Rankings / Mood, Anxiety & Stress
Mood, Anxiety & Stress
Antidepressants, anxiolytics, mood stabilisers, psychedelic medicines, and adaptogenic compounds for affective regulation. Prescription and natural agents combined.
| # | Compound | Ev | Bn | Sf | Grade · Score |
|---|---|---|---|---|---|
| 1 | TMS (transcranial magnetic stimulation) Non-invasive neuromodulation | 8 | 8 | 9 | A+ 8.4 |
| 2 | Meditation / mindfulness Other | 8 | 6.5 | 9 | A+ 8.2 |
| 3 | Propranolol Non-selective beta-blocker | 8 | 3.5 | 9 | A- 7.7 |
| 4 | Buspirone 5-HT1A partial agonist | 6 | 5 | 9 | B+ 7.1 |
| 5 | Inositol (myo-inositol / D-chiro-inositol) Sugar alcohol / second messenger | 6 | 5 | 9 | B+ 7.1 |
| 6 | Saffron extract (Crocus sativus) Herbal (crocin/safranal) | 6 | 5 | 9 | B+ 7.1 |
| 7 | Bupropion (Wellbutrin) NDRI | 8 | 8 | 5 | B 6.8 |
| 8 | Dextromethorphan-bupropion (Auvelity / AXS-05) NMDA antagonist + sigma-1 agonist + NDRI | 8 | 8 | 5 | B 6.8 |
| 9 | Electroconvulsive therapy (ECT) Procedural neuromodulation (induced seizure) | 8 | 8 | 5 | B 6.8 |
| 10 | SNRIs (venlafaxine / duloxetine) Dual SERT/NET reuptake inhibitor | 8 | 8 | 5 | B 6.8 |
| 11 | Xanomeline-trospium (KarXT / Cobenfy) M1/M4 muscarinic agonist + peripheral antagonist | 8 | 8 | 5 | B 6.8 |
| 12 | Zuranolone (Zurzuvae) GABA-A neurosteroid (positive allosteric modulator) | 8 | 8 | 5 | B 6.8 |
| 13 | Breathwork (structured breathing) Autonomic | 6 | 3.5 | 9 | B 6.8 |
| 14 | Lumateperone (Caplyta) Atypical antipsychotic | 8 | 6.5 | 5 | B 6.6 |
| 15 | Psilocybin Classic psychedelic / 5-HT2A agonist | 8 | 6.5 | 5 | B 6.6 |
| 16 | SSRIs (sertraline / escitalopram / fluoxetine) Selective serotonin reuptake inhibitor | 8 | 6.5 | 5 | B 6.6 |
| 17 | Gabapentin / pregabalin alpha-2-delta voltage-gated Ca channel modulator | 8 | 5 | 5 | B 6.4 |
| 18 | St. John's wort (Hypericum perforatum) Natural SSRI-SNRI-like | 8 | 5 | 5 | B 6.4 |
| 19 | Ashwagandha (Withania somnifera) Adaptogen | 6 | 5 | 7 | B- 6.3 |
| 20 | SAM-e (S-adenosylmethionine) Methyl donor | 6 | 5 | 7 | B- 6.3 |
| 21 | Lithium (microdose vs therapeutic) Mood stabilizer / geroprotector | 10 | 5 | 2 | B- High-risk profile 6.1 |
| 22 | Ketamine NMDA antagonist | 8 | 6.5 | 3.5 | B- High-risk profile 6 |
| 23 | Olanzapine + samidorphan (Lybalvi) Antipsychotic + opioid antagonist | 8 | 6.5 | 3.5 | B- High-risk profile 6 |
| 24 | LSD (lysergic acid diethylamide) Classic psychedelic / 5-HT2A agonist | 6 | 6.5 | 5 | C+ 5.7 |
| 25 | Kava (Piper methysticum) GABA-A modulator / TRPV1 | 6 | 5 | 5 | C+ 5.5 |
| 26 | Other beta-blockers (atenolol / metoprolol / nadolol) Beta-blocker / performance-anxiety agent | 6 | 5 | 5 | C+ 5.5 |
| 27 | GABA (gamma-aminobutyric acid) Inhibitory neurotransmitter / supplement | 3 | 2 | 9 | C+ 5.3 |
| 28 | Selegiline (L-deprenyl) MAO-B inhibitor | 6 | 3.5 | 5 | C+ 5.2 |
| 29 | MDMA (3,4-methylenedioxymethamphetamine) Entactogen | 6 | 6.5 | 3.5 | C High-risk profile 5.1 |
| 30 | Ayahuasca / DMT Classic psychedelic / 5-HT2A + MAOI combo | 4.5 | 6.5 | 3.5 | C- High-risk profile 4.4 |
| 31 | Tianeptine Atypical antidepressant / mu-opioid agonist | 6 | 5 | 2 | C- High-risk profile 4.3 |
| 32 | Ibogaine Iboga alkaloid / NMDA antagonist + kappa-opioid | 4.5 | 8 | 2 | C- High-risk profile 4 |
