Psychadelic Psychiatry and Psilocybin: A new era
RUNNER UP - SANDS COX CHARITY ESSAY PRIZE 2019
During the 1950s and 60s, there was huge research into uses of hallucinogenic ‘psychedelic’ drugs. Over a thousand papers were published investigating lysergic acid diethylamide (LSD) alone. Despite impressive results in alcoholism, smoking and depression, research was abruptly terminated in the 70s, as a result of non-medical pressures: a media backlash against the ‘hippy counterculture’, and Nixon’s 1971 ‘war on drugs’. However, over the past decade, there has been a research renaissance. Research centres have opened at several leading academic institutions, including Johns Hopkins University and Imperial College London. David Nutt, Professor of Neuropsychopharmacology at Imperial’s Centre for Psychedelic Research, has emerged as a prominent figure in this new era of psychedelic therapy.
Nutt’s research has focused primarily on use of Psilocybin in depression, with staggeringly impressive results. He demonstrated clinically significant and sustained improvements in patients with treatment-resistant depression after just two Psilocybin sessions. Indeed, results from Nutt and others indicate Psilocybin is one of the most exciting anti-depressants in the pharmacological pipeline. Psilocybin is better known as the active ingredient in Magic Mushrooms, a class A controlled drug. Nevertheless, further research has proved Psilocybin effective in other treatment-resistant mental health disorders, usually in combination with psychotherapeutic approaches. In smoking addiction trials, 80% of participants maintained 6-months of smoking-cessation compared to 35% with Verenicline, regarded as currently the most effective smoking-cessation drug. Other groups are currently investigating the impact of Psilocybin in post-traumatic stress disorder (PTSD), anorexia nervosa, anxiety related to terminal illness, alcohol addiction, Alzheimer’s and post-treatment Lyme disease syndrome, with promising preliminary findings. Equally exciting results with other hallucinogenic substances are also emerging. For example, a nasal-sprayed Ketamine-derivative has recently been approved by the FDA for severe depression and there is evidence that MDMA (‘ecstasy’)-assisted psychotherapy was a highly effective treatment for symptomatic control of PTSD in phase III trials.
The mechanisms by which these hallucinogens act is also a focus of research interest and in broad terms may result from a ‘hyper-connectivity’ in brain network dynamics (figure 1). However, such mechanisms may also account for their limitations in some populations; for example, they are contraindicated in those at risk of psychosis, certain personality disorders or existing cardiac pathologies. It is also difficult to predict the emotional intensity of an individual’s ‘trip’, with some participants reporting negative feelings during psilocybin therapy, despite long-term mood improvements afterwards. Consequentially, no research advocates recreational use of any of these ‘illicit’ drugs. Despite this stance and total complicity with relevant protocols Nutt has repeatedly described the difficulties with conducting clinical trials. He describes these rigid protocols impeding research and there are significant reservations shown towards his data by the scientific community. He ascribes this to the current ‘illicit’ status of psilocybin and, rather shockingly, describes being monitored ‘like a criminal’ by both government and academia. Other researchers similarly comment on hurdles they face in securing funding, restrictions on drug acquisition and research being banned by institutions or police. So, hopefully the recent declaration in support of illicit drug decriminalization by the Royal College of Physicians will catalyse further evidence-based research into this niche of pharmacology.
Wider-reaching benefits of drug decriminalization can be revealed by examining the non-academic setting. Scotland has the highest number of drug-related deaths in the world. By comparison, drug decriminalization in Portugal in 2001 had a phenomenal effect: no increase in drug use, more people seeking help for drug misuse, reduced HIV/AIDS rates, reduced adolescent drug use, reduced social costs of drug use and a factor to why Portugal has more than 40-times fewer drug-related deaths-per-million than Scotland. Yet for many and for a plethora of reasons, drug decriminalization remains a highly charged issue, clouding policy-making. Nutt’s response to this? ‘Let scientists tell you the truth about drugs’.
The resurgence of hallucinogenic drug research has achieved impressive results and is flourishing in spite of the various stumbling blocks. Yet given the relentless increase in mental health disorders, anti-depressant prescriptions alone have doubled in the past decade, this is a major area of clinical need. As with any drugs in development, further research is required, but this fledgling frontier of psychedelic therapy could provide revolutionary advances in the very near future.
Figure 1. Using a series of MRI scans this image is a simplified visualisation of intra-cranial neural connections. The aim is to show ‘Functional connectivity’ in a normal brain (a) and a brain whilst under the influence of Psilocybin (b). Whilst on Psilocybin it demonstrates ‘hyper-connectivity’, this allows for greater communication due to a decrease in constraint of neural networks available2.
Carhart-Harris RL, Bolstridge M, Nutt DJ et al., 2017, Psilocybin with psychological support for treatment-resistant depression: six-month follow-up, Psychopharmacology, Vol: 235, Pages: 399-408, ISSN: 0033-3158
Petri G, Expert P, Nutt D, et al F. Homological scaffolds of brain functional networks11J. R. Soc. Interface http://doi.org/10.1098/rsif.2014.0873
 Carhart-Harris RL, Bolstridge M, Nutt DJ et al., 2017, Psilocybin with psychological support for treatment-resistant depression: six-month follow-up, Psychopharmacology, Vol: 235, Pages: 399-408, ISSN: 0033-3158
 Petri G, Expert P, Nutt D, et al F. Homological scaffolds of brain functional networks11J. R. Soc. Interface