Persons With Spinal Cord Injury Report Peripherally Dominant Serotonin-Like Syndrome After Use of Serotonergic Psychedelics

Psychedelic-assisted therapy (PAT) has shown therapeutic promise for several mental health conditions and regulatory agencies have begun to expand access to agents such as MDMA and psilocybin. Clinical trials and emerging clinical programmes, however, have tended to exclude people with significant cardiovascular, autonomic or neurological comorbidities, a category that commonly includes persons with spinal cord injury (SCI). Earlier research therefore offers little guidance for clinicians or patients with SCI, despite a high prevalence of treatment-resistant psychiatric comorbidity in this population and anecdotal evidence that people with SCI are already using serotonergic psychedelics outside supervised settings. This paper sets out to document and explain a cluster of adverse autonomic and neuromuscular effects reported by people with SCI after taking classical serotonergic psychedelics (notably psilocybin and LSD). Using online forum reports, the authors aim to describe the phenomenon, propose a mechanistic hypothesis—that exposure to 5HT2A agonists can precipitate a peripherally dominant serotonin-like syndrome in persons with SCI—and to raise awareness for harm reduction, research and the development of SCI-specific guidance for clinicians and therapists. A planned follow-up survey of people with SCI is signalled as the next step to quantify and further characterise the phenomenon.

The investigators performed a targeted search of two public internet forums, Reddit and Shroomery, to identify self-reports by people with SCI describing their experiences with serotonergic psychedelics. They used the sites’ search functions and screened subforums and posts using keywords including "psychedelics," "spinal cord injury," "SCI," "magic mushrooms," "psilocybin," "LSD," "serotonergic," "spasms," "muscle jerks," "paralysis," and "paralyzed." Posts and comments were screened by title and content and retained only if they explicitly described both an SCI and use of a serotonergic psychedelic. Key information was extracted from included posts, principally details of the type/level of SCI, the psychedelic agent taken, and the subjective physiological and psychological effects reported. The extracted text does not provide a count of total posts screened or the number of posts ultimately included in the analysis, nor does it report a date range for the search. The analysis therefore is descriptive and based on self-reported online narratives that were matched to relevant clinical symptomatology rather than on systematically collected clinical data.

Across the included forum reports, people with SCI described a consistent constellation of autonomic and neuromuscular symptoms after ingesting serotonergic psychedelics. Reported effects included intense leg spasms, sensations of the feet feeling immobile or "locked," convulsive movements during attempts at voluntary movement, "jumping" legs, sharp pains in the spasming limbs, profuse sweating or cold sweats, sensations of overheating or extreme heat, dehydration and urinary incontinence. Some reports noted attempts to pre-medicate with antispasticity agents such as baclofen or with benzodiazepines (diazepam) to blunt the spasms. The forum narratives included people with lesion levels spanning cervical to thoracic segments (examples reported ranged from C4 to T10). Users commonly characterised these peripheral symptoms as severe and unpleasant enough to interfere with the subjective psychological benefits they experienced from the psychedelic. Despite the adverse effects, some individuals still reported meaningful psychological benefit—for example, a person with an incomplete T10 lesion described a substantial improvement in PTSD symptoms after psilocybin. The extracted text does not supply numerical incidence rates, counts, or systematically verified clinical assessments; no objective physiological recordings were reported and the accounts derive from self-report only. The authors note that comparable peripheral symptom clusters of this severity have not been documented in controlled psychedelic trials in people without SCI.

The authors propose a biological explanation centred on serotonergic receptor changes after SCI, particularly involving the 5HT2A receptor (5HT2A-R). Classical psychedelics act as agonists at 5HT2A-Rs, which are abundant in brain regions implicated in psychiatric effects but are also expressed on spinal interneurons, motor neurons and peripheral tissues (gastrointestinal tract, vascular and bronchial smooth muscle, platelets). After a complete spinal transection, descending serotonergic input is lost, and compensatory changes occur in spinal neuronal networks and in serotonin receptor expression. The investigators hypothesise that chronic reductions in serotonergic signalling post-SCI lead to upregulation or altered sensitivity of peripheral 5HT2A-Rs, producing a peripheral hypersensitivity such that exposure to 5HT2A agonists elicits an essentially peripherally dominant, serotonin-like syndrome. Serotonin syndrome (SS) is defined by mental-status changes, autonomic hyperactivity and neuromuscular abnormalities; it is usually associated with increased synaptic serotonin or direct receptor activation. The authors argue that in people with SCI the clinical picture after psychedelic use resembles a milder, peripherally focused SS-like state, manifesting primarily as autonomic and neuromuscular hyperactivity rather than the severe central features sometimes seen in classical SS. Supporting evidence cited in the text includes animal and human studies showing that monoaminergic receptor stimulation can reinstate locomotor activity and that acute 5HT2/a1 agonism increases motor-neuron excitability and spasticity in chronic SCI, paralleling the self-reported phenomena. The discussion also highlights the additional concern of autonomic dysreflexia (AD), a life-threatening rise in blood pressure and heart rate triggered by autonomic stimuli in people with lesions at or above T6; several forum reports of profuse sweating and hyperthermia are consistent with AD and could combine with the known cardiovascular effects of classical psychedelics to raise safety risks. To address these issues, the authors call for preclinical studies to test (1) post-administration changes in 5HT2A-R availability in the spinal cord after SCI, (2) acute and subacute changes in serotonergic neurotransmission following psychedelic exposure, and (3) how these interactions affect core SCI symptoms. They also acknowledge the limitations inherent to forum-derived data—namely the lack of clinical verification, the absence of incidence or prevalence estimates in the presented text, and reliance on self-report—while framing their work as a harm-reduction–oriented signal that warrants systematic follow-up. Finally, the authors position their account as a prompt for clinical caution, targeted research, and the development of SCI-specific protocols so that people with SCI who choose to use psychedelics can be better informed and, where appropriate, safely managed.

Abrams and colleagues present a descriptive account of consistent autonomic and neuromuscular hyperactivity—principally intense muscle spasms—reported by people with SCI after use of serotonergic psychedelics, and they propose a mechanism involving peripheral hypersensitivity of 5HT2A receptors following injury. They emphasise that these peripheral symptoms have not been reported in non-SCI clinical trials at comparable doses, call for further investigation through preclinical work and a planned follow-up survey to determine prevalence and clinical detail, and urge clinicians and researchers to develop SCI-specific guidance and harm-reduction strategies to support safe and informed decision-making in this population.