What do we know about the risks of psychedelics?

By Bridget Huber

For starters, assessing risk is tricky. A lot of what both scientists and the general public think they know about the potential risks of psychedelic use comes from the first wave of research and experimentation in the 1950s, 60s and 70s. But this body of knowledge includes studies that wouldn’t meet today’s scientific standards; urban legends; and sensational, unsubstantiated news stories.

Also, reporting and describing adverse events is often subjective to some extent, psychiatrist Rick Strassman noted in a 1984 paper. Some people consider the drug-induced state itself pathological, he wrote, while others believe even the worst reactions are part of “throwing off ‘straight’ society’s ‘shackles’ and in reaching a ‘higher’ level of consciousness.” And many of the more recent studies on the potential harms of LSD and other hallucinogens draw on data from the 1950s and 60s. Those studies had a lot of methodological problems; many lack baseline data about their subjects, didn’t use placebos and/or failed to specify the source of the drug or the setting in which it was given.1

Also, though it’s tempting to generalize from case reports or news stories, Krebs and Johansen argue it’s important to take a “statistical perspective to risk” and they point out that nothing we do without risk.2 Here are some of the specific reasons why they say case reports (and news reports, I’d argue) of mental distress/problems arising from psychedelic use should be taken with a major grain of salt.

Several issues are important to keep in mind when considering case reports. 1) Adverse effects of psychedelics are usually short-lived; serious psychiatric symptoms following psychedelic are typically resolved within 24 hours or at least within a few days. 2) Both mental illness and psychedelic use are prevalent in the population, likely leading to many chance associations; for instance, about 3% of the general public will have a psychotic disorder sometime in their lives. 3) The typical onset period of both mental illness and psychedelic use occurs in late adolescence and early adulthood, again possibly leading to mistaken causal inferences. 4) Most case reports do not rule-out preexisting psychiatric difficulties, life stresses, or use of other drugs. Many psychiatric disorders are believed to be heavily influenced by genetics and earlier experiences, even if symptoms are often first triggered by a stressful event. Note, however, that people with first-episode psychosis often have no apparent family or personal history of mental illness, whether or not if they have previously used psychedelics. 5) Because of the striking subjective effects of psychedelics, some people attribute psychiatric symptoms to the use of psychedelics even if the symptoms started months or years later. 6) Some health professionals may have a biased view since they meet people with mental health problems and have little or no contact with the majority of psychedelic users. 7) Caution should be used when generalizing from LSD to other psychedelics because of emerging evidence of unique effects of LSD. 8) Case reports of mental health problems following psychedelics are often comparable to case reports of mental health problems linked to intensive meditation, visiting holy sites or viewing beautiful artwork and sublime natural scenes.”3

To complicate things further: People may think they’ve taken LSD when they’ve really taken something else. For example, a West Virginia man was charged with murdering his wife in 2013. He and his wife took what they thought was LSD and the wife started having convulsions and died. There were a number of media reports blaming her death on LSD, but it later came out that the couple had unwittingly taken a synthetic hallucinogen 25b-NBOMe, which isn’t illegal in West Virginia. The husband then pled guilty to a lesser charge: involuntary manslaughter.4 I also found a case report about an 18-year-old man who called 911 saying he’d tried to kill himself after taking two hits of acid. He’d actually taken NBOMe, as well, which seems to be more dangerous and potent than LSD.5

General safety information

In Drugs – Without the Hot Air, David Nutt calls psychedelics “among the safest drugs we know of”.6 He and a team of experts in addiction, drug policy, psychology and other fields ranked 20 drugs on their harmfulness, using criteria ranging from drug-related mortality (death by overdose) to environmental damage. Overall, psilocybin mushrooms were ranked as the least harmful drug, followed by LSD and the addiction drug buprenorphine, which had the same score. Alcohol was ranked most harmful (more then ten times as harmful as mushrooms or LSD), followed by heroin, then crack. Referring to mushrooms and LSD, Nutt writes:

“It’s virtually impossible to die from an overdose of them; they cause no physical harm; and if anything they are anti-addictive, as they cause a sudden tolerance which means that if you immediately take another dose it will probably have very little effect.”7

