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The world's most-consumed psychoactive compound — a methylxanthine adenosine-receptor antagonist found in coffee, tea, and cocoa. A 43-year longitudinal study published in 2026 linked moderate caffeinated coffee consumption to an 18% lower dementia risk and slower cognitive decline; decaffeinated coffee showed no equivalent effect.

Acetylsalicylic acid — the first mass-produced synthetic drug (Bayer, 1899) and an irreversible covalent inhibitor of cyclooxygenase via acetylation of COX-1 Ser530. Beyond a century as the canonical analgesic, low-dose aspirin remains a workhorse of secondary cardiovascular prevention; primary-prevention guidance has tightened with the 2022 USPSTF reversal weighing bleeding risk against marginal ischemic benefit in healthy adults.

Midomafetamine (MDMA) — submitted to the FDA in 2024 as the first psychedelic to reach a PDUFA decision in modern history. The FDA issued a Complete Response Letter on 9 August 2024 requesting an additional Phase-3 trial despite Phase-3 data showing 67% of MDMA-arm participants no longer meeting PTSD diagnostic criteria (vs 32% on placebo); sponsor Lykos Therapeutics restructured by ~75%. In April 2026 the Trump administration's executive order directed the FDA to fast-track psychedelic drug review, with three companies' psilocybin and methylone programs accelerated.

Semaglutide — long-acting GLP-1 receptor agonist (Ozempic / Wegovy / Rybelsus) that reshaped weight management and type-2 diabetes care. Pictured is the lipid-modified Lys26 side-chain — the C18 fatty diacid plus γ-Glu/OEG2 spacer that gives semaglutide its multi-day half-life via albumin binding. On 28 January 2025 the FDA approved an additional Ozempic indication to reduce kidney-disease progression and cardiovascular death (FLOW trial: 24% RR reduction).

Psilocybin — the prodrug of psilocin, active in psilocybe mushrooms. FDA Breakthrough Therapy designation for treatment-resistant depression. Compass Pathways' COMP360 (synthetic psilocybin) hit its primary endpoint in a 258-patient Phase-3 trial in 2025: a single 25 mg dose vs placebo gave a -3.6 MADRS reduction (p<0.001), with onset as early as the next day and effects sustained through 26 weeks for responders. The Trump administration's April 2026 executive order then accelerated FDA review for three psilocybin and methylone programs, materially shortening expected approval timelines.