Can psychedelics be the treatment for the crisis in psychopharmacology ?

Genís Ona, José Carlos Bouso

ICEERS Foundation, Preprint · January 2019

DOI: 10.20944/preprints201901.0249.v1

Keywords : Mental health, psychedelics, psychopharmacology, psychiatry, innovative

1. Introduction

For the past few years, we have been witnessing a crisis in the field of psychopharmacology. Generally, it takes a decade and up to a billion dollars in investment to get a drug on the market. Furthermore, the majority of new drugs are ruled out during the pre-clinical phase. Less than 20% of the selected drugs make it to Phase-III evaluation involving humans. Drug development has never been an easy task. However, in psychiatric drug research there are additional difficulties that have led to the current crisis.

Tracing the history of psychiatric drug research helps map out the crisis that this field is currently facing. Before 1950s, only barbiturates and chloral hydrate were available for the treatment of psychiatric symptoms. These drugs were ineffective and were associated with serious adverse effects. But in the 1950s and early 1960s, several novel drug classes were discovered for the treatment of psychiatric disorders, a process that has been referred to as the “psychopharmacology revolution”.1 With more effective and safer drugs, the field of psychiatry developed new patterns of assistance, reducing the number of patients admitted to institutions and therefore improving their quality of life. The biomedical model that was developed based on these observations has been extensively criticized.2,3 Some authors suggest that this model has produced the current conceptual crisis in psychiatry,4 generating potentially erroneous situations such as excessive confidence in oversimplified treatments, including those based only on pharmacotherapy (or, worse, polypharmacy)5.

Additionally, early psychopharmacological research faced various limitations, as Horrobin6 explained in detail in an interesting text published in the Oxford Textbook of Medicine. He found that the five most successful therapeutic strategies to be used in the modern history of psychiatry were drugs developed (or rediscovered) during the 1950s or after: lithium, monoamine oxidase inhibitors, phenothiazines, tricyclic antidepressants, and benzodiazepines. The first three drugs listed were discovered by serendipity, and the final two were discovered through discredited screening techniques. Horrobin6 subsequently concluded that these discoveries were not dependent on the regular medical research strategy.

These and other issues mentioned by Horrobin more than 30 years ago were recently highlighted anew by Insel and Sahakian,7 as well as in statements from various eminent health professionals, suggesting that the state of psychopharmacology research has not changed significantly in the past few decades. Both DePaulo,8 past chairman of the Department of Psychiatry and Behavioral Sciences at Johns Hopkins University, and Insel,9 former Director of the National Institute of Mental Health, have noted that modern psychopharmacological treatments are not more beneficial than past ones, despite their higher cost. In addition, Fibiger,10 former Vice President of Neuroscience at Eli Lilly, has stated straightforwardly that psychopharmacology is in crisis. This is evidenced by the reality that not one innovative drug has reached the psychiatric market in more than 30 years. This is partly due to widely-used yet questionable practices, such as making minimal modifications to drugs that are already available and commercializing them as “new” products (known as “me-too” drugs). For this reason, our present psychiatric drugs are little better than those that were available in the 1950s.9,11 One of the constraints hampering drug development may be the fact that the molecular targets of psychiatric drugs have not changed in the last 50 years, and even today we do not understand some of the mechanisms through which they work.12 This lack of knowledge about the exact mechanisms is worsened by an inability to validate the fundamental hypotheses about mental disorders.13

Evidently, we are lacking innovative approaches, and we need to use creative and efficient strategies in order to improve our understanding of psychiatric drugs and their effects. Focusing on certain molecular targets exclusively would be a limited approach, at least if it is not combined with psychotherapy. Furthermore, chronic treatment with these medications might be more harmful than beneficial.14,15 This is evident in the case of benzodiazepines, one of the most widely-used classes of drugs.16 Based on the above, it can be deduced that psychiatry is facing serious challenges, since psychopharmacology (which offers the best therapeutic strategies in this regard) is in crisis. Furthermore, this crisis is having an inescapable negative impact on public health.17

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