An in-depth exploration of LSD, the culture-shaping psychedelic drug colloquially known as acid.
In the year 1938, A Swiss chemist by the name of Albert Hofmann, working out of Sandoz Pharmaceuticals, became the first man to synthesize Lysergic Acid Diethylamide (LSD). Active at the microgram level (one-millionth of a gram), LSD is the most potent psychoactive drug known to humankind.
It wasn't long after Hofmann’s discovery that LSD was being used by medical professionals to achieve behavioral and personality changes and to treat a variety of mental health conditions.
However, it soon leaked from the lab, quickly gained mainstream popularity, and became associated with the youth-led counterculture. This, in conjunction with sensationalist media reporting, provoked the drug’s classification as a schedule one substance in 1970.
Today, it is generally accepted that the scheduling of psychedelic drugs was less out of concern for the health and wellbeing of the public, and more to do with their ability to “dissolve opinion structures” — to quote the late, great, ethnobotanist and orator, Terence Mckenna.
Applied properly, LSD can induce awe-inspiring and powerfully therapeutic experiences. That said, the history of psychedelic use in the west teaches us that LSD is not a magic bullet cure-all, nor does it guarantee everlasting love and enlightenment.
Interested in derivatives of lysergic acid, an unnatural product of an ergot (Claviceps purpurea) alkaloid called ergotamine, Albert Hofmann was actually trying to obtain a central nervous system stimulant when he synthesized LSD.
Unimpressed by its mild stimulative effects, Hofmann decided to shelve the psychedelic ergoline for 5 years. Then, in April of 1943, Hofmann experienced a “peculiar presentment” that LSD deserved to be re-investigated, and in synthesizing it for the second time, he accidentally ingested a small dose that had a compelling threshold effect.
Noticing a pronounced alteration of his consciousness, Hofmann became enthralled by “unusual sensations”, which would soon develop into what he described in his autobiography, LSD, My Problem Child, as a “dreamlike state”, characterized by an “uninterrupted stream of fantastic pictures, extraordinary shapes with an intense, kaleidoscopic play of colors.”
3 days later on April 19, at 4.20 pm, Hofmann ingested 250 micrograms, about 1.5 times the typical recreational dose (although false quantification of dosages is very common), and became the first man in history to intentionally trip on LSD. Hofmann somehow managed to safely make it home on his bicycle with the help of his lab assistant, whom he had asked to accompany him on the 5-kilometer ride home.
Hofmann’s discovery of LSD’s effects is now commemorated on April 19, a.k.a. "Bicycle Day.”
After enduring the first-ever “bad trip”, one that was dyed with a fear of impending death, Hofmann experienced an afterglow effect in the proceeding days, remarking that “everything glistened and sparkled in a fresh light. The world was as if newly created.”
Convinced that LSD had discovered him, rather than vice versa, Hofmann predicted that LSD could be used as an effective adjunct to psychotherapy.
LSD’s effects typically take hold 20-60 mins after ingestion and last for 6-12 hours. At moderate doses, when taken in a safe environment after having properly prepared, one can expect to experience the following subjective effects:
Higher doses of LSD, when used responsibly, have been shown to reliably induce a mystical experience. Characterized by mind-bending psychological insights, a sense of universal interconnectedness, the transcendence of space and time, intense euphoria, and overwhelming love, LSD experiences can be powerfully transformative.
LSD can cause one's sense of self, or “ego”, to dissolve, which may feel like one is about to die, and can even make it difficult to distinguish oneself from everything else. Ego dissolution can be incredibly frightening (for obvious reasons) but it can also be welcomed as something positive depending on the person’s mindset going into the experience and the environment in which it takes place.
Experts agree that the key to successfully navigating this precarious sensation is to confront the fear. “Trust. Let go. Be open” — the wise words of Johns Hopkins psychologist, Bill Richards, who has served as a therapist for hundreds of patients in their psychedelic journeys. Of course, this is easier said than done but speaks to the importance of having a therapist or trusted person to provide support for the duration of the experience.
Once it isn’t resisted, ego dissolution may be accompanied by a transcendental sense of being a part of something greater than oneself, a powerful feeling of “at-onement” with the wider universe.
Mystical experiences, of which ego dissolution is a cardinal feature, have been associated with better therapeutic outcomes in clinical trials. The shift in perspective that follows an experience with something greater than oneself is often a catalyst for personal change.
LSD can sometimes cause an acute state of anxiety and confusion that is commonly referred to as a “bad trip”. So-called bad trips are regularly weaponized by the “just say no” opposers to personal sovereignty, typically the least equipped individuals to comment on drug safety, to warn against experimentation with one’s consciousness.
