Mescaline

Other names:

• Mescalito

Basics: Mescaline is found in several cacti including the San Pedro and the spineless peyote. Like LSD and psilocybin, mescaline is typically ingested orally. The onset of subjective effects begins after around an hour and lasts for ten to twelve hours. Mescaline is the least potent of the classic psychedelics, meaning more has to be ingested in order to occasion a certain intensity of effects.

Because peyote grows wild only in small portions of the southern United States and Mexico, the supply is in decline. A number of factors contribute to this scarcity: growing demand from non-Indigenous users who want to experience peyote; cattle ranching, agriculture, and oil and gas development have encroached on the desert land where it grows; and poaching and unsustainable harvesting practices have decimated the species. Because peyote is a slow-growing plant, it can take a decade or more for a seed to develop into a cactus with enough mescaline to consume. Today, peyote is considered a vulnerable species and some members of the Native American Church have asked non-Indigenous people to abstain from harvesting or using the plant.

History: Mescaline has been used for many generations and has played a role in Indigenous religious ceremonies in North America for over five thousand years. The compound was first isolated by the German chemist and physician Arthur Heffter, and in the 1950s the drug was used to simulate and study schizophrenia. Aldous Huxley made mescaline famous when he described his own psychedelic experiment with the drug in his landmark book The Doors of Perception. As with most other classic psychedelics, the 1970 Controlled Substances Act classified mescaline as a Schedule I drug in the United States, virtually halting scientific research into its clinical and medical potential.

The mescaline-containing cactus peyote is the sacramental medicine of the Native American Church. For over a century, U.S. federal and state governments variously prohibited and permitted Indigenous use of peyote, with permission finally granted under federal law in 1994 as an amendment to the American Indian Religious Freedom Act of 1978.

Potential Benefits: Mescaline induces experiences similar to other classical psychedelics, which include visual and auditory hallucinations and an altered perception of time. Some users also report the “geometrization” of three-dimensional objects, which appear flat and distorted.

Potential Risks and Side Effects: Mescaline can cause nausea and vomiting.

Therapy: Research suggests that mescaline could be effective in combination with therapy for treating addiction to alcohol and other drugs as well as reducing the effects of anxiety and depression.

Legality: In the United States, mescaline is listed in Schedule I of the Controlled Substances Act, making it illegal to use recreationally or in therapy outside of specially approved research settings. However, there are exemptions, and some Indigenous communities are permitted to use mescaline in connection with traditional religious practices.

Notable Studies:

• There are multiple reports of success using peyote to treat alcoholism among Native American Church members.
• A survey of mescaline users found the compound is associated with decreases in anxiety, depression, and substance abuse.

LSD

Other names:

• Acid
• Diethylamide
• L
• LSD-25
• Lysergic acid

Basics: LSD is a synthetic substance derived from ergot, a fungus that grows on rye and other cereal grains. LSD is usually ingested orally as drops of a liquid solution or through small squares of paper (“blotter”) containing the drug. The onset of noticeable effects begin after some twenty to forty minutes, depending on the dose and the person, and the experience lasts from eight to twelve hours.

History: The drug, first created in 1938, was the twenty-fifth in a series of compounds synthesized by the Swiss chemist Albert Hofmann, who was synthesizing chemicals that might have useful effects on circulation for the pharmaceutical company Sandoz Laboratories. However, it wasn’t until 1943, after he accidentally ingested some of his creation, that Hofmann realized the substance had psychoactive properties. In 1947, Sandoz dubbed the compound Delysid and began distributing it as an experimental psychiatric drug.

In the 1950s and ’60s, scientists studied whether LSD could be used to treat alcohol addiction and trauma. The U.S. government also launched a secret operation called MK-ULTRA, which covertly studied whether LSD could be used as a truth serum or mind-control agent, administering high doses to civilians, soldiers, and prisoners, often without their knowledge or consent. LSD was embraced by the counterculture of the 1960s, and in 1970 was classified as a Schedule I drug, effectively halting most human research into the drug’s therapeutic potential until the 1990s.

Potential Benefits: Responses to LSD vary but often the drug induces a sense of bliss, openness, and trust. It alters the perception of time, causes audiovisual synesthesia, and at higher doses can lead to mystical experiences. Some users also report having flashbacks in the days, weeks, or years after taking LSD.

