Across studies, the evidence of the effectiveness of psilocybin in treating existential distress is arguably among the strongest of any yet obtained in the field of psychedelic research.
A pioneering pilot study led by Charles Grob at UCLA examined the potential of psilocybin, which yielded safe physiological and psychological responses and no clinically adverse events. A reduction in anxiety was noted 1-3 months after treatment, with a long-term improvement in mood observed at six months post experience.
Another study explored the potential of LSD (at a dose of 200µg) in the treatment of anxiety associated with life-threatening diseases. No lasting adverse reactions from LSD administration were observed, with long-term benefits sustained over a 12-month period following a single dose, and highly significant reductions in anxiety were noted in over three-quarters of participants, with a rise in quality of life noted in two-thirds of participants.
Subsequent research studies conducted by Johns Hopkins and NYU built on this pioneering work, using a randomised controlled trial design to examine the effectiveness of psilocybin administration for the treatment of anxiety and depression among people with a terminal cancer diagnosis with greater rigour. In both trials, psilocybin was found to elicit rapid, substantial and sustained improvements in anxiety and depression, and reductions in cancer-related demoralisation and hopelessness. Trial participants, in addition to staff and community observers, rated participant moods, attitudes, and behaviours throughout the study to enhance the rigour of the findings.
At long-term follow-up, half a year following the psilocybin session, clinically significant reductions in depression and anxiety were sustained in 60-80% of participants across studies. Reductions in death anxiety and existential distress and improved attitudes towards death were also observed. These changes aside, increases in quality of life, well-being, life meaning, life satisfaction, optimism, and spiritual well-being were also noted by the substantial majority of participants, along with improvements in attitudes about life/self, mood, relationships, and spirituality. It was found that the occurrence of mystical experiences under the psilocybin mediated the therapeutic effect of psilocybin on anxiety and depression while predicting other therapeutic outcomes.
Research gaps have been highlighted in a recent scoping review of the effects of psychedelics on attitudes towards death, with it being highlighted that further work is warranted to better understand factors such as the psychological mechanisms that underpin such shifts in attitude, and the role of set and setting in shaping outcomes.
The late Dr Mark Kleiman, an expert in drug policy and criminal justice who was an advocate of more nuanced drug policy, has been credited with helping usher the USA’s shift away from the all-out war on drugs once mused:
The obvious application [of psychedelics] is people who are currently dying with a terminal diagnosis. But being born is a terminal diagnosis. And people’s lives might be better if they live out of the valley of the shadow of death.
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