Research Briefing: Flashbacks after psychedelics

This research briefing is co-published with the excellent Report on Psychedelics.

February 14th, 2022

In the Research Briefing

• Flashbacks are common in psychedelic research but participants don’t seem to mind
• LSD influences creativity, breaking down thought patterns and relocating them toward the new
• Psychedelics and society; thoughts on the past, present and future

Looking back on flashbacks in clinical psychedelic research

Reports of drug-induced flashbacks date back to the first era of psychedelic research in the 1950s and 1960s. At the time, research participants reported the reoccurrence of a psychedelic-like state long after the drug’s effects should have worn off. The risk of flashbacks quickly became commonplace in anti-drug campaigns. Now, as psychedelic research has progressed over the last 50 or so years, we have come to regard psychedelics as physically well-tolerated and non-addictive. However, we now know more about the side effects that accompany psychedelics and that people can experience flashbacks as a result of using psychedelics.

According to the World Health Organization, flashbacks are defined as episodic recurrences of drug effects after the acute pharmacological effects have subsided and are characterized as mostly very transient. Moreover, persisting flashbacks that cause clinically significant distress or impairment have been termed hallucinogen persisting perception disorder (HPPD). Despite the recent resurgence in clinical research with psychedelics, data regarding reoccurring drug-like experiences and HPPD remains limited. If psychedelics are to become widely available treatment options, it is important that we unearth the nature of all possible side effects.

The present study aimed to provide data on the prevalence of reoccurring drug-like experiences in modern clinical research with LSD and psilocybin. Data from six double-blind, randomized, controlled trials were analyzed yielding a total of 142 healthy participants who had received LSD (n=60), LSD, MDMA and d-amphetamine (n=27), LSD and psilocybin (n=31) as well as psilocybin and escitalopram (n=25). All participants were asked at the end-of-study visit, on average of 40 days from their last study session, if they had experienced any recurring drug effects since beginning the trial.

Looking back:

• 13 participants reported recurring drug-like experiences (LSD: seven, psilocybin: two, both: four) which were considered mild and perceived as neutral to pleasant.
• The occurrence of flashbacks was limited to the week after drug administration, except for two cases.
• 1.4% of all 142 participants reported distressing experiences related to flashbacks.
• No subjects reported impairment to daily life as a result of these symptoms.
• No reports met the criteria for HPPD.

The present study is one of the first to thoroughly analyse modern clinical research with psychedelics to assess the prevalence of recurring drug-like experiences and HPPD. The results show that these phenomena are relatively common in clinical trials with healthy participants although they tend to be experienced as benign, having little impact on daily life.

The authors do acknowledge limitations to their work including the relatively small sample size as well as the different screening criteria, dosing regimens and substances administered across the studies. Nonetheless, the findings suggest that flashbacks are not a clinically relevant problem in controlled studies with healthy participants.

Psychedelics may open an whole new creative lens

Creativity and psychedelics have long been intertwined. From psychedelic art to psychedelic rock, these substances are believed to possess the inherent ability to inspire creativity once consumed. With The Beatles, Star Wars creator George Lucas and even Apple Co-Founder Steve Jobs believed to have experimented with LSD, one must wonder could their creative success be linked to the use of psychedelics. The exact link between creativity and the use of psychedelics remains speculative at best and researchers are continuing to explore this avenue of psychedelic science.

The present paper used multimodal tasks and multidimensional approaches to assess the effects LSD has on creativity. Participants (n=24) were randomized and given either LSD (50 μg, low-medium dose) or an inactive placebo in a double-blind fashion. Near peak-drug experience, participants were given a range of tests including pattern meaning task (PMT), alternate uses task (AUT), picture concept task (PCT), creative metaphors task (MET) and figural creativity task (FIG). Creativity was then measured by scoring creativity criteria and calculating divergent/convergent thinking. The researchers break down their findings on a number of different levels.

The levels of creative inspiration:

• LSD, compared to placebo, changed creativity on several levels and seemed to elicit two opposing phenomena of ‘pattern break’, reflected by increased novelty (PMT), surprise (PMT), originality (FIG) and semantic distances (PMT), and decreased ‘organization’, reflected by decreased utility (PMT), convergent thinking (PCT) and, marginally but consistently across tasks.
• On a phenomenological level, LSD increased novelty and surprise and decreased utility of responses, indicating that responses were more remote and nonobvious but also ‘chaotic’ and less useful, while there was no change in the amount of highly creative responses.
• On a cognitive level, LSD increased title originality (FIG), while other originality parameters did not survive correction for multiple testing or remained unchanged.
• On a semantic level, LSD increased PMT semantic spread and semantic steps indicating a random semantic spread of ideas.
• On a behavioural level, metaphor and drawing content under LSD exhibited tendentially fewer objects, pointing to a weak but cross-modal phenomenon.
• On an ontological level, symbolic thinking and ambiguity emerged as the most noticeable data-driven features. LSD increased metaphor and drawing ambiguity pointing to a crossmodal feature.

