Psychedelic Safety: Are Psychedelics Safe? A Scientific Perspective

By Steve Beukema

NB: This article discusses the physiological safety of classic, serotonergic psychedelics, such as LSD, DMT, and psilocybin mushrooms. Other substances that are often grouped with classic psychedelics, such as ketamine and MDMA, are in a different pharmacological class and have different safety profiles. Always research safety recommendations for any individual substance carefully prior to consumption. Furthermore, while classic psychedelics are safe compared to most other substances, that does not mean that safety protocols should not still be followed, or that there are zero risks. For more information and a complementary perspective to this article, check out 12 Dangers of Psychedelics.

As psychedelics become increasingly popular and accepted in mainstream science, a lot of people begin to wonder if these substances are safe.

Compared to most drugs, psychedelics are safe. This is a simple answer to a complicated question, but there you have it. No seriously, that’s the answer. Compared to the vast majority of substances, PSYCHEDELICS ARE RELATIVELY SAFE. This answer will not satisfy many, because it’s not actually the question people want to ask. Some better questions might be: How can a mind-bending, thought-expanding drug be safe? When is it safe to take? Where is it safe to take it? Who can take it safely? But most importantly, most overwhelmingly, people really want to know: Why are psychedelics safe? 


Short half-life

First, psychedelics are safe because they are non-toxic and do not stay in the body for a long period of time. At the same time, it’s worth acknowledging that the half-life (duration of stay and rate of decay) of a drug has little to do with its safety. As is evident from the chart above, LSD has the highest rate of decay in the human body, which on the surface would seem to go hand-in-hand with its lower potential for harm. However, cannabis has a similar safety profile, and yet it sticks around in the body longer than any other drug. Cannabis has long been colloquially referred to as a “snitch” drug for this exact reason – it readily shows up in standard drug tests long after its initial use. While there are many better arguments in support of psychedelics, there is certainly some comfort in knowing you can safely experiment with them without fear of losing your job after a drug test.  

Clinging to the belief that psychedelics are dangerous is ironically more dangerous than simply acknowledging their safety. Yes, there are ways to abuse psychedelics, and there are ways to experience harm from psychedelics; however, if you replace the word psychedelics with any other noun, this notion would still hold true. Psychedelics are safe because cars are safe when operated properly, because peanuts are safe when you’re not allergic to them, because vending machines are safe when you don’t shake them. These comparisons become even more ridiculous when you consider that cars, peanuts, and vending machines routinely end lives and provide no therapeutic benefit to mental health. 

Addiction and Tolerance

Psychedelics are safe because they are non-addictive, physiologically. One main consideration when talking about drugs, specifically, is the concept of physiological addiction. Anything can be behaviorally addicting (e.g. television, cracking your knuckles, peanut butter), but drugs often have the ability to induce cravings at a biological and psychological level. This presents itself as:

  1. Compulsion to seek and take the drug.
  2. Loss of control in limiting intake.
  3. Emergence of a negative emotional state when access to the drug is prevented.

Physiological addiction relies on direct effects between the drug itself and the brains dopaminergic reward systems. When left to its own devices, our reward system motivates us to repeat functional behaviours like eating, having sex, and finding passion in new pursuits. However, these feelings of pleasure and motivational impulses can be simulated by introducing similar chemicals from an external source, using various drug forms as a vehicle. This can result in an individual seeking out a drug because it makes them feel good, and subsequently losing their control over the drug because they feel worse without it – the three telltale signs of physiological addiction.

Psychedelics are safe because you cannot become physiologically dependent on them, as ALL classic psychedelics are serotonergic substances and therefore do NOT have direct effects on brain dopaminergic systems. This is where the conversation can get a little confusing, as psychedelics are well known for their ability to produce feelings of pleasure amongst other positive psychological outcomes; that is to say, if serotonergic hallucinogens can produce feelings of elevated mood that are similar to those with dopaminergic dependent drugs, why aren’t they similarly addictive?

One possible answer is rooted in the concept of drug tolerance. The human brain is massively adaptable, and so when we introduce a drug that imitates a chemical it was already working with, the brain decides that it needs to produce less of the receptors available to that chemical in an attempt to modulate its effects. Psychedelics are safe because they have an immediate and rapid tolerance profile. Specifically, regarding psychedelics, a phenomenon known as tachyphylaxis occurs following ingestion, which is a medical term describing a sudden decrease in response to a drug after its administration. As a proof of concept, daily administration of LSD results in a complete loss of sensitivity to the drug by the fourth day, meaning that the experiential component of psychedelics is reliant on abstinence in the first place. Additionally, well-known animal models meant to produce addictive responses through self-administration of hallucinogens have all been unsuccessful. 

There is one exception to the tolerance effect described above, and that is for the psychedelic molecule N,N-Dimethyltryptamine (DMT) found in ayahuasca. Fascinatingly, there is no lasting tolerance to DMT, which means you can take the same amount tomorrow to feel the same effects from today. In fact, many people who take ayahuasca describe a reverse-tolerance effect, noticing that smaller amounts of the substance can produce equal or greater effects on subsequent doses. The underlying mechanism behind a non-addictive drug that does not build tolerance is not well understood, but what we do know is that the receptors that DMT binds to remain sensitive to DMT even after it degrades, unlike other common psychedelics (psilocybin, LSD). Considering that tolerance has been outlined above as advantageous for addiction, it may be tempting to conclude that DMT has addictive properties. However, the reality is that tolerance is only one piece of the puzzle necessary to create a model of addiction, and DMT lacks the rest of those pieces. Specifically, users of DMT do not experience the compulsion or the loss of control an addict might face, and most prominently there are no physiological withdrawal symptoms that are requisite for all addictive substances.

