The neurochemistry of psychedelics.
What classic psychedelics — and related compounds like MDMA, ibogaine, and ketamine — actually do to the brain's chemistry. For each system we lay out what a healthy expression looks like, what a dysfunctional one looks like, how each substance touches it, and ways to support that system naturally.
Two things to hold in mind
First: most classic psychedelics share one front door. Psilocybin, LSD, DMT (the active molecule in ayahuasca), mescaline (the active molecule in both the peyote cactus and the San Pedro cactus), and 5-MeO-DMT are all primarily agonists at the serotonin 5-HT2A receptor. Block that receptor and the characteristic effects largely disappear (Preller et al., 2018). What differs between them is the rest of their receptor profile — which other serotonin receptors, dopamine, adrenaline, sigma, and so on they also engage — and how long they last. MDMA, ibogaine, and ketamine work through substantially different mechanisms and are included here for comparison, not because they are classic psychedelics.
Second: a neurotransmitter is not "good" or "bad" — its pattern is what matters. The same molecule that keeps you calm and focused at one level drives anxiety, intrusive memory, or shutdown at another. Post-traumatic stress disorder, depression, and chronic stress are better understood as dysregulation — systems stuck too high, too low, or too rigid — than as a simple shortage of one chemical (Ressler et al., 2022; Prajapati et al., 2025). Throughout this page we describe each system's healthy expression and its dysfunctional expression side by side, because that contrast is where the therapeutic logic of these compounds lives.
A recurring theme ties the two together: across very different receptor targets, classic psychedelics and ketamine appear to converge on a common downstream effect — a burst of neuroplasticity, driven by glutamate, BDNF, and the TrkB/mTOR signaling pathway, that may briefly make the brain more able to rewire entrenched patterns — the closest thing the nervous system has to an after-action review where the wiring itself, not just the lessons learned, can be revised (Aleksandrova & Phillips, 2021; de Vos et al., 2021).
At the network level there's a parallel story. Classic psychedelics loosen the default mode network — the self-referential "autopilot" hub that runs the running commentary about you — and briefly raise the brain's flexibility, sometimes described as increased "entropy." Researchers have proposed this as one way the locked-in, rigid thinking of trauma and depression can become, for a window, more open to change — like a stuck mission autopilot briefly handed back to manual control (Preller et al., 2018). It's a working model, not settled fact — but it lines up with the cellular plasticity story above.
Plasticity is an opening, not an outcome. This is the most important caveat on the page. A more changeable brain can be shaped in any direction — the window these compounds may open doesn't decide what gets built in it. That comes from what follows: behavior, relationships, therapy, environment, and practice. It's why "set and setting" and the integration work afterward matter at least as much as the molecule, and why a dose with nothing built around it tends not to last.
Start from what you're dealing with
Pick the experience that fits best. We'll point you to the brain systems most tied to it — and, as secondary reading, the compounds that have been studied most for it. These are reading routes, not a diagnosis tool and not treatment matching.
PTSD — the alarm that won't switch off
Trauma tends to leave the threat-response system stuck "on" and pushes you away from people. The systems below map most directly onto hyperarousal, weakened fear inhibition, and disconnection.
Start with these systems
Most-studied compound · secondary reading
Human trials in veterans: MDMA research →
One caveat this page can't carry: combat PTSD isn't only fear and hyperarousal. Moral injury — the guilt, shame, betrayal, and loss of meaning that can follow events that violated your own code — runs through a partly separate process that neurochemistry speaks to less directly. It tends to need meaning-making and moral repair, which is integration work, not a receptor effect. More on integration →
Depression & treatment-resistant depression
Low drive, loss of pleasure, and stuck negative thinking track most closely with the brain's plasticity-and-reward machinery — its capacity to rewire and to anticipate reward.
Start with these systems
Most-studied compounds · secondary reading
Human trials in veterans: psilocybin research → · ketamine research →
Anxiety
Overestimated threat and worry that won't settle track with the brain's calming and braking systems — the internal counterweight to a revved-up nervous system.
Start with these systems
Most-studied compounds · secondary reading
Human trials in veterans: psilocybin research →
Addiction & substance use
Substance use disorders center on hijacked reward circuitry — and they frequently ride alongside PTSD. The reward and plasticity systems are the place to start.
