Use of MDMA and Psychedelics in Psychiatry Flashcards
Name 2 serotoninergic drugs
Psilocybin, 3,4-methylenedioxymethamphetamine (MDMA)/ ecstasy
Describe the effects of MDMA
Increased energy, euphoria, emotional warmth, empathy, distortions in sensory perception
Which receptors does MDMA stimulate?
5HT1A, 5HT2A
What is the mode of action of MDMA?
It acutely increases the amount of serotonin in the synapse by increasing its release, but then inhibits the synthesis of more serotonin resulting in a longer-term low serotoninergic state. It has a minor effect on dopamine
How many different receptors are there in the serotonin system?
14
Describe the effects of MDMA compared to placebo on the brain’s resting state in fMRI (Carhart-Harris et al, 2015)
MDMA decreased cerebral blood flow, particularly within the default mode network, frontal areas, and medial temporal areas. In certain medial temporal areas (amygdala and hippocampus), the decrease in blood flow correlated with intensity of subjective positive effects
When is the default mode network activated?
Self-reflection
Describe the effect of MDMA on brain connectivity (Berman et al, 2011)
It decreases connectivity between the medial prefrontal cortex and posterior cingulate cortex - connectivity associated with rumination
Describe the effect of MDMA on memories (Carhart-Harris et al, 2014)
It makes them more vivid, emotional, and positive
Describe the effect of MDMA on facial expression processing (Bedi et al, 2009, 2010)
When given to regular users, it decreases the accuracy of facial fear recognition and enhances the ventral striatal response to happy expressions
Describe the psychological effects of MDMA on cognition and memory (Oehen et al, 2013)
Increased imagination and association, increased contemplativeness, increased recall and tolerance of traumatic memories
Describe the psychological effects of MDMA on an individuals sense of self (Oehen et al, 2013)
Increased self-esteem and self-acceptance
Name 2 mental health conditions that MDMA has been trialled in treating
PTSD, alcohol dependence
State some risks of MDMA
Water poisoning due to hyperthermia encouraging excess consumption, serotonin depletion and toxicity
Why might animal studies overestimate the risk of MDMA?
They tend to use very high doses and inject it rather than giving it orally, leading to higher toxicity
Where do serotoninergic neurons arise from?
Raphe nucleus
Name a biomarker for the health of the serotonin system
Serotonin transporter (SERT)
Describe the effect of MDMA on the serotonin transporter (Erritzoe et al, 2011)
The greater the lifetime use of MDMA, the fewer serotonin transporters found in the brain. Studies have suggested this may cause compensatory upregulation of 5-HT2A receptors due to chronic serotonin depletion
Why might MDMA-induced serotoningeric changes be overestimated in trials? (Szigeti et al, 2018)
The subset of users studied in trials represent the top 5-10% of users, consuming 720% more pills in a year than the average user
Describe the relationship between ecstasy use and mood disorders (Lieb et al, 2002; Huzink et al, 2006)
Ecstasy is associated with mental health conditions including depression and anxiety, but studies have suggested that childhood anxiety and depression often precede starting the use - mental health disorders may promote risk-taking behaviour
What is a psychedelic? (Grinspoon & Barker, 1997)
A drug which, without causing physical addiction, craving, major psychological disturbances, delirium, disorientation, or amnesia, more-or-less reliably produces thought, mood, and perceptual changes rarely experienced except in dreams, contemplative and religious exaltation, flashes of involuntary memory, and acute psychosis
Describe the differences in hallucinations between psychosis and psychedelic use
Psychedelics tend to cause visual hallucinations, whereas psychosis tends to cause auditory hallucinations
Describe the mode of action of psychedelics
They act on the 5HT2A receptor, with a correlation between receptor affinity and psychedelic potency
Describe the effects of the psychedelic ‘peak’
Sense of unity, transcendence of time and space, deeply-felt positive mood, sense of sacredness, sense of paradoxicality, sense of transiency, long-lasting positive effects on behaviour and attitudes towards one’s self, others, and life
Name the active compound produced from psilocybin
Psilecin
Why would the psychedelic DMT not be suitable for therapeutic use?
Too short-lasting
Describe the effect of psilocybin on the brain on fMRI
It decreased cerebral blood flow, particularly in the default mode network and medial prefrontal cortex. It also decreased connectivity between the posterior cingulate cortex and medial prefrontal cortex, a connection associated with rumination
Describe the effect of psilocybin on memory, and how this could be useful in depression
It enhances recollection of autobiographical memories, making them more vivid, visual, and emotional. Depression causes a difficulty in recalling autobiographical memories
Describe the association between psychedelic use and psychological distress (Hendricks et al, 2015)
Lifetime psychedelic use is associated with significantly reduced odds of reporting psychological distress in the past month or suicidal ideation in the past year - the opposite to most illicit drugs
Describe the impact of psilocybin on treatment resistant depression (Carhart-Harris et al)
It reduced the depression severity by QIDS score, although this reduction in severity only remained for some participants
What was associated with the efficacy of psilocybin against treatment-resistant depression? (Roseman et sl, 2018)
The quality of the acute psychedelic experience correlated with its efficacy against treatment-resistant depression