Matthias Liechti recently published a paper in Nature that reviews all of the clinical research on LSD that’s been done in the past 25 years. In these controlled settings, subjects’ experience of LSD was “predominately positive”, he writes, and no severe adverse reactions to LSD were reported.8

Emergency Room visits
LSD and psilocybin accounted for just 0.005% of US emergency room visits, according to federal statistics published in 2013.9 There were an estimated 4,819 emergency department visits related to LSD use in 2011, according to the most recent federal data available. Another 8,043 ER visits that year were attributed to “miscellaneous hallucinogens”. Note that the substance use in both cases was self-reported, not toxicologically confirmed.10

For comparison:

Drug

Estimated number of ER visits in 2011
LSD

4,819

Misc. hallucinogens

8,043

Heroin

258,482

Marijuana

455,668

PCP

75,538

 

Toxicity and Overdose

In their 2008 guidelines for the safe administration of high doses of LSD and psilocybin in a clinical settings, Matthew Johnson, Bill Richards and Roland Griffiths write that hallucinogens aren’t considered addictive and they don’t appear to cause organ damage or neurotoxicity. They can cause side effects like dizziness, blurred vision, weakness and tremors, while they are active. The authors also note that hallucinogens can raise the pulse and blood pressure, but they say none of their patients ever experienced a medically-dangerous spike in blood pressure or had to take blood pressure drugs.11 I did find a report published this year of a 34-year-old man with an undiagnosed heart condition who went into cardiac arrest after taking LSD recreationally and died.12

Many of the papers I read said there haven’t been any documented deaths from LSD overdose. I did find one case report from 1985 of a 25-year-old man whose death was attributed to LSD overdose based on toxicological examinations. The paper’s authors described it as “the first reported fatal case of LSD poisoning”.13

Another case of a non-fatal but serious LSD overdose is cited in a couple of papers. In 1972, after a dinner party in San Francisco, eight people snorted a very high dose of LSD, after mistaking it for cocaine. They got really sick: five went into comas, three had to be intubated, four experienced mild generalized bleeding. But within 12 hours they were back to normal. Doctors followed five of the patients for a year and said they showed no apparent psychological or physical ills.14

By one estimate, the fatal dose of LSD is 1000 times larger than the dose that causes an effect. So, it would be much harder to accidentally overdose on LSD than most other drugs — the fatal dose of intravenous heroin, for example, is just 5 times larger than the effective dose.15

Physical harms caused by changes in perception/judgment

Even if psychedelics aren’t toxic, per se, there are a lot of pop-culture accounts of people getting hurt, dying or hurting others while on the drug — probably the most common stories are those of people think they can fly and fall to their deaths. But Johansen and Krebs write that these sorts of situations are very rare:

“Both the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) and the health authorities in the Netherlands, where hundreds of thousands of servings of psilocybin mushrooms are legally sold in shops each year, report that serious injuries related to psychedelics are extremely rare (EMCDDA, 2011; CAM, 2007). Furthermore, Dutch police report that legal sale of psilocybin mushrooms has not led to public order problems (Van Amsterdam et al., 2011).”16

Still, I did find a bunch of relatively recent news reports of people who either hurt themselves or other people, apparently while on LSD, though it was unclear in a lot of these stories whether that was toxicologically confirmed. (James Fadiman told one reporter that he’s investigated some stories of people apparently going crazy after taking LSD and found that they’ve actually taken another drug.)17

-In 2011, a 22-year-old died after jumping out of a vehicle after taking LSD: http://www.ocregister.com/2011/09/20/bad-lsd-trip-turns-into-deadly-nightmare/

-In 2016, a 20-year-old man on LSD caused a three-car crash that killed a man:

https://www.abqjournal.com/901960/police-man-high-on-lsd-caused-fatal-crash-2.html

-In 2017, a 15-year-old boy fell or jumped off a balcony after taking LSD and died: http://www.latimes.com/local/lanow/la-me-ln-student-dies-20170320-story.html