Start with these systems
Most-studied compounds · secondary reading
Human trials in veterans: ibogaine research →
PTSD + TBI — the Special Operations picture
Trauma layered on traumatic brain injury is common among Special Operations Forces veterans. Here the interest centers on the repair-and-regrowth systems alongside the stress and arousal axes.
Start with these systems
Most-studied compounds · secondary reading
Human trials in veterans: ibogaine (SOF/TBI) research →
Educational entry points only — not medical advice, not a diagnosis, and not a recommendation to take anything. These conditions overlap heavily and often co-occur; if you're navigating any of them, a clinician is the right partner. In crisis, dial 988 then press 1.
System by system
Tap each system to open it. You'll find what it does, what healthy vs. dysfunctional expression looks like (with a focus on the trauma and mood context most relevant to veterans), how psychedelics act on it, and natural ways to support it.
Serotonin — the 5-HT2A receptor+
5-HT2A is an excitatory serotonin receptor densely expressed on pyramidal neurons in the cortex. It shapes how flexibly the cortex processes information, and it's the receptor through which every classic psychedelic produces its signature effects.
Healthy expression
Supports flexible, context-sensitive cognition and perception; helps the cortex update its model of the world rather than running on autopilot. Tied to learning and adaptive mood.Dysfunctional expression
Altered cortical 5-HT2A signaling is reported in depression and suicidality; clinically it tracks with cognitive rigidity — the locked-in, negatively biased thinking common in depression and PTSD.How psychedelics act here
Psilocybin, LSD, DMT, mescaline and 5-MeO-DMT are direct 5-HT2A agonists. Acutely this drives the perceptual and "ego-dissolving" effects and, downstream, the glutamate-and-plasticity cascade. The 5-HT2A antagonist ketanserin blocks both the experience and much of the brain-connectivity change (Preller et al., 2018).Support it naturally
Healthy serotonergic tone is supported by morning bright-light / sunlight exposure, regular aerobic exercise, consistent sleep, time outdoors, and a varied diet that supplies tryptophan (serotonin's precursor); gut health matters too, since most of the body's serotonin is made in the gut.Serotonin — the 5-HT1A receptor+
5-HT1A is an inhibitory serotonin receptor that acts as a brake on over-activation and is closely tied to anxiety regulation and stress resilience. It's the receptor most engaged by 5-MeO-DMT.
Healthy expression
Dampens excess arousal, supports a calm baseline and emotional stability; well-functioning 5-HT1A signaling is associated with resilience to stress.Dysfunctional expression
Reduced 5-HT1A binding is reported in depression and anxiety disorders, consistent with a weakened internal "brake" on stress and worry.How psychedelics act here
Classic psychedelics also bind 5-HT1A, but 5-MeO-DMT is the standout — it has higher affinity for 5-HT1A than for 5-HT2A, which shapes its distinct, often less visual but more all-encompassing character (Reckweg et al., 2022).Support it naturally
Slow, extended-exhale breathing, meditation, yoga, and regular aerobic exercise all support calm serotonergic tone and the parasympathetic "rest and digest" state this receptor helps maintain.Glutamate & AMPA receptors+
Glutamate is the brain's main excitatory neurotransmitter and the engine of learning. A controlled, transient rise in cortical glutamate — acting on AMPA receptors — is the trigger that opens a window of synaptic plasticity.
Healthy expression
Precisely timed glutamate signaling drives long-term potentiation (LTP) — the cellular basis of learning, memory, and the ability to form new, healthier patterns.Dysfunctional expression
Chronic stress and trauma can push glutamate toward excitotoxic levels in the prefrontal cortex and hippocampus, contributing to dendritic atrophy, synapse loss, and impaired flexibility (Ressler et al., 2022).How psychedelics act here
By activating 5-HT2A on cortical pyramidal neurons, classic psychedelics produce a transient glutamate surge → AMPA activation → BDNF and mTOR signaling → new synapse growth. Ketamine reaches the same endpoint from the opposite direction, by blocking NMDA receptors (Aleksandrova & Phillips, 2021; Pham & Gardier, 2019).Support it naturally
The most reliable natural promoter of healthy glutamatergic plasticity is learning itself — novelty, skill-building, and challenge — paired with aerobic exercise and quality sleep, during which the day's synaptic changes are consolidated.BDNF, TrkB & neuroplasticity+
Brain-derived neurotrophic factor (BDNF) is a growth factor — fertilizer for neurons. Acting through its receptor TrkB, it supports the survival of neurons, the growth of new synapses, and the brain's overall capacity to adapt.
