The bizarre phenomena that medicine struggles to explain | David Linden: Full Interview

The mind-body connection operates through three primary biological pathways: rapid electrical signals via neurons (e.g., spinal cord to brain), slower hormonal signals via the bloodstream (e.g., from the gut to the brain), and the brain's continuous response to physiological rhythms like breathing and heartbeat. Conversely, the mind influences the body through volitional motor control, the subconscious autonomic nervous system (sympathetic/parasympathetic), hormones released by the brain, and control of the immune system via cytokines.

David Linden, a neuroscientist, details these mechanisms, explaining how interoceptive senses communicate bodily states to the brain and how the brain 'speaks back' to control bodily functions, including disease processes. He cites his father's psychiatric insights about brain changes from psychotherapy and highlights recent advances in understanding this biology.

GLP-1 based drugs (e.g., semaglutide, tirzepatide) are highly effective for weight loss by mimicking a natural gut hormone that slows gastric emptying and suppresses appetite. These modified peptides, engineered for longer bloodstream half-life, are showing promising, albeit early, indications of efficacy in suppressing other reward-driven behaviors such as alcohol consumption, psychoactive drug use, compulsive shopping, and gambling. This suggests a broader interaction with the brain's general reward circuitry beyond just appetite regulation.

Linden describes the chemical modification of natural GLP-1 by Novo Nordisk to create long-acting drugs. He notes the 12-17% body weight loss observed and the 'promising indications' from early research that these drugs can help control various addictive and compulsive behaviors, despite initial neuroscientific predictions that appetite circuits would be separate from general reward pathways.

Phenomena like 'voodoo death' – where a belief in a curse leads to actual death – and fatal misdiagnosis are not supernatural but have biological explanations. These events involve a 'one-two punch' of physiological responses: an initial hyper-arousal of the sympathetic nervous system followed by prolonged over-activation of the parasympathetic 'rest and digest' system. This combined effect can shut down the body, particularly in individuals whose belief systems make them susceptible to such psychological stressors.

Linden references Walter Kennan's 1942 documentation of voodoo death and updates the physiological theory with modern understanding of the sympathetic and parasympathetic nervous systems. He cites a case from the 1970s of a man who died after a misdiagnosis of liver cancer, with an autopsy revealing no serious illness, indicating his belief in a fatal condition was the cause.

The placebo effect, where sham treatments yield real benefits, is biologically mediated, particularly for pain relief, through the brain's natural opiate system (endorphins, enkephalins), as evidenced by its blockage by naloxone. Curiously, the placebo effect for pain has significantly strengthened over the last several decades, specifically in the United States (and New Zealand), making it harder for new pain drugs to demonstrate statistically significant superiority. The leading hypothesis for this anomaly is the widespread direct-to-consumer advertising of drugs in these countries, which may foster a stronger belief in medication efficacy.

Linden explains naloxone's role in blocking the placebo effect for pain. He highlights the observed trend of increasing placebo effect strength for pain in US clinical trials, noting its absence in other countries. He speculates on the role of direct-to-consumer drug advertising as a potential cause.

Psychosocial support, including deep personal connections and psychotherapy, has a measurable beneficial effect on cancer progression, though it's not a cure. This is biologically plausible, as stress hormone signaling promotes tumor growth, and psychotherapy reduces these hormones. Similarly, intense exercise is a powerful anti-cancer intervention, with randomized controlled studies demonstrating significant improvements in mortality, potentially by suppressing tumor growth through mechanisms like the lactate-phenylalanine conjugate and modulating the immune system. The speaker personally attributes his survival beyond a terminal diagnosis partly to the 'deep love' from his wife, hypothesizing it activates brain reward circuits that suppress tumor growth or boost immune function.

Linden discusses epidemiological evidence for psychosocial support's benefits and mouse studies showing activation of brain reward circuitry (dopamine, ventral tegmental area) improves heart attack recovery. He cites a 2025 Australian randomized controlled study on colon cancer patients showing a 30% improvement in mortality with exercise. He then connects his personal cancer experience to these biological hypotheses.