More on psychedelics

Further to my last post, when you go looking for studies on harm from hallucinogens/psychedelics, a hell of a lot of them start with something like "despite the rise in interest in psychedelics as potentially useful therapeutic tools in recent years, detailed and reliable studies about harmful effects have been lacking."    

Anyway, here are some of the more interesting things I have found, so far:

NMURx surveyed 267,268 adults representing 256,742,237 Americans (Table E1; available at http://www.annemergmed.com) over the study period. The prevalence of past year psychedelic use in nondecriminalized US states modestly increased from 2.4% (95% confidence interval [CI] 2.33% to 2.54%) in 2019 to 2020 to 2.84% (95% CI 2.74% to 2.95%) in 2021 to 2023. Oregon and Colorado rates have risen from 3.28% (95% CI 2.66% to 3.89%) in 2019 to 2020 to 5.44% (95% CI 4.63% to6.24%) in 2021 to 2023 

The background to that is that Oregon and Colorado " have already legalized and decriminalized the sale, possession, and growth of natural psychedelics for counseling, spiritual guidance, beneficial community-based use, and healing. As of August 2023, 22 states have active legislation on psychedelic medical use."  I don't know, but a state in which upwards of 5% having used a psychedelic in the last year sounds like a state with too many people using them.

 Going back to 2013, one open-access study found that regular users of psychedelics maybe had less mental health issues(!).   But the study itself acknowledges significant limitations.   And I see there is also perhaps a bit of the (many decades old) argument used regarding cannabis that if someone did get psychosis after doing the drug, maybe there were going to get schizophrenia anyway: 

There are very few case reports of prolonged psychiatric symptoms following psilocybin or mescaline [13], [52]. Almost all claims of psychiatric harm caused by peyote have been found on examination of medical records to be due to pre-existing schizophrenia or other causes [53], [54]. 

So, count me as suspicious of that study.

I see that the researchers in that study are quoted in a 2022 study which similarly seems determined to find that the risks are pretty low, and keeps emphasising that how they are used (you know, in a supportive, safe context, like a psych's office) makes it much safer.   Things like "how they are going to be used recreationally" don't get treated in much detail, for example:

 In unprepared individuals and/or in unsafe settings, effects of psychedelics may have the potential to escalate into dangerous behaviour (Johnson et al., 2008). Although very rare, there are reports of individuals jumping from buildings and ending their lives (e.g. Honyiglo et al., 2019; Keeler and Reifler, 1967). While these occurrences are uncommon compared with other psychoactive drugs – especially alcohol – they are widely reported in the media which contributes considerably to public perceptions of their risks.

And:

In Carbonaro et al.’s (2016) online survey about challenging experiences after consuming ‘mushrooms’, 11% of users reported putting themselves or others at risk of physical harm. This was often related to greater (estimated) dosage, difficulty of the experience and lack of physical comfort and social support – all of which can be controlled under clinical conditions. 

A study in Nature in 2023 is of limited use, given the small sample that it involved, but it's interesting that the abstract starts with the observation that a lot of studies seem to be biased towards the positive:

Recent controversies have arisen regarding claims of uncritical positive regard and hype surrounding psychedelic drugs and their therapeutic potential. Criticisms have included that study designs and reporting styles bias positive over negative outcomes. The present study was motivated by a desire to address this alleged bias by intentionally focusing exclusively on negative outcomes, defined as self-perceived ‘negative’ psychological responses lasting for at least 72 h after psychedelic use.  

Here's another questionable self selecting, self reporting, survey study, but it has this interesting part:

Taken as a whole, these studies provide convergent support for findings from clinical trials, including that psychedelic use (either lifetime or prospective) is associated with increased emotional well-being (19–26), reduced harmful substance use/misuse (i.e., illicit drugs/tobacco/alcohol) (27, 28), a tendency toward liberal political views and an enhanced sense of connection with nature (29, 30). These effects are reliably associated with the occurrence of various types of transformative mental states (e.g., mystical, emotional breakthrough, insight-type) during the acute psychedelic experience that have also predicted outcomes in clinical trials (6, 9, 11, 22, 31–33).  

 I can assure the reader that I did not become more Left leaning as I aged due to use of a drug!

