Effect of MDMA-assisted therapy on Mood and Anxiety symptoms in patients with advanced-stage Cancer Study

This study will seek to answer the question of whether MDMA-assisted therapy is a safe and potentially translatable therapy for treatment of depression and anxiety in the Palliative care population. This patient population is vulnerable to depression and anxiety, arguably the two most difficult to treat medical conditions with the greatest impact on quality of life and quality of death. Pain, nausea, fatigue, cachexia are all physical symptoms intricately linked to and exacerbated by pathological mental states. Current treatment paradigms are inadequate, due in part to the lack of access for patients to psychotherapeutic resources, and a degree of therapeutic nihlism on the part of clinicians as a result. By providing a new treatment that potentially accelerates the psychotherapeutic process, we would be providing a transformative and potentially more accessible approach to relieving the mental suffering of patients facing their mortality.

The KETDEP study was a neuroimaging study on ketamine as a potential rapid acting therapy for depression. Ketamine is a commonly used anaesthetic in pain management and surgery. However, the last 14+ years have seen a massive surge in interest from researchers, psychiatrists and patients in the potential for ketamine to alleviate depression. Not only does ketamine consistently produce rapid (less than 24 hour) reduction in symptoms, but it also sustains this for up to a week after just a single dose. Ketamine also alleviates depression in 70% of patients that currently available therapies have not helped. The KETDEP study showed that 70% of participants that had not responded to 2 or more other therapies experienced at least a 50% reduction in their depression symptoms. Using electroencephalography or EEG, the KETDEP study was the first in the world to show that an important plasticity mechanism in the brain called ‘long-term potentiation’ was increased just 3 hours after one dose, at the same time that the antidepressant effects also became significant. We were also able to show that short-term plasticity is also increased, and that this mechanism called ‘predictive coding’ is important for processing surprising or unexpected sensory information.

One of the most interesting things about ketamine is that it does not work in the brain the way classical antidepressants do, which means it is not yet clear what about ketamine makes it work as an antidepressant. The current study helps us to understand one of the mechanisms that makes ketamine such a powerful and fast acting antidepressant.

In this study, we will conduct a randomised controlled trial
of repeated microdoses of LSD under schedules similar to those suggested in the grey literature. 40
healthy volunteers will be randomised to first receive repeated doses of either inactive placebo or LSD
(10 μg oral) under double-blind conditions in a crossover design. A variety of physiological and
psychological measures will be recorded at baseline and after completion of each of two six-week dosing
regimens. Measures will include a validated personality scale, tests of creativity and attention, basic
physiological measures (heart rate, blood pressure), sleep and activity tracking, and participant self-
reports. Electroencephalography and magnetic resonance imaging will be used to directly measure brain
function and structure in each participant before and after treatment. Our results will thus enable a
rigorous evaluation of the purported benefits of psychedelic microdosing and will be relevant to the
question of whether microdosing may be a viable alternative treatment regimen for depression or
addiction, where full psychedelic doses are currently being investigated in clinical trials.

Advanced-stage cancer patients often experience high levels of anxiety and depression, however, psychological intervention in this context can be challenging. A recent renaissance of research investigating the therapeutic potential of psychedelic compounds to alleviate symptoms of psychological distress is promising. However, administration of psychedelic treatment that induces a hallucinogenic experience potentially poses many barriers to vulnerable and time-poor advanced cancer patients. A promising, although as yet unstudied, option lies in the possibility of combining psychological therapy alongside low (micro) dosing of psychedelics – at a dose that promotes openness and cognitive flexibility but does not overtly alter perception. Given the likely (mis)perceptions and attitudes related to psychedelics, before a proof-of-concept clinical trial is developed, formative evaluation of the overall concept is required. This work takes a two-stage mixed methods approach: Stage 1 involves a qualitative investigation of the attitudes and (mis)perceptions of end users and key stakeholders, and Stage 2 utilises a cross-sectional survey with advanced cancer patients to gauge levels of preliminary interest in regard to the concept of psychedelic microdosing- assisted psychological therapy.