Healthy expression
Robust BDNF/TrkB signaling maintains synaptic density, neurogenesis in the hippocampus, and psychological resilience — the raw material for recovery and change.Dysfunctional expression
Low BDNF is one of the most consistent findings in depression and PTSD, alongside reduced hippocampal and prefrontal volume and loss of dendritic spines.How psychedelics act here
This is the convergence point. Remarkably, LSD and psilocin (psilocybin's active form) bind directly to TrkB — with roughly 1,000-fold higher affinity than conventional antidepressants — where they act as positive allosteric modulators: they don't switch the receptor on by themselves, they potentiate the brain's own BDNF signaling (Moliner et al., 2023). Ketamine, MDMA, ibogaine and ayahuasca all also raise BDNF or related neurotrophic signaling (de Vos et al., 2021; Zanos & Gould, 2018).Support it naturally
Aerobic exercise is the single best-documented way to raise BDNF. It's reinforced by deep sleep, learning new skills, sunlight, social engagement, and reducing chronic stress — all of which nudge the same growth-and-repair machinery these compounds engage pharmacologically.Dopamine+
Dopamine drives motivation, reward learning, and the sense that something is worth paying attention to. It's central to drive and pleasure — and to where those systems go wrong.
Healthy expression
Balanced dopamine supports motivation, the capacity to anticipate and enjoy reward, and appropriate salience — noticing what genuinely matters.Dysfunctional expression
Blunted dopamine signaling underlies anhedonia (loss of pleasure) in depression; dysregulated reward/salience contributes to PTSD and to the substance-use disorders that frequently co-occur with it. Excess striatal dopamine is linked to psychosis risk.How psychedelics act here
LSD has direct dopamine D2 activity, and mescaline binds D1/2/3 receptors (Lawn et al., 2022; Vamvakopoulou et al., 2022). MDMA releases large amounts of dopamine — central to both its reward and its abuse potential (Heifets et al., 2019). Ibogaine appears to normalize the drug-driven dopamine surges that sustain addiction (Oña et al., 2023).Support it naturally
Protect dopamine by pursuing meaningful, goal-directed effort (the system rewards earned progress), staying physically active, getting adequate protein (tyrosine is dopamine's precursor), prioritizing sleep, and limiting "supernormal" stimuli — compulsive scrolling, gambling, and the like — that blunt the system over time.Norepinephrine (noradrenaline)+
Norepinephrine governs arousal, alertness, and the body's fight-or-flight response. For trauma survivors it's arguably the most clinically relevant system on this page — and the most physical: it's felt in the chest, the gut, the jaw, the startle. Much of what trauma "keeps" is held in this bodily alarm and in interoception — the brain's read of internal body signals — which is why body-based work (breath, movement, vagal practices) can target this system as directly as talk does.
Healthy expression
Sharpens attention and mobilizes the body under genuine threat, then settles — a responsive alarm that switches off when the danger passes.Dysfunctional expression
A hallmark of PTSD is a chronically hyperadrenergic state: hypervigilance, exaggerated startle, nightmares, and sleep disruption from an alarm that won't stand down. (This is the target of the PTSD medication prazosin.)How psychedelics act here
MDMA produces a strong noradrenergic surge — part of why it raises heart rate and blood pressure and warrants cardiac caution (Heifets et al., 2019). Mescaline has direct α-adrenergic activity (Vamvakopoulou et al., 2022). The classic tryptamines affect this system more indirectly.Support it naturally
Calm an over-active noradrenergic system with slow paced breathing and other vagal/parasympathetic practices, consistent sleep hygiene, regular exercise to discharge stress, and limiting caffeine and other stimulants — especially late in the day.GABA+
GABA is the brain's main inhibitory neurotransmitter — the counterweight to glutamate. It keeps excitation in check and is essential to the brain's ability to inhibit fear once a threat has passed. Practically, this is the system behind the felt sense of the body downshifting — shoulders dropping, breath slowing, the gut unclenching — when safety returns.
