Psychedelics and Neural Physicality

Aldous Huxley, sensing the end of his life approaching as he lay dying from laryngeal cancer, chose to pass on while high on 100 micrograms of LSD. (One microgram is a millionth of a gram.) 

Albert Hofmann, the research chemist who first synthesized lysergic acid diethylamide (LSD) in 1938, framed his invention as a means to access a “miraculous, powerful, unfathomable reality that was hidden from everyday sight.” 

Former Harvard psychologist Timothy Leary told a crowd of 30,000 people in San Francisco that experiencing LSD was more important than receiving an education. “Turn on, tune in, drop out,” he famously said at the 1967 ‘Human Be-In’ rally. “Drop out of high school. Drop out of college. Drop out of graduate school. Drop out of junior executive. Drop out of senior executive.”

Leary’s activism led to the 1968 federal bans of LSD possession in both Canada and the United States. American legislators classified it as a Schedule I substance, defined as having “no currently accepted medical use and a high potential for abuse,” while Canadian legislators classified it as a Schedule III substance. In Canada, Schedule III substances are prohibited for possession, but they have the lightest sentencing associated with possession charges — a maximum of three years in prison, compared to the other schedules that forbid possession.

Since the 1960s, LSD has gained a reputation as a party drug — something people take recreationally to experience the mutating hallucinations, the vibrant colours, and the disconnect from reality produced by the drug.

This May, food writer Michael Pollan published a book titled How to Change Your Mind. Pollan’s book detailed his experiences trying LSD, using psilocybin (‘magic mushrooms’), and smoking Sonoran Desert toad venom. The book was met by wide acclaim in The Globe and Mail, The New York Times, The Guardian, The Times, and The New Republic. 

Pollan’s foray into psychedelic drugs thrust an important question back into the mainstream — how do we manage the substances that change us? 

What exactly is LSD, and how does it work?

Pollan wrote, “The group of tryptamines we call ‘the classical psychedelics’ have a strong affinity with one particular type of serotonin receptor, called the 5-HT2A… Basically, the psychedelics resemble serotonin closely enough that they can attach themselves to this receptor site in such a way as to activate it to do various things.”

“Curiously,” Pollan continued, “LSD has an even stronger affinity with the 5-HT2A receptor—is ‘stickier’—than serotonin itself, making this an instance where the simulacrum is more convincing, chemically, than the original,” explaining why LSD-induced hallucinations seem realistic and convincing.

As for why the hallucinations are so chaotic, Pollan wrote, “Depending on the type of receptor in question and its location, serotonin is liable to make very different things happen—sometimes exciting a neuron to fire, other times inhibiting it.” 

In other words, LSD, which mimics serotonin, causes different effects on the brain, despite binding to the same type of receptor, depending on the receptor’s location in the brain.

The “specialized neural networks of the brain—such as the default mode network  [DMN] and the visual processing system,” wrote Pollan, “each become disintegrated, while the brain as a whole becomes more integrated as new connections spring up among regions that ordinarily kept mainly to themselves or were linked only via the central hub of the DMN.” 

The DMN is responsible for linking “parts of the cerebral cortex to deeper (and older) structures involved in memory and emotion,” Pollan wrote. Thus, LSD has the incredible power to literally reshape our brains — and this offers significant opportunities for research and innovation. 

This may also account for how LSD can break established beliefs and enhance suggestibility, as reported by the British Psychological Society (BPS). That explains why some researchers see LSD as a potentially useful tool in psychotherapeutic contexts. 

The promises of LSD

Due to the increased suggestibility of LSD users, the BPS reported that LSD is a potential psychotherapeutic tool for treating alcoholism. A “meta-analysis of a set of trials looking at LSD treatment for alcoholism,” according to a BPS Research Digest post,  “showed an effect that hasn’t been bettered by any other means.” In another post, the BPS also suggested potential for the use of LSD to treat post-traumatic stress disorder and depression but noted that current research is too sparse to draw definitive conclusions.

Pollan also reported that psychedelics are a potential tool for reducing anxiety about death in terminally ill patients. He pointed to a 2016 study by New York University and John Hopkins University researchers on psilocybin, which has similar cognitive and visual effects to LSD. In Pollan’s words,  “Some 80 percent of cancer patients showed clinically significant reductions in standard measures of anxiety and depression, an effect that endured for at least six months, after their psilocybin session.”

In a 1965 letter to Harper’s Magazine, physician Sidney Cohen described an anecdote from his “limited and inconclusive research project.” He recollected how a patient told him, while on a “minute dose of LSD,” that “I supposed that I’m detached — that’s it — away from myself and my pain and my decaying. I could die nicely now — if it should be so. I do not invite it, nor do I put it off.”