The present study sought to assess how psychedelics, in this case, LSD, alter creativity across a number of levels. LSD changed several creativity measurements pointing to pattern break, disorganization and meaning which seemed to fundamentally influence creative cognition and behaviour. Ultimately, the author’s findings suggest that “psychedelics may not merely disrupt cognitive-behavioural processes ‘away from normal’, but relocate them ‘towards the new’.“

A sociological lens on the past, present and future of psychedelic medicine

Research papers pertaining to the therapeutic potential of psychedelics are emerging on what is now a daily basis. These papers are providing us with the necessary clinical evidence that would see psychedelics transformed from Schedule I substances into viable therapy options, yet more can be done to facilitate this transformation. While evidence from clinical trials and laboratories is undoubtedly necessary, the field of psychedelics could benefit from a more multidisciplinary approach and widening its lens and delving deeper into the qualitative realms of science.

The present study does exactly that. In this paper, the authors identify and discuss some of the key sociological issues related to the medicalization of psychedelics. The sociological lens is rare in this field and offers perspective on the implications of the supposed paradigm shift of psychedelic medicine has on society. After briefly summarizing the history of psychedelics, the authors discuss three key areas of interest: 1) the role of advocacy in the advancement of scientific research and the destigmatisation of psychedelics; 2) issues related to the medicalisation and pharmaceuticalisation; 3) and integration into healthcare systems.

Key points:

1. Given the support from key organizations, institutions and individuals, the promotion of medical research in this field can be usefully understood as a form of health advocacy—the application of information and resources to reduce health problems and effect systemic change.
2. A sociological lens of medicalisation helps to illuminate the socio-medical frameworks and discourses that structure the advocacy and research paradigms that will shape the entry of psychedelic therapies into formal healthcare. Psychedelics present an unusual case for the creation of a medical treatment insofar as they have long histories and diverse cultural imaginaries attached to them.
3. The anticipated rescheduling of psychedelic compounds following recognition of their medicinal and therapeutic application raises several questions regarding what psychedelic medicine and psychotherapy would look like in practical application. 
4. The legal and cultural settings in the various countries where psychedelic medicines are proposed will shape processes of reclassification, regulation and control of these compounds. Negotiating the stigmas, the War on Drugs, the tensions between medicalisation and decriminalisation, as well as the structures of proposed regulation, will challenge authorities and likely have profound consequences.
5. There is little doubt that private interests will play a major role in shaping any future rollout of psychedelic-assisted therapies. A major concern for researchers, medical professionals and commentators alike is the potential disjuncture between for-profit business models and public health.

This paper is one of the few to take the view of the field of psychedelics through the lens of sociology. The key points provided here are brief but are eloquently expanded on within the text where the authors provided even more food-for-thought. The world of biomedicine tends to focus on the material and quantifiable but a lot can be learned from the less objective disciplines like sociology. Such perspectives ask the questions that numbers cannot answer and in doing so provoke thoughts, spur conversation and maybe even inspire a lab-based experiment or two.

Research Report Readout

Intranasal and IV racemic ketamine reduce symptoms of PTSD and depression. However, treatment with IV racemic ketamine led to greater reductions, suggesting that off-label use of IV racemic ketamine may be useful for those who do not respond adequately to FDA-approved intranasal ketamine.

Yet another microdosing study finds that the practice has little effect. In this double-blind placebo-controlled trial, participants received 13 ug (n=19) or 26 ug (n=19) of LSD or placebo (n=18). While the higher dose of LSD had modest subjective effects, negligible changes in mood or cognition were reported.

Researchers provide the foundations for producing non-hallucinogenic psychedelic analogues. The study presents structures of the serotonin receptor 5-HT2RA bound to psilocin, LSD, serotonin and the non-hallucinogenic analogue lisuride and specially designed non-hallucinogenic ligands with antidepressant effects in mice.

Another review explores the evidence that psychedelics may ameliorate symptoms of autism spectrum disorder (ASD), specifically reduced social behaviour and co-occurring anxiety and depression. The dysregulated neurobiological systems in ASD are discussed as well as research from the 1960s and 70s which assessed the use of psychedelics in the treatment of children with ASD.

Riccardo McMillan argues that psychedelic-using communities ought to be included in bioethical discussions that guide normative elements of psychedelic medicalisation. It is argued that psychedelic-using communities have a degree of epistemic expertise regarding psychedelics and that these communities are uniquely and heavily affected by psychedelic medicalisation.