The Evidence Base for Psychedelics in the Treatment of Depression – Highlights from RCPsychIC 2019
This article is based on the talk by Dr James Rucker at RCPsychIC 2019. Dr Rucker is a Consultant Psychiatrist and NIHR Clinician Scientist, Fellow. He is currently the principal investigator for a 5-year NIHR funded clinical trial exploring the feasibility, safety and efficacy of psilocybin as a treatment for people suffering from depression that has not responded to standard medical and psychological therapies.
1. Classical psychedelics are all structurally analogous to the neurotransmitter serotonin, which underpins their psychopharmacology. The UN Convention of Drugs 1967 saw LSD and other psychedelics removed from psychiatric use where they had been used for similar conditions now investigated today.
The classical psychedelic drugs include mescaline, psilocybin, dimethyltryptamine (DMT) and d-lysergic acid diethylamide (LSD). Coined by psychiatrist Humphrey Osmond in a letter he wrote to Aldous Huxley in 1956, the word ‘psychedelic’ is derived from the ancient Greek words psychē (ψυχή, translated as “soul” or “mind”) and dēlein (δηλειν, translated as “to reveal” or “to manifest”). Therefore, psychedelic literally translates as ‘mind manifesting’ or ‘soul revealing’. Other terms such as ‘hallucinogen’ and ‘psychotomimetic’ are less favoured, perhaps because they place too much emphasis on individual elements of a multi-faceted subjective state. [Rucker J et al., 2018]
2. A healthy research field existed before prohibition, and there are now more post-prohibition papers published due to a steady resurgence in recent years. Pre- and post-prohibition evidence is summarised in a recent review. [Rucker J et al., 2018]
3. Clinical trials reported in the pre-prohibition literature are not conducted to the same standards as today, but it is possible to aggregate patients according to disorder. Using broadly defined unipolar data, around 80% of those treated with psychedelics were thought, by their clinicians, to have improved. [Rucker J et al., 2016]
4. The best evidence that exists pre-prohibition for psychedelic therapy was in alcoholism, and a meta-analysis of six good quality trials published before 1970 was published in 2012. Good evidence for therapeutic efficacy of LSD in the treatment of alcoholism was shown in a cohort of 536 participants. [Krebs T & Johansen P, 2012]
5. Today, the best RCTs conducted in psychedelics so far are in existential distress, particularly anxiety and depression associated with major life-threatening diagnoses and the prospect of dying, e.g. in patients with a terminal illness. Results showed rapid and sustained reduction in anxiety and depression scores post-one-dose of psilocybin (0.3mg/kg) in conjunction with psychotherapy) vs active placebo (niacin) and psychotherapy. [Ross S et al., 2016]
6. In a second trial, high-dose (25 mg) psilocybin was compared with low-dose (1 mg) [Griffiths R et al., 2016]. Participants in the high dose group reported an increased quality of life, life meaning, and optimism. There were also fewer clinician and self-rated measures of depressed mood and anxiety.
7. A health volunteers cognitive study of psilocybin has been completed with analysis currently underway. Late phase 2 trials in treatment-resistant depression are now being performed with significant pharmaceutical company funding, and phase 3 trials are likely to be completed in around five years. If licensed, psilocybin therapy will likely be costly and only available in specialist centres.