Reviewed By: Brian Pilecki, Ph.D.

After decades of legal stigma, psychedelics are moving toward the mainstream. A growing number of clinical trials show that psychedelic drugs (and related compounds, like MDMA and ketamine) can help treat a variety of mental health disorders, including depression, PTSD, and addiction.

Study results are very promising. Initial clinical trials suggest that psychedelic-assisted therapy might double the efficacy of current leading treatments. Patients respond after only two or three therapy sessions, and the results seem to last for years. While these results are promising, one must be careful interpreting these results, as it is yet unclear how effective psychedelic-assisted therapy might be in real-world settings. 1,2,3

Psychedelic drugs show extraordinary potential—but as they approach legalization, it’s important to keep a tempering question in mind: who should avoid taking psychedelics?

Psychedelics Are Unique—and That Makes Them Hard to Prescribe

Like any medicine, psychedelics aren’t for everyone—and psychedelics may demand particular caution.

Most drugs are highly predictable. If you give someone a Xanax, you’ll see the same result, virtually every time: rapid anxiety relief, decreased panic, drowsiness, muscle relaxation. Xanax is Xanax, with largely the same effects, regardless of the context in which you take it.

Psychedelics are different. Their effects change based on set and setting—your mental state and the environment in which you take them.

That kind of variation makes it difficult to figure out who will respond well to psychedelics and who will have a negative experience.

That said, researchers are starting to figure out how psychedelics affect different people, how they change your brain, and who might be better off avoiding psychedelics.

Who Should Avoid Psychedelics?

It’s not yet fully clear who will do well with psychedelics and who may want to avoid them.

However, early research has found that psychedelics may be a riskier choice for certain populations. You may want to avoid psychedelics if you have:

  • History of psychosis or mania
  • Heart conditions
  • High trait neuroticism

History of psychosis

Psychedelics mimic several of the symptoms of a psychotic episode—hallucinations, disconnection from reality, mood swings, and, in some cases, paranoia.

As a result, most researchers screen for psychosis and related risk factors in psychedelic study participants. There’s a concern that psychedelics could trigger or exacerbate psychotic symptoms.

It’s not clear how well-founded that concern is. Early surveys suggest that there’s no correlation between psychedelic use and mental health problems, including psychosis. 4 In fact, an older survey from 2013 actually found a lower incidence of mental health problems among psychedelic users. 5 These are just correlational studies, though, and don’t tell us if psychedelics cause health problems or not.

On the other hand, recent research on cannabis and psychosis has found that cannabis consumption exacerbates psychotic symptoms and, in rare cases, can trigger permanent psychosis in previously healthy people. 6 While cannabis and psychedelics are quite different, some researchers are concerned that psychedelics may have a similar effect.

As of right now, the rule of thumb among researchers is to continue to avoid giving psychedelics to patients with psychotic disorders or a history of psychosis. That includes schizophrenia, schizoaffective disorder, and bipolar disorder, among others.

At the time of this article’s publication, there’s been no direct research on psychedelics and psychosis. Hopefully, future research will clarify how the two interact—but until then, it may be best to avoid psychedelics if you have a psychotic disorder or a history of psychosis.

Heart conditions

Similar caution exists around psychedelics and heart conditions.

Psychedelics work by increasing serotonin signaling in your brain. Some serotonergic drugs can aggravate existing heart conditions 7, particularly if they activate 5HT2B receptors. 8 LSD binds to 5HT2B receptors, 9 and in a 2011 study, researchers singled out drugs derived from ergot—the original source of LSD—as a possible factor in aggravating existing valve disease. 8

MDMA also activates 5HT2B receptors, and a 2007 study found that 28% of MDMA users had irregular heart valve activity, compared to 0% in the control group. 10 However, participants in this study were likely using MDMA more frequently than participants receiving MDMA-AT in MAPS trials, which did not find evidence of any negative cardiac outcomes.

It’s worth noting that there haven’t been any direct studies on psychedelics (or related compounds, like MDMA) and valvular heart disease.

However, until the relationship between psychedelics and heart function becomes more clear, you may want to avoid taking psychedelics if you have valve-related heart problems.

High trait neuroticism

Neuroticism is one of the traits on the Big Five inventory, the most validated and widely used personality test in psychology research.

Neuroticism is a measure of your tendency toward negative emotion and capacity to handle stress. People high in trait neuroticism tend to experience negative emotion more often, including more sadness, anxiety, fear, anger, depression, and loneliness. High neuroticism also predicts lower emotional stability and a lower capacity to handle stressful situations. 11,12

A 2018 study found that people with high neuroticism are more likely to have bad trips while on psilocybin mushrooms. 13 Higher neuroticism predicted greater feelings of fear, distress, grief, isolation, and paranoia during psychedelic trips.

