Lysergic acid diethylamide

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Lysergic Acid Diethylamide (LSD) is a Schedule I hallucinogenic compound derived from the rye fungus ergot which causes intense psychedelic experiences including distorted visual perceptions and perceived philosophical insights. Initially synthesized by Albert Hoffman in 1938, LSD consists of an ergoline ring structure with an activated diethylamide functional group. In the brain, the substance acts as an agonist on the 5-HT2 class G-Protein Coupled Receptors and causes intense effects, both physically but primarily mentally. The physical effects include pupil dilation and wakefulness. The neurological/psychological effects vary widely from intense euphoria to perceived visual distortions to profound philosophical insights. LSD was studied extensively immediately after discovery of its effects, but rarely examined after being made illegal in 1968. Recently, there has been an upsurge in volume of research regarding this substance, concentrating on mechanism of action and psychotherapeutic potential.

Discovery and History

Discovery

In 1938, Swiss chemist Albert Hoffman created LSD-25 while attempting to synthesize a respiratory agent. He discovered the psychoactive properties of the chemical five years later after accidentally absorbing some through his fingers, and noted the strange psychological effects. Several days later he intentionally ingested a large dose, and wrote about the new and intense psychedelic experiences which followed.

History

The shifts of consciousness, which embody the experience of the drug, made it popular among youth counter-culture communities, who clashed frequently with authority forces. Beat poets such as Allen Ginsberg and progressive thinkers such as Harvard professor Timothy Leary led these initial movements and encouraged widespread use of LSD. Concurrently, the covert MK-ULTRA experiment within CIA was conducting illegal human experimentation using LSD as a form of subject control. With public antagonism growing, and continued counterculture protestation, the government made the production and consumption of LSD illegal in 1968. Nonetheless, according to the National Survey on Drug Use and Health over seven percent of all Americans have used LSD at least once and research into its psychological benefits continues. Mechanism of Action

Serotonergic Agonism

The structure of LSD-25 is analogous both to other members of the ergoline family, such as mescaline and psylocibin, and to other ethneogens such as 3,4-Methylenedioxymethamphetamine (MDMA). Additionally, the chemical makeup and stereochemistry is similar to that of serotonin, a natural body neurotransmitter. LSD acts as an agonist of 5-HT2A and 5-HT2C receptors, G-Protein Coupled Receptors, and trigger a biochemical pathway which leads to exceptionally high levels of excitation of the serotonergic system. Miscommunications between neurons are responsible for the unique effects of hallucinogens, and LSD-25’s biochemical mechanism serves to amplify these through the agonism of serotonin receptors.

Additional Action Effects

Physical

The physical effects of LSD are minimal and often limited to pupil dilation, wakefulness, and reduced appetite. However, there are often secondary physical reactions based on psychosomatic actions such as increased heart rate, gurning or clenching of the jaw, and nausea.5

Psychological/Neurological

Known as a “trip,” the highly subjective psychological and neurological effects of LSD vary between users and are often affected by environment of the user. Common effects are characterized by distinct shifts in consciousness and perception. Users experience an altered state of consciousness characterized by philosophical and personal insights in addition to a novel manner of examination. Often there are distortions in perceived time, emotions, and senses. Visually, user often experience motion within static patterns as well as kaleidoscoping colors. A “trip” may leave lasting psychoemotional effects derived from the intensely altered reality encountered while under the influence.

Use in Psychotherapy

Immediately following his first intentional ingestion and the subsequent trip, Hoffman predicted important psychiatric benefits resulting from the novel exploration of the previously undecipherable human brain. However, little psychology experimentation was performed during the drug’s legal stage, investigators instead focused on the chemical properties and effects. One exception was a notable trial in which alcoholic subjects were given one dose with treatment and observed a reduction in recidivism over 50%. Recently, there has been support to add psychedelic therapy into the anthology of psychotherapeutic methods. Multiple studies have confirmed the contribution of controlled LSD use with appropriate guidance to reducing pathologies such as obsessive-compulsive disorder and post-traumatic stress disorder. Further research is being conducted by The Heffter Research Institute and examines the succor of psychedelic experiences for terminally ill patients.

Clusterbusters

LSD has been proposed as a treatment for the painful and debilitating cluster headaches known to affect 0.1% of the population in the U.S. The international organization Clusterbusters supports research regarding this ailment, and recently has begun to fund a Harvard Medical School study which aims to examine the effectiveness of psychedelics at terminating cluster headache cycles. John Halpern performed a wide-ranging survey of case studies and found strongly suggestive response trends which seem to indicate the usefulness of LSD in this manner. A human trial sequence has been initiated with the goal of determining possibility as a medical supplement.11, 12

References

 Jerome, L.  2008.  D-Lysergic Acid Diethylamide (LSD): Investigator’s Brochure.  Maps.org  <www.maps.org/research/lsd/swisslsd/IB_LSD.pdf>

 Ibid

 Hoffman, A.  1966.  LSD: Completely Personal  < http://www.maps.org/news-letters/v06n3/06346hof.html>

 Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4856Findings). Rockville, MD.

 Nichols, David E, 2004. Hallucinogens. Pharmacology and Therapeutics 101, 131-181.

 Sadzot B, Baraban Jm, Glennon RA, Lyon RA, Leonhardt S.  1989.  Hallucinogenci drug interactions at human brain 5-HT2 receptors: Implications for treating LSD-induced hallucinogenesis.  Psychopharmacology 98(4) 495-499.

 Fantegrossi WE, Murnane KS, Reissig CJ. 2007. The behavior pharmacology of hallucinogens.  Behavioral Pharmacology 75, 17-33.

 http://www.maps.org/media/nyt022204.html

 Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A.  2008.  The Pharmacology of Lysergic Acid Diethylamide: A Review.  CNS Neuroscience and Therapeutics 14, 295-314.

 http://www.heffter.org/

 http://www.clusterbusters.com/>

Sewell RA, Halpern JH.  2006.  Response of cluster headache to psilocybin and LSD.  Neurology (66) 1920-1922.