-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
AuthorNovember Figure 1 Cannabis In 4000 BC, cannabis (Cannabis sativa) was first recorded
.
Hemp is a member of the Moraceae Cannabis genus and is widely used as a durable fiber as well as an active ingredient-rich medicine
.
Hemp has a certain medicinal value, which has been recorded in "Shen Nong's Materia Medica" and "Compendium of Materia Medica".
The tablet is called hemp, and the whole body of marijuana can be used as medicine
.
But "Shen Nong's Materia Medica" also described cannabis as: "Eating too much will make you go crazy, and if you take it for a long time, you will lighten your body.
" Therefore, cannabis is a strictly controlled product in the United Nations Anti-drug Convention.
In China, marijuana is defined as a drug and is an addictive narcotic and psychotropic drug
.
However, countries including Canada and the United States have begun to approve the legalization of marijuana
.
This has brought increased attention to the use of cannabis in the scientific community, as well as a wide-ranging discussion
.
The main active ingredients in cannabis are tetrahydrocannabinol (∆9-Tetrahydrocannabinol, THC) and cannabidiol (Cannabidiol, CBD) [1], and the diversity of its biological activities indicates that it may have potential applications in a variety of diseases value
.
But because phytocannabinoids produce similar pharmacological effects through different mechanisms, choosing which phytocannabinoids to use for disease research is a daunting challenge
.
To this end, Tibor Harkany of the Medical University of Vienna, Austria, Vincenzo Di Marzo of the Italian Institute of Biomolecular Chemistry, and Erik Keimpema of the Medical University of Vienna published a paper in Science entitled Biological basis of cannabinoid medicines, discussing the biological basis of cannabinoids for medicinal purposes, and discussing the biological basis of cannabinoids.
The active ingredients, mechanism of action, and pharmaceutical directions are discussed
.
The role of THC in humans depends on the cannabinoid receptors CB1R and CB2R, which are the most abundant G protein-coupled receptors in the brain [1]
.
When CB1R on the plasma membrane is activated by G(i/o) protein, it inhibits Gαi-mediated STAT signaling or Gβγ-mediated adenylate cyclase, AKT or ERK signaling cascades (Figure 2).
.
For excitable cells such as neurons, activated CB1R inhibits Ca2+ influx through voltage-gated Ca2+ channels, thereby reducing neurotransmitter release
.
Most of the current research focuses on THC because of its psychostimulatory effects
.
And CBD is another abundant ingredient thought to have anti-inflammatory and tissue-protecting properties
.
In addition, studies have found that CBD enhances antioxidant cellular defenses by scavenging free radicals, and counteracts the intracellular effects of THC through CB1Rs on mitochondrial membranes [2]
.
Figure 2.
Pathways of cannabinoid action It is worth noting that these potential sites of cellular and molecular activity are not limited to the brain, but are widely present in various tissues such as pancreas, muscle, liver, and intestine, suggesting that cannabinoids may play a role in There are applications in different environments
.
And it’s important to realize that there’s more to phytocannabinoids than just THC and CBD
.
Many phytocannabinoids, which are present in small quantities in botanical preparations, may have powerful biological activities, and can even replace or alter the effects of THC and CBD, which is of great significance to the structure-function study of phytocannabinoids
.
Therefore, the combined use of phytocannabinoids may alleviate diseases of complex etiology, but also requires direct knowledge of each individual component
.
The role of receptor-mediated phytocannabinoids, especially THC, is mainly to replace high-affinity endocannabinoids, binding to CB1R, CB2R ligands, and alternative receptors including TRPV1, GPR55, and PPARγ.
body
.
This involves the endocannabinoid system (eCB), which is one of the main systems controlling excitatory and inhibitory neurotransmission and neuroplasticity in the hippocampus
.
Among them, Anandamide and 2-AG (2-arachidonoylglycerol) are the main molecules that make up the endocannabinoid system [3].
The two are functionally redundant and can be used to support cells The functional flexibility and diversity of autonomous activity, intercellular metabolic activity, and intracellular biological activity result from differences in the half-life of 2-AG and anandamide, as well as diversity in tissue and receptor distribution
.