Potential Risks and Side Effects: LSD can moderately increase heart rate, blood pressure, and body temperature. 

Therapy: Research suggests that LSD combined with therapy can be effective at reducing anxiety for people with a life-threatening illness, and for treating alcoholism, obsessive-compulsive disorder, and cluster headaches.

Microdosing: Ongoing studies are investigating whether microdosing—taking small amounts that don’t cause perceptual changes—could help treat chronic pain, depression, and inflammation caused by neurodegenerative diseases, but there is debate about whether the apparent benefits of microdosing are due to LSD or to the placebo effect.

Legality: In the United States, LSD is listed in Schedule I of the Controlled Substances Act, making it illegal outside of specially approved research settings.

Notable Studies:

• A review of twenty-five years of clinical trials for LSD, psilocybin, and ayahuasca-assisted therapy.
• Imaging shows how LSD affects brain activity.
• LSD has been used to help treat end-of-life anxiety in terminally ill patients.
• Research into how LSD affects creativity.
• How LSD and other psychedelics may affect the brain’s glutamate system, increasing neuroplasticity.

5-MeO-DMT

Other names:

• Bufo
• God molecule
• The Toad

Basics: 5-MeO-DMT is short for 5-methoxy-N,N-dimethyltryptamine. It’s found in several plants and in high concentrations in the secretion of the toad Bufo alvarius. It’s also possibly produced by the human body and has been found in human blood, urine, and cerebrospinal fluid. It’s usually inhaled through vaporizing or snorting. Like DMT, the experience is quick, starting just a few seconds after ingestion and lasting about twenty to thirty minutes. (Snorted material comes on a bit slower and can last a bit longer.)

History: There is evidence that Indigenous people have used 5-MeO-DMT for thousands of years, ingesting it through snuffs. The compound was first synthesized in 1936 by Japanese chemists Toshio Hoshino and Kenya Shimodaira.

It wasn’t until the mid-1980s that toad secretions became a popular source for this psychedelic compound. Recently, some scholars have worried that renewed demand for 5-MeO-DMT has put pressure on the Sonoran Desert toad population, which is already in decline. There is also concern about the cruelty of harvesting 5-MeO-DMT from toads; because the compound is secreted as a defense mechanism only when the amphibians are in stressful or dangerous situations, some herpetologists say there is no humane way to collect the secretion. 5-MeO-DMT can also be synthesized in the lab, although there is debate over whether the synthesized substance occasions different effects.

Potential Benefits: 5-MeO-DMT induces feelings of awe, visual and auditory hallucinations, and other sensations similar to other classic psychedelics.

Potential Risks and Side Effects: 5-MeO-DMT is sometimes paired with MAOIs, a class of antidepressants, which can make the experience longer and more intense. However, this combination can be dangerous, causing abnormally high body temperature and, in some cases, death.

In addition to effects shared with other classic psychedelics, some users have reported an empty or void experience similar to sensory deprivation. There are also reports of fear, shaking, and profound terror.

Therapy: Anecdotal reports and early studies suggest 5-MeO-DMT could help treat anxiety and depression, but further research is needed to determine its safety and effectiveness.

Legality: In the United States, 5-MeO-DMT is listed in Schedule I of the Controlled Substances Act. It’s illegal to use it recreationally or in therapy outside of specially approved research settings.

Notable Studies:

• There have been self-reported improvements in anxiety and depression after using 5-MeO-DMT.
• One study found evidence that 5-MeO-DMT causes structural changes in human brain cells that may inhibit neurodegeneration.
• A study measured the intensity of mystical experiences with 5-MeO-DMT compared to those with psilocybin.

DMT

Other names:

• spirit molecule
• Dimitri
• businessman’s trip
• elf spice

Basics: N,N-dimethyltryptamine (DMT) is a naturally occurring compound commonly found in plant and animal tissue. It’s one of only a few hallucinogens that’s naturally present in the human body, although its biological purpose is unclear.

DMT can be ingested in its chemical form by vaporizing and inhaling it or by intravenously injecting it. Both methods bypass the digestive system to reach the brain more rapidly, allowing DMT to take effect almost instantly.

