• Psychopharmacology, Neurotransmission, and Lateralization

  Acetaminophen (Paracetamol) is psychoactive and reduces positive empathy

  Posted by Matt Dorsey on October 17, 2022 at 4:04 pm

  Paper: ‘A Social Analgesic? Acetaminophen (Paracetamol) Reduces Positive Empathy‘

  From the abstract:

  “We thus hypothesized that acetaminophen may also impair affective processes related to the experience of positive empathy. We tested this hypothesis in a double-blind, placebo-controlled experiment. Specifically, we administered 1,000 mg acetaminophen or a placebo and measured effects on different of positive empathy while participants read scenarios about the uplifting experiences of other people.

  Results showed that acetaminophen reduced personal pleasure and other-directed empathic feelings in response to these scenarios…These findings suggest that (1) acetaminophen reduces affective reactivity to other people’s positive experiences and (2) the experience of physical pain and positive empathy may have a more similar neurochemical basis than previously assumed. Because the experience of positive empathy is related to prosocial behavior, our findings also raise questions about the societal impact of excessive acetaminophen consumption.“

  ________

  The authors mention that acetaminophen has been shown to reduce activity in the anterior insula and anterior cingulate. Of course, there’s no mention of any lateralization of this effect, but one would not expect that, as these sorts of papers rarely do.

  Here are some relevant quotes from ‘the Master and his Emissary’ on these structures:

  “Because of the right hemisphere’s openness to the interconnectedness of things, it is interested in others as individuals, and in how we relate to them. It is the mediator of empathic identification. If I imagine myself in pain I use both hemispheres, but your pain is in my right hemisphere. The same neurones in the right anterior cingulate cortex, an area known to be associated with the appreciation of pain, show activity whether we ourselves are hurt or we witness someone else undergoing a similar painful experience.”

  *

  “…neuroimaging correlates of both self-awareness and theory of mind lie in the right frontal and right cingulate cortex.”

  *

  “But referential language, with its huge vocabulary and sophisticated syntax, did not originate in a drive to communicate, and from this point of view, represents something of a hijack. It has done everything it can to repudiate both its bodily origins and its dependency on experience – to become a world unto itself. Despite all that, however, the urge to speak still does not come from Broca’s area, where the motor speech act originates. That’s evident from the fact that subjects with lesions in Broca’s area usually seem desperate to communicate. No, it comes from the anterior cingulate, a deeper lying region profoundly implicated in social motivation.”

  *

  “In a neuroimaging study exploring the neural correlates of hypnosis, activity decreases in the precuneus, posterior cingulate and right inferior parietal lobule, which is coherent, since as we saw earlier, in Chapter 2, these areas are known to be associated with the sense of individual agency.”

  *

  “The interpretation of faces is the prerogative of the right hemisphere; in looking at the face of one’s partner (compared with an unknown face) the right insula increases in activity.”

  ____________

  My thoughts:

  • 1,000 mg is a common daily dose, with many patients taking double, sometimes triple that amount
  • Note that acetaminophen is somewhat unique in that, despite the fact that it has a long history of use, its mechanisms of action are poorly understood
  • A former professor of mine, a physician for over 30 years, often decried the overuse of acetaminophen and believed, due to its toxic nature, that it should be a prescription drug
  • Acetaminophen depletes glutathione, which is essential for phase II detoxification, an essential step in the removal of xenobiotics, including heavy metals such as mercury that are highly neurotoxic and are connected to psychiatric disorders, especially psychopathy
  • The link between fetal exposure to this drug and development of autism and ADHD (see link in next section) could in part or in whole be a result of impaired clearance of xenobiotics that cause these changes in neurological function. Note that autism has been linked to abnormal testosterone / estrogen ratios in the developing fetus, and that reduced clearance of xenoestrogens may be implicated; Dr. McGilchrist mentions that testosterone is critical for development of the RH.
  • Because of the comorbidity of depression and other psychiatric disorders with chronic pain, one has to wonder how often patients are unconsciously self-medicating with acetaminophen in order to suppress certain kinds of emotional suffering

  ____________

  Here are some other interesting papers & articles (with links):

  • Acetaminophen Overdose as a Potential Risk Factor for Parkinson’s Disease
  • Effects of acetaminophen on monoaminergic systems in the rat central nervous system (suggests that serotonin is involved in some of acetaminophen’s mechanisms of action)
  • Acetaminophen Relieves Inflammatory Pain through Cannabinoid Receptors in the Rostral Ventromedial Medulla (it affects the endocannabinoid system)
  • NIH-funded study suggests acetaminophen exposure in pregnancy linked to higher risk of ADHD, autism (20% higher risk of autism and 30% higher risk of ADHD)
  • Tomorrow’s Anti-Anxiety Drug Is… Tylenol? (references a study in which those who took the drug had a blunted response to social rejection, possibly mediated through attenuation of the anterior cingulate cortex)

  ________________

  And here are some interesting videos:

  • Social rejection experiment
  • Empathy and the Pain Sensation – discusses ACC and anterior insula, shows pictures from imaging study that demonstrate lateralization

  Matt Dorsey replied 1 year, 6 months ago 1 Member · 0 Replies
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