Psychedelics Chapter 3 - Clincial History of Psychedelics

1897 Arthur Heffter

Discovered Mescaline, —> First Psychedelics alkaloid isolated, extracted from peyote cactus

1806 Morphine — 1817 Strychnine — 1820 Caffeine — 1828 Nicotine — 1897 Mescaline — 1901 Ibogaine — 1931 DMT

Know the progression

Peyote indigenous heritage

• Used ritualistically for centuries across northern Mexico and southwestern North America in religious, ceremonial, and healing contexts.

Dr. J. R. Briggs (1887):

Widely recognized as the first physician to bring formal scientific and medical attention to peyote in the United States, publishing an early clinical account in the New York Medical Journal.

Louis Lewin (1888–1894):

• Pioneering German pharmacologist who performed the first systematic chemical and pharmacological analyses of peyote (temporarily named Anhalonium lewinii).

Parke-Davis & Co. / F. A. Thompson (1890s):

• Developed commercial preparations and alkaloid extractions of 'mescal buttons' for clinical investigation.

Arthur Heffter (1896–1901):

•  Isolated pure mescaline from peyote and performed pioneering self-experiments to establish which specific fraction caused hallucinogenic visions.

Silas Weir Mitchell & Havelock Ellis (1896–1898):

• Conducted literary and physiological self-experiments in the English-speaking world, documenting vivid kaleidoscopic visions and heightened sensory awareness.

Ergotism ('St. Anthony's Fire'):

• Caused by Claviceps purpurea, a parasitic fungus blighting rye. Contaminated flour produced epidemics characterized by severe burning sensations, gangrene of extremities, convulsions, and hallucinations.

Historical Outbreaks:

• In 1093, the Order of St. Anthony was founded to care for victims (who improved when fed clean wheat bread). In 1692, damp weather causing ergotized rye is hypothesized to have precipitated the Salem Witch Trials.

Midwifery Use ('Tooth of Rye'):

• Used by midwives for centuries to stimulate uterine contractions and halt postpartum hemorrhage. By the 1800s, it was known as pulvis ad partum ('birth powder'), though unpredictable doses often led to uterine rupture.

Chemical Isolations:

• Sir Henry Dale and George Barger isolated ergotoxine (1906). In 1918, Arthur Stoll isolated pure ergotamine (marketed by Sandoz as Gynergen in 1921). In the 1930s, ergometrine/ergonovine was isolated for uterine management.

LSD Jacobs & Craig (1934):

• Working at the Rockefeller Institute, identified lysergic acid as the universal structural core of all ergot alkaloids.

Albert Hofmann (1938):

• Synthesized Lysergic Acid Diethylamide (LSD-25) at Sandoz in Basel, Switzerland, while seeking an analeptic circulatory/respiratory stimulant. Shelved after animal testing proved unremarkable.

Accidental Ingestion (April 16, 1943):

• Hofmann re-synthesized the molecule and absorbed a minute quantity through his fingertips, experiencing visual and cognitive shifts.

Bicycle Day (April 19, 1943):

• First intentional human self-experiment with 0.25 mg (250 mcg). Hofmann documented profound depersonalization, synesthesia, and kaleidoscopic visuals during his ride home.

Early psychiatric applications - Delysid

• Sandoz Laboratories patented and distributed LSD worldwide under this brand name for psychiatric research into neuroses, psychoses, and alcoholism.

Werner Stoll (1947)

•  Son of Arthur Stoll; published the first systematic clinical psychiatric trial of LSD on healthy subjects and psychiatric patients at the University of Zurich.

Becker (1949) & Busch and Johnson (1950):

Investigated LSD as a tool to produce experimental model psychosis ('psychotomimetic') and as an adjunct to accelerate psychodynamic psychotherapy by unlocking repressed memories.

The spring frove experiment

Institutional Scope:Conducted at Spring Grove State Hospital (Maryland Psychiatric Research Center) by Albert Kurland, Sanford Unger, and colleagues; over 700 patients treated for severe alcoholism, heroin addiction, and terminal cancer anxiety.

The spring frove experiment

• Clinical Core Finding: Researchers concluded that therapeutic improvement depended primarily on achieving a profound mystical or 'peak experience' within an optimized 'set and setting,' rather than raw chemical dosage.

The spring frove experiment

• Yielded a 33% sustained abstinence rate at six months post-treatment, compared to ~12% in standard control groups.

The spring frove experiment

•  Methodological challenges (double-blinding difficulties) coupled with political and social backlash from government scandals resulted in project closure.

Covert and Military Research programs

• Project MKUltra (CIA: 1953–1973): Directed by the CIA Technical Services Division to explore psychological warfare, mind control, and covert interrogation using LSD, psilocybin, and sensory deprivation. Routinely conducted on unwitting civilians, prisoners, and psychiatric patients without consent. Files largely destroyed in 1973; exposed by the Church Committee in 1975.

Covert and Military Research programs

• Edgewood Arsenal (U.S. Army: 1948–1975): Military-chemical program at Aberdeen Proving Ground, Maryland, evaluating chemical warfare and incapacitating agents (sarin, VX, BZ, PCP, LSD) on ~7,000 U.S. service members and ~1,000 civilians. Resulted in modern veteran class-action settlements for health evaluation and care.

5. Harvard Studies & The Regulatory Prohibition Timeline

• Harvard Psilocybin Project (1960–1963): Timothy Leary and Richard Alpert explored psilocybin across prison recidivism (Concord Prison) and healthy volunteer settings, sparking academic ethics controversies.

5. Harvard Studies & The Regulatory Prohibition Timeline

• The Good Friday Experiment (April 20, 1962): Walter Pahnke administered psilocybin vs. active placebo (niacin) to 20 theology students in Marsh Chapel, demonstrating that psilocybin could reliably elicit genuine mystical-type experiences.

5. Harvard Studies & The Regulatory Prohibition Timeline

• 1962 — Kefauver-Harris Amendments: Required substantial proof of drug efficacy and formalized informed consent prior to human clinical testing.

5. Harvard Studies & The Regulatory Prohibition Timeline

• 1965 — Drug Abuse Control Amendments: Outlawed unauthorized production and possession; prompted Sandoz to halt production of Delysid and Indocybin.

5. Harvard Studies & The Regulatory Prohibition Timeline

• 1968 — Food, Drug, and Cosmetic Act Amendment: Federally criminalized unauthorized personal possession of LSD.

5. Harvard Studies & The Regulatory Prohibition Timeline

• 1970 — Controlled Substances Act (CSA): Classified classic psychedelics into Schedule I (high abuse potential, no recognized medical value, lack of safety under supervision), terminating mainstream academic clinical trials.