What is LSD?

Lysergic acid diethylamide (LSD) is a potent hallucinogen that has a high potential for abuse and currently has no accepted medical use in treatment in the United States.

Street Names

Acid, Blotter Acid, Dots, Mellow Yellow, Window Pane

How is it abused?

LSD is available in saturated absorbent paper (e.g., blotter paper, divided into small, decorated squares, with each square representing one dose), tablets or “micro dots,” saturated sugar cubes, or in a liquid form. LSD is abused orally.

What is its effect on the body?

Dilated pupils, higher body temperature, increased heart rate and blood pressure, sweating, loss of appetite, sleeplessness, dry mouth, and tremors. While under the influence, the user may suffer impaired depth and time perception accompanied by: distorted perception of shape and size of objects, movements, colors, sound, touch, and the user’s own body image. The ability to make sound judgments and see common dangers is impaired, making the user susceptible to personal injury. It is possible for users to suffer acute anxiety and depression after an LSD “trip.” Hallucinogen Persisting Perception Disorder, which may include fragmentary recurrences of certain aspects of the drug experience or “flashbacks” have been reported days, and even months, after taking the last dose.

What are its overdose effects?

Longer, more intense “trip” episodes may occur with larger doses. Serious psychological harm can occur after administration, including fear, depression, anxiety, and paranoia, and can be long-lasting. Death after LSD use is rare.

An artistic representation of LSD (in blue) fitting into a serotonin receptor (the white ribbon).Bryan Roth

Lysergic acid diethylamide, or LSD, can alter perception (awareness of surrounding objects and conditions), thoughts, and feelings. It can also cause hallucinations—sensations and images that seem real even though they’re not. These “trips” can last many hours, long after LSD has been cleared from the bloodstream.

LSD was first synthesized in 1938, and its hallucinogenic effects discovered soon afterward. However, how the compound causes its effects in the brain hasn’t been well understood. LSD is a member of a class of drugs called ergolines, which are used to treat many conditions, including migraine headaches and Parkinson’s disease. Understanding how the compound exerts its unique effects could provide insights to guide the development of future therapeutics.

LSD interacts with proteins on the surface of brain cells called serotonin receptors. Serotonin is a chemical messenger that helps brain cells communicate. LSD appears to act through a particular receptor called 5-HT_2AR. To gain insights into LSD’s effects, a research team led by Dr. Bryan Roth at the University of North Carolina crystallized a related receptor, 5-HT_2BR, attached to LSD. The scientists used x-ray crystallography to visualize the structure. Their study was supported by NIH’s National Institute of Mental Health (NIMH). Results were published on January 26, 2017, in Cell.

Serotonin receptors activate 2 major signaling pathways within cells: through G-proteins and through β-arrestins. The researchers found that LSD binds its receptor in a way that causes it to act mostly through the β-arrestin pathway instead of the G-protein pathway. Related ergoline compounds, the scientists found, differ in the way they structurally interact with the receptor. Further laboratory experiments and computer analyses revealed that these distinct but similar compounds can shape the structure of the receptor to trigger different effects.

The team also found that the serotonin receptor closes a “lid” over the LSD molecule, preventing it from quickly detaching. This likely explains the drug’s long-lasting effects. A mutant form of the receptor with a weaker lid had reduced β-arrestin pathway activity, while leaving G-protein pathway activity unaffected.

“This study sheds light on the mechanism of psychoactive drug action, including how certain drugs activate one signaling pathway inside cells while avoiding another,” explains Dr. Laurie Nadler, chief of NIMH’s Neuropharmacology Program. “Taken together with other recent studies of drug-receptor complexes, this work provides proof-of-concept for the design of drugs with desired signaling properties and fewer undesired side-effects.”

Roth and other colleagues recently showed the potential of such structure-based design. Based on similar discoveries about an opioid receptor, they created a molecule that effectively alleviates pain in mice, but with fewer side effects than morphine.

A hallucinogen manufactured from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains. LSD is an abbreviation of the scientific name lysergic acid diethylamide.

How Do Hallucinogens Work?

Classic hallucinogens are thought to produce their perception-altering effects by acting on neural circuits in the brain that use the neurotransmitter serotonin (Passie, 2008; Nichols, 2004; Schindler, 2012; Lee, 2012). Specifically, some of their most prominent effects occur in the prefrontal cortex—an area involved in mood, cognition, and perception—as well as other regions important in regulating arousal and physiological responses to stress and panic.

What Are the Short-Term Effects of Hallucinogens?

Ingesting hallucinogenic drugs can cause users to see images, hear sounds, and feel sensations that seem real but do not exist. Their effects typically begin within 20 to 90 minutes of ingestion and can last as long as 12 hours. Experiences are often unpredictable and may vary with the amount ingested and the user’s personality, mood, expectations, and surroundings. The effects of hallucinogens like LSD can be described as drug-induced psychosis—distortion or disorganization of a person’s capacity to recognize reality, think rationally, or communicate with others. Users refer to LSD and other hallucinogenic experiences as “trips” and to acute adverse or unpleasant experiences as “bad trips.” On some trips, users experience sensations that are enjoyable and mentally stimulating and that produce a sense of heightened understanding. Bad trips, however, include terrifying thoughts and nightmarish feelings of anxiety and despair that include fears of losing control, insanity, or death.

