A new age for psychedelic science

In this first of a two-part series, I discuss the emerging scientific interest in the use of psychedelic medicines for neuroscience and therapeutic purposes. Researchers at major universities, research hospitals, and medical practices worldwide are seeking to learn more about the safety and efficacy of psychedelics in a modern, clinical context. Here at U-M in 2022, doors opened at M-PsyC, the Michigan Psychedelic Center, at Michigan Medicine.

Several clinical trials are underway worldwide and show promise for conditions ranging from depression to fibromyalgia. Preliminary research suggests that psychedelic-assisted psychotherapy produces lasting benefits and can change facets of personality that promote positive mental health.

Altered states

Psychedelics are a group of substances that change or enhance sensory perceptions, thought processes, and energy levels. These substances are also known as hallucinogenic drugs or simply hallucinogens. They come in different forms, ranging from chemicals such as LSD to plants like the peyote cactus.

‘Psychedelic’ derives from  Greek words that refer to ‘mind-manifesting’ or ‘mind-revealing.’ The Greek ψυχή translates as psyche (or soul, mind), and δηλοῦν (dēlóō), translates to manifest or to make visible, to reveal. The term psychedelic was coined in 1956 by English psychiatrist H. Osmond to describe these ‘mind-revealing’ substances. Osmond favored the psychedelic term because it was “clear, euphonious, and uncontaminated by other associations.”

Several terms are used to refer to the plant, fungal, and synthetic medicines capable of causing non-ordinary states of consciousness that change an individual’s perception or awareness of their surroundings and alter thoughts and feelings. Terms include ‘entheogen’ (accessing the divine within), ‘hallucinogen’ (wandering in mind), ‘psychotomimetic’ (mimicking psychosis), ‘psychotogenic’ (inducing a psychosis), and ‘psycholytic’ (loosening the mind).

Psychedelics act by directly affecting serotonin 2A receptors known to alter human consciousness, as well as such biological functions as mood, cognition, reward, learning, and memory. Other neurotransmitters are also affected differentially by psychedelics, and therefore each psychedelic substance can have different psychoactive effects.

A little history

Shamanic cultures dating as far back as 5,000 years have featured naturally occurring plant psychedelics in healing and spiritual rituals. Evidence of mind-altering substances appears throughout ancient texts, primitive art, and oral histories. The legendary Soma, an intoxicating plant juice (possibly containing a hallucinogenic mushroom) is found in the Sanskrit texts of ancient Hindu India as an offering to the gods. The Greeks used a drink that likely contained the hallucinogenic Ergot fungi during various ceremonies. More modern-day usage of psychedelic plants by non-Western cultures includes the Amazonian use of Ayahuasca, a plant compound containing DMT.

Many indigenous people of North America routinely used substances derived from the Peyote cactus during religious and other ceremonies. A Shaman, usually a respected elder of the tribe who acted as doctor and priest, led these rituals. Combining psychedelics with such non-drug techniques as drumming and chanting was discovered to induce a dreamlike state believed to open communication with the spiritual world. When practiced in groups, these cultures enjoyed a cohesive community effect and observed decreased levels of mental illness.

It is not only humans that show a natural tendency toward altering their state of consciousness. Many animals, from insects to mammals, are attracted to hallucinogenic plants and fungi, above and beyond the normal quest for food.

Hofmann’s bicycle ‘trip’

Swiss chemist and plant scientist Albert Hofmann was the first person to synthesize Lysergic acid diethylamide (LSD-25). He was working for Sandoz Laboratories in 1936, seeking to obtain a circulatory and respiratory stimulant. The project was shelved as unsuccessful, but Hofmann believed that his LSD-25 (his 25th iteration of the substance) contained properties missed by the initial laboratory testing.

Seven years later in 1943, Hofmann decided to resynthesize his dormant LSD-25. While working, he accidentally absorbed about 0.25mg of LSD-25 in his skin and recorded a remarkable experience that he attributed to the substance. A few days later, he ingested 0.25mg of LSD-25, with his assistant’s knowledge this time. Hofmann dosed himself at 4:20 p.m., diluting the substance in 10cc water. He noted it was tasteless. At 5 p.m., he wrote in his journal, “Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.” The journal went dark after that.

Two days later he wrote his “trip” had been most intense from 6-8 p.m. – and that during that time, he rode home on his bicycle. Intuitively, he had asked his assistant to escort him home. During this infamous bicycle ride, Hofmann tapped into the psychedelic effects of the drug and detailed the event in his book LSD, My Problem Child: Reflections on Sacred Drugs, Mysticism and Science. The book originally was published in 1979; the fourth edition appeared in paperback in 2017.

