Introduction
Public and Patient Involvement (PPI) aims to produce research “by” and “with,” rather than “to” or “for” people with lived experience (NIHR). PPI is effective across health research (1, 2), particularly in mental health research (3, 4), and is an emerging topic in the psychedelic field (5). By incorporating non-researcher, e.g., patient and public input into various parts of the research cycle, PPI produces relevant, transparent, and accountable research (6, 7). This PPI venture was undertaken to involve people with lived experience (“contributor”) in the design phase of a future trial investigating the effects of psilocybin in people with fibromyalgia. The fibromyalgia population was chosen for potential psychedelic application because of its relatively common occurrence, central nervous system involvement, and high rates of mental health co-morbidities.
Those living with chronic pain report feeling misunderstood and invalidated (8, 9). This highlights the need for intentional communication at early stages of research to ensure thoughtful design that prioritizes the specific needs of people with chronic pain. The accordingly selected methods of in-depth, open-ended discussions (10, 11) and the thematic analysis thereof (1, 12–14) are widely used in PPI. Further, such conversations effectively facilitate early involvement at the design stage of research (10, 15). The product is a nuanced exploration of the chronic pain experience and warrants the following background to adequately contextualize.
Roughly 20% of the global population live with chronic pain (16), and it is considered one of the global leading causes of disability (17). Chronic pain is defined as pain lasting over three months and may remain even if the original injury has formally healed (18, 19). Common chronic pain conditions include Chronic Low Back Pain, Headache, and Chronic Widespread Pain e.g. Fibromyalgia Syndrome. Living with chronic pain significantly impacts a person's ability to work, resulting in high levels of lost productivity, reportedly costing the UK economy £10.7 billion annually (20). The social implications of chronic pain are also considerable; over half of pain patients report that their condition has prevented them from seeing family and friends and that their pain contributes to significant social anxiety (21). Such increases in social isolation, as well as the general stress from constant pain, directly impact patients' psychological wellbeing; it is estimated that 20% of people with chronic pain experience comorbid depression (22), with rates up to 60% in conditions such as Fibromyalgia Syndrome (23). This well observed bidirectional relationship links stress to an increased likelihood of developing chronic pain (24, 25).
Current guidelines recommend education, physical therapy and pharmacological interventions, such as non-steroidal anti-inflammatory drugs (NSAIDs), weak opioids, and antidepressants or anticonvulsants off-label (26, 27). Second line treatments graduate to invasive procedures such as neurosurgery, neuromodulation, nerve blocks and radiofrequency denervation (27, 28). However, several problems with the current strategies for treatment of chronic pain remain. Firstly, existing medications carry a number of unwanted side effects and can be habit forming, for example long-term opioid use is linked to dependence and has directly contributed to the ongoing international opioid crisis (29). Secondly, conventional interventions, both pharmacological and invasive, have high Number-Needed-to-Treat values and are only effective in up to 80%, leaving ~1 in 5 sufferers without pain relief (30). Finally, these treatments either neglect or fail to adequately address the psychological impact of chronic pain conditions, leading to growing numbers seeking alternative treatments and experiment with self-treatment (31, 32). In cases where pain persists, patients can be referred to multidisciplinary pain management programmes (PMPs), which aim to support individuals to effectively manage and live with their pain through education, physical therapy and psychological therapies such as Cognitive Behavioral Therapy (CBT) (33) or Acceptance and Commitment Therapy (ACT) (34). CBT and ACT are well-established trans-diagnostic behavior-based psychological therapies which aim to improve awareness and reduce harm caused by negative thought patterns. Their shared foundation focuses upon Cognitive Reframing/Restructuring, a process in which thoughts and beliefs are identified, examined, their relative importance is reviewed, and maladaptive beliefs are updated with therapeutically useful, often positive, ones (35). Evidence suggests such cognitive reframing is transdiagnostically useful, resulting in improved outcomes in healthy populations (36), depression (37), Post-Traumatic Stress Disorder (PTSD) (35), and chronic pain (38). While PMPs are the sole treatment option to directly address the prevalent mental health comorbidities associated with chronic pain, their efficacy is largely limited to the short term (39–42) and attrition/relapse rates remain high (43, 44).
