“delta 9Tetrahydrocannabinol (THC) has been shown to inhibit the activity of adenylate cyclase in the N18TG2 clone of murine neuroblastoma cells. The concentration of delta 9THC exhibiting half-maximal inhibition was 500 nM. delta 8Tetrahydrocannabinol was less active, and cannabinol was only partially active. Cannabidiol, cannabigerol, cannabichromene, olivetol and compounds having a reduced length of the C3 alkyl side chain were inactive. The metabolites of delta 8THC and delta 9THC hydroxylated at the C11 position were more potent than the parent drugs. However, hydroxylation at the C8 position of the terpenoid ring resulted in loss of activity. Compounds hydroxylated along the C3 alkyl side chain were equally efficacious but less potent than delta 9THC. These findings are compared to the pharmacology of cannabinoids reported for psychological effects in humans and behavioral effects in a variety of animal models.”
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Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L.
“Chemical investigation of the pollen grain collected from male plants of Cannabis sativa L. resulted in the isolation for the first time of two flavonol glycosides from the methanol extract, and the identification of 16 cannabinoids in the hexane extract. The two glycosides were identified as kaempferol 3-O-sophoroside and quercetin 3-O-sophoroside by spectroscopic methods including high-field two-dimensional NMR experiments. The characterisation of each cannabinoid was performed by GC-FID and GC-MS analyses and by comparison with both available reference cannabinoids and reported data. The identified cannabinoids were delta9-tetrahydrocannabiorcol, cannabidivarin, cannabicitran, delta9-tetrahydrocannabivarin, cannabicyclol, cannabidiol, cannabichromene, delta9-tetrahydrocannabinol, cannabigerol, cannabinol, dihydrocannabinol, cannabielsoin, 6a, 7, 10a-trihydroxytetrahydrocannabinol, 9, 10-epoxycannabitriol, 10-O-ethylcannabitriol, and 7, 8-dehydro-10-O-ethylcannabitriol.”
Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology.
“Cannabinoids, consisting of alkylresorcinol and monoterpene groups, are the unique secondary metabolites that are found only in Cannabis sativa. Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabichromene (CBC) are well known cannabinoids and their pharmacological properties have been extensively studied. Recently, biosynthetic pathways of these cannabinoids have been successfully established. Several biosynthetic enzymes including geranylpyrophosphate:olivetolate geranyltransferase, tetrahydrocannabinolic acid (THCA) synthase, cannabidiolic acid (CBDA) synthase and cannabichromenic acid (CBCA) synthase have been purified from young rapidly expanding leaves of C. sativa. In addition, molecular cloning, characterization and localization of THCA synthase have been recently reported. THCA and cannabigerolic acid (CBGA), its substrate, were shown to be apoptosis-inducing agents that might play a role in plant defense. Transgenic tobacco hairy roots expressing THCA synthase can produce THCA upon feeding of CBGA. These results open the way for biotechnological production of cannabinoids in the future.”
Thermal isomerization of cannabinoid analogues.
“Thermal isomerization of CBC(an) to THC(an) [nonaromatic analogues of plant cannabinoids cannabichromene (CBC) and Delta(1)-tetrahydrocannabinol (THC), respectively] is predicted in silico and demonstrated experimentally. Density functional theory calculations support a similar isomerization mechanism for the corresponding plant cannabinoids. Docking studies suggest that THC(an), although nonaromatic, has a CB(1) receptor binding affinity similar to that of natural THC.”
The effect of cannabichromene on adult neural stem/progenitor cells.
“Apart from the psychotropic compound Δ(9)-tetrahydrocannabinol (THC), evidence suggests that other non-psychotropic phytocannabinoids are also of potential clinical use.
This study aimed at elucidating the effect of major non-THC phytocannabinoids on the fate of adult neural stem progenitor cells (NSPCs), which are an essential component of brain function in health as well as in pathology.
We tested three compounds: cannabidiol, cannabigerol, and cannabichromene (CBC), and found that CBC has a positive effect on the viability of mouse NSPCs during differentiation in vitro.
Taken together, our results suggest that CBC raises the viability of NSPCs while inhibiting their differentiation into astroglia, possibly through up-regulation of ATP and adenosine signalling.”
Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the ‘runner’s high’
“Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the ‘runner’s high’, which may function to encourage habitual aerobic exercise. Endocannabinoids (eCBs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise…”
Recent work supports direct links between eCB signaling and exercise in humans…
It is possible that neurobiological rewards induced by eCB signaling are an ancient human trait that evolved to encourage aerobic activity, and that the rewards explain the evolution…
The fact that running, and endurance exercise in general, remains an enjoyable and psychologically beneficial recreational activity for tens of millions of humans today suggests that we still may respond to a neurobiological trait that evolved early in our lineage.”
http://jeb.biologists.org/content/215/8/1331.long
Intense exercise increases circulating endocannabinoid and BDNF levels in humans–possible implications for reward and depression.
“The endocannabinoid system is known to have positive effects on depression partly through its actions on neurotrophins, such as Brain-Derived Neurotrophic Factor (BDNF). As BDNF is also considered the major candidate molecule for exercise-induced brain plasticity, we hypothesized that the endocannabinoid system represents a crucial signaling system mediating the beneficial antidepressant effects of exercise…
These findings provide evidence in humans that acute exercise represents a physiological stressor able to increase peripheral levels of AEA and that BDNF might be a mechanism by which AEA influences the neuroplastic and antidepressant effects of exercise.”
http://www.ncbi.nlm.nih.gov/pubmed/22029953
“Neuroplasticity – exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms… We can only speculate which central regions and peripheral sources in particular circulating BDNF originates from,…” http://www.ncbi.nlm.nih.gov/pubmed/20726622
“Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans… cannabinoids modulate brain-derived neurotrophic factor (BDNF)… Delta(9)-THC increased serum BDNF levels…” http://www.ncbi.nlm.nih.gov/pubmed/18807247
“Antidepressant-like effects of Δ⁹-tetrahydrocannabinol…” http://www.ncbi.nlm.nih.gov/pubmed/22634064
“Antidepressant-like effects of cannabidiol… CBD treatment did not change hippocampal BDNF levels… CBD induces antidepressant-like effects…” http://www.ncbi.nlm.nih.gov/pubmed/20002102
Exercise-induced endocannabinoid signaling is modulated by intensity.
“Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward. Recent work shows that exercise activates the eCB system in humans and other mammals, suggesting eCBs are partly responsible for the reported improvements in mood and affect following aerobic exercise in humans.
However, exercise-induced psychological changes reported by runners are known to be dependent on exercise intensity, suggesting that any underlying molecular mechanism should also change with varying levels of exercise intensity.
Here, we examine circulating levels of eCBs following aerobic exercise (treadmill running) in recreationally fit human runners at four different intensities.
We show that eCB signaling is indeed intensity dependent, with significant changes in circulating eCBs observed following moderate intensities only (very high and very low intensity exercises do not significantly alter circulating eCB levels).
Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise.
Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account.”
Effects of exercise stress on the endocannabinoid system in humans under field conditions.
“The effects of physical exercise stress on the endocannabinoid system in humans are almost unexplored. In this prospective study, we investigated in a crossover design and under field conditions at different altitudes the effects of physical exercise on the endocannabinoid system (ECS) in 12 trained healthy volunteers…
We conclude that the ECS is activated upon strenuous exercise whereas the combination with hypoxic stress further increases its activity.
In summary, physical exercise activates the endocannabinoid system, whereas the combination with high altitude enhances this activation.”
http://www.ncbi.nlm.nih.gov/pubmed/22101870
Endocannabinoids and exercise.
“Exercise induces changes in mental status, particularly analgesia, sedation, anxiolysis, and a sense of wellbeing. The mechanisms underlying these changes remain unknown.
Recent findings show that exercise increases serum concentrations of endocannabinoids, suggesting a possible explanation for a number of these changes…
At first glance, it appears that the runner’s high phenomenon is, at present, not a scientific problem because it is built on circumstantial evidence and lacks a plausible mechanistic explanation. However, recent data in our laboratory showed that endurance exercise activates the endocannabinoid system, suggesting a new mechanism underlying exercise induced alterations of mental status.”
http://bjsm.bmj.com/content/38/5/536.long