Healthy expression
Adequate GABAergic tone produces calm, balanced excitation/inhibition, and effective "fear inhibition" — the capacity to turn off a threat response.Dysfunctional expression
Reduced function of GABAergic interneurons (including somatostatin-expressing cells) is implicated in PTSD, weakening fear inhibition and contributing to anxiety and intrusive symptoms (Ressler et al., 2022).How psychedelics act here
Ketamine's mechanism runs largely through GABA: by blocking NMDA receptors preferentially on GABAergic interneurons, it disinhibits the cortex, releasing the glutamate surge behind its rapid antidepressant effect (Zanos & Gould, 2018; Pham & Gardier, 2019). Classic psychedelics affect GABA more indirectly, through cortical circuit dynamics.Support it naturally
Yoga and slow breathing have measurably raised brain GABA in studies; meditation, adequate sleep, and limiting alcohol (which props up GABA short-term but causes rebound anxiety as it wears off) all support healthier inhibitory tone.Oxytocin+
Oxytocin supports social bonding, trust, and the felt sense of safety with others — and it helps the brain learn that it's safe to lower its guard, which matters for processing trauma. This is co-regulation — one nervous system helping settle another — and it's as much a body state as a feeling: safe connection is often what finally lets the noradrenergic alarm above stand down.
Healthy expression
Facilitates connection, trust, and co-regulation with people you're close to; supports fear extinction and buffers the stress response.Dysfunctional expression
Trauma is often marked by social withdrawal, difficulty trusting, and disrupted attachment — the relational disconnection that compounds PTSD and isolates veterans from support.How psychedelics act here
MDMA's signature is here: it stimulates oxytocin release and, via serotonin acting in the nucleus accumbens, produces its hallmark openness and trust — the prosocial state that makes it a candidate adjunct to trauma psychotherapy (Heifets et al., 2019).Support it naturally
Oxytocin rises with genuine social connection — warm physical contact (hugs, a hand on the shoulder), time with loved ones and pets, singing or making music together, shared meals, and acts of service. For many veterans, peer community is the most powerful lever here.Sigma-1 receptor+
The sigma-1 receptor is a "chaperone" protein inside the cell that helps neurons cope with stress and supports neuroprotection, plasticity, and the birth of new neurons. It's a distinctive target of DMT.
Healthy expression
Supports cellular stress resilience, neuroprotection, and adult neurogenesis — part of the brain's capacity to repair and renew.Dysfunctional expression
Altered sigma-1 function has been implicated in depression and neurodegenerative conditions, reflecting reduced cellular resilience.How psychedelics act here
DMT is an endogenous sigma-1 agonist, and in animal studies this action drives new neuron production in the hippocampus and improves learning and memory — an effect blocked when sigma-1 is antagonized (Morales-García et al., 2020; James et al., 2022). Ibogaine also engages sigma receptors (Oña et al., 2023).Support it naturally
There's no consumer "sigma-1 supplement," but the same fundamentals that protect neurons broadly — exercise, sleep, stress reduction, and an anti-inflammatory diet rich in omega-3s — support the cellular resilience this receptor helps coordinate.The HPA axis & cortisol+
The hypothalamic–pituitary–adrenal (HPA) axis is the body's central stress-response system, releasing cortisol and then shutting itself off through negative feedback. It's the thermostat for stress.
Healthy expression
A crisp cortisol rise to meet a challenge, a strong daily rhythm (high in the morning, low at night), and reliable negative feedback that returns the system to baseline.Dysfunctional expression
PTSD is associated with a dysregulated HPA axis and altered glucocorticoid signaling (including the stress-gene FKBP5) — the thermostat miscalibrated, so the system over- or under-responds and struggles to reset (Ressler et al., 2022; Prajapati et al., 2025).How psychedelics act here
Acutely, full-dose classic psychedelics and MDMA raise cortisol as part of the experience. Over time, the therapeutic interest is in whether repeated or supported use helps recalibrate stress reactivity rather than simply spiking it.Support it naturally
Steady the HPA axis with a consistent sleep–wake schedule and morning daylight (which anchors the cortisol rhythm), moderate exercise, mindfulness or breathwork, time in nature, and limiting alcohol and excess caffeine.Bottom line for vets
These aren't simple "low serotonin" problems. Trauma and depression are patterns stuck too high, too low, or too rigid across several systems at once — and the common path to change is the plasticity (BDNF) machinery that lets the brain re-wire. That's the same machinery your movement, sleep, and connection habits feed every day.