The scope of action of endocannabinoid molecules gradually expands with the deepening of research
.
Functional studies of 2-AG acting on CB1Rs in the brain suggest that endocannabinoids modulate synaptic plasticity by limiting Ca2+-dependent neurotransmitter release
.
When cannabis preparations with active ingredients such as THC are used, the over-activation of CB1R in the plasma membrane and in the cell leads to some neuropsychiatric effects, which destroys the attenuation precision of the regulation of endocannabinoids, and the effect of endocannabinoids needs to be fully restored to normal.
hours to weeks
.
Therefore, marijuana is classified as a moderately addictive drug
.
Regarding medicinal value, cannabinoid-related research is applied to the treatment of epilepsy [4], phytocannabinoids can inhibit neuronal excitability in mouse and human epileptic foci, and can be used to rescue neurons from oxidation by means such as CBD Injury and mitochondrial dysfunction may partly support a reduction in seizure frequency in clinical trials
.
Phytocannabinoids are also used in aging-related diseases, and THC can improve cognition by inhibiting faulty synaptic neurotransmission through CB1R activation
.
Long-term low-dose THC treatment in a mouse model of Alzheimer's disease rescues memory deficits, neuronal morphology, and abnormal gene transcription [5]
.
This also demonstrates a biphasic response to cannabinoids, with beneficial effects at low concentrations and detrimental effects at high concentrations, so dosage is also an important consideration for cannabinoid use
.
Cannabinoid therapy may also be suitable for the treatment of neuropathic pain due to injury or disease of the somatosensory nervous system, as well as inflammatory pain, since inhibition of excitatory neurotransmission at the level of spinal neural circuits can reduce pain perception in rodents [6]
.
Its mechanism of action is to inactivate the TRPV1 channel, because the excessive activation of TRPV1 will enhance the sensitivity of pathological touch and lead to pain, so it has certain medical significance
.
In addition, the role of intercellular endocannabinoids determines the size of the neural stem cell pool and the lineage fate decision, migration, synaptogenesis and synapse maintenance of daughter cells, so the endocannabinoid system is also involved in the development of the brain As well as regulating the proliferation rate of cells during organ development to determine tissue size
.
In addition, there are also studies that introduce THC and CBD into the treatment of tumors, because they are involved in the increased production of ceramides, which in turn triggers autophagy-mediated tumor cell death [7]
.
The growing understanding of endocannabinoid mechanisms and cannabinoid components has led to the development of synthetic cannabinoids, including THC analogs, high-affinity and selective CB1R antagonists and inhibitors, various lipases and hydrolases, etc.
Catalyzes the synthesis and inactivation of endocannabinoids
.
Some of these synthetic ligands, rimonabant, nabilone, orlistat, etc.
, have entered clinical practice or are undergoing clinical trials
.
We must admit that as a drug, cannabis has broad therapeutic appeal
.
Rather than exploiting the pleiotropic and synergistic effects of phytocannabinoids, a more systematic study of individual components of cannabis is more conducive to "finding where to play" and for market control than a mixture of phytocannabinoids
.
As knowledge of the endocannabinoid system continues to expand, the utilization of phytocannabinoids may truly move from "toxic" to "medicine"
.
Original link: https:// Publisher: Eleven References 1 Devane, WA, Dysarz, FAI, Johnson, MR, Melvin, LS & Howlett, ACJMP Determination and characterization of a cannabinoid receptor in rat brain.
34, 605-613 (1988).
2 Jimenez-Blasco, D.
et al.
Glucose metabolism links astroglial mitochondria to cannabinoid effects.
Nature 583, 603-608, doi:10.
1038/s41586-020 -2470-y (2020).
3 Maccarrone, M.
, Guzmán, M.
, Mackie, K.
, Doherty, P.
& Harkany, T.
Programming of neural cells by (endo)cannabinoids: from physiological rules to emerging therapies.
Nature Reviews Neuroscience 15, 786-801, doi:10.
1038/nrn3846 (2014).
