In the last decade or so, there has been a renaissance of interest in the therapeutic potential of psychedelics. While natural psychedelic substances have been used by humans for many thousands of years, psychedelics had a massive cultural impact on the West in the 1950s and 1960s. Albert Hoffman, a research scientist working for the Swiss pharmaceutical company Sandoz, accidentally invented LSD (lysergic acid diethylamide) in 1938 and discovered its psychedelic properties five years later. In 1955, a New York banker named Gordon Wasson sampled the psilocybe (magic) mushroom in Mexico and published an article on his experience in Life magazine.

Scientists discovered the role of neurotransmitters in the brain in the 1950s, and psychedelics inspired scientists to search for the neurochemical origins of mental disorders previously thought to be psychological. Psychedelics were also used in psychotherapy to treat various disorders, including alcoholism, anxiety and depression, with some promising results, although these studies generally did not reach modern standards of research design.

However, psychedelics were also embraced by the counterculture and became linked in the mind of authorities with youth counterculture and the anti-Vietnam war protests. By the end of the 1960s, most Western governments had outlawed and forced underground the psychedelic drugs which had been legal in most places previously, and also shut down all scientific research.

In the 1990s small groups of scientists managed to start conducting various trials of the therapeutic uses of psychedelics and this has led to the so-called psychedelic “renaissance” in which larger well-designed trials of psychedelic use for treating a range of mental disorders are being carried out by research groups at institutions such as Imperial College London, Johns Hopkins University and New York University. Just today, it was announced that the Australian government will be providing $15 million funding for clinical trials into the use of psilocybin and other psychedelics for the treatment of mental illnesses, including depression and PTSD. Michael Pollan’s book How to Change Your Mind gives an excellent account of the history of psychedelics, both above ground and underground, and the psychedelic renaissance, and was a best seller. See also this article by Michael Pollan on the “Psychedelic Renaissance”.

As part of my work on the global burden of disease for the World Health Organization (WHO), I carried out several assessments of the direct and indirect health impacts of the use of drugs, alcohol and tobacco. I recently did an approximate update to year 2019 for deaths directly due to drug use disorders (overdoses and directly toxic effects) and indirect deaths from road injury, suicide and infectious diseases attributable to drug use. A proportion of HIV, hepatitis B and hepatitis C deaths can be attributed to injecting drug use with contaminated needles. The great majority of direct and indirect deaths due to drug use are due to the use of opioids, both illicit and pharmaceutical opioids. Very few deaths are associated with psychedelic drug use, but I was curious to get a ballpark estimate for comparison with other drug deaths. I will present a brief summary of the broad estimates of drug-attributable deaths, then review evidence on the likely contribution of psychedelic drugs.

I have posted elsewhere a more detailed summary of my analysis of drug, alcohol and tobacco-attributable deaths. I estimate that there were around 186,000 deaths in 2019 globally due to drug use disorders (predominantly accidental drug overdose) of which 67% were attributable to opioid use. The second largest cause of drug-attributable deaths is hepatitis C, responsible for an estimated 156,000 deaths due to infection with contaminated injecting equipment. The following two figures and table show the contributions of the various causes for five main groups of drugs. The “other” category includes deaths due to misuse of pharmaceutical drugs other than opioids and amphetamines. Overall, a little over half a million deaths were attributable to drug use in 2019.

The following table and figure include recent WHO estimates for total deaths attributable to tobacco and alcohol use (around 8 million and 3 million respectively). When poor health is taken into account as well as mortality, the overall burden of disease becomes somewhat more prominent for alcohol and drug use . Unlike tobacco which kills most people at older ages with relatively limited periods of disability, alcohol and drug use are associated with significant loss of health at younger ages, and drug deaths in particular tend to occur at younger adult ages rather than older ages (see my other post for details).

Turning now to look at mortality associated with use of psychedelics, the literature is very consistent in finding that risks of mortality are extremely low or non-existent for LSD and psilocybin. Most countries do not include a separate category for reporting deaths associated with psychedelic drugs, and many countries lump them in with opioids and other hallucinogens in a single category. For example, Switzerland reports deaths for a single category “narcotics and psychodysleptics [hallucinogens]”. This is misleading.  It is rather like reporting deaths due to HIV infections and toxoplasmosis as a single category. That would likely lead the casual reader to assume that infection with toxo virus carries significant risk of death, and on public health and that on policy grounds these two infections can be treated as a single group. Many countries criminalize psychedelic use with penalties similar to those of non-medical opioid use.

