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~ Traumatic Brain Injury ~
Preferred Strains
Preferred Methods to Medicate
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Raphael Mechoulam, PhD
Brain Trauma, Neuroprotection & Cannabinoids Hebrew University, Israel presents research at Sixth National Clinical Conference on Cannabis Therapeutics in Warwick, Rhode Island, April 2010 |
Raphael Mechoulam, PhD
Anti-inflammatory & Neuroprotective Properties Professor at Hebrew University in Jerusalem, Dr. Mechoulam describes the role of Cannabinoids as anti-inflammatory for arthritis, as neuroprotectant for brain injury and as a possible treatment for PTSD. Dr. Mechoulam first isolated THC in 1964. |
Traumatic Brain Injury, Overview:
Traumatic brain injury (TBI), also known as intracranial injury, occurs when an external force injures the brain. TBI can be classified based on severity, mechanism (closed or penetrating head injury), or other features (e.g., occurring in a specific location or over a widespread area). Head injury is a broader category that may involve damage to other structures such as the scalp and skull. TBI can result in physical, cognitive, social, emotional, and behavioral symptoms, and outcome can range from complete recovery to permanent disability or death.
Causes include falls, vehicle collisions, and violence. Brain trauma occurs as a consequence of a sudden acceleration or deceleration within the cranium or by a complex combination of both movement and sudden impact. In addition to the damage caused at the moment of injury, a variety of events in the minutes to days following the injury may result in secondary injury. These processes include alterations in cerebral blood flow and the pressure within the skull.
Causes include falls, vehicle collisions, and violence. Brain trauma occurs as a consequence of a sudden acceleration or deceleration within the cranium or by a complex combination of both movement and sudden impact. In addition to the damage caused at the moment of injury, a variety of events in the minutes to days following the injury may result in secondary injury. These processes include alterations in cerebral blood flow and the pressure within the skull.
~ How Cannabis Aids ~
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Traumatic brain injuries TBI, To date have littlie if no treatement. with the odd case of needing surgery usually for relieving pressure. after the initial trauma one is not out of the woods as the excitotoxins and inflammation continues to create brain damage, such as glutamate. A study published in 2002 (Mechoulam et al) demonstrated that production of anandamide and 2-AG increased in the brain following TBI, and that production of substances known to cause neural damage—tumour necrosis factor-a and reactive oxygen species (ROS)—was inhibited by the presence of anandamide & 2-AG, or THC/CBD. It is thought that the endocannabinoid system’s role in inhibiting release of neurotransmitters such as glutamate (the main transmitter in glutamatergic synaptic transmission, which plays a major role in nervous impulse modulation as well as in cognitive functions such as learning and memory), as well as in modulating the inflammatory response, is significant in this context.
Various studies have confirmed these findings. Another study published in 2002 by Mechoulam et al demonstrated that endogenous levels of anandamide and 2-AG also increase following TBI to protect the brian against further damage.
several cannabinoids act to inhibit the release of such toxins, preventing further damage.
the evidence for the antioxidative and anti-inflammatory properties of various cannabinoids has become well-established, and our understanding of the role they play in modulating neurotransmission too has grown. Thus, serious consideration is now being given to their potential as neuroprotective agents. Cannabinoids have been shown to prevent neuronal death in acute neuronal injury, still promoting cellular death if ireversable, all the while promoting neurogenesis, nueropasticity & Neuroprotectant, making cannabis a majir first step in TBI. It was also noted that 2-AG was more effective when administered with similar compounds in the fatty acid glycerol ester class. Which the Cannabis plant is loaded with making cannabis a ideal treatement. Cannabiniods/cannabis/2-AG is known to play a significant role in vascular modulation, which increases its effectiveness following TBI—by counteracting vasoconstriction (narrowing of blood vessels) caused by release of endothelins (21-amino acid compounds, which are the most potent vasoconstrictors known), it helps to restore the blood supply to the affected area. Furthermore cannabinoids are showing properties in strengthening the blood brain barrier.