But LSD is not just for the terminally or mentally ill. For the psychologically and physically healthy, it can be used as a tool to promote creativity and innovation. Online magazine Slate reported that Steve Jobs had described it as “one of the two or three most important things” that he has ever done; that John Lennon attributed a Beatles album to LSD use; and that molecular biologist Francis Crick “reportedly claimed to have envisioned the structure of DNA during an acid trip.”

To better understand these experiences, as well as the severe risks associated with taking LSD, one must understand how LSD changes one’s psychology and perception.

What does dosing on LSD feel like?

The New York Times reported that “an amount [of LSD] the size of a grain of salt can induce swirls of emotion, and shimmering clear senses in which the ordinary becomes extraordinary, luminous, and meaningful.” How this translates into a human experience can be better understood by reviewing the journals of the scientist who created and first tried the drug. 

Hofmann first synthesized LSD in 1938, as a result of his investigation into components of the ergot fungus. He discovered the psychoactive effects of LSD when he accidentally came into physical contact with a small, unknown quantity of the substance  on April 16, 1943. Documenting his unintentional ingestion of the substance, Hofmann wrote:

“Last Friday… I was forced to interrupt my work in the laboratory in the middle of the afternoon and proceed home, being affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.”

Hofmann then intentionally ingested 250 micrograms of LSD in his lab on the following Monday, which, according to his calculations, was “the smallest quantity that could be expected to produce some effect.” That is actually 12.5 times the upper bound of the threshold amount, which ranges from 10–20 micrograms.

At the start of his 250-microgram ‘trip,’ Hofmann recorded his initial feelings of “dizziness, [a] feeling of anxiety, visual distortion, symptoms of paralysis, [and a] desire to laugh.” Feeling ill and struggling “to speak intelligbly,” Hofmann decided to take a bicycle ride home, accompanied by his lab assistant. 

“Everything in my field of vision wavered and was distorted as if seen in a curved mirror.” Once he reached his home, Hofmann recalled his surroundings as having “transformed themselves in more terrifying ways. Everything in the room spun around, and the familiar objects and pieces of furniture assumed grotesque, threatening forms. They were in continuous motion, animated, as if driven by an inner restlessness.” This is likely a result of LSD temporarily dissolving the neural networks associated with visual processing.

Describing his cognitive distortions, Hofmann wrote, “I was taken to another world, another place, another time. My body seemed to be without sensation, lifeless, strange. Was I dying? Was this the transition? At times I believed myself to be outside my body, and then perceived clearly, as an outside observer, the complete tragedy of my situation.” This is perhaps the result of LSD dissolving the DMN.

Yet despite his cognitive distortions, Hofmann still “had brief periods of clear and effective thinking,” which made him “just barely capable” of asking his assistant to call a doctor and request milk from his neighbours as a “nonspecific antidote for poisoning.”

When his neighbour arrived to deliver milk, however, Hofmann’s cognitive distortions returned with increased intensity. He failed to recognize her as “Mrs. R., but rather a malevolent, insidious witch with a colored mask,” Hoffman wrote. He then began to spiral. Convinced that he was be dying, he felt “fear and despair” about his wasted life — regrets that “a young family should lose its father,” and that he would leave his “chemical research work, which meant so much to [him], unfinished in the midst of fruitful, promising development.”

Once the doctor arrived, he confirmed that Hofmann physically had no “abnormal symptoms other than extremely dilated pupils” and monitored him without prescribing medication. The effects soon faded. “The horror softened and gave way to a feeling of good fortune and gratitude, the more normal perceptions and thoughts returned, and I became more confident that the danger of insanity was conclusively past.”

To Hofmann, some of the most positive effects appeared the following day, while sober. The next morning, he woke “refreshed, with a clear head, though still somewhat tired physically. A sensation of well-being and renewed life flowed through me.” Describing his newfound appreciation for life, Hofmann recalled, “Breakfast tasted delicious and gave me extraordinary pleasure. When I later walked out into the garden, in which the sun shone now after a spring rain, everything glistened and sparkled in a fresh light. The world was as if newly created.”

But Hofmann’s recollections only documented what he personally experienced; anecdotal stories only record experiences based on an individual, rather than a population. The Centre for Addiction and Mental Health (CAMH)  largely corroborates Hoffman’s experiences based on studies of populations, reflecting the up-and-down nature of LSD trips. 

On a physical level, LSD “may include numbness, rapid heartbeat, reduced co-ordination, chills, nausea, tremor, weakness and dilated pupils,” according to CAMH’s website. “Sensations of gravity may be altered, ranging from feeling weighted down, to feeling light and floating.”

