College 7: psychedelics

Question 1

Types of psychedelics

Answer 1

• Psilocybin
• DMT
• LSD (works on serotonin)
• Mescaline
• 5-MEO DMT

Question 2

Albert Hoffman

Answer 2

Discovered different psychedelics, like lysergic and LSD. He was very positive about the clinical benefits of this, but the funding of this research was cut off, because of the negative image of drugs.

Question 3

The psychotropic effect

Answer 3

• Mood: high arousal, more positive mood
• Perception: visual pattern morphing
• Cognition: loss of ego and los of sense of self, sense of becoming part of a larger entity..

Question 4

Psychedelics in the brain

Answer 4

Drugs work on:
- Dopamine
- Norepinephrine
- Serotonin (most important)

Where the receptors in the brain are divided, is important for the effects of the drugs of the brain. Like when the PFC is stimulated, this can alter our reality.
Drugs interfere with the way neurons receive and process signals via neurotransmitters.

Question 5

Serotonin (5HT-2A and 5HT1A receptors)

Answer 5

Serotonin receptor types important for many psychedelics to bind on.

Question 6

Blocking the 5HT-2A receptor

Answer 6

When the serotonin receptors are blocked, the psychedelics can’t bind on these receptors and there is NO psychedelic experience.

Question 7

Receptor down-regulation

Answer 7

When you take too many psychedelics, the receptors are being overstimulated, which causes a change in the chemical binding of serotonin. This can result in a reduction of anxiety symptoms. This is a tempary affect, after 5 months the balace is normal against and the level of anxiety is the same as before.

Question 8

2A-receptor signalling effects in animals

Answer 8

• Decrease in 2A stimulation –> perseveration and compulsive behaviour.
• Increase in 2A stimulation –> increased sensitivity to the environment and faster learning in new environment.
• LSD: makes rats more flexible is cognitive learning and rapid learners
• 2A receptors stimulates neuroplasticity in the hippocampus, which causes better spacial navigation.

Question 9

SSRIs vs psychedelics

Answer 9

• SSRIs –> 5T1A (serotonin) reuptake blocking, which causes anxiety to go down, but also causes bluntness in emotions (negative side-effects).
• SSRIs: passive coping
• Psychedelics –> increase in signalising of 5-HT2A receptors, pessimism and rigid thinking is reduced, plasticity is improved, more adaptability and environmental sensitivity (positieve side-effects)/
• Psychedelics: active coping.

Question 10

What do psychedelics do during therapy?

Answer 10

• Decrease defences
• Facilitates emotional approach during therapy.
• Less inhibition of emotions and memories.
• Stimulating flexibility and learning
• Less anxiety and improved general well-being during post-acute ‘afterglow’.

Question 11

fMRI about the effects of psilocybin

Answer 11

A brain scan during a resting state on psychedelics (psilocybin). When people get instructed to do nothing they still think about their life, the past and the future.
Psilocybin decreases activity in association ara’s like the:
- PCC
- ACC
- Medial PFC
- Thalamus
This causes the brain to freely interpret the environment, goes into a dream-like state, ego-dissolution (losing sense of self), more flexible neurological traffic among the whole brain.

Question 12

Brain connection

Answer 12

When we take a psychedelic drugs, this increases the connectivity / cross-talk among different brain regions. This increases integrity / feeling of oneness and more flexible neurological traffic among the whole brain.

Question 13

Psilocybin and affect

Answer 13

One week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, and positive affect and response to emotionally-conflicting stimuli were increased.

Question 14

Psychedelics vs. placebo

Answer 14

One study found that, over time, psilocybin micro-dosing does not affect emotion processing or symptoms of anxiety and depression compared to placebo.

How can we explain discrepancies?
- The studies differ in how high de dosis was.
- The seconds studie only selected healthy participants, which is why they didn’t improve much in anxiety.

Question 15

Clinical trials can cause:

Answer 15

• Abstinence from smoking
• Decreased drinking
• Reduced symptoms of OCD
• Decreases anxiety (in life-treathening illness)
• More openness to experience
• Decrease of chronic depression symptoms

Question 16

Criticism to research to psychedelics

Answer 16

• No good control groups
• Combined with therapeutic interventions
• Low sample size
• Publication bias

Question 17

The effect of psychedelics on depression (hypothesis)

Answer 17

When you’re depressed, there is often an increase focus on the self and decrease in focus on the external world. Psychedelics can cause a decreased focus on the self and a shift to focus of the external world, which can improve depression symptoms.

Question 18

Psilocybin and depression

Answer 18

• Causes reduced emotional reactivity to negative stimuli –> better coping.
• Causes increased positive affect relative to placebo.
• Causes less activity in the amygdala.
• Reduces activation of pain regions during social exclusion.
• Increases emotionally empathy and feeling of connection to others.

Question 19

Negative experiences of psychedelic drugs

Answer 19

Psychedelic drugs can also cause negative experiences. People who report (little) harm when using psychedelics drug don’t show improvement in mental wellbeing –> the effect of psychedelics depends on your genetic background and differs per individual.

Question 20

Duration of the effects

Answer 20

A lot of people only show short-term effects of psychedelics and bounce back after few months.