| 33 | 5-HTP (5-hydroxytryptophan) Serotonin precursor | 3 | 3.5 | 5 | D+ 3.9 |
| 34 | Phenibut (β-phenyl-GABA) GABA-B agonist (with weak GABA-A activity) | 3 | 5 | 2 | D High-risk profile 2.9 |
This category spans prescription antidepressants and anxiolytics, neuromodulation, the psychedelic frontier, and over-the-counter adaptogens. Prescription drugs and procedures have the deepest evidence bases; psychedelic interventions remain promising but early, while supplement trials generally report smaller effects. The populations, delivery settings, and outcomes differ substantially across these groups.
The deepest evidence
SSRIs and SNRIs have large, durable evidence bases for depression and anxiety disorders; average effects over placebo are modest but heavily replicated. Bupropion has a separate evidence base and side-effect profile. In treatment-resistant depression, TMS has strong evidence and relatively low procedural risk, while comparative literature reports some of the largest acute effects for ECT alongside cognitive side effects. Dextromethorphan-bupropion (Auvelity, 2022) added a faster-onset oral treatment context.
The psychedelic frontier
Psilocybin-assisted therapy produced substantial antidepressant effects in Phase 2 trials and is now in Phase 3, but it is not approved and is delivered under supervision. Ketamine and esketamine (Spravato) are the psychedelic-adjacent options already approved for treatment-resistant depression, with rapid effects. MDMA-assisted therapy for PTSD hit an FDA setback in 2024, when the agency requested more data rather than approving it. These stay labelled investigational or clinic-only here.
Adaptogens — modest, not magic
Ashwagandha has a comparatively developed supplement evidence base in this category: small RCTs report modest reductions in perceived stress and cortisol. Saffron performed comparably to SSRIs in some small trials, and EPA-heavy omega-3 carries a modest antidepressant signal. These findings involve smaller studies and effects than much of the treatment literature for diagnosed disorders.
Frequently asked
Do adaptogens like ashwagandha actually work for stress?
Ashwagandha has a comparatively developed supplement evidence base here: small randomised trials report modest reductions in perceived stress and cortisol. The studies and effect sizes are smaller than much of the treatment literature for diagnosed anxiety or mood disorders.
Is psilocybin a proven depression treatment?
Promising, not yet approved. Phase 2 trials showed substantial antidepressant effects under therapeutic supervision and Phase 3 is ongoing. Ketamine and esketamine are the psychedelic-adjacent options already approved for treatment-resistant depression.
How do ECT and TMS evidence profiles compare for severe depression?
ECT has among the largest acute effects reported for treatment-resistant or severe depression, alongside cognitive side effects. TMS has a smaller effect profile with lower procedural risk in many studies. Both are clinician-delivered interventions studied in specific diagnostic contexts.
Scores reflect the published evidence, not a recommendation to use any compound or protocol. Nothing here is medical advice. How we score →