Those who are well-versed in psychedelia know that, when taken responsibly, the subjective effects of psychedelics may pose some risk of inducing challenging or even terrifying experiences. Although such experiences can cause considerable distress, and may in exceedingly rare cases have lingering psychological consequences, they are generally insightful and therapeutic. The vast majority of clinical trial participants and recreational users consider their challenging psychedelic experiences to be highly beneficial and extraordinarily meaningful.
The therapeutic power of challenging experiences is evidenced in a landmark study led by Johns Hopkins psychopharmacologist, Dr. Roland Griffiths, where one-third of participants who reported their psilocybin journey to be one of the most terrifying experiences of their entire lives, also reported it to be the most spiritually significant of their entire lives.
LSD experiences can bring into question some of our most basic assumptions of reality, ourselves, and the people in our lives. Once termed “non-specific amplifiers of mental processes” by the revered LSD psychotherapist and author Stanislav Grof, psychedelics tend to summon to the surface uncomfortable material that had hitherto been suppressed in the unconscious mind.
Although this can be frightening, it should not be viewed as a bad thing. On the contrary, it is quite extraordinary.
In a clinical context, challenging experiences may be necessary to help suffering individuals break free from negative rumination and constricted worldviews. In the aftermath of a challenging experience, the majority of patients are returned with fresh perspectives to a state of consciousness more conducive to living a happy and healthy life.
Marketing it as an effective model for psychosis, Sandoz pharmaceuticals sent supplies of LSD to mental health professionals all over the world who believed it could be used as a psychotomimetic i.e. a drug capable of producing an effect on the mind similar to a psychotic state.
As a consequence, scientists, who up until that point were under the illusion that psychiatric disorders were the result of bad parenting, began to make the connection between brain chemistry and behavior — this connection may seem obvious now, but it was considered quite radical at the time.
Then, in 1953, a biochemist by the name of Betty Twarog became the first person to isolate serotonin in the mammalian brain, much to the disbelief of her supervisor. It can be said that Albert Hofmann’s discovery of LSD sparked a revolution in neuroscience, led at least in part, by the determined Betty Twarog.
Pharmacologically rich, LSD is jokingly said to be a promiscuous molecule due to its activity at a whole host of brain receptors. The most important of these to remember is the 5-HT2A serotonin receptor, which is the essential receptor for producing LSD’s mind-expanding psychedelic effects.
LSD also has an affinity to dopaminergic and adrenergic receptors, unlike other psychedelics. However, interaction with these receptors appears not to be in any way responsible for its effects.
When LSD enters the 5-HT2A receptor cell, it essentially gets trapped there and takes the place of serotonin. Unlike serotonin, LSD doesn't directly activate the receptor. Surprisingly, for such a potent compound, LSD is a rather weak agonist.
Responding to LSD, the receptor changes its form to accommodate the larger, more rigid LSD molecule, which then interacts with the exterior part of the cell and couples to signaling molecules. The specific signaling patterns subsequently stimulated are what mediate the psychedelic actions of LSD.
Signaling patterns are dependent on the nature of the chemical inside, and so LSD-induced signaling events are altogether different from those produced by serotonin and other drugs. This phenomenon (activation by different agonists leading to different signaling events) is known as functional selectivity.
Recent research indicates that the LSD-bound serotonin receptor may form a "lid" that keeps the LSD molecule inside the receptor for long stretches. The formation of this lid could provide a molecular explanation for LSD’s sticktoitiveness and long duration of action despite its weak agonism.
Clinical studies conducted between the 1950s and 1970s investigating the therapeutic potential of LSD yielded positive outcomes up until research was strictly prohibited.
During that period, three different LSD therapy approaches were employed in clinical trials: “psycholytic therapy”, wherein low doses of LSD were used in continuing therapy sessions, “psychedelic-chemotherapy”, which used high doses with limited therapeutic input, and plain old “psychedelic therapy”, in which a single high dose was administered to induce a mystical-type experience to be monitored by a therapist or nurse.
LSD was observed to reduce pain, anxiety, and depression, and treat alcohol-use disorder, and heroin-use disorder. Other studies involving larger patient samples demonstrated LSD’s extraordinary safety profile (it does not entail physical dependency or exhibit physiological toxicity) and positive outcomes in terminally ill cancer patients.
These studies largely fail to meet the design criteria of contemporary clinical investigation. As a consequence, it is best to interpret early this evidence of LSD’s healing power as preliminary evidence of therapeutic efficacy.
Now, however, LSD is regaining traction as a therapeutic aid. The first double-blind, randomized, active placebo-controlled study conforming to modern standards observed that LSD-assisted psychotherapy significantly reduced anxiety in patients with life-threatening diseases.
Additionally, the clinical-stage biopharmaceutical company MindMed recently announced the results of their Phase 2 study of LSD-assisted psychotherapy for anxiety, also reporting significant and enduring reductions in symptoms.
After a decades-long hiatus in LSD research, this fascinating, mystical experience occasioning compound is again showcasing its therapeutic potential.
Content from the community