Like LSD and psilocybin, DMT produces its effects through action at serotonin (5-HT) receptors in the brain (Strassman, 1996). Some research has suggested that DMT occurs naturally in the human brain in small quantities, leading to the hypothesis that release of endogenous DMT may be involved in reports of alien abductions, spontaneous mystical experiences, and near-death experiences, but this remains controversial (Barker, 2012).

Specific short-term effects of LSD, psilocybin, peyote, DMT, and ayahuasca include:

LSD

• Increased blood pressure, heart rate, and body temperature
• Dizziness and sleeplessness
• Loss of appetite, dry mouth,and sweating
• Numbness, weakness, and tremors
• Impulsiveness and rapid emotional shifts that can range from fear to euphoria, with transitions so rapid that the user may seem to experience several emotions simultaneously

Psilocybin

• Feelings of relaxation (similar to effects of low doses of marijuana)
• Nervousness, paranoia, and panic reactions
• Introspective/spiritual experiences
• Misidentification of poisonous mushrooms resembling psilocybin could lead to unintentional, potentially fatal poisoning

Peyote

• Increased body temperature and heart rate
• Uncoordinated movements (ataxia)
• Profound sweating
• Flushing

DMT

• Increased heart rate
• Agitation
• Hallucinations frequently involving radically altered environments as well as body and spatial distortions

Ayahuasca

• Increased blood pressure
• Severe vomiting (induced by the tea)
• Profoundly altered state of awareness and perceptions of otherworldly imagery

Short-Term General Effects of Hallucinogens

Sensory Effects

• Hallucinations, including seeing, hearing, touching, or smelling things in a distorted way or perceiving things that do not exist
• Intensified feelings and sensory experiences (brighter colors, sharper sounds)
• Mixed senses (“seeing” sounds or “hearing” colors)
• Changes in sense or perception of time (time goes by slowly)

Physical Effects

• Increased energy and heart rate
• Nausea

What Are the Long-Term Effects of Hallucinogens?

LSD users quickly develop a high degree of tolerance to the drug’s effects, such that repeated use requires increasingly larger doses to produce similar effects. Use of hallucinogenic drugs also produces tolerance to other drugs in this class, including psilocybin and peyote. Use of classic hallucinogens does not, however, produce tolerance to drugs that do not act directly on the same brain cell receptors. In other words, there is no cross-tolerance to drugs that act on other neurotransmitter systems, such as marijuana, amphetamines, or PCP, among others. Furthermore, tolerance for hallucinogenic drugs is short-lived—it is lost if the user stops taking the drugs for several days—and physical withdrawal symptoms are not typically experienced when chronic use is stopped.

The long-term residual psychological and cognitive effects of peyote remain poorly understood. Although one study found no evidence of psychological or cognitive deficits among Native Americans who use peyote regularly in a religious setting, those findings may not generalize to those who repeatedly abuse the drug for recreational purposes (Halpern, 2005). Peyote users may also experience hallucinogen persisting perception disorder (HPPD)—also often referred to as flashbacks. The active ingredient mescaline has also been associated, in at least one report, to fetal abnormalities (Gilmore, 2001).

Long-term effects of DMT use and abuse and addiction liability are currently unknown. Unlike most other hallucinogens, DMT does not appear to induce tolerance (Winstock, 2013).

As with some other hallucinogens, there is little information to suggest that ayahuasca use creates lasting physiological or neurological deficits, especially among those using the brew for religious activities.

Overall, two long-term effects—persistent psychosis and HPPD—have been associated with use of classic hallucinogens (see text box below). Although occurrence of either is rare, it is also unpredictable and may happen more often than previously thought, and sometimes both conditions occur together. While the exact causes are not known, both conditions are more often seen in individuals with a history of psychological problems but can happen to anyone, even after a single exposure. There is no established treatment for HPPD, in which flashbacks may occur spontaneously and repeatedly although less intensely than their initial occurrence. Some antidepressant and antipsychotic drugs can be prescribed to help improve mood and treat psychoses, however. Psychotherapy may also help patients cope with fear or confusion associated with visual disturbances or other consequences of long-term LSD use. More research on the causes, incidence, and long-term effects of both disorders is being conducted.

