Table 1.

Pharmacological properties of key psychedelic compounds used for treating PTSD. Adapted from Lepow et al. (2023) [38].

Compound	Receptor Binding Profile	Usual Route and Dose Range in Clinical Research	Duration of Effects	Common Acute Side Effects	Overview of Hypothesized Mechanisms of Action	References
MDMA	Inserra et al., 2021; Ray, 2010: I1, 5-HT2B, Ca+ Channel1A, α2C, α2B, M3, α2A, M5, M4 Inserra et al., 2021: TAAR1, NMDAR, VMAT2, 5-HT1A, SERT Oeri, 2021: 5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C, 𝛼1, 𝛼2A, β, D1, D2, M1 and M2, H1, n, AChR	Route Oral Dose 75-125 mg	3-6 hours	Anxiety, paranoia, racing thoughts, loss of self control, overwhelming emotions, vivid recollection of negative memories, muscle tightness, decreased appetite, nausea, hyperhidrosis, feeling cold, restlessness, mydriasis, postural dizziness, bruxism & nystagmus	Increases • Serotonin, norepinephrine & dopamine via inhibition of reuptake transporters & activation of presynaptic release into synaptic cleft. • Oxytocin via activated SERT & 5HT4 receptors→ Metaplastic upregulation of oxytocin receptors → LTD of excitatory transmission → Reopening critical period of social reward learning. • 5HT4 receptor activation on oxytocin neurons→ Increased oxytocin release → Heightened feelings of closeness & empathy → Positive social interactions. • RSFC between hippocampus and amygdala → Enhanced emotional memory processing & reconsolidation. Decreases • Cerebral blood flow to amygdala + ↓ coupling between mPFC and hippocampus → ↓ in fear, ↑ fear extinction, ↓ amygdala hyperactivity. • Emotional processing of negative social stimuli and negative impacts of social rejection.	[263, 292, 302, 303, 326, 332, 333, 467, 512, 533]
Psilocybin	5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6, 5-HT7, D1, D3	Route Oral Dose 10-30 mg	4-6 hours	Headache, nausea, hypertension, tachycardia, dysphoria, paranoia, anxiety, fear, vomiting, physical discomfort, anxiety, confusion	Increases • Striatal dopamine concentration → Euphoria & depersonalization. • Transcription of neuroplasticity-related genes in PFC. • Cerebral blood flow in frontal & temporal regions. • Bottom-up processing → Increased entropy of spontaneous cortical activity → Reduced precision of higher-level priors. Enhanced integration of sensory and somatic-motor brain networks, weakened integration of associative brain networks.	[36, 280, 421, 498, 499, 500, 511, 512, 525, 533, 550, 736]
LSD Tryptamines (Ergolines)	5-HT1B, 5-HT7, 5-HT6, 5-HT1A, 5-HT1D, 5-HT5A, 5-HT2A, D3, 5-HT2B, 5-HT2C, 𝛼2A, 5-HT1E, D2, D4, D1, D5	Route Oral Injection Dose Oral: 100-200 µg Injection: 75 µg	2.5-4.5 hours	Anxiety, panic, nausea, decreased appetite, headache, dizziness, lightness in limbs, trembling, sweating, salivation, bradycardia, hypotension.	Decreases • Reactivity of amygdala to negative stimuli → Decreased processing of negative emotional stimuli & enhanced positive mood → Possible antidepressant action. • Amygdala cerebral blood flow + ↓ Parahippocampal-mPFC functional connectivity + ↑ PFC-inferior lateral parietal cortex RSFC → Reduced symptoms of depression. • Cerebral blood flow in subcortical & occipital regions. • Connectivity between amygdala & striatum. • Functional connectivity in DMN → Antidepressant effects. • Inflammation & norepinephrine uptake → Possible analgesic effects Mediates • 5HT2A receptors in PFC & cortical regions→ Psychedelic effects. • 5HT1A receptors → Visual effects & disruption of attention. • 5HT2A, TrkB & mTOR signaling pathways → Synaptogenesis. • 5-HT2A receptors on cortical pyramidal cells/GABA interneurons disrupt thalamocortical information flow → ↑ bottom-up processing → ↑ sensory perception & cognitive disturbances.	[280, 510, 512, 533, 778]
DMT/ Ayahuasca	5-HT7, 5-HT1D, 5-HT2B, 𝛼2B, 𝛼2C, D1, 5-HT2C, 5-HT1E, 5-HT6, 5-HT5A, I1, 𝛼1B, 𝛼2A, 𝛼1A, 5-HT2A, SERT, S1R	DMT: Route Oral Dose 15-115 mg Ayahuasca: Route Oral Dose 1 ml/kg (0.36 mg/ml DMT) -2.2 ml/kg (0.8 mg/ml DMT)	1.5-2 hours	Nausea, vomiting, transient anxiety, headaches, restlessness, dizziness, increased body temperature, mydriasis.		[280, 453, 503, 512, 533]
Ketamine	NMDAR, HCN1, GABA uptake, GABAAR, M1 mAChR, M2 mAChR, M3 mAChR, nAChR (muscle type), D2R, DAT, 5-HT2R, 5-HT3R, 5-HT3AR, SERT, NET, μ opioid receptor, k opioid receptor, δ opioid receptor, σ1/2R	Route Intravenous (IV; most common) Intranasal (FDA-approved esketamine nasal spray for treatment of depression) Intramuscular Oral Dose Intravenous: 0.50 mg/kg (sub-anesthetic IV ketamine) Intranasal: 56-84 mg Intramuscular: 0.25-0.50 mg/kg Oral: 2.0-2.5 mg/kg	2.5-3 hours	Dizziness, drowsiness, nausea, altered perceptions & dissociative effects; long-term: psychotic symptoms, memory impairment, bladder damage.	Increases • Glutamate release in mPFC via NMDAR antagonism on GABAergic interneurons → Glutamate binding to postsynaptic AMPARs → Release of BDNF & downstream activation of mTOR → ↑ Neuroplasticity & dendrite growth → Reverses synaptic deficits caused by long-term stress • mTORC1 levels in the mPFC → Supports fear extinction Decreases • Excitation of amygdala to vmPFC circuitry → ↑ vmPFC top-down inhibition of amygdala → normalization of amygdala response to perceived threat & ↓ PTSD symptom severity	[263, 636, 646, 651, 652, 661, 668, 681, 682, 684, 696, 698, 703]