4 Thiele, EA et al.
Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial.
JAMA neurology 78, 285-292, doi: 10.
1001/jamaneurol.
2020.
4607 (2021).
5 Bilkei-Gorzo, A.
et al.
A chronic low dose of Δ(9)-tetrahydrocannabinol (THC) restores cognitive function in old mice.
Nature medicine 23, 782-787, doi: 10.
1038/nm.
4311 (2017).
6 Calignano, A.
, La Rana, G.
, Giuffrida, A.
& Piomelli, D.
Control of pain initiation by endogenous cannabinoids.
Nature 394, 277-281, doi:10.
1038/28393 (1998).
7 Salazar, M.
et al.
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
The Journal of clinical investigation 119, 1359-1372, doi:10.
1172/jci37948 (2009).
Instructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
The copyright of all works published is owned by BioArt6 Calignano, A.
, La Rana, G.
, Giuffrida, A.
& Piomelli, D.
Control of pain initiation by endogenous cannabinoids.
Nature 394, 277-281, doi:10.
1038/28393 (1998).
7 Salazar, M.
et al.
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
The Journal of clinical investigation 119, 1359-1372, doi:10.
1172/jci37948 (2009).
Notes for reprinting【Original article】BioArt original article , Personal reposting and sharing are welcome.
Reprinting is prohibited without permission.
The copyright of all published works is owned by BioArt6 Calignano, A.
, La Rana, G.
, Giuffrida, A.
& Piomelli, D.
Control of pain initiation by endogenous cannabinoids.
Nature 394, 277-281, doi:10.
1038/28393 (1998).
7 Salazar, M.
et al.
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
The Journal of clinical investigation 119, 1359-1372, doi:10.
1172/jci37948 (2009).
Notes for reprinting【Original article】BioArt original article , Personal reposting and sharing are welcome.
Reprinting is prohibited without permission.
The copyright of all published works is owned by BioArtInstructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
The copyright of all works published is owned by BioArtInstructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
The copyright of all works published is owned by BioArt
.
BioArt reserves all legal rights and violators will be held accountable
.
.
Hemp is a member of the Moraceae Cannabis genus and is widely used as a durable fiber as well as an active ingredient-rich medicine
.
Hemp has a certain medicinal value, which has been recorded in "Shen Nong's Materia Medica" and "Compendium of Materia Medica".
The tablet is called hemp, and the whole body of marijuana can be used as medicine
.
But "Shen Nong's Materia Medica" also described cannabis as: "Eating too much will make you go crazy, and if you take it for a long time, you will lighten your body.
" Therefore, cannabis is a strictly controlled product in the United Nations Anti-drug Convention.
In China, marijuana is defined as a drug and is an addictive narcotic and psychotropic drug
.
However, countries including Canada and the United States have begun to approve the legalization of marijuana
.
This has brought increased attention to the use of cannabis in the scientific community, as well as a wide-ranging discussion
.
The main active ingredients in cannabis are tetrahydrocannabinol (∆9-Tetrahydrocannabinol, THC) and cannabidiol (Cannabidiol, CBD) [1], and the diversity of its biological activities indicates that it may have potential applications in a variety of diseases value
.
But because phytocannabinoids produce similar pharmacological effects through different mechanisms, choosing which phytocannabinoids to use for disease research is a daunting challenge
.
To this end, Tibor Harkany of the Medical University of Vienna, Austria, Vincenzo Di Marzo of the Italian Institute of Biomolecular Chemistry, and Erik Keimpema of the Medical University of Vienna published a paper in Science entitled Biological basis of cannabinoid medicines, discussing the biological basis of cannabinoids for medicinal purposes, and discussing the biological basis of cannabinoids.
The active ingredients, mechanism of action, and pharmaceutical directions are discussed
.
The role of THC in humans depends on the cannabinoid receptors CB1R and CB2R, which are the most abundant G protein-coupled receptors in the brain [1]
.
When CB1R on the plasma membrane is activated by G(i/o) protein, it inhibits Gαi-mediated STAT signaling or Gβγ-mediated adenylate cyclase, AKT or ERK signaling cascades (Figure 2).