-In 2016 a man attacked his girlfriend, tried to cut off his penis and jumped out a window after taking LSD:

http://metro.co.uk/2016/04/20/man-high-on-lsd-attacked-girlfriend-and-tried-to-hack-off-his-penis-before-throwing-himself-out-window-5829027/

-In 2016, a college student murdered his girlfriend after taking LSD: http://www.tri-cityherald.com/news/local/crime/article67693647.html

Serious mental health issues

Despite horror stories about people having psychotic breaks or other mental health problems after taking psychedelics, two recent large-scale studies (which examine a similar set of US data) suggest people who have used psychedelics may be less likely to have serious mental health problems or be suicidal than those who have not.

One paper, published in 2015 by a team of researchers from Johns Hopkins and the University of Alabama, analyzed data collected from more than 191,382 people between 2008 and 2012 during the annual National Survey on Drug Use and Health. More than 13 percent of those surveyed (27,235 people) had used “classic psychedelics” (which the researchers defined as DMT, ayahuasca, LSD, mescaline, peyote or psilocybin) at some point in their life. The respondents who had used a classical psychedelic were 19 percent less likely to have been in psychological distress during the previous month, 14 percent less likely to have had suicidal thoughts over the last year, 29 percent less likely to have made plans for suicide and 36 percent less likely to have attempted suicide in the past year than the survey respondents who had never used psychedelics. Interestingly, the use of other, non-psychedelic drugs was associated with more psychological distress and suicidality in this group. Of course, the study had limitations — for one, people self-reported both drug use and psychological distress. Also, these sort of studies can only demonstrate association, not causation.18

The same year, Johansen and Krebs published a paper that looked at responses to the same survey from a slightly different time period. Of 135,000 US adults surveyed, 19,299 had used LSD, psilocybin, mescaline or peyote. The respondents who had used psychedelics were no more likely to have experienced serious psychological distress, suicidal thoughts or behavior, anxiety, depression or to have needed or received mental health treatment in the past year than those who had not. In fact, people who had used psychedelics were less likely to have undergone inpatient psychiatric treatment than never-users. Johansen and Krebs concluded: “There is little evidence linking psychedelic use to lasting mental health problems. In general, use of psychedelics does not appear to be particularly dangerous when compared to other activities considered to have acceptable safety.”19
Data from the first wave of psychedelic research seems to support this idea. About 10,000 patients are thought to have participated in LSD research in the 1950s and 60s and the rate of psychotic reactions, suicide attempts and suicides during treatment “appears comparable to the rate of complications during conventional psychotherapy” according to an analysis of data from this era done in 2008 by IDENTIFY HIM Torsten Passie.20
More recently, a 2011 paper by Erich Studerus, Franz Vollenweider and colleagues analyzed data from eight double-blind, placebo-controlled psilocybin studies conducted in their laboratory over the past decades. They looked at 110 subjects who’d undergone a total of 227 psilocybin sessions. None of the subjects had prolonged psychotic reactions to the psilocybin sessions and schizophrenia-spectrum disorders were not precipitated in any of the subjects. One subject did seek treatment for symptoms of anxiety, emotional disability and depression.21
In their safety guidelines for hallucinogen research, Johnson and co-authors note that psychedelics could possibly provoke the onset of prolonged psychosis, but they say the chances are low. In their clinical research, they exclude people who meet the criteria for a diagnosis of schizophrenia, bipolar I or II or other psychotic disorders. They also exclude people with a first or second degree relative with those disorders.
Here they describe some of the earlier evidence of psychotic breaks related to psychedelics given in a therapeutic setting:

In a survey of investigators who had administered LSD or mescaline, Sidney Cohen (1960) reported that only a single case of a psychotic reaction lasting more than 48 hours occurred in 1200 experimental (non-patient) research participants (a rate of 0.8 per 1000). Notably, the individual was an identical twin of a schizophrenic patient and thus would have been excluded under the proposed guidelines. Prolonged reactions over 48 hours were slightly more frequent in patients undergoing psychotherapy than in experimental non-patient participants, but still relatively rare, occurring at a rate of 1.8 prolonged reactions per 1000 patients. Cohen (1960) also reported that suicide attempts and completed suicides occurred at a rate of 1.2 and 0.4, respectively, per 1000 patients. The causal link between hallucinogen exposure and suicide or suicide attempt was only clear for a portion of these cases in patients, and no suicides or suicide attempts were noted for the 1200 non-patient, experimental participants. However, it is important when evaluating these data to consider that only 44 of the 62 researchers queried by Cohen returned survey results (Cohen, 1960; Novak, 1997). Although Cohen and Ditman (1962) subsequently expressed misgivings over the increased incidence of adverse effects due to the increasing recreational use of LSD and some questionable clinical practices, they maintained that when used under the proper guidelines, LSD was an important tool for use in human research (cf., Novak, 1997). McGlothin and Arnold (1971) reported 1 case out of 247 individuals who received LSD in either experimental or psychotherapeutic studies in which an LSD-related psychotic reaction lasting more than 48 hours occurred. That single case was a patient who received repeated LSD administrations in a psychotherapeutic context. Although very rare, care must be taken to minimize the risks of such an episode.

Bad trips & other short term ill-effects

The most common adverse reaction to psychedelics is the bad trip, which can involve feelings of fear, anxiety, dysphoria and/or paranoia. Johnson et al write: “Distressing effects may be experienced in a variety of modalities: sensory (e.g., frightening illusions), somatic (e.g., disturbing hyperawareness of physiological processes), personal psychological (e.g., troubling thoughts or feelings concerning one’s life) and metaphysical (e.g., troubling thoughts or feelings about ultimate evil forces.” Hallucinogens often intensify people’s emotional experiences, they write, which could lead to erratic and potentially dangerous behavior if people aren’t properly prepared and supervised.22 Other short-lived but negative effects can include: “temporary paranoid ideation and, as after-effects in the days following a LSD experience, temporary depressive mood swings and/or increase of psychic instability.”23
I didn’t find much information about how common bad trips are — one 2010 analysis of psilocybin studies done between 1999 and 2008 looked at the experiences of 110 patients. Negative experiences weren’t common and seemed to be dose-dependent — higher doses of psilocybin were associated with higher rates of adverse reactions. All of the short-term adverse reactions were “successfully managed through interpersonal support” and didn’t require taking any drugs and seemed to have no lasting effects, based on follow-up interviews.24
A group of Johns Hopkins researchers conducted an online survey of 1993 people who had had a difficult or challenging experience with psilocybin mushrooms. Only 2.1 percent of the respondents took psilocybin in a setting that resembled a controlled clinical environment. For 39 percent of the respondents, the bad trip ranked among the top five most challenging experiences of their lifetime. More specifically:

“11% reported putting themselves or others at risk of physical harm, 2.6% reported behaving in a physically aggressive or violent manner, and 2.7% reported getting medical help during the occasion. Of those whose session occurred at least 1 year earlier, 7.6% reported that they sought treatment for one or more psychological symptom they attributed to the challenging psilocybin experience. Three cases appeared associated with onset of enduring and impairing psychotic symptoms and three cases with attempted suicide.”25

But, interestingly enough, despite these negative experiences, many of the survey respondents still found even these bad trips to be meaningful and spiritually important. For 34 percent of participants, their most challenging trip on psilocybin was ranked among the top five most meaningful experiences of their life. And 31 percent said it was among the top five most spiritually significant experiences of their life. Eighty-four percent of the respondents said they had benefitted from the challenging parts of their trip and 46 percent said they would repeat that session if they could, despite the challenges.26

Flashbacks

There’s not a lot of conclusive information about how common and/or debilitating flashbacks are. Reports of flashbacks have been around for a very long time — in 1898 Havelock Ellis described a heightened sensitivity to ‘‘the more delicate phenomena of light and shade and color’ since he’d taken mescaline.27 In 1986, hallucinogen flashbacks were first described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and then revised in the DSM-IV under the diagnosis Hallucinogen Persisting Perception Disorder with the following diagnostic criteria:

A) The reexperiencing, following cessation of use of a hallucinogen, of one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen (e.g., geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of color, intensified colors, trails of images of moving objects, positive after- images, halos around objects, macropsia and micropsia).