Abbreviations: 5-HT: 5-hydroxytryptamine, α: Alpha adrenergic, β: Beta adrenergic, AchR: Acetylcholine receptor, AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, BDNF: Brain-derived neurotrophic factor, Ca: Calcium , D: Dopaminergic, DAT: Dopamine transporter, DMN: Default Mode Network, DMT: N, N-dimethyltryptamine, GABA: Gamma-aminobutyric acid, H: Histamine, HCN: Hyperpolarization-activated cyclic nucleotide, I: Imidazoline, IV: Intravenous, LSD: Lysergic acid diethylamide, LTD: Long-term depression, M: Muscarinic, mAChR: Muscarinic acetylcholine receptor, MDMA: 3,4-Methylenedioxy-methamphetamine, mPFC: Medial prefrontal cortex, mTOR: Mammalian target of rapamycin, N: Nicotinic, nAChR: Nicotinic acetylcholine receptor, NET: Norepinephrine transporter , NMDAR: N-methyl-D-aspartate receptor, PFC: Prefrontal cortex, PTSD: Post-Traumatic Stress Disorder, RSFC: Resting state functional connectivity, S: Sigma, SERT: Serotonin transporter, TAAR: Trace amine-associated, TrkB: Tropomyosin receptor kinase B, VMAT: Vesicular monoamine transporter, vmPFC: Ventromedial prefrontal cortex.