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Psilocybin — the main psychedelic compound in magic mushrooms — is the most famous and best-studied psychedelic substance. But beyond psilocybin, there are many other psychedelic compounds, some naturally occurring, some made in labs. Scientists, mental health professionals and individual psychonauts are exploring these alternate psychedelics for their psychological benefits, and investors are betting billions on their revenue-generating potential.
Acid, Ecstasy, Toad and Peyote (a.k.a LSD, MDMA, DMT and Mescaline)
LSD, MDMA, DMT and mescaline are the main non-psilocybin psychedelics being studied for their therapeutic potential. Let’s break them down one at a time.
1. LSD (lysergic acid diethylamide). Also known as acid, LSD is probably the most best-known (and most infamous) psychedelic substance besides mushrooms. First synthesized by Swiss scientist Albert Hofmann in 1938, LSD is derived from ergot, a fungus that infects grain. LSD has played a pivotal role in American history, from the discovery of the serotonin neurotransmitter system, the CIA’s MK Ultra experiments and Ken Kesey’s acid tests to its enthusiastic adoption by the psychology department of Harvard and the birth of the psychedelic music scene.
What’s less well known is that, as early as the 1950s, North American psychiatrists were already finding success with LSD as a therapeutic treatment for alcoholism and other mental health problems. Between the years of 1950 and 1965, more than 40,000 patients were prescribed some type of LSD therapy. But as LSD became a hallmark of the American counterculture and the anti-war movement, the Nixon Administration used criminalization to vilify and persecute these groups, and the U.S. government outlawed LSD in 1968.
Because it’s classified as a Schedule 1 drug, LSD is difficult to research, but it’s currently being studied for the treatment of anxiety as well as depression. Biotech company MindMed is in the midst of a placebo-controlled clinical trial evaluating LSD as a treatment of anxiety disorders. LSD cannot be patented, but psychedelic investors hope to profit from patenting new formulations as well as delivery and dosing methods.
2. MDMA. MDMA (3,4-Methylenedioxymethamphetamine) also known as ecstasy or molly, is both a psychedelic and a stimulant. Though it’s primarily associated with recreational use and rave culture, MDMA has been dubbed “empathy” and “the love drug” for its ability to induce empathetic, positive emotions.
First developed by a German pharmaceutical company in 1912, MDMA apparently had a small following among psychiatrists in the late 1970s and early 1980s, who nicknamed it “Adam,” because they felt it returned patients to a state of primal innocence and openness. That ended in 1985 when the DEA declared an emergency ban and classified MDMA as a Schedule I drug.
MDMA has shown promise for the treatment of PTSD. Randomized, double-blind, placebo-controlled clinical trials of patients with severe PTSD, including those with depression, addiction and childhood trauma, have found that “MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated.” The Food and Drug Administration granted breakthrough therapy status to MDMA-assisted psychotherapy in 2017.
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3. DMT. N,N-Dimethyltryptamine (DMT) is an alkaloid that occurs naturally in plants and animals. It can induce intense episodic hallucinations and is famously one of the major psychoactive compounds found in various shamanistic compounds (e.g., ayahuasca, yagé) used in indigenous societies for centuries.
Banned in the U.S. since 2011, DMT has been dubbed “the god molecule.” A similar compound, 5-MeO-DMT, is found in the venom of the Sonoran toad — sadly, the species is now threatened in New Mexico because of toad poaching brought about by increasing interest in trying DMT. (PSA: Don’t lick the toads!)
A DMT trip is comparatively brief, typically lasting around thirty minutes. It comes on within seconds and is known for its explosive intensity. Michael Pollan tried DMT after being warned that it was “the Everest of psychedelics” and found the “violent narrative arc” of his trip overwhelming. Researchers say DMT could be a useful addition to the psychedelic pharmacopeia “because of its short duration of action…and putatively higher rates of ego-dissolution and mystical experiences.” A small study published in Psychopharmacology found that a single inhalation of 5-MeO-DMT was associated with sustained improvements in life satisfaction, mindfulness and reduced psychopathological symptoms.
DMT may also help with addiction treatment. A 2018 survey published in the Journal of Psychopharmacology found that, of the 263 respondents with substance abuse problems, around 60 percent claimed DMT had improved their condition — twice the improvement result found with conventional therapies. (Respondents reported the drug helped with depression, PTSD and anxiety symptoms as well.) A clinical trial currently underway at King’s College Hospital in London is examining DMT’s efficacy for treating patients with alcohol use disorder (AUD).
4. Mescaline (peyote). Mescaline is another naturally occurring psychedelic hallucinogen, found in the peyote cactus, the San Pedro cactus and the Peruvian torch cactus, among others. Aldous Huxley recorded his experience with mescaline in his book The Doors of Perception, and it’s well known for its ancient history in Native American rituals. Classified as a Schedule I drug in the U.S., mescaline is only legal in specific religious ceremonies conducted by Native Americans. A peyote-induced hallucinogenic experience typically begins in 60 minutes after consumption and lasts about 8 to 12 hours. It often comes with intense visual distortions and can cause vomiting and nausea.
Peyote is an extremely slow-growing cactus. New interest in mescaline plus industrialization in the American Southwest have made it a vulnerable species in decline. (PSA: Don’t pick the peyote!)
Funded by biotech company MindMed, the first-ever clinical trials of mescaline are underway at the University Hospital in Basel, Switzerland. Several other pharmaceutical companies are developing new mescaline-based compounds that could eliminate the vomiting sometimes associated with the drug. In Canada, XPhyto Therapeutics is developing mescaline synthesis processes, which could lead to controlled microdoses given with transdermal patches or sublingual strips.
Expanding the Psychedelic Pharmacopoeia
Though psychedelic substances have commonalities, their differing molecular structure may offer different therapeutic benefits to the human brain. It benefits all of us for scientists to understand how these compounds work and what illnesses they may be able to treat.
