LSD (lysergic acid diethylamide) is thought to be an extensively researched hallucinogenic drug. It is extremely potent, illegal, and better known as “acid.” its effects have been described on a wide spectrum, from stimulating to mind-altering to “bad trips” and paranoia. Some people say it was life-changing for them, while others don’t notice any long-term impact. Read on to learn what scientific research says about LSD.
Disclaimer: LSD is classified as a Schedule I substance. This means that it is an illegal drug with high potential for harm and no known medical uses. We highly advise against the use of LSD until future studies determine its safety and efficacy in medically-supervised and safe settings. The only aim of this post is to outline research findings.
What is Lysergic Acid Diethylamide (LSD)?
Overview
Lysergic acid diethylamide (LSD) belongs to a class of drugs known as hallucinogens.
LSD is illegal. It is classified as a Schedule I drug under the Controlled Substances Act. Schedule I drugs are considered to have a high potential for abuse, no currently accepted medical use, and lack of accepted safety for use under medical supervision.
It is a clear white odorless material and has many other street names including Acid, Blotter, Dots, and Yellow Sunshine. It’s produced in illegal, clandestine labs. The purity of street-bought drugs like LSD is unknown. LSD is typically either swallowed or held under the tongue [1, 2].
LSD was first made by Albert Hofman in Switzerland in 1938 from ergotamine, a chemical from the fungus ergot that grows on rye and other grains. The psychoactive effects of LSD were discovered in 1943, and it was introduced as a drug for research purposes under the trade name “Delysid” in 1947 [3].
Possession of LSD was made illegal in the United States in 1968. And from 1971 until today, LSD remained classified as a Schedule I drug.
According to The National Survey on Drug Use and Health (NSDUH), more than 22 million people (9.1% of the population) have used LSD at least once in their lives [4].
Most people use LSD for recreational and social reasons. Some say they take it for “spiritual reasons,” hoping that an LSD “trip” will provide them with new insights about their life. However, the effects of LSD are highly unpredictable and can be a terrifying experience for certain people. A “bad trip” is sometimes described as “living hell” and it can cause serious side effects.
Some researchers think that while this drug is widely abused, it does not appear to be addictive. This is likely because many people avoid it after having a bad or unpredictable trip. However, the risk of addiction may be higher in people who suffer from polysubstance abuse disorder (abuse of various street drugs, usually at the same time) [5].
A research paper from 1968 states that tolerance to LSD develops rapidly in humans but is easily lost. Back then, they described withdrawal symptoms, including slight restlessness and irritability, as absent or mild [6].
However, recent research points to hallucinogen-persisting perception disorder (HPPD), which is when hallucinogenic effects, distorted perception, and flashbacks persist long after the “trip” is over. Although rare, HPPD is hard to treat and can lead to lifelong disability due to mental health disturbances [7, 8].
People say LSD intoxication may cause increased sensory perception and mental imagery, illusionary changes of perceived objects, synesthesia (to taste sounds, smell colors or see scents). They mention how emotions are intensified, thoughts accelerated and their scope usually broadened (including new associations and modified interpretation and meanings of relationships and objects).
Another aspect users mention is a weakening of ego identification. Various authors have compared the “psychedelic” state of consciousness to a daydream… but one that can quickly turn into a nightmare (see “The Doors of Perception: Heaven and Hell” from Aldous Huxley).
Recently, researchers have been investigating the effects of LSD and other psychedelics for end-of-life anxiety, post-traumatic stress disorder (PTSD), cancer, and addiction treatment. Despite some promising findings, no large-scale clinical trials have yet demonstrated their safety and efficacy [4].
Hoffman’s Story
Albert Hofmann first synthesized LSD in 1938. Allegedly, the main intention of the synthesis was to obtain a respiratory and circulatory stimulant. It was set aside for five years, until 1943, when Hofmann decided to reexamine it.
He said that, while re-synthesizing LSD, he accidentally absorbed a small quantity through his fingertips and thus discovered its effects.
He described what he felt as being:
“… affected by a remarkable restlessness, combined with a slight dizziness. At home, I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with an intense, kaleidoscopic play of colors. After some two hours, this condition faded away.”