.
For excitable cells such as neurons, activated CB1R inhibits Ca2+ influx through voltage-gated Ca2+ channels, thereby reducing neurotransmitter release
.
Most of the current research focuses on THC because of its psychostimulatory effects
.
And CBD is another abundant ingredient thought to have anti-inflammatory and tissue-protecting properties
.
In addition, studies have found that CBD enhances antioxidant cellular defenses by scavenging free radicals, and counteracts the intracellular effects of THC through CB1Rs on mitochondrial membranes [2]
.
Figure 2.
Pathways of cannabinoid action It is worth noting that these potential sites of cellular and molecular activity are not limited to the brain, but are widely present in various tissues such as pancreas, muscle, liver, and intestine, suggesting that cannabinoids may play a role in There are applications in different environments
.
And it’s important to realize that there’s more to phytocannabinoids than just THC and CBD
.
Many phytocannabinoids, which are present in small quantities in botanical preparations, may have powerful biological activities, and can even replace or alter the effects of THC and CBD, which is of great significance to the structure-function study of phytocannabinoids
.
Therefore, the combined use of phytocannabinoids may alleviate diseases of complex etiology, but also requires direct knowledge of each individual component
.
The role of receptor-mediated phytocannabinoids, especially THC, is mainly to replace high-affinity endocannabinoids, binding to CB1R, CB2R ligands, and alternative receptors including TRPV1, GPR55, and PPARγ.
body
.
This involves the endocannabinoid system (eCB), which is one of the main systems controlling excitatory and inhibitory neurotransmission and neuroplasticity in the hippocampus
.
Among them, Anandamide and 2-AG (2-arachidonoylglycerol) are the main molecules that make up the endocannabinoid system [3].
The two are functionally redundant and can be used to support cells The functional flexibility and diversity of autonomous activity, intercellular metabolic activity, and intracellular biological activity result from differences in the half-life of 2-AG and anandamide, as well as diversity in tissue and receptor distribution
.
The scope of action of endocannabinoid molecules gradually expands with the deepening of research
.
Functional studies of 2-AG acting on CB1Rs in the brain suggest that endocannabinoids modulate synaptic plasticity by limiting Ca2+-dependent neurotransmitter release
.
When cannabis preparations with active ingredients such as THC are used, the over-activation of CB1R in the plasma membrane and in the cell leads to some neuropsychiatric effects, which destroys the attenuation precision of the regulation of endocannabinoids, and the effect of endocannabinoids needs to be fully restored to normal.
hours to weeks
.
Therefore, marijuana is classified as a moderately addictive drug
.
Regarding medicinal value, cannabinoid-related research is applied to the treatment of epilepsy [4], phytocannabinoids can inhibit neuronal excitability in mouse and human epileptic foci, and can be used to rescue neurons from oxidation by means such as CBD Injury and mitochondrial dysfunction may partly support a reduction in seizure frequency in clinical trials
.
Phytocannabinoids are also used in aging-related diseases, and THC can improve cognition by inhibiting faulty synaptic neurotransmission through CB1R activation
.
Long-term low-dose THC treatment in a mouse model of Alzheimer's disease rescues memory deficits, neuronal morphology, and abnormal gene transcription [5]
.
This also demonstrates a biphasic response to cannabinoids, with beneficial effects at low concentrations and detrimental effects at high concentrations, so dosage is also an important consideration for cannabinoid use
.
Cannabinoid therapy may also be suitable for the treatment of neuropathic pain due to injury or disease of the somatosensory nervous system, as well as inflammatory pain, since inhibition of excitatory neurotransmission at the level of spinal neural circuits can reduce pain perception in rodents [6]
.
Its mechanism of action is to inactivate the TRPV1 channel, because the excessive activation of TRPV1 will enhance the sensitivity of pathological touch and lead to pain, so it has certain medical significance
.
