Scientific Reports
June 27, 2019
Jon G Dean, Tiecheng Liu, Sean Huff et al.
111 citations
The psychedelic compound N,N-dimethyltryptamine (DMT) is produced naturally in mammals, but whether it is made in the brain was unclear. This study found that the enzymes needed to synthesize DMT are present in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans. In rat brain tissues, the two key enzymes were found together, unlike in peripheral tissues. DMT concentrations in the cerebral cortex of behaving rats were similar to those of neurotransmitters like serotonin. DMT levels in the visual cortex rose significantly after cardiac arrest, even without the pineal gland. These findings indicate the rat brain can synthesize and release DMT at neurotransmitter-like levels, suggesting human brains might do the same.
Frontiers in Neuroscience
April 23, 2018
Jon G Dean
39 citations
N,N-dimethyltryptamine (DMT) is a potent serotonergic psychedelic whose exogenous administration produces striking effects in humans. DMT and related compounds, along with the enzyme indolethylamine-N-methyltransferase (INMT) that synthesizes DMT from tryptamine, have been found in human and other mammalian tissues. Hypotheses for endogenous DMT's physiological role include immunomodulation and involvement in naturally occurring altered states of consciousness, but no clear relationship has been established from in vivo assays. The authors propose that genetic screening of single nucleotide polymorphisms (SNPs) in INMT, which may affect DMT synthesis and levels, could overcome limitations of bodily fluid assays and help clarify whether DMT has a physiological role.
Pharmacology Research & Perspectives
February 2, 2021
Benjamin Stewart, Jon G Dean, Adriana Koek et al.
15 citations
Functional neurological disorders (FNDs) are common, disabling neuropsychiatric conditions with limited treatment options. They present with sensory or motor symptoms that mimic other neurological conditions but arise from mechanisms other than identifiable structural neuropathology, often triggered by psychological factors. Preliminary evidence supports psychedelic-assisted therapy for several psychiatric illnesses, including FNDs. This review examines theoretical arguments for and against exploring psychedelic-assisted therapy for FNDs, discusses prior cases of psychedelic use for psychosomatic conditions, and analyzes therapeutic outcomes through recent neuroimaging studies on psychedelics and FNDs.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2024
Lora Khatib, Jon G Dean, Valeria Oliva et al.
9 citations
Mindfulness meditation directly reduces evoked chronic low back pain through non-opioidergic processes, not by activating the body's opioid system. In a double-blind, randomized, placebo-controlled trial with a drug crossover design, 59 individuals with chronic low back pain completed a four-session mindfulness or sham mindfulness-meditation intervention. During intravenous naloxone (an opioid blocker) or saline infusion, both mindfulness and sham mindfulness groups showed significant pain reductions during meditation compared to rest. However, the mindfulness group reported significantly lower pain than the sham group, and its effects were more pronounced, suggesting unique benefits from non-reactive appraisal processes. Pain severity and interference scores also decreased.
Biological Psychiatry
January 1, 2025
Gabriel Riegner, Jon G Dean, Tor D Wager et al.
Pain is shaped by experience, thoughts, and expectations rather than being a direct readout of injury. The placebo effect reduces pain through mechanisms shared with active treatments, and some have assumed mindfulness meditation works the same way. Using brain-based multivariate pattern analysis across two clinical trials with 115 healthy participants, mindfulness meditation produced significantly greater reductions in pain intensity and unpleasantness ratings, and lowered nociceptive-specific and negative affective brain signatures, compared to placebo cream, sham mindfulness, and a control. Placebo cream specifically lowered the placebo-based signature. The results show mindfulness and placebo engage distinct neural pain signatures to reduce pain.
Anesthesia and analgesia
June 1, 2022
Michael A. Brito, Duan Li, Christopher W Fields et al.
Cortical acetylcholine levels correlate with neurophysiologic complexity and frontoparietal connectivity during altered states of consciousness. In rats under isoflurane anesthesia, subanesthetic ketamine (10 mg/kg/h) produced sustained increases in brain complexity and high gamma connectivity, accompanied by progressive rises in prefrontal (104%) and parietal (159%) acetylcholine. Nitrous oxide caused a transient increase in complexity and connectivity with smaller acetylcholine increases (prefrontal 56%, parietal 43%), followed by a later phase of decreased acetylcholine, reduced complexity, and weaker connectivity. These findings link cortical acetylcholine to changes in consciousness level.