After the psychedelic trip is over!

After the trip is over: what does the literature say about the long-term therapeutic effects of psychedelics?

?

Introduction

The resurgence of interest in psychedelics as potential treatments for mental health conditions is an exciting development in modern psychiatry. Recent studies indicate the promising effects of psychedelics in managing a variety of conditions, including depression, anxiety, post-traumatic stress disorder (PTSD), and addiction, signalling a major shift in our approach to mental health care.

?

This wave of optimism is not unfounded; many patients and healthcare professionals alike are in search of a transformative solution—a 'magic bullet'—that could revolutionize the treatment of complex, treatment-resistant cases and offer hope to those who seem beyond reach.

?

However, our excitement must come along with caution and critical inquiry. Despite the encouraging outcomes, many questions remain unanswered: What are the true long-term implications of therapeutic psychedelics? How enduring are their therapeutic effects? What are the risks?

?

The existing body of research, though promising, is limited by small sample sizes, brief follow-up durations, and a reliance on self-reported data. These constraints highlight the preliminary nature of our current understanding and underscore the need for rigorous, large-scale studies.

?

As we stand on the brink of potentially groundbreaking advancements in psychiatric treatment, the urgency for an evaluation of psychedelics' long-term effects has never been more apparent. As the field of psychedelic research continues to expand at an unprecedented rate, it is crucial to critically assess what we know—and what remains to be discovered—about these substances.

?

?

The positive lasting effects of psychedelics

A 2020 systematic review in Neuroscience and Biobehavioral Reviews made inroads in consolidating our knowledge about enduring impact using data across 34 studies with a follow-up period of at least two weeks. The reviewers noted significant and lasting changes across multiple domains. Some individuals maintained lower levels of depression long-term, while others returned to baseline. In seven out of eight of the studies looking at long-term impacts on anxiety, psychedelic treatment led to a significant reduction in symptoms.

?

?

These positive effects on symptoms of depression and anxiety may be due to the mystical experience – characterized by deep feelings of meaning/sacredness, interconnectedness, transcendence of time and space, ineffability, and a strong positive mood. In two of the studies reviewed, one or two doses of psilocybin were related to significant improvements in depressive symptoms 6 months later and the more mystical the experience, the greater the reductions in depression at the 6-month follow-up.

?

These findings were echoed in a 2020 meta-analysis which found that psilocybin was associated with large reductions in depression and anxiety across four recent studies, with significant effects at 6 months. However, there were concerns about the studies' reliability due to variations in study design, potential biases, lack of blinding and limited racial-ethnic variation.

?

Other studies in the review found psychedelics were related to increases in pro-social behaviour, decreased likelihood of criminal behaviour, and increased levels of relatedness to nature, creativity and altruism.

?

All good then?

?

Well, yes and no. While the systematic review certainly underscores the potential of psychedelics to induce long-lasting beneficial changes across various domains of life there are still limitations. Of all of the studies included in the systematic review, the highest sample size was 51. The mean sample size was 16 and more than half of them didn’t include a control. So, while promising, this emphasizes the necessity for further research to fully understand these effects, particularly regarding their sustainability and the mechanisms underlying them.

?

The small sample sizes used in psychedelic research mean that a dedicated meta-analysis would allow us to draw some quantitative conclusions across the studies and clarify inconsistencies.

?

One such meta-analysis, published in Psychological Medicine reviewed the long-term psychological impact of classic psychedelics – LSD, psilocybin, and DMT – observing their effects more than 24 hours after administration. Spanning 34 studies with an average follow-up period of one year, the analysis noted that psychedelics may have substantial positive psychological outcomes. Notably, they showed a statistically significant improvement in targeted symptoms compared to placebo in randomized controlled trials. This effect was comparable to or beyond those seen in psychotherapy vs waiting lists and in antidepressants vs placebos.

?

The benefits of psychedelics were diverse, affecting targeted psychiatric symptoms, depression, negative and positive emotions, social dynamics, and existential or spiritual well-being. Effect sizes varied from moderate in improving positive affect to very large in alleviating depression with consistent results immediately after treatment and at follow-up.

?

Despite the promising findings, the researchers acknowledged several study limitations, such as the challenge of maintaining effective blinding due to the distinctive effects of psychedelics, potential publication and selection biases, small total sample size (549 participants), and considerable methodological diversity across studies which could not be fully accounted for.

?

These limitations noted, this data still aligns with previous meta-analyses and reinforces the idea that psychedelics have earned the right to further scientific investigation, but this time, in high-quality, placebo-controlled, large-scale trials.

?

The negative effects of psychedelics

But as we delve into the realm of psychedelics and their therapeutic potential, it's critical to examine the other side—the possible negative effects. A comprehensive 2022 review published in the Journal of Psychopharmacology sought to dispel common misconceptions and provide evidence-based analysis of potential harms.

?

Contrary to widespread concerns, the incidence of serious psychological changes, such as psychosis or persistent mental health problems following psychedelic use, is quite rare. A survey cited in the review, which included nearly 2,000 individuals who had challenging psychedelic experiences, reported that only a fraction (0.15%) encountered prolonged psychotic symptoms. However, many modern studies extensively screen out individuals with personal or family histories of psychiatric conditions, which raises some questions about their real-world applicability in the psychiatric patient population.

?

However, naturalistic studies and large-scale epidemiological studies may clarify risks, and one US survey of over 130,000 people found no link between psychedelic use and an increase in mental health conditions like depression or anxiety. Interestingly, psychedelic users were less likely to have sought mental health treatment within the past year compared to non-users. This is by no means condoning the recreational use of psychedelics, though it is interesting data to consider.

?

From a physical health perspective, psychedelics have been deemed physiologically safe with no long-term neurocognitive deficits reported. While they can cause temporary physiological responses such as increased heart rate or blood pressure, serious complications like organ toxicity or brain damage, as once feared, are not supported by modern research findings.

?

Regarding the risk of death, the review found it to be exceptionally low. In the rare instances where deaths were reported, they were typically associated with extremely high doses or the concurrent use of other substances. Moreover, psychedelics like LSD and psilocybin have a remarkably low rate of emergency hospital admissions, especially when compared to other recreational drugs.

?

The potential for dependency and misuse of psychedelics also appears to be lower than for many other substances. While this evidence is reassuring, it's paramount that we approach the therapeutic use of psychedelics with prudence. Careful screening and preparation of patients, especially those with a predisposition to psychotic disorders, are essential safeguards in clinical trials and treatments. This level of caution ensures that the risks are minimized, and patients are safely guided through their experiences.

?

?The final word

Compelling evidence of positive impacts on mental health conditions—be it depression, anxiety, PTSD, or addiction—cannot be ignored. Such findings suggest these substances could indeed be long-sought-after agents of change, reshaping psychiatric care for those grappling with the most tenacious of mental health challenges.

?

Yet, it is with a blend of optimism and a sobering sense of responsibility that we must proceed. The promising results observed should be weighed against the constraints of current research. This gap in knowledge calls for well-designed, large-scale, placebo-controlled trials to ensure that the initial ‘magic’ of psychedelics can be translated into enduring, safe, and effective treatments.

?

As researchers, clinicians, and leaders in this space, we must navigate this renaissance with both the excitement of explorers and the disciplined rigour of scientists. Only through this balanced approach can we truly unlock the full potential of psychedelics.