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Δ9-THC: Δ-9-tetrahydrocannabinol

ADHD: attention-deficit/hyperactivity disorder

AIDS: acquired immune deficiency syndrome

AUD: alcohol use disorder

CBD: cannabidiol

CDC: U.S. Centers for Disease Control and Prevention

CRF: corticotropin-releasing factor

CSA: Controlled Substances Act

DA: dopamine

DAT: dopamine transporter

DEA: U.S. Drug Enforcement Administration

DMT: dimethyltryptamine

DSM-5: Diagnostic and Statistical Manual of Mental Disorders (fifth edition)

GABA: γ-aminobutyric acid

GPCR: G protein-coupled receptor

5HT: serotonin (5-hydroxytryptamine)

KOR: κ (kappa) opioid receptor

LSD: d-lysergic acid diethylamide

MDA: methylenedioxy-amphetamine

MDMA: 3,4-methylenedioxy-methamphetamine

MOR: µ (mu) opioid receptor

MPH: methylphenidate

NDEWS: National Drug Early Warning System

NDTA: National Drug Threat Assessment

NE: norepinephrine

NIAAA: National Institute on Alcohol Abuse and Alcoholism

NIDA: National Institute on Drug Abuse

NMDA: N-methyl-D-aspartate

OUD: opioid use disorder

PCP: phencyclidine

psilocybin: 4-phosphoryloxy-N,N-dimethyltryptamine

PTSD: posttraumatic stress disorder

SAMSA: Substance Use and Mental Health Services Administration

SUD: substance use disorder


Addictive and hallucinogenic substances have been used throughout mankind’s cultural history. Traditionally, these substances have been used by healers for medicinal purposes and by priests in religious ceremonies. Hallucinogenic plants and mushrooms were used in pre-Columbian Mesoamerican cultures, opium has been known to man since prehistoric times, and alcoholic substances have been widely socially accepted for thousands of years. The advent of chemistry and pharmaceutical companies in the 19th century allowed for the analysis of psychoactive substances in coca leaves and poppy seeds, leading to the extraction and identification of the active ingredients and the synthesis of new compounds that were modeled after the botanical material. The hope was to find substances that could cure medical conditions and relieve pain without some of the addictive or adverse properties of the botanical extracts. Cocaine, morphine, and heroin were synthesized, and, although it seems absurd from today’s vantage point, were marketed as less addictive and more beneficial for addiction treatment. Morphine was a blessing during the American Civil War, as it was 100 years later during the U.S. involvement in Vietnam, and in both wars, many soldiers developed dependencies.

Regulatory Responses in the U.S. to Issues of Purity, Use, and Misuse of Drugs

Initial steps to regulate pharmaceuticals were introduced with the Pure Food and Drugs Act in 1906. That act stipulated that active ingredients be listed on the label of a drug’s packaging and that drugs could not fall below purity levels established by the U.S. Pharmacopeia (National Formulary). However, addictive drugs continued to be legally available without prescriptions as long as they were properly labeled. In 1908, with opium dens in most major cities, the first Opium Commissioner was appointed, and in 1914, the Harrison Narcotics Act was enacted. It regulated and taxed the production, importation, and distribution of heroin and cocaine. For the first time, doctors and pharmacists had to keep records of prescriptions.

The temperance movement and Prohibition, solidified ...

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