We Are Beginning to Understand the Power of Psychedelics

This 2026 explainer from science YouTuber Ben Miles traces LSD's story from Albert Hofmann's accidental 1943 discovery through Cold War CIA experiments to today's psychedelic neuroscience, and asks whether the hallucinogenic "trip" itself is necessary for the therapeutic effect.

Discovery, early trials, and a darker turn

Chemist Albert Hofmann first synthesized LSD in 1938 and accidentally dosed himself in 1943, describing a dreamlike state of vivid color. Sandoz Laboratories then distributed it to researchers as Delysid. Early Saskatchewan studies with volunteers, plus a project giving LSD to more than 100 artists, suggested the drug loosened habitual patterns of thought, though Miles notes the studies would not meet modern scientific standards. Cold War fears about "brainwashing" then led the CIA to buy large quantities of LSD for the MK Ultra program, including covert, non-consensual dosing of the public, before concluding it was too unpredictable for mind control.

Treating alcoholism, then finding the mechanism

The same researchers gave higher, guided LSD doses to patients with alcohol use disorder alongside therapist support; by 1957 they reported treating over 700 patients, with around half no longer relapsing, though the mechanism was unclear then. It began to emerge when researchers Woolley and Shaw noticed LSD shares a chemical backbone with serotonin, linking it to related compounds also on Psylopedia, psilocybin and DMT.

How psychedelics act on the brain

LSD binds tightly to the 5-HT2A serotonin receptor for hours rather than milliseconds. A 2014 Imperial College London fMRI study found sharply increased connectivity between brain regions that don't normally communicate, alongside reduced integrity of the default mode network, tied to self-reflection. Miles links this to a surge in BDNF, a molecule involved in neuroplasticity, calling the result "not just a trip, but a destination."

Turning psychedelics into medicine

Trials at Johns Hopkins, NYU, and Imperial College found psilocybin outcomes depend heavily on setting: preparation, a supervised session, and integration afterward, what the video calls the "therapeutic container." A 2025 Nature Medicine trial found a single short intravenous DMT infusion associated with reduced depression scores lasting weeks to months. Miles also covers the FDA's 2024 rejection of MDMA-assisted therapy for PTSD, tied to the difficulty of blinding trials when patients can usually tell they received an active drug.

Separating the effect from the trip

The video closes on emerging preclinical research suggesting the plasticity-promoting effect may not require the hallucinogenic experience, possibly depending instead on whether a molecule reaches receptors inside the cell. Miles highlights tabernanthalog, which produced comparable neuroplastic changes in animal models without the usual proxy for hallucination, though it has not yet entered human trials.

Key takeaways

• ●Hofmann discovered LSD's psychoactive effects by accident in 1943, decades before it became tightly restricted.
• ●Early Saskatchewan alcoholism trials reported roughly half of about 700 patients stopped relapsing, though the mechanism was unclear at the time.
• ●The CIA's MK Ultra program used LSD in covert, non-consensual experiments and judged it too unpredictable for mind control.
• ●LSD, psilocybin, and DMT act on the same 5-HT2A serotonin receptor, with very different durations and doses.
• ●A 2014 Imperial College fMRI study found increased cross-brain connectivity and reduced default mode network integrity.
• ●A 2025 trial found a single short DMT infusion associated with reduced depression symptoms lasting weeks to months, though the FDA has flagged trial blinding as a broader hurdle for psychedelic medicine.
• ●Compounds like tabernanthalog raise the possibility of neuroplastic benefits without the hallucinogenic experience, though this remains unproven in humans.