The molecules, one by one
Each substance's neurochemical "fingerprint," with the strongest peer-reviewed sources. Where it's relevant, we flag how a sub-perceptual microdose may differ from a full journey dose.
Psilocybin+
Psilocybin is a prodrug for psilocin, a 5-HT2A agonist (with 5-HT1A activity). Beyond the receptor, psilocin binds the BDNF receptor TrkB directly and drives the glutamate → AMPA → mTOR plasticity cascade shared across this drug class.
LSD+
LSD has the broadest receptor profile of the classics — agonist activity across serotonin (5-HT2A, 5-HT1A, 5-HT2C) and dopamine (D1, D2) receptors — and the highest TrkB affinity yet measured among these compounds.
DMT & Ayahuasca+
N,N-DMT is a short-acting 5-HT2A agonist that is also an endogenous sigma-1 receptor ligand. Ayahuasca is the Amazonian brew that combines DMT with harmala alkaloids (β-carbolines) — MAO inhibitors that let DMT survive digestion and become orally active, extending the experience to hours.
Mescaline (Peyote & San Pedro)+
Mescaline is the oldest known psychedelic and the active compound in both the peyote cactus (Lophophora williamsii) and the San Pedro cactus (Echinopsis/Trichocereus species) — so the two cacti are, neurochemically, the same story with different plants. It's a phenethylamine, not a tryptamine, and the longest-acting of the classics.
5-MeO-DMT+
5-MeO-DMT (found in some toad secretions and plants, and made synthetically) is unusual among the classics because its highest affinity is for 5-HT1A, not 5-HT2A. The result is a very short, very intense, often non-visual but all-encompassing experience.
MDMA+
MDMA doesn't primarily activate serotonin receptors — it forces the release of serotonin, dopamine, and norepinephrine by reversing their reuptake transporters, and it triggers oxytocin, vasopressin, and cortisol. That combination produces its characteristic warmth, openness, and emotional accessibility.
Ibogaine+
Ibogaine (from the African iboga shrub) has perhaps the most complex pharmacology here — there is no single "ibogaine receptor." It and its long-lived metabolite noribogaine touch NMDA, κ- and μ-opioid, sigma, serotonin and dopamine systems, inhibit the serotonin transporter and VMAT2, and upregulate neurotrophic factors including GDNF and BDNF.
Ketamine+
Ketamine is included because it reaches the same plasticity endpoint as classic psychedelics from the opposite chemical direction — and because it's the one compound here that's legally available (esketamine is FDA-approved for treatment-resistant depression).
Bottom line for vets
No single molecule maps to a single diagnosis. The classic psychedelics share the 5-HT2A front door and the plasticity payoff; MDMA, ibogaine, and ketamine get there by different routes — and ibogaine in particular carries real cardiac risk that protocols screen for. Read the biology here, then see what's actually been tested in veterans on the research page.
The neurochemical fingerprint chart
A qualitative synthesis of the literature on this page — the direction and prominence of each substance's effect on each system, at a typical full/journey dose unless noted. This is a map, not a measurement: it compresses complex, sometimes still-debated pharmacology into a single cell.
