Use of MDMA and Psychedelics in Psychiatry

Question 1

Name 2 serotoninergic drugs

Answer 1

Psilocybin, 3,4-methylenedioxymethamphetamine (MDMA)/ ecstasy

Question 2

Describe the effects of MDMA

Answer 2

Increased energy, euphoria, emotional warmth, empathy, distortions in sensory perception

Question 3

Which receptors does MDMA stimulate?

Answer 3

5HT1A, 5HT2A

Question 4

What is the mode of action of MDMA?

Answer 4

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

Question 5

How many different receptors are there in the serotonin system?

Answer 5

14

Question 6

Describe the effects of MDMA compared to placebo on the brain’s resting state in fMRI (Carhart-Harris et al, 2015)

Answer 6

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

Question 7

When is the default mode network activated?

Answer 7

Self-reflection

Question 8

Describe the effect of MDMA on brain connectivity (Berman et al, 2011)

Answer 8

It decreases connectivity between the medial prefrontal cortex and posterior cingulate cortex - connectivity associated with rumination

Question 9

Describe the effect of MDMA on memories (Carhart-Harris et al, 2014)

Answer 9

It makes them more vivid, emotional, and positive

Question 10

Describe the effect of MDMA on facial expression processing (Bedi et al, 2009, 2010)

Answer 10

When given to regular users, it decreases the accuracy of facial fear recognition and enhances the ventral striatal response to happy expressions

Question 11

Describe the psychological effects of MDMA on cognition and memory (Oehen et al, 2013)

Answer 11

Increased imagination and association, increased contemplativeness, increased recall and tolerance of traumatic memories

Question 12

Describe the psychological effects of MDMA on an individuals sense of self (Oehen et al, 2013)

Answer 12

Increased self-esteem and self-acceptance

Question 13

Name 2 mental health conditions that MDMA has been trialled in treating

Answer 13

PTSD, alcohol dependence

Question 14

State some risks of MDMA

Answer 14

Water poisoning due to hyperthermia encouraging excess consumption, serotonin depletion and toxicity

Question 15

Why might animal studies overestimate the risk of MDMA?

Answer 15

They tend to use very high doses and inject it rather than giving it orally, leading to higher toxicity

Question 16

Where do serotoninergic neurons arise from?

Answer 16

Raphe nucleus

Question 17

Name a biomarker for the health of the serotonin system

Answer 17

Serotonin transporter (SERT)

Question 18

Describe the effect of MDMA on the serotonin transporter (Erritzoe et al, 2011)

Answer 18

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

Question 19

Why might MDMA-induced serotoningeric changes be overestimated in trials? (Szigeti et al, 2018)

Answer 19

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

Question 20

Describe the relationship between ecstasy use and mood disorders (Lieb et al, 2002; Huzink et al, 2006)

Answer 20

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

Question 21

What is a psychedelic? (Grinspoon & Barker, 1997)

Answer 21

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

Question 22

Describe the differences in hallucinations between psychosis and psychedelic use

Answer 22

Psychedelics tend to cause visual hallucinations, whereas psychosis tends to cause auditory hallucinations

Question 23

Describe the mode of action of psychedelics

Answer 23

They act on the 5HT2A receptor, with a correlation between receptor affinity and psychedelic potency

Question 24

Describe the effects of the psychedelic ‘peak’

Answer 24

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

Question 25

Name the active compound produced from psilocybin

Answer 25

Psilecin

Question 26

Why would the psychedelic DMT not be suitable for therapeutic use?

Answer 26

Too short-lasting

Question 27

Describe the effect of psilocybin on the brain on fMRI

Answer 27

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

Question 28

Describe the effect of psilocybin on memory, and how this could be useful in depression

Answer 28

It enhances recollection of autobiographical memories, making them more vivid, visual, and emotional. Depression causes a difficulty in recalling autobiographical memories

Question 29

Describe the association between psychedelic use and psychological distress (Hendricks et al, 2015)

Answer 29

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

Question 30

Describe the impact of psilocybin on treatment resistant depression (Carhart-Harris et al)

Answer 30

It reduced the depression severity by QIDS score, although this reduction in severity only remained for some participants

Question 31

What was associated with the efficacy of psilocybin against treatment-resistant depression? (Roseman et sl, 2018)

Answer 31

The quality of the acute psychedelic experience correlated with its efficacy against treatment-resistant depression