Psychedelics

Question 1

Describe how the relationship between serotonergic psychedelic / MDMA
administration and non-drug therapeutic approaches differs from other
approaches for PTSD and MDD

Question 2

What receptor do psychedelics bind to?

Answer 2

-5-HT2A agonist
-many targets but that is the big one

Question 3

MDMA MOA

Answer 3

-reversal of VMAT2: increase intracellular 5-HT
-Reversal of 5-HT through SERT
-Substrate / Releaser at
monoamine transporters (SERT
/ NET/ DAT)

Question 4

Metabolism of LSD

Answer 4

-metabolized by CYP2D6
-a little by 3A4, 1A2, 2C9, 2E1

Question 5

Common dose of LSD

Answer 5

100-200 mcg
-elimination half life: 2.6 +/- 0.6 h
-subjective Effect Duration (200 mcg): 11.6 ±
1.7 h

Question 6

Metabolism of Psilocybin

Answer 6

-undergos glucuronidation and other metabolism enzymes
-MAO-A
-UGT1A10 and 1A9
aldehyde dehydrogenase
-Few drug interactions

Question 7

Metaboloism of DMT

Answer 7

-CYP2D6 and MAO-A
-little 2C19

Question 8

DMT dose range

Answer 8

-0.1-0.4 mg/kg IV
-30-50 mg inhaled
-Elimination half life 9-12 minutes
-Effect duration: 25 minutes

Question 9

Metabolism of 5-MeO-DMT

Answer 9

-CYP2D6 and MAO-A

Question 10

Metabolism of MDMA

Answer 10

-CYP2D6
-CYP3A4
-MAO-A
-COMT
-most likely to cause drug interactions

Question 11

Common MAO inhibitors

Answer 11

-Selegiline
-Tranylcypromine
-Isocarboxazid

Question 12

Common strong CYP2D6 inhibitors

Answer 12

-Bupropion
-Fluoxetine
-Paroxetine
-Quinidine
-Terbinafine

Question 13

Common moderate CYP2D6 inhibitors

Answer 13

-Duloxetine
-Cinacalcet
-Mirabegron
-Rolapitant

Question 14

Common weak CYP2D6 inhibitors

Answer 14

-Escitalopram
-Fluvoxamine
-Sertraline

Question 15

Haloperidol and psilocybin

Answer 15

-no effect
-increase the ‘dread of ego dissolution’: made them scared

Question 16

Risperidone and psilocybin

Answer 16

-reduced all the parameters of the APZ-OAV
-reduction in dread of ego
dissolution

Question 17

Lithium and psychedelics

Answer 17

-47% of lithium + psychedelics reports involved seizures
-serious seizure risk for this combo

Question 18

Drug interactions with MDMA

Answer 18

-MAOIs and MDMA
-dangerous elevation in synaptic serotonin
-causes most deaths

Question 19

Bupropion and MDMA

Answer 19

-increase risk of seizure
-stimulant toxicity
-Serotonin syndrome

Question 20

(Citalopram, fluoxetine, paroxetine) and MDMA

Answer 20

-increase drug effects by 30-80%
-physiological effects increase 6-14%

Question 21

Duloxetine and MDMA

Answer 21

-increase heart rate and BP
-effect on mood was significantly reduced by duloxetine

Question 22

Chronic Psychedelic Use and Drug-
Induced Valvular Heart Disease
Considerations

Answer 22

-chronic 5-HT2B agonism is a concern with microdosing