Bicycle Day is the day scientist Albert Hoffman took an intentional dose of lysergic acid diethylamide (LSD) and then rode his bike home.
Hoffman’s intentional dose on 19 April 1943 was actually his second “contact” with LSD. The macro dose day is the memorable bicycle ride home; the unintentional first dose was at a micro level absorbed through his skin (or somehow). Hoffman wasn’t ever very clear on how that happened; he did note a slight modulation from the micro experience … enough to convince him to try the macro.
LSD works because it modulates one’s serotonin system and its plethora of receptors (15 last time I checked). Hoffman was the first to experience the synaptic serotonin effects LSD yields – yet we all modulate our bodies via serotonin … we just do it daily in a micro way (it’s in us).
Below is a four-part science story from the National Institutes of Health (PubMed): it includes a dialogue between our immune and serotonin systems, an early microbiota life tale, a circadian clocks discussion, and talk of bowels (irritable and otherwise) and the brain-gut axis. The links and quotes are from PubMed.
Think of cannabinoids as the wheel’s hub and serotonin as the transmission: for certain, as Albert Hoffman attested, it’s a neurotransmission without equal.
Happy Bicycle Day 2014 Everyone!
I. A Dialogue (immune and serotonin systems)
“Neuropsychiatric disorders have long been linked to both immune system activation and alterations in serotonin (5-HT) signaling. In the CNS, the contributions of 5-HT modulate a broad range of targets, most notably, hypothalamic, limbic and cortical circuits linked to the control of mood and mood disorders. In the periphery, many are aware of the production and actions of 5-HT in the gut but are unaware that the molecule and its receptors are also present in the immune system where evidence suggests they contribute to the both innate and adaptive responses. In addition, there is clear evidence that the immune system communicates to the brain via both humoral and neuronal mechanisms, and that CNS 5-HT neurons are a direct or indirect target for these actions.”
A dialogue between the immune system and brain, spoken in the language of serotonin.
Baganz NL, Blakely RD.
ACS Chem Neurosci. 2013 Jan 16;4(1):48-63. doi: 10.1021/cn300186b. Epub 2012 Dec 7. Review.
PMID: 23336044 [PubMed - indexed for MEDLINE] Free PMC Article
II. Early Life (immune, endocrine and serotonin systems)
“Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. … Regulation of the microbiome-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. … However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. … Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission.”
The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner.
Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF.
Mol Psychiatry. 2013 Jun;18(6):666-73. doi: 10.1038/mp.2012.77. Epub 2012 Jun 12.
PMID: 22688187 [PubMed - indexed for MEDLINE]
III. Circadian Clock (chickens and serotonin biosynthesis)
“Serotonin in blood plasma is primarily synthesized in the duodenum [first section of the small intestine], as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD). … Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function.”
Biological clocks in the duodenum and the diurnal regulation of duodenal and plasma serotonin.
Ebert-Zavos E, Horvat-Gordon M, Taylor A, Bartell PA.
PLoS One. 2013 May 30;8(5):e58477. doi: 10.1371/journal.pone.0058477. Print 2013.
PMID: 23737937 [PubMed - indexed for MEDLINE] Free PMC Article
IV. Bowels (irritable and otherwise: brain-gut axis)
“Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterized by abdominal discomfort, pain and changes in bowel habits, often associated with psychological/psychiatric disorders. It has been suggested that the development of IBS may be related to the body’s response to stress, which is one of the main factors that can modulate motility and visceral perception through the interaction between brain and gut (brain-gut axis). … Several lines of evidence indicate that 5-HT and its receptor subtypes are likely to have a central role in the pathophysiology of IBS. 5-HT released from enterochromaffin cells regulates sensory, motor and secretory functions of the digestive system through the interaction with different receptor subtypes. It has been suggested that pain signals originate in intrinsic primary afferent neurons and are transmitted by extrinsic primary afferent neurons. Moreover, IBS is associated with abnormal activation of central stress circuits, which results in altered perception during visceral stimulation.”
Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome.
Stasi C, Bellini M, Bassotti G, Blandizzi C, Milani S.
Tech Coloproctol. 2014 Jan 15. [Epub ahead of print]
PMID: 24425100 [PubMed - as supplied by publisher]
Plus ~ Today's Video ~
Serotonin and the Gut Brain Connection
Posted by Bryan W. Brickner