Psychedelic Therapy: A 'Middle Way' Forward for Psychiatry

Article by Hannah Douglass and Dr Robin Carhart-Harris

Doctors issued 36 million prescriptions for antidepressant drugs in 2008, one decade later this number had more than doubled to a staggering 70.9 million.

Two years previously, in 2016, a 6% annual increase in the number of prescriptions was recorded, the largest increase of any prescription item for the fourth year running.

With depressive disorders listed as the third-leading cause of disability in 2017 and an estimated 10% of the population being afflicted by this debilitating disorder at some point in their lives.

Why then, is the increase in antidepressant prescription rates not having more of an impact on the prevalence of depression?

Not much more than half of patients show a clinically meaningful response to first-line antidepressant medications. Of the remaining non-responders many exhibit resistance to subsequent treatments.

The most detailed and up-to-date meta-analyses suggest that antidepressants have only a modest superiority over placebo and questions remain over their side-effects and treatment adherence, plus systematic biases in their evidence-base related to the massive industrysponsorship and dissemination of antidepressant drug research.

The pharmacological and cognitive revolutions in psychiatry and psychology, which culminated in the discovery of the selective serotonin reuptake inhibitors (SSRIs) and development of cognitive behavioural therapy (CBT), were heralded as successors to the obscurantism and dogmatism of psychoanalysis.

However, whatever the limitations of psychoanalytic psychotherapy, the fact remains that most patients prefer talking-therapy over drug treatments, and yet, unlike antidepressant drugs, even the brief, evidence-based talking-therapies such as CBT are comparatively expensive, and schemes designed to improve access to them have not been hugely successful, with patients often sitting on waiting lists for several months before being seen.

Added to this, psychotherapy appears to have no better efficacy than antidepressants and problems remain over its typically slow therapeutic action, poor treatment adherence and high rates of relapse.

There has existed, for too long, a stark and artificial schism in mental health between the biomedical and person-centred approaches. It cannot be the case that one side of this divide is right and the other wrong, although such perspectives have been commonplace in mental health, particularly among a certain generation.

Psychiatry has always been the black-sheep of medicine, as the focus of its practice is the intrinsically subjective human mind.

Try-as-it might to convince the world that it is just as biological and objective as other domains of medicine, the fact remains that it cannot be: however intimately related there may be, the human mind and brain are categorically distinct phenomena and it is an error to neglect either side of this unique coin.

With positive public engagement initiatives currently underway to change the way mental health is viewed, one can feel hopeful that such progressiveness will extend up to psychedelic therapy – a truly hybrid or “middle-way” therapeutic model that seeks to combine precision pharmacotherapy with psychotherapy in a synergistic way.

This approach rests on an increasingly popular principle in mental health research that the brain is not an isolated organ, neither from the rest of the body or its environmental context.

With its emphasis on the importance of synergies between complementary approaches - i.e. a specific drug and brain action combined with the shaping of a particular psychosocial context - psychedelic therapy is in many ways an exemplar “biopsychosocial” therapeutic model.

The history of psychedelic therapy is a history of unrealised potential. Psychedelic plants such as psilocybin-containing mushrooms (i.e. “magic mushrooms”) have been used since ancient times by certain cultures.

Catalysed by the discovery of LSD in the 1940s, psychedelics were prescribed and researched extensively in psychiatry the 1950s and 60s – before becoming the target of a conservative prohibitionist campaign fuelled by misinformation and scare-mongering. Meta-analyses of the research done during this period have tended to support the view that psychedelics can be very effective when used appropriately.

Fast-forward half century to the present day and a growing evidence-base is amounting for psychedelic therapy.

Building on a foundation of human neuro-imaging research and a small-scale feasibility study of psilocybin-therapy for treatment resistant depression, our newly founded Centre for Psychedelic Research at Imperial College London is presently halfway through a 60 patient double-blind randomised control trial comparing psilocybin therapy with a 6-week course of SSRIs.

Recruiting for this trial has been a challenge but initial results are promising, with the blind broken at the primary endpoint (6 weeks after treatment inception) so that normal care can resume.

The primary outcome measure in this trial is emotional processing and its neural correlates, measured via functional magnetic resonance imaging (fMRI). Based on previous work, we have hypothesised that psychedelic therapy works differently to SSRIs because of a differential action on emotional processing.

More specifically, we predicted that effective psychedelictherapy enhances an individual’s ability to accept, release and process intense emotions, whereas treatment with SSRIs works via moderating emotionality so that the individual can more easily “get by”.

In recent years, to supplement our controlled research, we have begun to sample naturalistic-use of psychedelics using a web-based survey tool (psychedelicsurvey.com) completed in a prospective way: before and after planned-use of a psychedelic.

Different surveys have been created for different contexts: e.g. “micro-dosing” with a psychedelic (i.e. the semi-regular use of very low doses of a psychedelic), use of psychedelics within organised retreats (some of which are legal in certain countries) and use of psychedelics in any other context.

Part of the motivation behind these surveys has been to collect so-called “big data” so that we can acquire a solid evidence-base for informing harm reduction messages while simultaneously identifying how best to harness the therapeutic effectiveness of psychedelics.

Unsurprisingly, initial results have revealed that responses to psychedelics are highly context dependent, being contingent on such factors as:

1) the intention one brings to an experience,

2) the people one is with when the drug is taken, and

3) personality traits that are predictive of sensitivity to the drugs’ effects.

Given our special interest in how the effects of psychedelics compare with those of conventional antidepressant medications, we recently set-up a sister project to these psychedelic surveys, with harmonized outcome measures so that we can compare findings from naturalistic-use of psychedelics with standard clinical-use of SSRIs.

However, for this project to be successful, we are entirely dependent on the support of primary and secondary care professionals, who we hope will refer patients to this study by providing them with a weblink and encouraging them to sign-up as soon as they begin a course of standard antidepressant drugs.