CBD has been the subject of much investigation as a neuroprotectant. It has been shown to increase cerebral blood flow following TBI thereby aid in mitigating infarct volume; its effective even after fourteen days of repeated treatment. For this reason, it is seen as having greater therapeutic potential than THC in this area of research. CBD has also been shown to reduce inflammation caused by release of interleukin-1, nitric oxide, and tumour necrosis factor-a following TBI.
research demonstrated that both THC and CBD increased neuroprotection and also reduced NMDA, AMPA and kainate receptor neurotoxicities. Furthermore, the level of neuroprotection was not increased by the action of specific cannabinoid receptor antagonists, indicating that the mechanism of action was independent of the cannabinoid receptors. Previous studies had concluded that cannabinoid receptor agonists were the key agents of neuroprotection; however, cannabidiol is not an agonist, so its neuroprotective potential must therefore be realised elsewhere.
CBD was also shown to reduce hydroperoxide (a type of ROS) toxicity in neuron cell cultures—further proving its effectiveness as an antioxidant. CBD’s ability to reduce toxicity was tested against two other known antioxidants, a-tocopherol and ascorbate, and was proven to be superior to both in terms of neuroprotective capacity.
The function of the endocannabinoid system in the nervous system is more than just homeostatic prevention of too much excitation or too much inhibition. There is a significant protective and repair function, and the endocannabinoid system is heavily involved in neuroplasticity.
Neuroplasticity involves the sprouting and pruning of synapses, changes in dendritic spine density, and changes in neurotransmitter pathways. It gives rise to all types of adaptive learning, including recovering from a stroke, the conscious act of gaining a new skill, and the unconscious acquisition of a new emotional response. It is also involved in pathological processes such as central sensitization to pain. There are multiple mechanisms by which cannabinoids modulate neural plasticity, including neurogenesis (the formation of new neurons), aiding in long-term potentiation and long-term depression. Research in humans has shown that the administration of exogenous cannabinoids can cause neuroplastic changes. One study that looked at volunteers who were heavy cannabis users found neuroplastic changes in the nucleus accumbens and amygdala.
Various studies have confirmed these findings. Another study published in 2002 by Mechoulam et al demonstrated that endogenous levels of anandamide and 2-AG also increase following TBI to protect the brian against further damage.
several cannabinoids act to inhibit the release of such toxins, preventing further damage.
the evidence for the antioxidative and anti-inflammatory properties of various cannabinoids has become well-established, and our understanding of the role they play in modulating neurotransmission too has grown. Thus, serious consideration is now being given to their potential as neuroprotective agents. Cannabinoids have been shown to prevent neuronal death in acute neuronal injury, still promoting cellular death if ireversable, all the while promoting neurogenesis, nueropasticity & Neuroprotectant, making cannabis a majir first step in TBI. It was also noted that 2-AG was more effective when administered with similar compounds in the fatty acid glycerol ester class. Which the Cannabis plant is loaded with making cannabis a ideal treatement. Cannabiniods/cannabis/2-AG is known to play a significant role in vascular modulation, which increases its effectiveness following TBI—by counteracting vasoconstriction (narrowing of blood vessels) caused by release of endothelins (21-amino acid compounds, which are the most potent vasoconstrictors known), it helps to restore the blood supply to the affected area. Furthermore cannabinoids are showing properties in strengthening the blood brain barrier.
CBD has been the subject of much investigation as a neuroprotectant. It has been shown to increase cerebral blood flow following TBI thereby aid in mitigating infarct volume; its effective even after fourteen days of repeated treatment. For this reason, it is seen as having greater therapeutic potential than THC in this area of research. CBD has also been shown to reduce inflammation caused by release of interleukin-1, nitric oxide, and tumour necrosis factor-a following TBI.
research demonstrated that both THC and CBD increased neuroprotection and also reduced NMDA, AMPA and kainate receptor neurotoxicities. Furthermore, the level of neuroprotection was not increased by the action of specific cannabinoid receptor antagonists, indicating that the mechanism of action was independent of the cannabinoid receptors. Previous studies had concluded that cannabinoid receptor agonists were the key agents of neuroprotection; however, cannabidiol is not an agonist, so its neuroprotective potential must therefore be realised elsewhere.