The above chart (adapted from Drug Toxicity cgu.edu) neatly summarizes what’s been mentioned so far. Psychedelics have an extremely low potential for dependence compared to any known drug in existence. Additionally, the amount of psychedelics required to experience a shift in perception, versus the amount of psychedelics required to lethally overdose, is so vast that there are currently only estimates as to what a lethal dose could be – as there are no documented cases of it ever occurring. Psychedelics are safe because they do not have the capacity to be physiologically addicting or lead to dependence from a biological perspective. 

Psychological Risks

Psychedelics are physiologically safe, but still have some psychological risks, especially when used casually or recreationally. We are in desperate need for a cultural shift towards accepting the overwhelming benefits psychedelics can provide, but part of respecting their therapeutic potential involves acknowledging their potential for harm. For most, this translates into what many refer to as a “bad trip” – when the psychedelics provoke fears and anxieties that the user can’t escape from. Yet, when we look at the incident rate of negative psychedelic experiences objectively, we see a more positive story emerge. First, that the difficulty of these events was correlated with higher (less manageable) doses, indicating a potential lack of knowledge or some level of abuse. More importantly though, these difficult experiences were positively associated with enduring increases in well-being for these individuals, with 84% endorsing psychedelics despite these difficulties.  

Although a comparison between psychedelics and other drugs is not the main focus of this article, it is worth briefly noting how frustrating it is to have these conversations in a society that so enthusiastically accepts and distributes alcohol. If only to further highlight the safety of psychedelics, it is necessary to ask why this discrepancy exists given the extraordinarily high potential for harm and addiction with alcohol use. Take a look at the chart above, which lists various categories in which a drug can pose harm to an individual. It becomes immediately evident that if we truly did live in a society that wanted to protect individuals from dangerous substances, alcohol would be illegal. It is also worth noting that the categories of harm for psychedelics are simply “drug-related impairments of mental functioning” – which is the entire purpose of these substances. 

Schizophrenia and HPPD

Many people worry that psychedelics can trigger mental illness. Schizophrenia and hallucinogen persisting perception disorder (HPPD) are two outcomes from psychedelic use that understandably provoke concern. Regarding people with a predisposition for schizophrenia, there is a standing belief that psychedelics can trigger an episode or the onset of the condition itself. Perhaps this belief stems from the similar presentation of hallucinogenic drugs and genuine schizophrenia, or perhaps it’s because psychedelics and antipsychotic medications both preferentially select for the same serotonin receptors. While this is certainly a valid cause for concern, recent data is starting to question these claims, asserting that the harms of psychedelics have been overstated. In support of this notion, data drawn from the National Survey on Drug Use and Health (NSDUH) showed that participants who reported a lifetime use of psychedelics had no increased rate of any negative mental health outcome; In fact, psychedelics were instead associated with better mental health outcomes.

The second negative outcome regards HPPD, colloquially referred to as “flash-backs.” Essentially, this refers to a resurgence of symptoms associated to psychedelic use, long after the drugs have left the system and the expected perceptual experience has worn off. This can manifest itself as experiencing after-images, movement of inanimate objects, blurring of small patterns, halo effects and so forth during a time that these perceptions may be inappropriate or unwanted. However, the clinical relevance of HPPD is also openly disputed, with researchers claiming that HPPD is likelier in higher recreational doses of LSD, yet evidence is so scarce it’s nearly impossible to study without a higher incidence rate.

Las setas psicodelicas y el LSD, drogas seguras? - Cien... en Taringa!

Conclusion

Psychedelics are safe for the following reasons: you cannot get addicted, grow physiologically dependent, lethally overdose, damage organs, suffer negative withdrawal symptoms, or even get caught with them in your system provided you took them a few days ago. However, psychedelics are potent tools that deserve to be approached with respect and proper guidelines. Check out the PEx general psychedelic safety guide here. Furthermore, the science behind psychedelics is still very new, and this article merely scratches the surface of psychedelic safety using what little evidence exists thus far. As we work towards decriminalizing psychedelic substances and integrating them into society, we will continue to learn more about the positive and potentially negative outcomes related to psychedelic use. Unfortunately, for now we are making up for lost time as we try to educate the world about these tremendously therapeutic substances that were banned many decades ago.


Steve Beukema is a research scientist with a knack for adventure and novelty. His academic pursuits range from investigating language processing patterns of vegetative state patients in his M.Sc, to uncovering arousal-based pupil mechanics of the human eye during his PhD. Steve believes that education about psychoactive substances is more crucial now than ever before, and that science has fallen behind public perception surrounding psychedelics. Through Psychedelic Experience, he plans to combine his knowledge of neuroscience and passion for cultivation to help resolve this misinformation from spreading further.