On a perceptual level, colours “become more intense, halos or rainbows may appear around objects, and shapes may become fluid in form,” CAMH reported. “Rapidly changing brightly coloured geometric patterns and other images may be seen, whether the eyes are open or shut.” 

On a psychological level, the effects are “unpredictable.” According to CAMH, “Individual reactions to the drug can range from ecstasy to terror, even within a single drug-taking experience. People who have used the drug before, and had a positive experience, may have a negative experience if they take it again.”

A wealth of reports of individuals sharing what they’ve felt and experienced while on LSD can be found on an online database called Erowid, whose founders were profiled in The New Yorker in 2015. Analyzing its users’ anecdotes, Erowid  published a figure like the one on the next page explaining the duration and intensity of the effects of LSD.

The duration aligns with CAMH’s findings: “The effects of LSD come on gradually within an hour of taking the drug, peak at two to four hours and gradually taper off, with the entire trip lasting up to 12 hours. The intensity of the effect depends on the size of the dose.”

The sinusoidal wave at the top of the figure refers to how the psychological effects of LSD intensify and de-intensify, peaking and receding for the duration of the most intense parts of the ‘trip.’ This explains how Hofmann was able to call for a doctor and milk, during his “brief periods of clear and effective thinking,” despite feeling the full effects of LSD.

The risks of LSD

LSD can be psychologically addicting. Regular users of LSD “do not experience physical withdrawal symptoms when they stop taking the drug,” according to CAMH. However, “it can be addictive. Some people who use LSD repeatedly feel compelled to take it. The drug takes on an exaggerated importance in their lives, leading to emotional and lifestyle problems.”

As an analogy, consider a disturbing scene in the 2010 film Inception. A chemist in Kenya named Yusuf describes to a foreigner named Eames about how 20 people “come every day” to his laboratory, seeking the psychoactive effects of a substance named ‘somnacin,’ which enables them to hallucinate via lucid dreaming upon falling asleep.

“They come here every day to sleep?” Eames asks.

“No,” replies an elderly man overhearing the conversation. “They come to be woken up. The dream has become their reality. And who are you to say otherwise?”

People psychologically addicted to LSD, especially at high doses, may believe that the distorted world on LSD is more ‘real’ than reality itself. This can cause them to neglect their personal and interpersonal responsibilities.

Another substantial risk is that of developing hallucinogen persisting perception disorder (HPPD), in which the visual distortions of LSD persist for days or even years after a person is sober. HPPD, whose “risk factors, causes, and effective treatments remain a mystery,” according to The New Yorker, can cause visual “streaking and trailing” of moving objects and the perception of a “ghostly afterimage” of written text after turning a page.

In 2013, poet Jacob Scheier wrote an op-ed in the Toronto Star about his personal experience with LSD and his ongoing struggle with HPPD. He’d struggled with the disorder for about eight years at the time of publication, after he took LSD weekly beginning at age 16. Scheier was admitted to a psychiatric ward and later nearly committed suicide. Eventually, he decided to cope with his condition rather than attempt to cure it, “discovering that sometimes the only way to fix something is to let it remain broken.”

Visions of the future 

One of the most intriguing tools for psychological development is LSD; yet it can also derail one’s life, due to psychological addiction, HPPD, or the consequences of one’s actions while experiencing hallucinations. Furthermore, its illegality and association with the hippie culture of the 1960s serves to delegitimize it in the public eye. 

An opinion piece in The Washington Post by Daniel Miller argued that psychedelics ought to be tightly regulated because “they’re simply too powerful to be left to the free market.”

Yet, recognizing the potential for LSD as a psychological tool, Miller also sketched a possible plan for regulated access to LSD. “Patients could be recommended for treatment by their doctors, screened for serious mental illness and certain heart conditions, prepped about what to expect and monitored by a medical professional (with whom they built a trusting relationship) over six to eight hours in case of anxiety and fear.” Miller continued, “The psychedelic experience should also be integrated into the participant’s life through some form of follow-up therapy.”

Citing New York University professor Mark Kleiman, Miller argued for the importance of “containing the experience” during and after the experience, “for the purposes of safety.”

Hofmann himself wrote, “The history of LSD to date amply demonstrates the catastrophic consequences that can ensue when its profound effect is misjudged and the substance is mistaken for a pleasure drug.” Clearly, a substance that rewrites the brain — itself already a mystery to scientists — requires some kind of regulation. 

“Special internal and external advance preparations are required; with them, an LSD experiment can become a meaningful experience,” wrote Hofmann. “Wrong and inappropriate use has caused LSD to become my problem child.”