It features recollections like this:

“Kaleidoscopic, fantastic images surged in on me, alternating, variegated, opening and then closing themselves in circles and spirals, exploding in colored fountains, rearranging and hybridizing themselves in constant flux … It was particularly remarkable how every acoustic perception, such as the sound of a door handle or a passing automobile, became transformed into optical perceptions. Every sound generated a vividly changing image, with its own consistent form and color.”

Hofmann was unaware of the importance of his discoveries and actions, not to mention the effects they would set in motion. His discoveries ushered a burgeoning period of scientific and cultural exploration in the 1950s and ’60s for all natural and synthetic hallucinogenic substances.

The major psychedelics

	LSD (Lysergic acid diethylamide) – Made from a substance found in ergot, a fungus that grows on rye and other grains. LSD, commonly known as acid, looks like a clear or white material. People usually soak small squares of blotting paper in the LSD and swallow these acid tabs. LSD also comes as a tablet or capsule.
	Psilocybin – A naturally occurring substance found in various hallucinogenic fungi. There are more than 100 psilocybin (magic) mushroom varieties. When consumed the fungi converts to psilocin or psilocybin, the psychoactive ingredient. Psilocybin mushrooms are found in tropical and subtropical regions of the U.S., Mexico, and South America. Psilocybin mushrooms are consumed raw or boiled into a brew.
	Peyote – A small, spineless cactus containing the naturally occurring psychoactive ingredient mescaline. The top of the peyote cactus, also referred to as the crown, consists of disk-shaped buttons that people cut from the roots, dry, and then chew. Buttons also can be soaked in water to produce an intoxicating liquid. Peyote (mescaline) can also be manufactured in the laboratory.
	DMT (N, N-dimethyltryptamine) – Structurally similar to psilocin, an alkaloid found in a variety of psilocybin mushrooms. It can be synthesized in the laboratory but is also a naturally occurring component in several plants. It is the psychoactive ingredient found in the ayahuasca plant.
	Ayahuasca – A concentrated liquid brewed into tea by prolonged heating or boiling of the Banisteriopsis caapi vine with the leaves of the Psychotria viridis shrub. Both plants, naturally occurring in South and Central America, contain the active chemical DMT (dimethyltryptamine) and monoamine oxidase inhibitors (MAOIs) — the first laboratory-developed antidepressant.
	Ketamine – A dissociative drug that acts on different chemicals in the brain to produce visual and auditory distortion and detachment from reality. When it’s sold illegally, ketamine usually comes as a white or off-white powder. It also be made into pills or dissolved in a liquid.
	Salvia divinorum – A plant found in southern Mexico and Central and South America. People usually ingest salvia by chewing its leaves or by drinking juices extracted from the plant. They also smoke or vaporize and inhale the dried leaves of the salvia plant. Other names include “sage of the seers” and “the diviner’s sage.”
	Ipomoea corymbose (Ololliuqui) – A species of morning glory plant, native to Latin America from Mexico as far south as Peru and widely grown elsewhere. It is known to natives of north and central Mexico as Ololliuqui, which means ’round thing,’ referring to its small, brown, oval seeds. The seeds classify as a hallucinogenic and are consumed as is, or softened in ½ cup of water. Ololliuqui effects are comparable to magic mushrooms and peyote
	MDMA (Methylenedioxymethamphetamine) – Commonly known as ecstasy (tablet form); and Molly or Mandy (crystal form). It is a potent entheogen with stimulant and minor hallucinogenic properties.

Psychedelics’ future as medicine

At this time in history, research studies and clinical trials testing the therapeutic properties of psychedelics are at an all-time high. This worldwide research explosion has already revealed promising uses of psychedelics for treating anxiety, depression, post-traumatic stress disorder, and more.

Congress passed the Breakthrough Therapies Act in 2017, allowing for faster drug development of promising medications. These medications must provide more benefits compared to available medications. The U.S. Food and Drug Administration has designated the following as “Breakthrough Therapies” for the treatment of different mental health disorders:

• MDMA-assisted psychotherapy for PTSD
• Psilocybin for treatment-resistant depression
• Ketamine for depression and anxiety

In my next Health Yourself column, I will review what the research — not the hype — shows regarding these different psychedelics and their use as medicines.

(Read more about the psychedelic renaissance at U-M in Medicine at Michigan magazine.)

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