Shortly after Albert Hoffman discovered the psychoactive properties of LSD in 1943, Sandoz Laboratories began widespread distribution of LSD to researchers in 1949. Throughout the 1950s and 1960s, scientists in several countries conducted extensive research into experimental chemotherapeutic, and psychotherapeutic uses of psychedelic drugs. In addition to spawning six international conferences and the release of dozens of books, over 1,000 peer-reviewed clinical papers detailing the use of psychedelic compounds (administered to approximately 40,000 patients) were published by the mid-1960s. Proponents believed that psychedelic drugs facilitated psychoanalytic processes, making them particularly useful for patients with conditions such as alcoholism that are otherwise difficult to treat. However, many of these trials did not meet the methodological standards that are required today.
Researchers like Timothy Leary felt psychedelics could alter the fundamental personality structure or subjective value-system of an individual to great potential benefit. Beginning in 1961, he conducted experiments with prison inmates in an attempt to reduce recidivism with short, intense psychotherapy sessions. Participants were administered psilocybin during these sessions weeks apart with regular group therapy sessions in between.[9] Psychedelic therapy was also applied in a number of other specific patient populations including alcoholism, children with autism, and persons with terminal illness.
Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level–dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network.
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