with psychedelics. Sixty-seven percent of participants with treatment-resistant depression (TRD) had significantly reduced depression symptoms at 1 week, with 40% of participants showing a sustained response at 3 months post-dose (Carhart-Harris et al. 2016a). Furthermore, there were lasting benefits at 6-month follow-up in some participants (Carhart- Harris et al. 2018a). Notwithstanding the open-label design, with a small sample size, this study showed marked clinical improvements, rarely seen in the field of psychiatry. No doubt the Food and Drug Administration was influenced by their work when psilocybin was given ‘breakthrough therapy’ status last year. The Imperial College group are now comparing psilocybin to escitalopram in the treatment of depression (ClinicalTrials.gov Identifier: NCT03429075), et al. the results of which have the potential to introduce psilocybin into clinical psychiatry. Furthermore, an open-label pilot study to investigate the safety and efficacy of psilocybin in people with chronic anorexia nervosa has just started (NCT04052568).