Salvia divinorum

Salvia divinorum

Other names:

  • Diviner’s sage
  • Maria Pastora
  • Sally-D
  • Salvia

Salvia divinorum is a perennial herb native to regions in Oaxaca, Mexico. The Mazatec people indigenous to the area have used its leaves for centuries as a treatment for illnesses, including headaches and gastrointestinal problems, and as part of their divinatory and spiritual practices.

The method of consumption can affect the duration of the experience. Traditionally, the Mazatec consumed salvia by rolling fresh leaves into a thick wad and chewing or sucking on it, absorbing it through their cheeks, which results in a milder and longer-lasting experience. The Mazatec would also grind the leaves and mix them into a drinkable infusion. 

Over the last decade, salvia has become more popular as a recreational drug. Users typically vaporize the dried, crushed leaves of the salvia through a pipe or bong, which causes a nearly immediate, intense hallucinogenic experience that lasts only fifteen to twenty minutes. Users also drop a small amount of salvia-containing tincture under the tongue. This method takes up to ten minutes to produce effects, but the entire experience can be prolonged for up to two hours.

Studies on participants who smoked salvia report intense visual and auditory effects similar to those of LSD and psilocybin, though with unusual hallmarks, such as feeling like a two-dimensional shape or perceiving the world as flat, like a coat of paint. At higher doses it also caused participants to disconnect from reality and dissociate, reducing their ability to control or feel their bodies.

Salvinorin-A has been identified as the primary psychoactive chemical in Salvia divinorum. Unlike LSD and other classic hallucinogens, salvinorin-A doesn’t act on serotonin receptors. Instead, salvinorin-A interacts with kappa-opioid receptors, which play a role in pain perception. For this reason, researchers hypothesize that derivatives of this molecule might be useful in the treatment of disorders characterized by perceptual distortions, like schizophrenia and bipolar disorder.

Researchers have also conducted pre-clinical exploration of salvinorin-A and other chemical derivatives based on it for the treatment of cocaine abuse.

In the United States, Salvia divinorum and salvinorin-A are not federally controlled substances but are illegal in some states.

MDMA

MDMA

Other names:

  • Adam
  • E
  • Ecstasy
  • Molly
  • X
  • XTC

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic drug first made in 1912 by the German pharmaceutical company Merck. It was used as an intermediate chemical in making a drug intended to stop blood loss. At that time, MDMA itself was not tested pharmacologically.

In 1977, the chemist and psychedelics pioneer Alexander “Sasha” Shulgin introduced the drug to Leo Zeff, a psychotherapist and also an early proponent of psychedelics in therapy. Over the next twelve years, Zeff treated more than 4,000 patients with MDMA and trained 150 therapists to use it in their work.

During the 1980s, MDMA became a popular recreational drug at nightclubs and raves. In 1985, the Drug Enforcement Administration placed MDMA on the list of Schedule I controlled substances, effectively stalling research into its therapeutic potential.

Users typically consume MDMA orally in a pill or capsule and begin to feel its effects thirty to forty-five minutes later. MDMA is known as an empathogen because while it does alter mood and has some psychedelic qualities, its effect profile differs significantly from that of the classic psychedelics. Rather than mystical-type experiences, MDMA produces a mellower experience during which people feel more empathic, more open to bonding with others, and better able to process emotional or traumatic memories. The entire experience lasts about three to four hours.

MDMA interacts with neuronal connections (synapses) and causes the release of serotonin, norepinephrine, and dopamine neurotransmitters, with the largest effect being on serotonin. The transient increase in the actions of these neurotransmitters in the brain impacts arousal, attention, emotion, and memory.  MDMA also activates the sympathetic branch of the autonomic nervous system, causing transient increases in heart rate and blood pressure.

In 2011, researchers published the results of the first clinical trial that showed MDMA could be used alongside therapy to treat post-traumatic stress disorder. Subsequent studies suggest it’s also effective at reducing social anxiety in autistic adults and in people with life-threatening illnesses, eating disorders, and substance-abuse disorders.

In 2021, researchers in the United States, Canada, and Israel published the results of a phase III clinical trial using MDMA-assisted therapy to treat post-traumatic stress disorder. The trial studied ninety participants and found that the treatment was safe and that for the majority of participants who received it, MDMA relieved many, or in some cases most, of their symptoms. 

In the United States, MDMA 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.

Ketamine

Ketamine

Other names:

  • K
  • Special K

Ketamine, a synthetic drug not known to occur in nature, was first synthesized in 1962. In 1970, the Food and Drug Administration approved the medicine, trade-named Ketalar, for use as an anesthetic.

Ketamine is used widely as an anesthetic, especially for children and soldiers, and as an animal tranquilizer. It is also sometimes used to treat chronic pain. At lower doses, ketamine can alter one’s perception and sense of time and space. At higher doses, the drug can cause a dissociative state, sometimes called a “k-hole,” during which people experience oblivion and are unable to perceive or interact with the outside world. These effects have some overlap with the general effect profile of classic psychedelics.

Clinically, ketamine is administered intravenously, by intramuscular injection, or as a lozenge placed under the tongue. Outside of medical settings, powdered ketamine is also snorted.

In the 1970s, use of ketamine recreationally or as a tool for personal exploration began to increase. It was popularized in books like The Scientist by John Lilly and Journeys into the Bright World by Marcia Moore and Howard Alltounian.