Used in combination with psychological support, psychedelic drugs [e.g., Lysergic Acid Diethylamide (LSD), Psilocybin (the psychoactive component of magic mushrooms), and dimethyltryptamine (DMT)] appear to exhibit promising therapeutic effects in conditions such as depression (45–47), addiction (48, 49), and end-of-life anxiety (50–53). The safety profile of psychedelics is well-established as largely physiologically benign (54), though psychologically challenging periods are common during acute experiences (55). Case reports of persisting perceptual changes exist, though these are rare (54, 55). Historically, there has been interest in using psychedelics to treat chronic pain; preliminary studies from the 1960s and 70s suggest that psychedelic drugs may be therapeutically useful, specifically for cancer pain and phantom limb pain (56–61). Although the results of these historical trials all show promising results, they lacked the methodological rigor of modern trials making it difficult to draw strong inferences on their findings. Contemporary studies suggest that psychedelics may be therapeutically useful in treating intractable headaches such as migraine and cluster headaches (62–64), and two recent reviews hypothesize potential mechanisms and applications for psychedelics in chronic pain (65, 66). Pharmacologically, this concept is plausible. The primary mechanism of action of classic psychedelics is via the 5-HT2A serotonin receptor, which is integral to inflammatory pain (67, 68). Data suggests that psychedelics reduce inflammation (69–71) via the downstream effects of 5-HT2A agonism such as TNF regulation (72), and may result in desensitized central pain responses (66). The acute effects of psychedelics may also contribute toward an analgesic response by reorienting attention away from unpleasant sensations toward altered perceptions, e.g., visual hallucinations (73).
While research has stalled for decades due to the legal status of psychedelic drugs, public interest has not. Psychedelic self-medication has grown in popularity in recent years, reportedly making up 14.8% of self-reported psychedelic substance use (74) and first time LSD-use having increased ten-fold in 10 years in adults over 26 (75). Methods of use range from the semi-regular taking of sub-perceptible doses (known as “microdosing”) to isolated high dose sessions emulating clinical contexts to address mental health concerns (76). Notably, anecdotal reports of effective management of chronic pain have been prevalent; online forums such as Erowid and Reddit contain hundreds of reports of effective treatment for chronic pain conditions such as Fibromyalgia (ErowidFMS) (77, 78), Chronic Back Pain (ErowidCBP), and Rheumatoid pain (RedditEDS) (79). The largest group of reports concern chronic cluster headaches and migraines (80), with over 10,000 people participating in the organization “Clusterbusters,” dedicated to the treatment of headaches with psychedelics (81). This has given rise to a cache of largely untapped knowledge held by psychedelic users who, through self-experimentation and extensive online publishing of “trip reports,” have independently attempted to develop a public library detailing the effects of different substances. This PPI initiative takes advantage of existing public interest and knowledge with the objective of infusing context and input from people with lived experience into various aspects of trial development, and directly influence study design, therapeutic protocols, and outcome measures.
For this PPI investigation, 11 public contributors were invited for 1-to-1 open ended discussions with one of the researchers developing the upcoming trial. The aim of these discussions was to explore (i) how people with chronic pain self-medicate with psychedelic drugs, (ii) whether people have found psychedelics to be effective, and (iii) to gain some insight on specific practices that contributors feel are important for treatment success. While safeguards against bias were employed (see section Materials and Methods), we do not claim that the following work is free of bias or generalisable to the larger population.
Discussion
This project was undertaken as a PPI venture for an upcoming trial, aimed at learning from the lived experiences of people with chronic pain and leveraging these data toward the development of trial design and procedures. To our knowledge, this is the first work detailing PPI for chronic pain in the context of psychedelics. Using thematic analysis, we highlight some common factors that contributors referred to as being linked to perceived successful outcomes from their self-medication. These were: positively reframed perspectives and strengthened sense of embodiment, as well as incorporating adjunct approaches. In interpreting these results however, we recognize that this work is subjective in two respects: (i) qualitative analysis is inherently subjective (90) which (ii) rests upon the subjective reports of, in this case, highly motivated contributors.
Broadly, the following are recommendations that can be taken forward from these reports into the development of the upcoming trial. Adequate preparation was highlighted as essential and included understanding the potential intensity of the experience, both physically and emotionally. All contributors in some way underscored the importance of trust, surrender, or openness for a beneficial outcome [see (91, 92)]. This included openness to the experience itself and contributors especially emphasized developing rapport and trust with their “guides” if used clinically (93–97). Using additional modalities (see below) was also viewed as a key component of the experience. Although the specific choice(s) varied between each contributor, intentionally engaging with the body through movement and/or breath was frequently highlighted. Physical catharsis, whether through physical movement, somatic discharge (see below), or even through art was also valued. This will be incorporated into the trial (details below). Finally, integration and aftercare, while not reported by everyone, were viewed as essential to the perceived longevity of therapeutic benefit.
