Table 8.

Summary of psilocybin and esketamine features.

Substance	Psilocybin	Esketamine
Mechanisms of action	Activates the 5-HT2A receptors	Blocks subsets of NMDA receptors on GABA interneurons
Conjunction	In conjunction with psychotherapy	In conjunction with SSRI, SNRI
Depression tupe	Under research in Major Depressive Disorder and Depression Related to Life-Threatening Diseases	Treatment-Resistant Depression, Major Depressive Disorder with Suicidal Thoughts or Behaviors
Influence on cognitive functions	Mind-altering effects, “hallucinations”	Dissociation
Influence on suicidal thoughts	Likely reducing	Reducing
Advantages	Neither addictive nor hepatotoxic, and not toxic to tissues; Route of administration: oral; Rapid onset and long-term effects (up to 6 months) Seems to produce no serious adverse events Probably no or little abuse potential	Route of administration: nasal; Rapid onset and long-term effects (up to 7 weeks)
Limitations	Mind-altering side-effects, misuse potential (must be administered under monitored conditions) Caution: may increase the risk of mania in patients with bipolar disorder, and may increase the risk of cardiac arrest and death in patients with cardiovascular diseases	Mind-altering side effects (administration must take place in a clinic and be closely monitored) Not recommended for use during pregnancy or in women of age, not applicable to children under 7 years of age Reproductive Contraindications: hypersensitivity (also to ketamine), aneurysm, intracerebral hemorrhage, recent heart attack Can have abuse potential
Adverse Events	Minor side effects: transient increase in blood pressure, body tremors, fear and sadness, mild to moderate transient headache	Can produce serious adverse events (e.g., suicidal ideation, suicidal attempt, lacunar stroke, seizures) Other: sedation, transient increase in blood pressure