The leading theory about how ketamine works is that it acts on receptors for the neurotransmitter glutamate, which may play a role in regulating mood. Over the last twenty years, numerous studies have suggested that ketamine can be used to treat chronic depression, bipolar depression, obsessive compulsive disorder, anxiety, and post-traumatic stress disorder. Some participants in clinical trials reported side effects including headache, dizziness, nausea, blurred vision, drowsiness, and poor memory, but these resolved quickly after treatment sessions. Prolonged ketamine exposure has been associated with neurodegeneration in newborn rhesus monkeys. Some people become addicted to ketamine, which can be very difficult to overcome.

In the United States, ketamine is a Schedule III drug, meaning that it is legal when prescribed for medical use as an anesthetic. It can also be prescribed legally for off-label use, like for the treatment of depression. In 2019, the FDA approved Spravato, delivered as a nasal spray made from esketamine, half of the mirror image of ketamine, for use in treating treatment-resistant depression or TRD. Because it is under patent, the price of Spravato can be hundreds of times the price of generic ketamine.

Licensed providers can legally offer ketamine-assisted therapy.

Ibogaine

Ibogaine

Ibogaine is a naturally occurring psychoactive compound found in the root bark of the Tabernanthe iboga, a shrub native to Central and West Africa. For centuries, members of the Bwiti religion have used iboga as a sacrament in rituals to bind themselves across time with their ancestors and descendants or with each other through a shared experience of consciousness. It is still used today by the Gabonese Fang people in religious ceremonies and as a stimulant and appetite suppressant.

Purified ibogaine hydrochloride was first introduced to European consumers in 1939 under the name Lambarène. It was sold in France until around 1970 as an antidepressant that could improve mood and physical strength, and was used by athletes and those recovering from illness. In his 1973 book The Healing Journey, Chilean psychiatrist Claudio Naranjo described his experiences taking ibogaine and other psychedelics and their therapeutic uses.

How ibogaine works in the brain is not well understood. It interacts with numerous neurotransmitters in the central nervous system, including components of the acetylcholine, serotonin, dopamine, glutamate, and opioid systems. Its effects are prolonged, beginning half an hour to three hours after ingestion and peaking after eighteen to thirty-six hours.

The experience is often described as being in a “waking dream.” At first users experience visual and sensory distortions. Some describe watching a panoramic readout or “slideshow” of past memories. Afterward, they report going through a period of reflection and having residual effects including heightened awareness, mild stimulation, and disturbed sleep for up to seventy-two hours. In high doses, ibogaine can induce intense hallucinations.

Ibogaine’s potential to interrupt drug addiction was first recognized in 1962 by Howard Lotsof, at the time a heroin addict who experimented with ibogaine. Since then, numerous studies have shown that ibogaine can help treat heroin, cocaine, and opioid withdrawal and addiction. 

However, ibogaine can be dangerous. There are numerous reports in the scientific literature of fatal cardiac events after taking ibogaine. Other side effects range from nausea and tremors to (less commonly) psychosis and mania to seizures and comas. Because ibogaine can affect the heartbeat, it can be particularly risky for people with preexisting cardiac problems or when mixed with other drugs. 

In the United States, ibogaine is listed in Schedule I of the Controlled Substances Act, making both ibogaine and ibogaine-assisted therapy illegal outside of specially approved research settings. Some ibogaine clinics operate in countries where ibogaine is not legal or is in a gray area, including Mexico and New Zealand; responsible providers give it only with close medical supervision that includes cardiac monitoring.

Mescaline

Mescaline

Other names:

  • Mescalito

Mescaline is found in several cacti including San Pedro and the spineless peyote. It has been used for many generations and has played a role in Indigenous religious ceremonies in North America for over five thousand years.

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.

Mescaline 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. 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. 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. However, 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. Now, 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.

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. 

LSD

LSD

Other names:

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

LSD is a synthetic substance derived from ergot, a fungus that grows on rye and other cereal grains. 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. It wasn’t until 1943, after accidentally ingesting 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 1960s, 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.

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. 

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. 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. 

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

5-MeO-DMT

5-MeO-DMT

Other names:

  • Bufo
  • God molecule
  • The Toad

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.

5-MeO-DMT was first synthesized in 1936 by Japanese chemists Toshio Hoshino and Kenya Shimodaira. 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.) The substance 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.

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.

Some worry 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 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. 

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.

DMT

DMT

Other names:

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

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 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.

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

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.”

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. It also has been shown to reduce anxiety and depression in rats.

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.

Ayahuasca

Ayahuasca

Other names:

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

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). This tea 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.

On its own, DMT won’t produce psychedelic effects if it’s 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, though with a greater likelihood of shaking, vomiting, and diarrhea. 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.

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.

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 (UDV), a Brazilian church, to use ayahuasca in its religious practices. In 2009, an Oregon judge granted a similar exemption to The Church of the Holy Light of the Queen, an Ashland, Oregon, congregation in the Santo Daime tradition.

Psilocybin

Psilocybin

Other names:

  • Magic mushrooms
  • Mushrooms
  • Shrooms

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.

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 1960s, 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.” Since then, 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.

In a 2016 survey study, nearly two thousand respondents reported effects associated with their worst “bad trip” on psilocybin mushrooms. Eleven percent said they had put themselves or others at risk of physical harm, and 8 percent said they had sought treatment for enduring psychological symptoms at least a year after their trip. The survey also found that three cases appeared associated with the onset of enduring psychotic symptoms and three others with attempted suicide. Despite the negative effects, 84 percent of respondents reported that they benefited from the challenging aspects of their sessions.

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-assisted therapy is legal in Oregon. In other states, some patients can receive this therapy by participating in federally-approved clinical trials. (Learn more about clinical trials here.)

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