top of page

The pendulum swings: views on psychedelics among professionals and the public

Historically psychedelics and related substances (PARS) played a part in rituals of healing in several indigenous Southern, Central and Northern American cultures. In the mid-20th century, when few approved psychopharmacologic agents existed, some psychiatrists and psychologists started to experiment with the use of psychedelics.



Following isolation of psilocybin from certain mushroom types in 1958, LSD and psilocybin were used as an adjunct to psychotherapy over the next 15-20 years as reviewed by Koning et al (1). A case in point in the Nordic countries is the recent study by Larsen et al on the use of psilocybin and LSD in the treatment of 324 patients at Frederiksberg hospital in Denmark from 1960 to 1973 (2). Indications for such treatment were quite broad, including most commonly neurosis characterogenes, but also neurosis anxiosa, neurosis obsessiva-compulsiva, neurosis sexualis and psychosis paranoides. Interestingly, depressio mentis endogenica was the main diagnosis among 7 patients (2.5%) only. ´The Controlled Substances Act´ classified psychedelics as Schedule I substances in the US in 1970, triggering legislative changes that substantially restricted psychedelic research domestically and influenced policies in Canada and Europe. Such classification implies three criteria: high abuse potential, no accepted medical use, and lack of accepted safety standards for use under medical supervision. It is undisputeded that users may experience unpredictable and intense experiences during psychedelic trips, and that such experiences can feel overwhelming and leave psychological scars. Still, the first criterion is debatable since classic psychedelics have a low potential for activating the brain´s reward pathways and cause physical dependence as drugs of abuse typically do (3). Assessing abuse potential for candidate medicines is though complex and must today include a comprehensive '8-factor' analysis (3).


Due to reports of adverse effects commonly arising during the treatment with psychedelics in Denmark from 1960 to 1973, the Danish Parliament passed the LSD Damages Law in 1986 which allowed patients to apply for reparatory compensation (2). Of 324 psychedelic-treated patients whose patient records were reviewed by Larsen and colleagues a rather high proportion, 93 (28.7%), applied for compensation and applicants were significantly more likely to have experienced psychosis or flashbacks than non-applicants (18.2% vs. 5.2%, p<0.001) (2).


While psychedelics share 5-HT2A agonism, they vary in their propensity to give rise to visual hallucinations (audio-visual synesthesia, elementary imagery and complex imagery) as well as in their pharmacokinetic half-lives. LSD and psilocybin have for example much longer half-lives than DMT or variants thereof such as mebufotenin (5-MeO-DMT) (4). Both dimensions can have implications for safety, tolerability and not the least scalability in the clinic if these substances will be adapted as components of clinical treatments in the future. The longer the half-life, the longer patients´safety must be ensured by two individuals in a private room during the ensuing psychedelic trip after the substance is administered. For psilocybin, supervised monitoring typically lasts about 6–8 hours (5).


Because effective doses cause distinctive sensory, emotional and cognitive effects, maintaining participant blinding in trials-versus placebo or subtherapeutic doses-is challenging if not impossible.

There is little doubt though that these substances have different mechanisms of action to currently available psychotropic medicines and may be effective when other treatments have failed. Furthermore, it is undisputed that there is an urgent need for novel treatments that may lessen suffering in treatment-resistant depression and severe post-traumatic stress disorder (PTSD). Therefore, it is not surprising that in the early 2000s the public and professional discourse on the potential efficacy of psychedelics and other PARS was gradually reopened, the recent focus most commonly being on their use in psychedelic assisted psychotherapy for PTSD and treatment-resistant depression. Legislative changes in the US and elsewhere have since facilitated research into the potential efficacy of such treatments and hundreds of studies have been launched to examine their efficacy and safety. Two phase III MDMA-assisted PTSD trials have been completed and one is currently being carried out on psilocybin for treatment-resistant depression. Numerous other studies have been or are being carried out by dozens of companies and hundreds of start-ups and pre-clinical biotech companies (https://blossomanalysis.com/all). Given past use, misuse and adverse effects of psychedelics (e.g., flashbacks, psychotic symptoms), regulators like the FDA and EMA remain cautious about approving psychedelic treatments alone or as part of assisted psychotherapy.


In recent years microdosing, most commonly with psilocybin, i.e. using doses much smaller than those that clinical trials have indicated are needed for efficacy, has been much discussed in the media and on the internet. Abstract mushroom art, image by Wix Media.
In recent years microdosing, most commonly with psilocybin, i.e. using doses much smaller than those that clinical trials have indicated are needed for efficacy, has been much discussed in the media and on the internet. Abstract mushroom art, image by Wix Media.

Ketamine, a phencyclidine derivative and not a classic psychedelic, is at present the only drug in the PARS group that is currently licenced for treatment of a mental disorder. It has been used for decades as an anesthetic. Ketamine acts as an NMDA-antagonist and is currently licenced for treatment-resistant depression in the form of nasal esketamine in the medication Spravato. Spravato used in combination with an SSRI or an SNRI antidepressant was approved for treatment-resistant depression in Europe and the US in 2019. As of January 2025 Spravato has also been licenced as monotherapy by the FDA in the US for adults with major depressive disorder who have had an inadequate response to at least two oral antidepressants.


