Psilocybin-assisted therapy for depression : How do we advance the field ?
Sally E Meikle, Paul Liknaitzky, Susan L Rossell, Margaret Ross, Nigel Strauss, Neil Thomas, Greg Murray, Martin Williams, David J Castle
Australian & New Zealand Journal of Psychiatry, 2019, 1–7
Doi : 10.1177/0004867419888575
In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.
Keywords : Psilocybin, psychedelics, depression
There is no doubt that we need new treatment options for mental illnesses, with novel mechanisms of action. In depression, we have been flogging the monoamine reuptake inhibition horse for decades now. Agomelatine has arguably been the only ‘novel’ antidepressant to come to market in many years (Rouillon, 2006). But now we are seeing renewed interest in ‘old’ drugs – licit and illicit – being repurposed to treat various mental illnesses. Medicinal cannabis is being explored for a number of indications (Hill, 2015); ketamine is all the rage (Krystal et al., 2019), with studies of intravenous and oral ketamine, and now intranasal esketamine (Canuso et al., 2018) demonstrating rapid improvements in depression and suicidality; 3,4-methylenedioxymethamphetamine (MDMA) has been usefully employed as an adjunct to psychotherapy in posttraumatic stress disorder (PTSD) (Mithoefer et al., 2019); and we can now add psilocybin to this list, which in conjunction with psychotherapy has shown benefit for end-of-life depression and anxiety, with emerging evidence of usefulness in addressing treatment-resistant depression. Indeed, the US Food and Drug Administration has designated psilocybin-assisted psychotherapy as a Breakthrough Therapy in the treatment of depression, expediting its development towards a prescription medication (see Williams and Warner, 2019).
Relevant to this discourse, three recent articles in The Australian and New Zealand Journal of Psychiatry serve as a ‘call to arms’ for Australian psychiatry, encouraging serious consideration of, and contribution to, the growing body of research into psychedelic therapies for maladies of the mind (Inserra, 2019; Puspanathan, 2017; Strauss et al., 2016). Here, we consider the next steps that Australian psychiatry might take in meeting this challenge. We focus specifically on psilocybin, as the first modern psilocybin trial in Australia is soon to commence psilocybin-assisted psychotherapy to treat end-of-life anxiety and depression) and an Australian study of medicinal psilocybin for treatment-resistant depression is in advanced planning. Also, a recent study ranking drugs of abuse in Australia according to their potential to do harm has confirmed a very low harm rank for psilocybin (Bonomo et al., 2019).
Psilocybin is a naturally occurring molecule found in a number of mushroom species. Recreational use of psilocybin-containing ‘magic mushrooms’ for their ability to occasion an altered state of consciousness is widespread in Australia and globally, and users have long attested to beneficial mood effects (Carhart-Harris and Nutt, 2010). Indeed, through the 1950s and 1960s, tens of thousands of individuals participated in psychedelic research, mostly using lysergic acid diethylamide (LSD; a molecule close in structure and effect to psilocybin), with many of them showing positive mood and clinical improvements (Baumeister et al., 2014; Nichols, 2016). While few of these early studies stand up to current methodological standards, over the past decade, psilocybin’s ability to alleviate affective and addictive disorders has been tested in leading labs by highly credentialed researchers and with modern scientific rigour (see Williams and Warner, 2019).
Two of these studies – one from New York University and one from Johns Hopkins – focussed on end-of-life depression and anxiety in palliative care settings. The New York study (Ross et al., 2016) involved 29 patients in a randomised double-blind active placebo-controlled crossover design. Antidepressant response was recorded in 83% of the psilocybin group, and the effect was very rapid (within a day). Only 14% of those in the control condition had an antidepressant response. Following only nine psychotherapy sessions, one psilocybin session, and one placebo session, positive effects found post-intervention were for the most part sustained at 6-month follow-up.