| Substance | 5-HT2Aagonism | 5-HT1Aagonism | Serotoninrelease | Glutamate/ AMPA | NMDAreceptor | BDNFplasticity | Dopamine | Nor- epinephrine |
Oxytocin | Sigma-1 | HPAcortisol (acute) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Psilocybin | ▲▲ | ▲ | — | ▲ | — | ▲▲ | ● | ● | ● | — | ▲ |
| LSD | ▲▲ | ▲ | — | ▲ | — | ▲▲ | ▲ | ● | ● | — | ▲ |
| DMT / Ayahuasca | ▲▲ | ▲ | — | ▲ | — | ▲ | ● | ● | — | ▲▲ | ▲ |
| Mescaline | ▲▲ | ▲ | — | ● | — | ● | ▲ | ▲ | — | — | ▲ |
| 5-MeO-DMT | ▲ | ▲▲ | — | ▲ | — | ▲ | ● | ● | — | ▲ | ▲ |
| MDMA | ● | — | ▲▲ | ● | — | ▲ | ▲▲ | ▲▲ | ▲▲ | — | ▲▲ |
| Ibogaine | ● | ● | ▼ | ● | ▼ | ▲ | ● | ● | — | ● | ● |
| Ketamine | — | — | — | ▲▲ | ▼▼ | ▲▲ | ▲ | ▲ | — | ● | ● |
What we still don't know
Plenty. How long benefits last (some — like psilocybin for depression — tend to fade over 6–12 months); why a meaningful minority of people don't respond at all; how these compounds interact with traumatic brain injury; whether microdosing does anything beyond placebo (the controlled evidence is thin and mixed); and how best to pair a dose with the body-based and integration work that may carry the lasting change. Treat confident claims in either direction with caution.
You can move these systems without a substance
Every system above responds to daily behavior — often through the very same machinery these compounds engage pharmacologically. None of this is a treatment for PTSD or a substitute for professional care, and none of it replaces what a supported therapeutic experience might offer. But the foundations are real, free, legal, and worth building first.
The high-leverage basics
Aerobic exercise is the closest thing to a universal lever: it raises BDNF, supports serotonin and dopamine, discharges excess norepinephrine, and steadies the HPA axis. Sleep consolidates the plasticity that everything else sets up and resets the stress thermostat. Morning daylight anchors serotonin and the cortisol rhythm at once.
For a calmer nervous system
If hyperarousal is the problem — the racing, on-guard, can't-stand-down state — the most direct natural levers are slow, long-exhale breathing, yoga (shown to raise brain GABA), and meditation, all of which shift the body toward the parasympathetic state that norepinephrine and GABA help govern. Limiting alcohol and late caffeine removes two common saboteurs.
For connection and mood
Genuine social connection — peer community, time with people and animals you trust, making music, shared meals, service to others — is the natural route to oxytocin and a buffer on the stress response. For many veterans this is also the hardest and highest-return lever, because trauma pulls in the opposite direction. Meaningful, goal-directed effort protects the dopamine system far better than passive stimulation does.
The throughline
Notice how short the list of inputs is — movement, sleep, light, breath, food, connection, purpose — and how many systems each one touches. That overlap is the point: the brain's repair-and-regulate machinery is shared, so a handful of consistent habits move many neurochemicals at once. Psychedelic and related compounds are being studied because they may open an unusually wide plasticity window; what gets built in that window still depends on the same foundations.
The part that lasts
Veterans consistently say the community-and-integration side does the heaviest lifting — making sense of an experience and staying connected to people who get it. That's its own page: Integration & Support →
Sources
Peer-reviewed sources cited above, listed alphabetically. Mechanistic reviews and primary studies; retrieved via PubMed.