Three days later, Hofmann performed a self-experiment to determine the effects of LSD, intentionally ingesting 250 micrograms of the substance, an amount he predicted to be a threshold dose (an actual threshold dose is 20 micrograms).
Less than an hour later, Hofmann experienced sudden and intense changes in perception. He asked his laboratory assistant to escort him home and, as the use of motor vehicles was prohibited because of wartime restrictions, they had to make the journey on a bicycle.
On the way, Hofmann’s condition rapidly deteriorated as he struggled with feelings of anxiety, alternating in his beliefs that the next-door neighbor was a malevolent witch, that he was going insane, and that the LSD had poisoned him. When the house doctor arrived, however, he could detect no physical abnormalities, save for a pair of incredibly dilated pupils. Hofmann was reassured, and soon his terror began to give way to a sense of good fortune and enjoyment, as he later wrote…
“… little by little I could begin to enjoy the unprecedented colors and plays of shapes that persisted behind my closed eyes. 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 …”
Hofmann considered that LSD may have value as a psychiatric tool; because of its intense and introspective nature, he couldn’t imagine anyone using it recreationally. He later summarized his thoughts about psychedelics, including LSD and psilocybin, in the book “LSD – My Problem Child”.
Mechanism
Studies suggest that LSD is an activator of serotonin receptors in the locus coeruleus (LC), the raphe nuclei (RN), and the cortex. The hallucinogenic effect of LSD has been linked to its affinity for the serotonin receptor [9].
According to some research, LSD at high doses decreases the dopaminergic neural activity in the ventral tegmental area, the main source of dopaminergic neurons in the brain implicated in the pathogenesis of psychosis [10].
LSD Areas of Research
The studies listed below are highly experimental. We summarized them with the aim of sharing the latest research with the general population. The existing studies should guide further investigation efforts. They should not be interpreted as supportive of any health benefit
Remember that LSD is still an illegal drug with high potential for harm. We highly advise against the use of LSD until future studies determine its safety and efficacy in medically-supervised and safe settings.
1) Anxiety and Pain in Terminally Ill Patients
LSD-assisted psychotherapy reduced anxiety associated with life-threatening diseases in one recent study of 12 advanced-stage cancer patients in a medically-supervised, safe environment. Treatment included drug-free psychotherapy sessions and two LSD-assisted psychotherapy sessions 2 to 3 weeks apart [11].
At the 2-month follow-up, anxiety was significantly reduced; no acute or chronic adverse effects persisted beyond 1 day after treatment or treatment-related serious adverse events. Anxiety reductions were sustained for 12 months. However, this study included only 12 people and no solid conclusions can be drawn from it [12].
Studies from the ‘60s suggested that LSD might reduce pain and improve sleep in cancer patients. However, these studies all suffer from methodological flaws and small sample sizes. None of their findings have been verified [13].
One research group recently postulated that LSD might reduce psychological pain in the terminally ill by breaking the cycle of anticipating pain and helping people cope with the fear of death. This theory, however, remains to be confirmed in large-scale studies [14].
2) Emotional Empathy, Sociality, and Suggestibility
In a recent within-subject, placebo-controlled study, healthy volunteers who were administered intravenous LSD (40 – 80 µg) gave a significantly higher rating for CIS (Creative Imagination Scale). These results suggested that LSD enhances the influence of suggestion, which may have implications in psychotherapy [15].
The authors of this study found that suggestions must be of sufficient duration and level of detail to be enhanced by the drug. Individuals with high trait conscientiousness were especially sensitive to the suggestibility-enhancing effects of LSD (implied) [16].
In a 2016 placebo-controlled, double-blind, random-order crossover study, 100 µg LSD in 24 subjects and 200 µg LSD in 16 subjects (25 – 65-year-old volunteers) produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy. Scientists hypothesize LSD acutely impaired fear recognition and enhanced emotional empathy and sociality [17].
However, no other recent studies looked into the effects of LSD on suggestibility, sociality, or empathy. The only remaining available studies are low-quality clinical experiments dating to the ’60s. Their findings are highly questionable and need to be explored in modern clinical trials.