In addition, the role of intercellular endocannabinoids determines the size of the neural stem cell pool and the lineage fate decision, migration, synaptogenesis and synapse maintenance of daughter cells, so the endocannabinoid system is also involved in the development of the brain As well as regulating the proliferation rate of cells during organ development to determine tissue size
.
In addition, there are also studies that introduce THC and CBD into the treatment of tumors, because they are involved in the increased production of ceramides, which in turn triggers autophagy-mediated tumor cell death [7]
.
The growing understanding of endocannabinoid mechanisms and cannabinoid components has led to the development of synthetic cannabinoids, including THC analogs, high-affinity and selective CB1R antagonists and inhibitors, various lipases and hydrolases, etc.
Catalyzes the synthesis and inactivation of endocannabinoids
.
Some of these synthetic ligands, rimonabant, nabilone, orlistat, etc.
, have entered clinical practice or are undergoing clinical trials
.
We must admit that as a drug, cannabis has broad therapeutic appeal
.
Rather than exploiting the pleiotropic and synergistic effects of phytocannabinoids, a more systematic study of individual components of cannabis is more conducive to "finding where to play" and for market control than a mixture of phytocannabinoids
.
As knowledge of the endocannabinoid system continues to expand, the utilization of phytocannabinoids may truly move from "toxic" to "medicine"
.
Original link: https:// Publisher: Eleven References 1 Devane, WA, Dysarz, FAI, Johnson, MR, Melvin, LS & Howlett, ACJMP Determination and characterization of a cannabinoid receptor in rat brain.
34, 605-613 (1988).
2 Jimenez-Blasco, D.
et al.
Glucose metabolism links astroglial mitochondria to cannabinoid effects.
Nature 583, 603-608, doi:10.
1038/s41586-020 -2470-y (2020).
3 Maccarrone, M.
, Guzmán, M.
, Mackie, K.
, Doherty, P.
& Harkany, T.
Programming of neural cells by (endo)cannabinoids: from physiological rules to emerging therapies.
Nature Reviews Neuroscience 15, 786-801, doi:10.
1038/nrn3846 (2014).
4 Thiele, EA et al.
Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial.
JAMA neurology 78, 285-292, doi: 10.
1001/jamaneurol.
2020.
4607 (2021).
5 Bilkei-Gorzo, A.
et al.
A chronic low dose of Δ(9)-tetrahydrocannabinol (THC) restores cognitive function in old mice.
Nature medicine 23, 782-787, doi: 10.
1038/nm.
4311 (2017).
6 Calignano, A.
, La Rana, G.
, Giuffrida, A.
& Piomelli, D.
Control of pain initiation by endogenous cannabinoids.
Nature 394, 277-281, doi:10.
1038/28393 (1998).
7 Salazar, M.
et al.
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
The Journal of clinical investigation 119, 1359-1372, doi:10.
1172/jci37948 (2009).
Instructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
The copyright of all works published is owned by BioArt6 Calignano, A.
, La Rana, G.
, Giuffrida, A.
& Piomelli, D.
Control of pain initiation by endogenous cannabinoids.
Nature 394, 277-281, doi:10.
1038/28393 (1998).
7 Salazar, M.
et al.
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
The Journal of clinical investigation 119, 1359-1372, doi:10.
1172/jci37948 (2009).
Notes for reprinting【Original article】BioArt original article , Personal reposting and sharing are welcome.
Reprinting is prohibited without permission.
The copyright of all published works is owned by BioArt6 Calignano, A.
, La Rana, G.
, Giuffrida, A.
& Piomelli, D.
Control of pain initiation by endogenous cannabinoids.
Nature 394, 277-281, doi:10.
1038/28393 (1998).
7 Salazar, M.
et al.
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.
The Journal of clinical investigation 119, 1359-1372, doi:10.
1172/jci37948 (2009).
Notes for reprinting【Original article】BioArt original article , Personal reposting and sharing are welcome.
Reprinting is prohibited without permission.
The copyright of all published works is owned by BioArtInstructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
The copyright of all works published is owned by BioArtInstructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
The copyright of all works published is owned by BioArt
.
BioArt reserves all legal rights and violators will be held accountable
.