The effects of DMT last only twenty to thirty minutes. Because the trip is so short, DMT has been called the “businessman’s trip” or “businessman’s lunch.”

History: DMT is a central component of ayahuasca, which Indigenous people in the Amazon basin have used for religious, divinatory, or medical purposes for over a thousand years. It was first synthesized in 1931 by the Canadian chemist Richard Manske, but it wasn’t until 1956 that chemist Stephen Szára reported that DMT occasions psychedelic experiences similar to those of LSD. In 1990, Rick Strassman, a psychiatry professor at the University of New Mexico, received the first new approval from the U.S. government in decades to run human trials with DMT. Over the course of five years, Strassman supervised more than four hundred DMT sessions with sixty participants.

Potential Benefits: DMT’s effects are similar to those of other hallucinogens, including possible mystical-type encounters. At least one study found that “God-encounter experiences” were reported more often with DMT than with psilocybin or LSD.

Potential Risks and Side Effects: DMT can increase heart rate and blood pressure.

Therapy: Although the acute drug experience is short, research suggests that DMT can have significant impacts. Studies show that it could play a role in neuroregeneration, that it reduces chronic inflammation in the central nervous system, and that it may help in treating Alzheimer’s disease. There is a lack of research assessing the therapeutic potential of DMT, though some studies have shown it reduced anxiety and depression in rats.

Legality: In the United States, DMT is listed in Schedule I of the Controlled Substances Act. It’s illegal to use it recreationally or in therapy outside of specially approved research settings.

Notable Studies:

• In the 1990s, Rick Strassman conducted a number of studies assessing the subjective effects and psychopharmacology of DMT.
• The link between DMT and sigma one receptors may help explain how DMT affects the brain and body. It may also mean that by activating these receptors DMT can be neuroprotective.

Ayahuasca

Other names:

• Chacruna (for the Psychotria viridis plant)
• Hoasca (tea)
• Yajé 

Basics: Ayahuasca is the Quechua name for a vine, Banisteriopsis caapi, and also for a brew made by combining the vine with leaves of plants, usually the Amazonian shrub Psychotria viridis, which contains N,N-dimethyltryptamine (DMT). On its own, DMT won’t produce psychedelic effects if taken orally, because the molecule is deactivated primarily in the gut by an enzyme called monoamine oxidase. But Banisteriopsis caapi contains monoamine oxidase inhibitors (MAOIs), which keep that enzyme from destroying DMT, allowing the psychoactive molecules to reach the brain. The effect profile of ayahuasca overlaps with that of the classic psychedelics generally. For some people, there is an enhanced likelihood of visions. The experience usually begins about thirty minutes after drinking the tea and continues for roughly four hours.

History: Ayahuasca has been used for over a thousand years by Indigenous people in Brazil, Peru, Bolivia, Colombia, and Ecuador in shamanic practices and to help with the diagnosis or treatment of various medical, psychological, or spiritual conditions.

In the twentieth century, the Santo Daime and the União do Vegetal religions emerged in Brazil. These syncretic traditions, which fuse aspects of Indigenous religions with Christianity, mysticism, and other influences, use ayahuasca as a sacrament during ceremonies.

Potential Benefits: Like other classic psychedelics, ayahuasca can cause visual and auditory distortions or changes; hypersensitivity to touch, light, and sound; an altered or slowed perception of time; and synesthesia.

Potential Risks and Side Effects: Ayahuasca can cause shaking, vomiting, and diarrhea and can significantly raise blood pressure. It can have adverse reactions with medications including selective serotonin reuptake inhibitors. It has also been shown to exacerbate psychiatric disorders, including schizophrenia.

Therapy: Research suggests that ayahuasca could be used in carefully structured settings to treat addiction, depression, and anxiety. Some users report that after taking ayahuasca they feel more creative, loving, and empathetic; see improvement in their memory and concentration; and generally have a more positive mood. Long-term use of ayahuasca has been shown to produce changes in brain chemistry and personality.