In one study from the ‘60s involving 24 healthy participants, suggestibility was significantly enhanced by LSD and mescaline. In another similarly limiting study, LSD improved suggestibility in hospitalized patients with neurosis and schizophrenia, but less so in patients with depression [18, 19].
3) Alcohol and Drug Addiction
The hallucinogens like LSD for addiction is highly controversial. The risks of such practices are high and clinical data are sparse. A meta-analysis of controlled trials suggested that hallucinogens and high-dose LSD should be further studied in the treatment of addictions since they show some potential [20].
According to a 2012 quantitative meta-analysis of 536 participants and six trials, LSD may have some positive effects. However, large-scale controlled trials are lacking [21].
One study reviewed the use of LSD in the treatment of drug dependencies and the authors considered that it might help in the recovery of drug dependency – possibly involving a serotonin mechanism. This theory remains unproven [22].
4) Cluster Headaches
Surveys indicate that hallucinogens have been increasingly used by cluster headache patients outside of physician recommendation, mainly to abort a cluster period [23].
The use of hallucinogens for headaches is controversial, and only sporadic reports mention it. No proper clinical trials have been conducted [24].
According to a group of researchers who interviewed 53 cluster headache patients, 7 of 8 LSD users reported cluster period termination and 4 of 5 users reported an extension of no symptoms. No medically-valid information can be based on Interviews, as this method is unreliable and subjective [25].
5) Mood Disorders and Depression
According to one study, the recent behavioral and neuroimaging data suggest that psychedelics like LSD may modulate neural circuits that have been implicated in mood disorders. Some scientists believe they hold potential for reducing the clinical symptoms of these disorders, but clinical studies are lacking [26].
Researchers were interested in LSD’s potential mechanisms. In animal models, LSD affected serotonin in the brain (“re-balance of hippocampal 5-HT2/5-HT1A signaling”) [27].
6) Creativity
We don’t know how and if LSD affects creativity.
The only available findings are based on anecdotal experiments that were carried out in the ‘60s. Although interesting to some, no valid conclusions can be drawn from such experiments.
It was extremely easy to study LSD and other psychedelics back them, and researchers didn’t need any sort of approval.
One such scientist that gave LSD to artists at the time and claimed to have documented the process was Oscar Janiger, a California-based psychiatrist. In one study, Janiger gave LSD to a mixed group of 60 visual artists over a 7-year period. He said that the artists produced over 250 drawings that were demonstrated to be “improved” by LSD [13].
Aspects of the artists’ work that counted as “improved” were highly-subjective descriptions like more expressionism, sharpening color, greater freedom from prescribed mental sets, increased syntactical organization, deeper accessibility of past impressions, and a heightened sense of emotional excitement [13].
In another study from the 50s, a group of researchers claimed that LSD improved the work od graphic artists [28].
In a 1966 pilot study in a group of individuals engaged in various industries – like engineers, theoretical mathematicians, physicists, architects, and designers – the authors said that LSD improved creativity [29].
In a 1967 experiment conducted on 19 graduate students, creativity test data was allegedly improved by LSD [30].
7) Autism
The effects of LSD on autism remain unknown.
Findings from the published studies are speculative and unreliable.
Some researchers issued reports on the use of LSD in the treatment of children with autism mostly between 1959 and 1974. Several positive outcomes were reported with its use but most of the studies lacked proper experimental controls and presented largely experimental/narrative data [31].
There are several studies which were based on the modification of autistic behavior with LSD-25 and also the treatment of autistic schizophrenic children with LSD-25 and UML-491 [32, 33].
8) Anti-inflammatory Effects
Researchers want to determine if LSD, as an activator of serotonin receptors, blocks inflammatory effects of Tumor Necrosis Factor-alpha (TNF–α) induced expression of pro-inflammatory cell adhesion molecules (Icam-1, Vcam-1), cytokines (IL-6, IL-1β), and chemokines (Mcp-1, Cx3cl1) genes, and expression of the VCAM-1 protein. They are carrying out research in cells and animals [34].
Some scientists are also investigating its effects on the production of interleukin-6 in cells [35].
However, the effects of LSD on inflammation in humans remains to be determined.