A common psychological component seen in those with chronic pain is pain catastrophising (98). Core aspects of this phenomenon were widely expressed by contributors and include a tendency toward pessimism, helplessness, and fear (99), the result being exaggerated experience of overall discomfort. Individuals with chronic pain judge the potential threat of pain through magnification and rumination, eventually compromising their perceived agency over their situation (100). Evidence supports a causal relationship between catastrophising and pain, to varying degrees (101–105). There is also a known relationship between catastrophising and depression (104, 106) and tolerance of uncertainty (107, 108), and negative mental affect has widely been linked to worsened pain outcomes (25, 106). There can develop a self-potentiating or self-fulfilling cycle, in which the continuing experience of pain seemingly verifies the negative expectations that contribute to its maintenance. This is diametrically opposed to the tenets of optimism (109), hope (110), and openness (111) that characterize mental wellbeing, as well as improved core pain outcomes (112–114). This trend, as well as the above recommendations concerning rapport, informed our preparation process which will now include added time and additional resources.
In addition, many contributors suggested some degree of cognitive reframing, with perceived psychological states shifting from overwhelming depression, disempowerment, anxiety, and hopelessness, toward connection, acceptance, agency, and hope. This transition from catastrophising toward clarity, and in most cases, perceived optimism, reportedly ameliorated contributors' perceived ability to effectively manage their pain; they described feeling more “prepared” and no longer overwhelmed. These results speak toward cognitive, specifically positive, reframing as a driving mechanism of outcomes following psychedelic self-medication for chronic pain and bear relevance to previously discussed change mechanisms in the context of psilocybin therapy for depression research (86). Even though many contributors reported still experiencing chronic pain following their experiences, they claimed feeling a newfound sense of agency and optimism regarding their pain. The perceived relevance of these trends further put into question the mind-body dichotomy of current pain treatments, where psychological interventions are largely considered as secondary, if at all.
Changes in perspective described by contributors were often galvanized during the acute psychedelic experience, and often persisted for 2+ months. This is consistent with existing psychedelic data suggesting transdiagnostically significant long-term outcomes in openness (115), attitude (116), personality (117), depression and anxiety (86, 118) reported for months to years (119) following treatment. PPI discussions did not include assessment of specific personality traits. Therefore, no generalizations linking specific personality or psychological traits to outcomes can be made. The acute psychedelic experiences conformed to previous findings (86) and generally centered around feelings of connection, love, compassion, and trust. As with previous studies (86, 87), these sentiments, particularly connection with the self and body, endured and precipitate the development of larger shifts in perspectives. Feelings of compassion, empowerment, and hope were closely linked and contributed to a growing sense of agency and control over their pain, and life more generally. Increased subjective acceptance of pain was also claimed, specifically shifting from a defeated resignation to an active acceptance and served as an impetus to impact other aspects of life. A noteworthy minority of contributors (5) were reportedly more committed to taking an active stance in their recovery in various ways, from seeking professional help to cultivating new behaviors conducive to general health and wellbeing [see (120)]. Overall, the subjective reclamation of identity, agency, and hope emerged as drivers in the perceived efficacy of pain management. Fostering this process has consequently developed into a central aspect of our therapeutic approach spanning the duration of the study. Reinforced integration support will aim to support the longevity of changes by providing tools for independent support and additional follow-ups.
Such outcomes are the goal of numerous treatment strategies, particularly PMPs using CBT and ACT, which aim to reframe thought processes and encourage independence. While fairly widespread, PMPs are moderately effective at best, particularly at long-term follow-ups (39–42, 121). In contrast, contributors perceived a “profound shift” in perspective, which they felt contributed to the longevity of outcomes. Such claims of insight are well-supported in the psychedelic field, particularly in the context of psychological flexibility (122, 123) and further, relaxed beliefs (124) and may account for the effects reported here. Psychological flexibility facilitates well-adjusted individuals to adapt their mindset to life's ever-evolving situations, regardless of social, emotional, or stress factors (125). Existing literature points toward prodigious upregulations of neural plasticity following psychedelic experiences, translated experientially to changed perspectives (124). This is particularly relevant in populations with maladaptive, entrenched thought patterns such as depression (126), and indeed chronic pain (99). Consistent with this PPI project, therapeutically useful changes in outlook are linked to certain noetic experiences (127), allowing individuals to move “above” themselves toward a more equanimous state free of unwarranted pessimism. The cumulative results are an amalgam of self-confidence, inspiration, and acceptance (123) and directly counter the effects of pain catastrophisation.