Legality: Ayahuasca therapy and ayahuasca use are illegal in the United States because DMT, its main active ingredient, is a Schedule I controlled substance, though exemptions under the Religious Freedom Restoration Act have been granted. A 2006 Supreme Court decision cleared the way for the União do Vegetal to use ayahuasca in its religious practices. In 2009, an Oregon judge granted a similar exemption to Church of the Holy Light of the Queen, an Ashland, Oregon, congregation in the Santo Daime tradition.

Notable Studies:

• A small, double-blind, randomized, placebo-controlled trial found that in an appropriate setting, ayahuasca can cause significant and rapid positive improvement in patients with treatment-resistant depression.
• A larger, meta-review that found psilocybin, ayahuasca, and LSD could be effective treatments for drug dependence and anxiety and mood disorders.
• Interviews with Western mental health professionals and Indigenous healers who both use ayahuasca suggest ayahuasca can help treat addiction and a survey found ayahuasca users reported less problematic alcohol consumption.
• A study on the long-term effects of ayahuasca found that it may enhance neuroplasticity and structurally change parts of the default mode network.

Psilocybin

Other names:

• Magic mushrooms
• Mushrooms
• Shrooms

Basics: Psilocybin is a naturally occurring chemical compound found in more than one hundred mushroom species. It is usually consumed orally by eating either dried or fresh mushrooms, adding them to food or tea, or by taking a capsule of its dried material. It usually takes under an hour for the psychedelic effects to become noticeable, and the experience usually peaks one to three hours later. The entire trip can last six to eight hours.

History: Indigenous communities in Mexico and Central America have used psilocybin-containing mushrooms in celebrations, healing rituals, and religious ceremonies for millennia. In the 1950s and ’60s, psychiatrists investigated the therapeutic potential of psilocybin, though less extensively than LSD. In the United States, most human psychedelic research halted in 1971 after President Nixon’s Controlled Substances Act—Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970—went into effect, designating psilocybin as a Schedule I drug.

In 2000, researchers at Johns Hopkins University received federal and institutional approvals to give psilocybin to human volunteers who had never taken a psychedelic, leading to the landmark 2006 publication “Psilocybin Can Occasion Mystical-type Experiences Having Substantial and Sustained Personal Meaning and Spiritual Significance.”

Potential Benefits: Like other classic psychedelics, psilocybin can cause visual and auditory distortions or changes; hypersensitivity to touch, light, and sound; an altered or slowed perception of time; and synesthesia.

Potential Risks and Side Effects: Psilocybin can cause nausea, vomiting, headache, and can increase heart rate and blood pressure.

Therapy: Studies have suggested that in combination with therapy psilocybin can be used to alleviate anxiety and depression in cancer patients, substance abuse disorders, and post-traumatic stress disorder.Researchers are also investigating the use of psilocybin to treat anorexia nervosa and neurodegenerative diseases like Alzheimer’s and dementia. In some research volunteers, psilocybin has been shown to increase nature relatedness and overall well-being and life satisfaction.

Microdosing: There is a belief that taking small, sub-perceptual amounts of psilocybin can improve cognitive function, mental and physical well-being, and creativity. Other anecdotal evidence suggests that microdosing can be used to manage pain from migraines and cluster headaches. However, data on the effectiveness of microdosing is mixed and the possible side effects are unknown.

Legality: In the United States, psilocybin is listed in Schedule I of the Controlled Substances Act, making it illegal outside of specially approved research settings, though some states including Oregon, Rhode Island, and New Jersey, as well as municipalities including Denver, Oakland, and Detroit, have decriminalized it or deprioritized the local enforcement of laws against it.

Psilocybin services (which, according to Oregon law, must not include diagnosis or treatment of mental health conditions), are now legal at the state level, while according to federal law, those services remain illegal even in Oregon. In other states, some patients can receive this therapy by participating in federally approved clinical trials.

Notable Studies:

• A meta-review of evidence suggesting psilocybin could be used to treat many conditions, including alcoholism.
• A randomized clinical trial testing psilocybin-assisted therapy for depression.
• Brain scans suggest that psilocybin-assisted therapy can promote cognitive and neural flexibility in people with severe depression. Another study shows that this therapy changes which areas of the brain are active.
• A large survey of the enduring positive and negative effects of psilocybin on users.