 The study does turn up this figure for harms:

...not all participants reported unqualified benefit from psychedelic usage. Thirteen percent identified at least one harm, and these participants reported receiving significantly less mental health benefit from their psychedelic usage than participants not endorsing any harms. 

 OK, so a very recent study from Norway did some more survey stuff, and it's really hard to follow from the paper what they found!   It does have some interesting passages, though:

Adverse events as conceived in the context of clinical trials (e.g. any undesirable experience associated with the use of a medical product in a patient) overlap with the non-medical concept of ‘challenging experiences’ arising from self-experimentation with psychedelics. In clinical trials, the most common adverse events reported after ingestion of psychedelics are headaches, nausea and transient anxiety (Andersen et al., 2021). However, serious adverse events have been reported after the administration of psilocybin for treatment-resistant depression, such as severe suicidal (Goodwin et al., 2023) and cases of extreme anxiety induced by LSD requiring the use of benzodiazepines to contain the situation (Holze et al., 2023). In clinical trials, high anxiety during the psychedelic drug administration have been associated with worse clinical outcomes (Roseman et al., 2018). Anxiety following a high dose of psilocybin or LSD is also common among healthy subjects, as 30 % of participants in controlled studies experience fear and panic, and 17–34 % experience paranoid ideation (Griffiths et al., 2006, 2011; Schmid et al., 2015). Recently, there has been increased attention to possible negative effects resulting from both clinical and non-clinical use of psychedelics (Evans et al., 2023), and criticism of the field for not properly assessing and appreciating risks (van Elk and Fried, 2023). Challenging psychedelic experiences during acute effects are quite common, but to what extent and through which mechanisms they are implicated in prolonged negative effects needs more research. 

Well, that's a pity, because it's the more prolonged negative effect rate that I'm interested in! 

The next paragraph contains the now familiar refrain - more research needed:

The increased interest in psychedelics from researchers and the public merits translation of validated questionnaires for assessing the qualitative nature of subjective states and outcomes resulting from using these compounds. Epidemiological studies indicate that psychedelic drug use is increasing and that more people report difficulties during acute effects and seek help for post-psychedelic health complaints (Bouso et al., 2022; Miech et al., 2023; Simonsson et al., 2023; Tate et al., 2023). It is therefore paramount that researchers pay attention to negative and complex reactions to psychedelic drugs in the general population, as well as to their possible benefits. Measurements that capture these themes are also highly relevant in psychedelic-assisted psychotherapy, where processing difficult cognitive and emotional material is core to the treatment modality.

 Another paragraph talks about research that has looked at the adverse effects:

While not affecting most psychedelic users, there are indications that a significant proportion experience substantial distress and challenges with functioning after psychedelic experimentation (Simonsson et al., 2023). The types and precise causes of enduring negative effects after psychedelics are an ongoing area of research. At present there are studies and reports suggesting increases in anxiety, trauma-like symptoms, feelings of disconnection and dissociative experiences, depersonalization and derealization, existential confusion and loss in sense of purpose, and perceptual abnormalities such as Hallucinogen Persisting Perceptual Disorder (HPPD) (Bouso et al., 2022; Bremler et al., 2023; Evans et al., 2023; Kvam et al., 2023; Vis et al., 2021). In addition, there are credible reports of worsening and triggering of psychotic symptoms and manic or hypomanic states, induction of suicidal ideation, as well as negative impact on traits among people with personality disorders (Barber et al., 2022; Kramer et al., 2023; Marrocu et al., 2024; Morton et al., 2023). Having pre-existing psychiatric diagnoses is a risk factor for challenging psychedelic experiences in these studies, but not a prerequisite as it also occurs without known psychological risk factors and relates to variables such as higher dose, younger age, chaotic contexts, and absence of social support (Simonsson et al., 2023; Vizeli et al., 2024). These contextual factors appear to play a key role in the development of lasting negative effects and likely apply not only during the acute phase of a challenging psychedelic experience but also in the period afterward. In the future, we suggest that it is fruitful to study post-drug trajectories in combination with emphasis on the broad and varied range of mediating factors that interact with the psychedelic experience.  

Well, there's a hell of a lot of links there to go looking at, but I've spent enough time on this for now.