The broader category “hallucinogens” includes not only the classical psychedelics (such as LSD, mescaline, psilocybin, MDMA etc) but also dissociatives (such as Nitrous oxide, ketamine, phencyclidine (PCP)) and deliriants (such as atropine, Benadryl and zolpidem (Ambien)).

The Office for National Statistics has published numbers of deaths from selected psychedelic substances from 1993 to 2014 for England and Wales here. This actually tabulates the numbers of deaths mentioning LSD or psilocybin on the death certificate, so its not necessarily the case that these deaths are causally attributable to the psychedelic use. A significant proportion of drug deaths are associated with multiple drug use, and studies have found that in many of these the primary factor was an opioid or alcohol. So how many deaths were there that mentioned LSD or psilocybin (with or without other drugs)?  In total for the 22 year period there 4 deaths in which LSD was mentioned and 1 death where LSD and psilocybin were mentioned, none with psilocybin only. That amounts to an average of 1 death per four years, although all the deaths were actually concentrated in the first decade 1993-2003.

An Australian study by Darke et al (2019) examined all hallucinogen-related deaths in Australia in the period 2000 to 2017. There were 82 deaths, with the majority associated with phenethylamines, a group that includes amphetamines, methamphetamine and MDMA (ecstasy). No mention is made of any deaths associated with psychedelics other than MDMA, and its unlikely there were any. Another paper on MDMA-related deaths in Australia by Roxburgh et al (International Journal of Drug Policy 2020)  identified 392 deaths between 2001 and 2018 in which MDMA was mentioned. Just under half of these were attributed to multiple drug toxicity, and only 34 resulted from MDMA toxicity alone. The remaining 38% were primarily due to motor vehicle accidents with MDMA listed as a contributory factor. MDMA is the only psychedelic for which small but significant numbers of deaths do occur. These are primarily associated with hyperthermia or over-heating. This relates not only to an apparent lack of knowledge among MDMA users about appropriate fluid consumption and the need to cool off when using MDMA, but also to the risk of overdosing due to the unknown concentration of MDMA in illicit tablets. Tablet testing and education are known to substantially reduce MDMA deaths, but many governments refuse to allow tablet testing.

LSD has been associated with deaths of people jumping out windows etc in the popular mind due to scare stories published in the media in the 1960s. Closer examination of most of these incidents has not found strong evidence for a causal association (see for example here or here), though there may have been a few deaths associated with risky behaviour during the heyday of unconstrained LSD use in the 1960s.

There is some evidence that psychedelic use may trigger psychotic episodes in people at risk of schizophrenia.  A review of cannabis use concluded that it may advance the onset of schizophrenia by a year or two on average in those who were going to get it in due course, but did not cause additional cases of schizophrenia. The evidence was not considered strong enough to include schizophrenia as an adverse outcome in the WHO assessment of the attributable burden of cannabis use several years ago.

Professor David Nutt and colleagues published a study in 2007 which developed a rational scale to assess the harm of drugs of potential misuse and concluded that, among other things, psychedelics are considerably less dangerous than alcohol and are misclassified with very harmful drugs in public policy. As a result, he was sacked from his position as the UK government’s chief drug advisor. See also this interview with him. Here are two graphs from his study which summarize the relative risks of dependency, fatal overdose and physical harms for various types of drug.

The following graph compares the study’s assessments of overall harm associated with various drugs with the public perceptions of harm. There is reasonable congruence of heroin and cocaine. However, the harm associated with alcohol is drastically underestimated and that for the psychedelics drastically overestimated. The tobacco and cannabis estimates by the study seem somewhat dubious to me, they seem to overstate the cannabis harm and understate the tobacco harm (both are in the 20’s on the overall harm score) whereas tobacco kills many orders of magnitude more people than cannabis. I will have to look more closely at their methodology.

Its clear that the psychedelics don’t even register on the harm scale associated with the tobacco, alcohol, opioids, cocaine or amphetamines. And in fact, that LSD and mushrooms are two of the safest drugs and it is bizarre to class them with the illicit opioids with similar criminal penalties. MDMA and ecstasy are responsible for small numbers of deaths, and these could be largely avoided if they were legalized and pill contents regulated, or even if pill testing was widely accessible. Cannabis is not quite as harmless as the psychedelics, and does have some risk of psychological addiction, unlike them. However, it also is much less harmful than other legal drugs such as tobacco and alcohol. And for many of these drugs, the harms associated with use are substantially lower than the harms associated with criminalization, which range from large scale incarceration and subsequent family destruction and impoverishment, to the corruption of police and public officials, and the subsidizing and encouragement of organized crime.