- Aleksandrova, L. R., & Phillips, A. G. (2021). Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics. Trends in Pharmacological Sciences, 42(11), 929–942. https://doi.org/10.1016/j.tips.2021.08.003
- de Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. (2021). Psychedelics and neuroplasticity: A systematic review unraveling the biological underpinnings of psychedelics. Frontiers in Psychiatry, 12, 724606. https://doi.org/10.3389/fpsyt.2021.724606
- Heifets, B. D., Salgado, J. S., Taylor, M. D., Hoerbelt, P., Cardozo Pinto, D. F., Steinberg, E. E., Walsh, J. J., Sze, J. Y., & Malenka, R. C. (2019). Distinct neural mechanisms for the prosocial and rewarding properties of MDMA. Science Translational Medicine, 11(522), eaaw6435. https://doi.org/10.1126/scitranslmed.aaw6435
- James, E., Keppler, J., L Robertshaw, T., & Sessa, B. (2022). N,N-dimethyltryptamine and Amazonian ayahuasca plant medicine. Human Psychopharmacology, 37(3), e2835. https://doi.org/10.1002/hup.2835
- Kiilerich, K. F., Lorenz, J., Scharff, M. B., Speth, N., Brandt, T. G., Czurylo, J., Xiong, M., Jessen, N. S., Casado-Sainz, A., Shalgunov, V., Kjaerby, C., Satała, G., Bojarski, A. J., Jensen, A. A., Herth, M. M., Cumming, P., Overgaard, A., & Palner, M. (2023). Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats. Molecular Psychiatry, 28(9), 3829–3841. https://doi.org/10.1038/s41380-023-02280-z
- Lawn, T., Dipasquale, O., Vamvakas, A., Tsougos, I., Mehta, M. A., & Howard, M. A. (2022). Differential contributions of serotonergic and dopaminergic functional connectivity to the phenomenology of LSD. Psychopharmacology, 239(6), 1797–1808. https://doi.org/10.1007/s00213-022-06117-5
- Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V., Biojone, C., Enkavi, G., Antenucci, L., Kot, E. F., Goncharuk, S. A., Kaurinkoski, K., Kuutti, M., Fred, S. M., Elsilä, L. V., Sakson, S., Cannarozzo, C., Diniz, C. R. A. F., Seiffert, N., Rubiolo, A., Haapaniemi, H., … Castrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature Neuroscience, 26(6), 1032–1041. https://doi.org/10.1038/s41593-023-01316-5
- Morales-García, J. A., Calleja-Conde, J., Lopez-Moreno, J. A., Alonso-Gil, S., Sanz-SanCristobal, M., Riba, J., & Perez-Castillo, A. (2020). N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo. Translational Psychiatry, 10(1), 331. https://doi.org/10.1038/s41398-020-01011-0
- Oña, G., Reverte, I., Rossi, G. N., Dos Santos, R. G., Hallak, J. E. C., Colomina, M. T., & Bouso, J. C. (2023). Main targets of ibogaine and noribogaine associated with its putative anti-addictive effects: A mechanistic overview. Journal of Psychopharmacology, 37(12), 1190–1200. https://doi.org/10.1177/02698811231200882
- Pham, T. H., & Gardier, A. M. (2019). Fast-acting antidepressant activity of ketamine: Highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & Therapeutics, 199, 58–90. https://doi.org/10.1016/j.pharmthera.2019.02.017
- Prajapati, S. K., Majumdar, S., Murari, S., MachhindraVadak, K., & Krishnamurthy, S. (2025). Neurochemical, neurocircuitry, and psychopathological mechanisms of PTSD: Emerging pharmacotherapies and clinical perspectives. ACS Chemical Neuroscience, 16(13), 2355–2370. https://doi.org/10.1021/acschemneuro.5c00335
- Preller, K. H., Burt, J. B., Ji, J. L., Schleifer, C. H., Adkinson, B. D., Stämpfli, P., Seifritz, E., Repovš, G., Krystal, J. H., Murray, J. D., Vollenweider, F. X., & Anticevic, A. (2018). Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. eLife, 7, e35082. https://doi.org/10.7554/eLife.35082
- Reckweg, J. T., Uthaug, M. V., Szabo, A., Davis, A. K., Lancelotta, R., Mason, N. L., & Ramaekers, J. G. (2022). The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Journal of Neurochemistry, 162(1), 128–146. https://doi.org/10.1111/jnc.15587
- Ressler, K. J., Berretta, S., Bolshakov, V. Y., Rosso, I. M., Meloni, E. G., Rauch, S. L., & Carlezon, W. A. (2022). Post-traumatic stress disorder: Clinical and translational neuroscience from cells to circuits. Nature Reviews Neurology, 18(5), 273–288. https://doi.org/10.1038/s41582-022-00635-8
- Vamvakopoulou, I. A., Narine, K. A. D., Campbell, I., Dyck, J. R. B., & Nutt, D. J. (2022). Mescaline: The forgotten psychedelic. Neuropharmacology, 222, 109294. https://doi.org/10.1016/j.neuropharm.2022.109294
- Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811. https://doi.org/10.1038/mp.2017.255
Bibliographic data retrieved via PubMed. This page summarizes mechanism research; it does not establish that any substance treats any condition.
Curious what's actually been tested in veterans?
This page is the biology. For the human trials — what's been studied in veterans and service members, by substance — see the research library and the live studies directory.
See the veteran research →