Long-lasting analgesic effect of the psychedelic drug changa: A case report

This paper is an individual case report. The subject, referred to as JM, is a 57-year-old male physician with a 10-year history of progressive musculoskeletal pain, fatigue, sleep disturbance and related functional impairment. Three years prior to the events described he was diagnosed with fibromyalgia and chronic fatigue. Prior treatments recorded in the case narrative included non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, dexketoprofen) with little benefit, a 2-month cognitive therapy workshop that temporarily reduced pain from 8 to 3/10 on a numerical rating scale, ozone therapy with brief benefit, and fluoxetine which improved pain and fatigue to a 3–4/10 level but was stopped after 6 weeks because of emergence of autolytic ideation and intrusive rumination. His drug history included a single ayahuasca experience 5 years earlier. The intervention consisted of participation in multiple changa sessions provided in a group ritualistic setting with an underground therapist. Each session began with about 30 minutes of meditation; participants smoked a single prepared cigarette containing freebase DMT extracted from Mimosa hostilis and ground Peganum harmala seeds. The content of the cigarette was analysed and confirmed by a harm‑reduction organisation using gas chromatography–mass spectrometry, according to the extracted text. JM attended five sessions in total. The extracted timeline indicates the first session was unsuccessful for him because he was unfamiliar with smoking technique; the second session was 1 week later and produced intense psychoactive effects; the third session occurred 2 weeks after the second; the fourth session followed 15 days later; and a fifth session took place approximately 1 month after the fourth. Outcomes were recorded as clinical observations and the patient’s report rather than as a structured protocol; the extracted text does not clearly report standardised post‑intervention pain scores or systematic adverse‑event monitoring.

After the second changa session JM reported near-complete disappearance of his pain for about 2 weeks. Following the third session he experienced additional psychosocial benefits: improved mood, resolution of autolytic ideation, and reportedly brighter colour perception. Similar benefits—greater emotional stability, pain relief and a modest reduction in fatigue—were reported after the fourth session. After the fifth session he again reported reduced pain, with relief lasting up to 15 days. Earlier, JM’s pain had responded transiently to cognitive therapy (from 8 to 3/10) and to fluoxetine (3–4/10) but had returned after cessation of those interventions; the extracted text links the disappearance of suicidal ideation to the period following changa use. The report does not provide numerical pain ratings tied to each changa session, nor does it document formal adverse‑event surveillance; no acute medical complications from the changa sessions are described in the extracted text.

Ona and Troncoso discuss multiple pharmacological and non‑pharmacological mechanisms that might account for the prolonged analgesia reported. They note that DMT is a broadly acting indole alkaloid: a partial agonist at several serotonin receptors (5‑HT1A, 5‑HT2A, 5‑HT2C) and an agonist at sigma‑1 (σ1) receptors, with additional indirect receptor interactions. The authors link serotonergic activity to mood elevation and remind readers that antidepressant drugs can have analgesic effects independent of mood change, although they also highlight that noradrenergic mechanisms are often important for pain control. The σ1 receptor is discussed as a modulator expressed in central and peripheral structures involved in pain processing; the authors cite preclinical and early clinical evidence that modulation of σ1 can influence pain and note mixed reports of analgesia from both σ1 antagonists and agonists in different pain models. DMT’s capacity to induce neuronal plasticity is raised as another plausible contributor to longer‑term changes in pain perception. Regarding the Peganum harmala constituent, the authors discuss β‑carbolines (notably harmaline and harmine) and quinazolines such as vasicine. These compounds bind multiple targets (including 5‑HT, dopamine, GABA, imidazoline I2 and adrenergic α2 receptors), interact with opioid receptors in some assays, and are potent inhibitors of monoamine oxidase A (MAO‑A). Traditional use and preclinical studies of P. harmala extracts have shown analgesic and neuroprotective effects; in some animal models naloxone pretreatment abolished the extract’s antinociceptive effect, suggesting involvement of opioid‑modulated pathways. Vasicine’s anti‑inflammatory properties are also noted as a possible contributor to analgesia. The authors acknowledge a pharmacokinetic conundrum: the active constituents have relatively short elimination half‑lives (reported in the extracted text as around 260–532 minutes), which by themselves would not explain analgesia lasting weeks. Psychological and contextual factors are therefore considered important: single psychedelic administrations are known to produce prolonged effects in other settings, and mechanisms proposed include peak mystical‑type experiences, increased suggestibility and an amplified placebo response in ritual contexts, changes in metacognitive interpretation of pain, and longer‑term biological changes such as neuroplasticity or epigenetic modifications. The discussion stresses the complexity of changa’s pharmacology and the likelihood that multiple interacting mechanisms—pharmacodynamic, psychological and contextual—could underlie the observations. Finally, the authors call for further research to clarify specific mechanisms and to investigate indirect system changes such as receptor density alterations; they also point to reports of analgesia after ayahuasca as potentially relevant corroboration.

The authors conclude that, despite the intense psychedelic effects of changa which limit its immediate clinical applicability, this case suggests changa may produce a long‑lasting analgesic effect. They emphasise that the observation is preliminary and that further research is required to determine the specific mechanisms involved and to evaluate safety and therapeutic potential.