B) The symptoms in Criterion A cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C) The symptoms are not due to a general medical condition (e.g., anatomical lesions and infections of the brain, visual epilepsies) and are not better accounted for by another mental disorder (e.g., delirium, dementia, Schizophrenia) or hypnopompic hallucinations.

Using this criteria, Halpern and Pope analyzed 20 studies of people who’d experienced flashbacks that were conducted between 1955 and 2000. In general, they found that the term “flashback” had been used in so many different ways that it was “virtually useless”. They also found that the studies reported wildly different rates of flashbacks — some researchers saw hardly any, but others said more than 33 percent and 77 percent of participants who had taken LSD had flashbacks. They also noted that people who’d taken LSD in therapeutic or research settings seemed to have far lower rates of flashbacks. The studies’ designs also made it hard to rule out confounders like underlying medical conditions and the use of other drugs. Still, the authors did conclude that: “Despite all of these reservations, it seems inescapable that at least some individuals who have used LSD, in particular, experience persistent perceptual abnormalities reminiscent of acute intoxication, not better attributable to another medical or psychiatric condition, and persisting for weeks or months after last hallucinogen exposure.”28

More recently, Halpern and other researchers have distinguished between two types of flashbacks. The first type are “brief re-experiences of alterations in perception, mood, and/or consciousness, as previously experienced during a hallucinogenic intoxication.” The person experiencing these typically realizes they are having a flashback and the frequency of the experiences, which can be pleasurable, often diminishes over time.29

Halpern describes the second, more severe sort like this:

Type 2 HPPD (consistent with Abraham (1983) and part of the definition in the DSM-V) entails constant or near-constant visual effects. These can include the following:

A. Palinopsia: the persistent perception of an object removed from view;

B. halos: a brightening glow or colored shining/shimmering surrounding 
objects;

C. trails or akinetopsia: a series of discrete positive afterimages following in the 
wake of moving objects; and

D. visual snow: a TV static-like graininess superimposed upon the visual field.

Symptoms may occur alone or in combination. Sound and other perceptions are unaffected. In most cases, visual phenomena are reported to be uncontrollable and disturbing, though some individuals regard them as enriching (Baggott et al. 2011). Claimed constant visual phenomena are often accompanied by mild-to-moderate depersonalization, derealization, anxiety, or depression (Holland and Passie 2011). These psychopathological states are claimed to trigger the occurrence and intensity of visual phenomena (Abraham 1982, 1983; Abraham and Duffy 1996, 2001) depending on the waxing and waning nature of current affect.30

But Halpern notes that this second type of flashback wasn’t clearly reported in the 1960s nor was it described in the studies of the 10,000 or so people who took psychedelics in the 1950s and 60s in research settings.

In terms of how common psychedelic-induced flashbacks or HPPD may be, Halpern basically said we don’t know:

Data do not permit us to estimate, even crudely, HPPD’s prevalence according to DSM-V or ICD-10 criteria. Although millions of doses of hallucinogens were consumed by millions of individuals since the 1960s (SAMHSA 2011), few large HPPD case series were reported. Horowitz (1969), Cohen (1960, 1977) estimate the incidence of Type 1 HPPD in a population of regular hallucinogen users in the 1960–1970s as 1:20. Type 2 HPPD, if it exists as a reliable and distinct entity, appears to be very rare (Hermle et al. 2008, 2015; Holland and Passie 2011). Grinspoon and Bakalar (1997) estimate that Type 2 HPPD occurs in 1 of 50,000 hallucinogen users. Baggott et al. (2011) collected data online in a Web-based questionnaire from 2455 individuals reporting visual experiences while drug-free that resembled a past hallucinogen intoxication. Most of these experiences were simple, non-disturbing “flashbacks,” while 4.2 % found these visual phenomena significant enough to at least contemplate seeking treatment.31