In recent years microdosing, most commonly with psilocybin, i.e. using doses much smaller than those that clinical trials have indicated are needed for efficacy, has been much discussed in the media and on the internet. In Iceland a few celebrities have for instance praised microdosing in webinars as well as in popular shows on TV. A very prominent one stated that microdosing has made him better able to function psychologically, that he is simply more at peace with himself and his traumatic past. Unfortunately, we rarely see or hear celebs praising CBT og antidepressant treatments in such settings and it would probably not be regarded as newsworthy. That may give members of the public the impression that microdosing works better than approved treatments for common mental disorders like PTSD, anxiety disorders or depression.


To date, well-designed studies have not shown that psilocybin microdosing is an efficacious treatment for any mental disorder. Nonetheless, such use clearly has appeal – despite how easy it is to substantiate within seconds using AI in our cell phone that there is no evidence that demonstrates that microdosing of psychedelics is efficacious. Taking a pill is easier than making important and often challenging amends in our daily lifestyle, be it in the use of alcohol, nicotine, opiods, making dietary changes or doing regular exercise. Such is life – it is a part of our human nature to be lured by quick fixes.


We live in a post-factual or post-truth era with polarization on the rise in most of our societies. Established facts on topics like climate change and vaccinations have diminishing influence, as research findings that over decades have built a solid evidence base can easily be distorted by personal narratives spread on social media, often in online echo chambers but also by very influential politicians.


While mainstream media can still influence many middle aged and older adults in our democracies, reaching younger people probably requires publishing research that AI systems can access.

The fourth power or the fourth estate refers to the media´s watchdog role as a check on the executive, legislative and judicial branches of power in a democracy by keeping the public informed about often inconvenient facts. The judicial powers are being eroded in some Western democracies, and politicians with a totalitarian agenda are becoming less and less concerned about its role in keeping their executive powers in check. One could argue that the online echo chambers of today are increasingly becoming the fourth power in at least some pockets of society and may influence the opinions of many individuals from the younger generations (Y and Z) more than conventional media. Many from the same generations also rely increasingly on guidance from artificial intelligence (AI) tools which still are and hopefully will remain a more reliable source of information than what comes our way on social media. We should aim for and hope that AI-provided information will be harder to manipulate than social media content has been in the recent past, for example in the run up to important national elections.


In our quest to keep the public informed by research and evidence-based medicine, we can take some comfort in the observation that the more severe the disorder, the more likely the individuals are to find their way to public health services. Those who have sought treatment in ´wellness clinics‘ over the past 15 years in the US and Europe, clinics that offer all-sort of integrative, holistic, aesthetic or complementary-health services are probably not suffering from a mental disorder of a degree that matches that experienced by those who seek primary or secondary health services. Individuals who prefer to try microdosing or private wellness clinics to public health services may more commonly be struggling due to stressful experiences, such as challenges in relationships or in the work place, than to be suffering from severe recurrent or treatment-resistant mental disorders.


Psychiatrists must determine the most effective ways to provide the public with reliable, evidence based information about treatment efficacy and safety. The individuals most susceptible to online echo chambers are also least likely to accept professional guidance on trustworthy sources, statistical hypothesis testing, and academic approaches to bias. While mainstream media can still influence many middle aged and older adults in our democracies, reaching younger people probably requires publishing research that AI systems can access. AI tools can be configured to prioritize scientific literature and are rapidly improving at identifying sources that meet predefined quality criteria. Individuals from generations Y and Z-and increasingly others-will only rely more by the year on AI for everyday information in the near future; traditional web search is declining. Therefore, we must continue to do research that meets academic benchmarks. Through AI we now have better tools than ever before to disseminate our findings and communicate facts to the public. □



References


  1. Koning E, Chu EM, Brietzke E. The historical opposition to psychedelic research and implications for credibility in psychiatry. CNS Spectr. 2024 Nov 21:1-6. doi: 10.1017/S1092852924002141. Epub ahead of print. PMID: 39568211.

  2. Larsen JK, Kølbæk P, Østergaard SD. Treatment with LSD and psilocybin at the department of psychiatry at Frederiksberg Hospital in Denmark from 1960 to 1973: an analysis of 324 cases. Nord J Psychiatry. 2025 Oct;79(7):475-482. doi: 10.1080/08039488.2025.2529449. Epub 2025 Jul 10. PMID: 40635579.

  3. Henningfield JE, Coe MA, Griffiths RR et al. Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling. Neuropharmacology. 2022 Nov 1;218:109220. doi: 10.1016/j.neuropharm.2022.109220. Epub 2022 Aug 17. PMID: 35987353.

  4. Uthaug MV, Lancelotta R, van Oorsouw K et al. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology (Berl). 2019 Sep;236(9):2653-2666. doi: 10.1007/s00213-019-05236-w. Epub 2019 Apr 13. PMID: 30982127; PMCID: PMC6695371.

  5. Goodwin GM, Aaronson ST, Alvarez O et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443. PMID: 36322843.d


bottom of page