Contributors' physical experiences of their body and pain were another point often referred to. Initially, contributors reported severe day-to-day pain, described as “burning,” “exhausting,” “looming,” “tight,” “stabbing,” and “blinding,” which left all contributors with impaired general function. Therefore, contributors were “shocked” and “in disbelief” at the perceived efficacy; 9 out of 11 contributors claimed partial or complete analgesia in the acute psychedelic stage [see (128) for similar findings]. Most contributors regained function, e.g., the ability to walk unencumbered, and described experiencing their body as “healthy.” This was reported with both high (macro) and microdoses. Effect duration varied and ranged from no relief beyond the acute experience to over a year—most contributors (8), regardless of dose taken, reported feeling reductions in pain for at least 3–5 days following their experience, with pain levels gradually increasing over time. Other changes were longer lasting though; most contributors (9) reported enduring increases in positive embodiment and interoception, which inspired a desire to treat the body better in the future.
The process toward pain relief often involves an improved sense of Somatic Presence, or “mindfulness of body.” Theories exist about the impact of trauma on somatic symptoms, e.g., chronic fatigue and chronic pain (129, 130). According to these theories, an act of intense physical expression/release, such as through shaking, vocalizing, or unconscious movement (also termed “somatic discharge”) can be profoundly cathartic and processing/working through associated symptoms (88, 131). Preliminary evidence suggests that somatic discharge may be effective not only for trauma therapy (132), but also in the context of chronic pain (32). Something akin to somatic discharge was described by two contributors in our group, who were interestingly also the only contributors who reported total analgesia indefinitely after their experience. The remaining contributors reported more subdued physical release, often associated with self-imposed elements of body- and breathwork. This largely resulted in muscular relaxation translating to subjective pain relief and heightened embodiment. These reports inspired the inclusion of behavioral investigations on interoception and body awareness in future studies Further, optional movement elements aimed at an embodied experience may be incorporated in dosing and integration sessions. Finally, references to potential elements of somatic discharge stimulated the development and implementation of a physical catharsis measure.
Importantly, not all contributors reported acute pain relief; three contributors reported amplified pain during the acute psychedelic experience. Pain reportedly grew in intensity and became “distressing” and “overpowering” before returning to baseline after the experience. While unpleasant, two contributors reported that this was a useful learning experience for them. One contributor branded this experience an outlier attributed to a “recklessly” high dose taken “rashly” and without proper consideration regarding attitude and intention. Other contributors echoed that taking very high doses in sub-optimal contexts (inadequate preparation, negative mental state, stressful environment) contributed to unfavorable experiences, although this did not necessary result in perceived pain amplification. We have therefore developed preparation sessions specifically tailored for chronic pain populations and will emphasize trust, transparency, and intention.
Due to the clandestine nature of illicit substance use, there is no standard protocol for self-medication. Interestingly, many contributors intentionally recreated a clinical setting in an effort to facilitate a therapeutic experience; they set specific intentions, laid back comfortably with their eyes closed, listened to especially chosen music, and focused on the internal journey, though this was largely without an accompanying “guide” or “sitter.”
Psychedelics were routinely combined with other adjunct practices. Supplementary modalities included breathwork, mindfulness, meditation, and movement, e.g., Yoga, Qi Gong, physical therapy exercises, and using expressive outlets such as art, journaling, and dance to manifest and process emotional content during and after the experience. These suggestions were incorporated into our therapeutic model with particular emphasis on mindfulness and movement.
The goal of this PPI project was not to produce formal research; it did not test hypotheses or draw any confirmatory claims. However, the most pertinent limitation of this project concerns both contributor and investigator bias. We invited collaborators through targeted advertisements which disproportionally attract people with positive experiences, causing selection bias. This was reinforced by lack of financial compensation and the time commitment of the project, ultimately resulting in a small, self-selected, and highly motivated cohort that was almost definitely biased by compelling personal outcomes. Further, recency, recall, response, and confirmation bias may have affected perceived efficacy and accuracy of reports. While we attempted to minimize researcher bias during analysis by cross-referencing for inter-coder-reliability, the inherently subjective process cannot eliminate potential confirmation bias. Equally, though discussions followed a consistent structure, unintentional interviewer bias (e.g., via body language) cannot be excluded. We reiterate therefore, that these reports are best viewed as a collection of discussions used to inform our upcoming trial and do not imply causation, generalizability of results, viability of treatment, or future study outcomes.
Beyond bias, most contributors approximated doses, challenging the accuracy of self-report quantities. Even if contributors accurately reported, there are distribution inconsistencies in both organic and synthetic materials. Additionally, evaluating the differences between microdosing and macrodosing is difficult due to potentially discrete processes (133). Duration between self-medication and discussion necessarily varied, contributing to differences in follow-up times reported and the perceived duration and efficacy of therapeutic effects. Finally, psychedelics were used in concert with other modalities, which likely confounded outcomes. If undertaken as formal research, future improvements may include more rigorous contributor selection criteria, further standardized discussion formats, and including additional cross-referencing techniques to address subjectivity concerns.