9) Crime
A study by researchers from the University of Alabama at Birmingham and Johns Hopkins University School of Medicine collected data on 25,622 individuals under community corrections supervision in Treatment Accountability for Safer Communities and found that hallucinogen use predicted a reduced likelihood to fail the TASC program. Results suggest that hallucinogens may promote alcohol and other drug abstinence and prosocial behavior in a population with high rates of recidivism [36].
Another controversial experiment – The Concord Prison Experiment – dates back to the ‘60, led by famous psychedelic advocate Timothy Leary [37].
Leary claimed that, compared to the average recidivism rate of 60 percent for American prisoners in general, the recidivism rate for those involved in his project dropped to 20 percent. He believed that a combination of psilocybin and group psychotherapy should be used in prisons. No proper clinical data support his claims and no reliable follow-up studies have been carried out.
10) Brain waves
Some researchers think that – just like Psilocybin and Peyote – LSD may increase beta brain waves, associated with alertness and awareness, and LSD increases the variability of brain waves [38]. Limited data from the ‘60s suggested that chronic LSD users (15 – 300 total doses) have an increase in energy for all brain waves accompanied by a faster reaction time [39].
No recent trials speak to the effects of LSD on brain waves.
Side Effects of LSD
Long-term
The long-term side effects of LSD use are unknown.
In one small anecdotal study, 22 mental health professionals who self-experimented with LSD were interviewed. They didn’t report long-term negative effects, but it’s impossible to draw valid data from this experiment [40].
Case reports of long-term psychiatric problems attributed to LSD include psychosis, panic attacks, other anxiety disorders and depression [2].
Animals given LSD long-term developed symptoms of schizophrenia [41].
A side effect associated with the use of LSD is the partial or total recurrence of perceptual disturbances which previously appeared during intoxication, despite the absence of recent use. These are commonly referred to as “flashbacks” or Hallucinogen Persisting Perception Disorder (HPPD).
Two case reports of patients with a prior history of LSD turned to psychiatric consultation following episodes of HPPD [42].
Another report describes the use of LSD among alcoholism treatment facility inpatients and a degree of subjective distress experienced during flashbacks [43, 7].
Short-term
LSD may cause loss of appetite, sleeplessness, pupil dilation, dry mouth, salivation, flushing of the face, excessive sweating, nausea, and inner trembling. LSD also causes increased body temperature, heartbeat, blood pressure, and blood sugar [9, 44].
If you suffer from any of these symptoms, urgently see a doctor for help.
Dosage
There is no safe dosage of LSD. LSD is an illegal drug that can cause serious side effects. Therefore, we strictly advise against taking LSD.
This section summarizes research data.
LSD produces intense effects in extremely small quantities. The minimally recognizable dose of LSD in humans is about 25 μg. Clinical trials considered a dosage for a typical LSD reaction to be in the range of 100 – 200 μg [9].
LSD is generally taken orally. After ingestion, LSD is completely absorbed in the gut. After 100 – 250 μg LSD, psychological and physical effects peak after 1.5 – 2.5 h (although effects are felt for hours after). The effects of LSD usually last for up to 8 hours [9].
How Long Does LSD Stay in the Body?
A 2017 review of two clinical studies found the following [45]:
100 μg Dose (all values are averages):
- Maximum blood concentration: 1.3 (1.2 – 1.9) ng/mL
- Time to reach max blood concentration: 1.4 hours
- Half-life: 2.6 (2.2 – 3.4) hours
- Subjective effect duration: 8.2 ± 2.1 hours
- Subjective peak effects: 2.8 hours
200 μg Dose (all values are averages):
- Average maximum blood concentration: 3.1 (2.6 – 4.0) ng/mL
- Time to reach max blood concentration: 1.5 hours
- Half-life: 2.6 (2.2 – 3.4) hours
- Subjective effect duration: 11.6 ± 1.7 hours
- Subjective peak effects: 2.5 hours
In summary, after oral administration of LSD, it takes about 1.5 hours to reach the maximum concentration in the body, 2.5 hours to produce effects, and the effects can last anywhere from 8.2 to 11.6 hours depending on the dose.