It’s worth mentioning that bad trips can lead to good outcomes. They aren’t always a negative thing long-term. A 2016 study found that 84% of people reported a bad trip being good for them in the long run.  14 In about 7% of people, however, bad trips lead to lasting mental distress that drove them to seek therapy.

If you have high neuroticism, your odds of having a bad trip increase, and you may want to avoid psychedelics.

Final Thoughts

Psychedelics are exceptionally promising tools for mental health. More and more evidence suggests that psychedelics could revolutionize mental health treatments, especially for depression, PTSD, and addiction.

Psychedelics are also quite safe for most people. They have no known overdose potential. (The exceptions are ketamine and MDMA, which have overdose risk and abuse potential.) They don’t cause side effects in healthy people. Even bad psychedelic trips rarely cause lasting psychological harm—in fact, in most cases, bad trips seem to improve long-term mental health.

With the recent rush of positive research, it’s tempting to paint psychedelics as a cure-all, some sort of magic bullet for mental well-being.

But that kind of fanfare can lead to disappointed patients—patients who go into a trip thinking it will solve all their problems and come out wondering why their lives aren’t perfect. It can lead to rushed research that anticipates positive outcomes and glosses over negative ones. It can turn people into evangelists who promote psychedelics to everyone, instead of treating them with the care that powerful, mind-altering compounds demand.

Before we jump to conclusions about psychedelics, we should remember that there’s a lot we still don’t know about them. Researchers are just beginning to understand how psychedelics work in the brain, and almost all psychedelic research has been on highly screened participants. How will it translate to the general public?

Until we can answer these questions, it’s best to be cautiously optimistic when it comes to psychedelics. There’s a lot of cause for excitement—but there’s a lot to learn, too.



Dr. Brian Pilecki is a clinical psychologist at Portland Psychotherapy specializing in psychedelic-assisted therapy and treating anxiety disorders, trauma, and PTSD. He graduated from Fordham University and completed a postdoctoral fellowship at the Warren Alpert Medical School of Brown University.


1. Johnson MW, Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. 2017;43(1):55-60. doi:10.3109/00952990.2016.1170135

2. Davis AK, Barrett FS, May DG, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021;78(5):481-489. doi:10.1001/jamapsychiatry.2020.3285

3. Muttoni S, Ardissino M, John C. Classical psychedelics for the treatment of depression and anxiety: A systematic review. J Affect Disord. 2019;258:11-24. doi:10.1016/j.jad.2019.07.076

4. Johansen P-Ø, Krebs TS. Psychedelics not linked to mental health problems or suicidal behavior: a population study. J Psychopharmacol (Oxford). 2015;29(3):270-279. doi:10.1177/0269881114568039

5. Krebs TS, Johansen P-Ø. Psychedelics and mental health: a population study. PLoS ONE. 2013;8(8):e63972. doi:10.1371/journal.pone.0063972

6. Hasan A, von Keller R, Friemel CM, et al. Cannabis use and psychosis: a review of reviews. Eur Arch Psychiatry Clin Neurosci. 2020;270(4):403-412. doi:10.1007/s00406-019-01068-z

7. Rothman RB, Baumann MH. Serotonergic drugs and valvular heart disease. Expert Opin Drug Saf. 2009;8(3):317-329. doi:10.1517/14740330902931524

8. Hutcheson JD, Setola V, Roth BL, Merryman WD. Serotonin receptors and heart valve disease–it was meant 2B. Pharmacol Ther. 2011;132(2):146-157. doi:10.1016/j.pharmthera.2011.03.008

9. Wacker D, Wang S, McCorvy JD, et al. Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell. 2017;168(3):377-389.e12. doi:10.1016/j.cell.2016.12.033

10. Droogmans S, Cosyns B, D’haenen H, et al. Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease. Am J Cardiol. 2007;100(9):1442-1445. doi:10.1016/j.amjcard.2007.06.045

11. Thompson ER. Development and Validation of an International English Big-Five Mini-Markers. Pers Individ Dif. 2008;45(6):542-548. doi:10.1016/j.paid.2008.06.013

12. Ormel J, Riese H, Rosmalen JGM. Interpreting neuroticism scores across the adult life course: immutable or experience-dependent set points of negative affect? Clin Psychol Rev. 2012;32(1):71-79. doi:10.1016/j.cpr.2011.10.004

13. Barrett FS, Johnson MW, Griffiths RR. Neuroticism is associated with challenging experiences with psilocybin mushrooms. Pers Individ Dif. 2017;117:155-160. doi:10.1016/j.paid.2017.06.004

14. Carbonaro TM, Bradstreet MP, Barrett FS, et al. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol (Oxford). 2016;30(12):1268-1278. doi:10.1177/0269881116662634