CBD was also shown to reduce hydroperoxide (a type of ROS) toxicity in neuron cell cultures—further proving its effectiveness as an antioxidant. CBD’s ability to reduce toxicity was tested against two other known antioxidants, a-tocopherol and ascorbate, and was proven to be superior to both in terms of neuroprotective capacity.
The function of the endocannabinoid system in the nervous system is more than just homeostatic prevention of too much excitation or too much inhibition. There is a significant protective and repair function, and the endocannabinoid system is heavily involved in neuroplasticity.
Neuroplasticity involves the sprouting and pruning of synapses, changes in dendritic spine density, and changes in neurotransmitter pathways. It gives rise to all types of adaptive learning, including recovering from a stroke, the conscious act of gaining a new skill, and the unconscious acquisition of a new emotional response. It is also involved in pathological processes such as central sensitization to pain. There are multiple mechanisms by which cannabinoids modulate neural plasticity, including neurogenesis (the formation of new neurons), aiding in long-term potentiation and long-term depression. Research in humans has shown that the administration of exogenous cannabinoids can cause neuroplastic changes. One study that looked at volunteers who were heavy cannabis users found neuroplastic changes in the nucleus accumbens and amygdala.
Clinical Studies
2013 - Study ~ Selective Activation of Cannabinoid Receptor 2 in Leukocytes Suppresses Their Engagement of the Brain Endothelium and Protects the Blood-Brain Barrier.
2013 - Study ~ Palmitoylethanolamide is a New Possible Pharmacological Treatment for the Inflammation Associated with Trauma
2013 - Study ~ Cannabinoid receptor modulation of the endothelial cell inflammatory response
2013 - Study ~ The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain
2013 - Study ~ Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
2013 - News ~ Marijuana's Memory Paradox
2012 - Study ~ Prolonged oral Cannabinoid Administration prevents Neuroinflammation, lowers beta-amyloid Levels and improves Cognitive Performance
.2012 - Study ~ Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions.
2012 - Study ~ A cannabinoid type 2 receptor agonist attenuates blood-brain barrier damage and
neurodegeneration in a murine model of traumatic brain injury.
2011 - Study ~ Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study.
2011 - Study ~ Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement.
2011 - Study ~ Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ(9) -tetrahydrocannabinol in BV-2 microglial cells.
2008 - Study ~ Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats.
2008 - Study ~ Cannabinoid CB2 receptors in human brain inflammation.
2008 - News - Marijuana reduces memory impairment.
2006 - News ~ Anandamide, an endocannabinoid, protects neurons from inflammation after brain damage
2013 - Study ~ Palmitoylethanolamide is a New Possible Pharmacological Treatment for the Inflammation Associated with Trauma
2013 - Study ~ Cannabinoid receptor modulation of the endothelial cell inflammatory response
2013 - Study ~ The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain
2013 - Study ~ Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
2013 - News ~ Marijuana's Memory Paradox
2012 - Study ~ Prolonged oral Cannabinoid Administration prevents Neuroinflammation, lowers beta-amyloid Levels and improves Cognitive Performance
.2012 - Study ~ Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions.
2012 - Study ~ A cannabinoid type 2 receptor agonist attenuates blood-brain barrier damage and
neurodegeneration in a murine model of traumatic brain injury.
2011 - Study ~ Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study.
2011 - Study ~ Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement.
2011 - Study ~ Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ(9) -tetrahydrocannabinol in BV-2 microglial cells.
2008 - Study ~ Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats.
2008 - Study ~ Cannabinoid CB2 receptors in human brain inflammation.
2008 - News - Marijuana reduces memory impairment.
2006 - News ~ Anandamide, an endocannabinoid, protects neurons from inflammation after brain damage
Patents
US6410588B1 1998-04-14 2002-06-25 anti-inflammatory agents The Mathilda And Terence Kennedy Institute Of Rheumatology Use of cannabinoids as anti-inflammatory agents
US6630507 Autoimmune/Neuro Disorders; Cannabiniods as antioxidants & neuroprotectants
US6630507 Autoimmune/Neuro Disorders; Cannabiniods as antioxidants & neuroprotectants
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