Long-Term Effects of Hallucinogens

Persistent psychosis

• Visual disturbances
• Disorganized thinking
• Paranoia
• Mood disturbances

Hallucinogen Persisting Perception Disorder (HPPD)

• Hallucinations
• Other visual disturbances (such as seeing halos or trails attached to moving objects)
• Symptoms sometimes mistaken for neurological disorders (such as stroke or brain tumor)

Classic Hallucinogens*

LSD (d-lysergic acid diethylamide)—also known as acid, blotter, doses, hits, microdots, sugar cubes, trips, tabs, or window panes—is one of the most potent mood- and perception-altering hallucinogenic drugs. It is a clear or white, odorless, water-soluble material synthesized from lysergic acid, a compound derived from a rye fungus. LSD is initially produced in crystalline form, which can then be used to produce tablets known as “microdots” or thin squares of gelatin called “window panes.” It can also be diluted with water or alcohol and sold in liquid form. The most common form, however, is LSD-soaked paper punched into small individual squares, known as “blotters.”

Psilocybin(4-phosphoryloxy-N,N-dimethyltryptamine)—also known as magic mushrooms, shrooms, boomers, or little smoke—is extracted from certain types of mushrooms found in tropical and subtropical regions of South America, Mexico, and the United States. In the past, psilocybin was ingested during religious ceremonies by indigenous cultures from Mexico and Central America. Psilocybin can either be dried or fresh and eaten raw, mixed with food, or brewed into a tea, and produces similar effects to LSD.

Peyote (Mescaline)—also known as buttons, cactus, and mesc—is a small, spineless cactus with mescaline as its main ingredient. It has been used by natives in northern Mexico and the southwestern United States as a part of religious ceremonies. The top, or “crown,” of the peyote cactus has disc-shaped buttons that are cut out, dried, and usually chewed or soaked in water to produce an intoxicating liquid. Because the extract is so bitter, some users prepare a tea by boiling the plant for several hours. Mescaline can also be produced through chemical synthesis.

DMT (Dimethyltryptamine)—also known as Dimitri—is a powerful hallucinogenic chemical found naturally occurring in some Amazonian plant species (see “Ayahuasca”) and also synthesized in the laboratory. Synthetic DMT usually takes the form of a white crystalline powder and is typically vaporized or smoked in a pipe.

Ayahuasca—also known as hoasca, aya, and yagé—is a hallucinogenic brew made from one of several Amazonian plants containing DMT (the primary psychoactive ingredient) along with a vine containing a natural alkaloid that prevents the normal breakdown of DMT in the digestive tract. Ayahuasca tea has traditionally been used for healing and religious purposes in indigenous South American cultures, mainly in the Amazon region.

Dissociative Drugs

PCP (Phencyclidine)—also known as ozone, rocket fuel, love boat, hog, embalming fluid, or superweed—was originally developed in the 1950s as a general anesthetic for surgery. While it can be found in a variety of forms, including tablets or capsules, it is usually sold as a liquid or powder. PCP can be snorted, smoked, injected, or swallowed. It is sometimes smoked after being sprinkled on marijuana, tobacco, or parsley.

Ketamine—also known as K, Special K, or cat Valium—is a dissociative currently used as an anesthetic for humans as well as animals. Much of the ketamine sold on the street has been diverted from veterinary offices. Although it is manufactured as an injectable liquid, ketamine is generally evaporated to form a powder that is snorted or compressed into pills for illicit use. Because ketamine is odorless and tasteless and has amnesia-inducing properties, it is sometimes added to drinks to facilitate sexual assault.

DXM (Dextromethorphan)—also known as robo—is a cough suppressant and expectorant ingredient in some over-the-counter (OTC) cold and cough medications that are often abused by adolescents and young adults. The most common sources of abused DXM are “extra-strength” cough syrup, which typically contains around 15 milligrams of DXM per teaspoon, and pills and gel capsules, which typically contain 15 milligrams of DXM per pill. OTC medications that contain DXM often also contain antihistamines and decongestants.

Salvia divinorum—also known as diviner’s sage, Maria Pastora, Sally-D, or magic mint—is a psychoactive plant common to southern Mexico and Central and South America. Salvia is typically ingested by chewing fresh leaves or by drinking their extracted juices. The dried leaves of salvia can also be smoked or vaporized and inhaled.

*In this report, the term “hallucinogen” will refer to the classic hallucinogenic drugs LSD and Psilocybin.

A hallucinogen is one of a class of drugs that results in profound alterations in sensory and perceptual experiences (Figure 4.18). In some cases, users experience vivid visual hallucinations. It is also common for these types of drugs to cause hallucinations of body sensations (e.g., feeling as if you are a giant) and a skewed perception of the passage of time.

Figure 4.18 Psychedelic images like this are often associated with hallucinogenic compounds. (credit: modification of work by "new 1lluminati"/Flickr)

As a group, hallucinogens are incredibly varied in terms of the neurotransmitter systems they affect. Mescaline and LSD are serotonin agonists, and PCP (angel dust) and ketamine (an animal anesthetic) act as antagonists of the NMDA glutamate receptor. In general, these drugs are not thought to possess the same sort of abuse potential as other classes of drugs discussed in this section.

Drugs and Their Effects