Krebs and Johansen, meanwhile, expressed strong skepticism about the idea of HPPD in a 2013 paper that analyzed responses to the National Survey on Drug Use and Health from 2001 and 2004, and concluded, overall, that psychedelic use was not an independent risk factor for mental health problems. Here’s what they say about flashbacks:

In this study, lifetime use of psychedelics and past year use of LSD was not associated with past year symptoms of visual phenomena (‘‘seeing something others could not’’), panic attacks, psychosis, or overall serious psychological distress. Thus, our findings does not support either the idea of ‘‘flashbacks’’ described in extreme cases as recurrent psychotic episodes, hallucinations, or panic attacks, or the more recent ‘‘hallucinogen persisting perceptual disorder’’ (HPPD) described as persistent visual phenomena with accompanying anxiety and distress. All of the purported symptoms of HPPD are also present in people who have never used psychedelics. Occasional visual phenomena are common in the general population, especially among people with anxiety disorders. Recent randomized controlled trials with psilocybin do not report any cases of ‘‘flashbacks’’ or persistent visual phenomena. Interviews with over 500 regular participants in Native American peyote ceremonies did not identify anyone with ‘‘flashbacks’’ or persistent visual symptoms. Interviews with 120 adults in the US complaining of persistent visual symptoms found that only 5% had ever used LSD (in comparison, over 10% of the general US adult population has used LSD) and there did not seem to be any relationship between drug use and visual symptoms. Only two small studies have reported higher rates of visual symptoms in LSD users compared to non-users. Both studies had serious methodological problems: participants in both studies were psychiatric inpatients who knew that the purpose of the studies was to document harms from LSD; the LSD group and the control groups were not matched on other drug use or psychiatric diagnosis; and in the first study several of the people included in the LSD group were later found to have epilepsy, panic, anxiety, affective disorder, or temporoparietal abnormalities that may be related to visual symptoms. In case reports of ‘‘flashbacks’’ or HPPD, symptom onset is often weeks, even years, after last psychedelic use, and a causal relationship between persistent perceptual symptoms and use of psychedelics remains unproven. Overall, the validity of the HPPD diagnosis remains scant. HPPD appears to fit within the somatic symptom disorders. In an llustrative case example, a young man was diagnosed with HPPD by the originator of the diagnosis; symptoms began in conjunction with major life changes and several weeks after taking LSD; on initial consultation with physicians, he was told that his vision was fine and somatization disorder was implied; he improved after psychotherapy for his depression and worries, and reassurance that his visual experiences were ordinary perceptual phenomena that most people ignore.32

Bridget Huber is Michael’s research assistant.


1 Strassman 1984
2 Johansen and Krebs, 2015
3 Krebs and Johansen 2013
4 See http://www.wvgazettemail.com/News/201312170156 AND http://www.wsaz.com/home/headlines/New-Drug-Blamed-for-Overdose-Death-194512531.html
5 Suzuki 2014
6 Nutt 2012, pg. 254
7 Nutt 2012 pg. 254
8 Liechti 2017
9 Johansen et al 2015
10 Drug Abuse Warning Network – National Estimates of Drug-related Emergency Department Visits, 2004 – 2011
11 Johnson 2008
12 The poster abstract is only available online: http://www.atsjournals.org/doi/pdf/10.1164/ajrccm-conference.2017.195.1_MeetingAbstracts.A3773
13 Fysh et al, 1985
14 Klock 1973
15 Gable 2004 and 2006
16 Johansen and Krebs 2015
17 http://www.thestranger.com/features/2017/03/08/25008382/adventures-in-microdosing
18 Hendricks et al, 2015
19 Johansen and Krebs, 2015
20 Passie 2008
21 Studerus et al 2011
22 Johnson 2008
23 Passie 2008
24 Nichols 2016
25 Carbonaro 2016
26 Carbonaro 2016
27 Halpern and Pope 2002 (quoting from Havelock’s “Mescal: A new artificial paradise”, published in The Contemporary Review in 1898)
28 Halpern and Pope 2003
29 Halpern et al 2016
30 Halpern 2016
31 Halpern 2016
32 Krebs and Johansen 2013


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