|
Changing Medicine Together
|
|
|
~ Bipolar ~
|
Page Legend
|
|
Preferred Strains
Cannabis (Cannabinoids) Relieve Bipolar Symptoms: Follow physicians suggestions, then with help from family members, try medical marijuana for symptom relief:
Look for strains with higher CBD-Cannabidiol levels. Sativa's have higher CBD levels than Indica's. Hashish has highest amounts of CBD's. "Durban Poison" has higher CBD levels.
- appetite stimulant (Sativa's)
- mood elevators (Sativa's)
- fatigue (Sativa's)
- sleep disturbances (Indica's)
- hyperactivity (Indica's)
- mania (Indica's)
- focus (Sativa's)
Look for strains with higher CBD-Cannabidiol levels. Sativa's have higher CBD levels than Indica's. Hashish has highest amounts of CBD's. "Durban Poison" has higher CBD levels.
Preferred Methods to Medicate
Raw Kief/Greens
Ideally one should be eating Raw Kief/Greens for the A molecule THCA, CBDA etc, Over and above the preferred method of medicating, each cannabinoid & Terpenes plays a roll in healing.
Medicating
Ideally one should be eating Raw Kief/Greens for the A molecule THCA, CBDA etc, Over and above the preferred method of medicating, each cannabinoid & Terpenes plays a roll in healing.
Medicating
- Drops/Oil Dropped under tongue for faster absorption (Soft membrane tissue).
- Sprays, if for internal best applied through nasal sprays for soft tissue. (If Issue is eye's or ear's, apply to correlation)
|
+
+ + + + + + + ++ |
|
|
|
|
Bipolar, Overview:
Bipolar disorder, previously known as manic depression, is a mental disorder that causes periods of depression and periods of elevated mood.[3][4] The elevated mood is significant and is known as mania or hypomania, depending on its severity, or whether symptoms of psychosis are present.[3] During mania, an individual behaves or feels abnormally energetic, happy, or irritable.[3] Individuals often make poorly thought out decisions with little regard to the consequences.[4] The need for sleep is usually reduced during manic phases.[4] During periods of depression, there may be crying, a negative outlook on life, and poor eye contact with others.[3] The risk of suicide among those with the illness is high at greater than 6 percent over 20 years, while self-harm occurs in 30–40 percent.[3] Other mental health issues such as anxiety disorders and substance use disorder are commonly associated.[3]
The causes are not clearly understood, but both environmental and genetic factors play a role.[3] Many genes of small effect contribute to risk.[3][6] Environmental factors include a history of childhood abuse, and long-term stress.[3] The condition is divided into bipolar I disorder if there has been at least one manic episode, with or without depressive episodes, and bipolar II disorder if there has been at least one hypomanic episode (but no manic episodes) and one major depressive episode.[4] In those with less severe symptoms of a prolonged duration, the condition cyclothymic disorder may be diagnosed.[4] If due to drugs or medical problems, it is classified separately.[4] Other conditions that may present in a similar manner include attention deficit hyperactivity disorder, personality disorders, schizophrenia, and substance use disorder as well as a number of medical conditions.[3] Medical testing is not required for a diagnosis, though blood tests or medical imaging can be done to rule out other problems.[7]
The causes are not clearly understood, but both environmental and genetic factors play a role.[3] Many genes of small effect contribute to risk.[3][6] Environmental factors include a history of childhood abuse, and long-term stress.[3] The condition is divided into bipolar I disorder if there has been at least one manic episode, with or without depressive episodes, and bipolar II disorder if there has been at least one hypomanic episode (but no manic episodes) and one major depressive episode.[4] In those with less severe symptoms of a prolonged duration, the condition cyclothymic disorder may be diagnosed.[4] If due to drugs or medical problems, it is classified separately.[4] Other conditions that may present in a similar manner include attention deficit hyperactivity disorder, personality disorders, schizophrenia, and substance use disorder as well as a number of medical conditions.[3] Medical testing is not required for a diagnosis, though blood tests or medical imaging can be done to rule out other problems.[7]
Geneic & Environmental Influences
Behavioral genetic studies have suggested that many chromosomal regions and candidate genes are related to bipolar disorder susceptibility with each gene exerting a mild to moderate effect.[35] The risk of bipolar disorder is nearly ten-fold higher in first degree-relatives of those affected with bipolar disorder when compared to the general population; similarly, the risk of major depressive disorder is three times higher in relatives of those with bipolar disorder when compared to the general population.[12]
Although the first genetic linkage finding for mania was in 1969,[42] the linkage studies have been inconsistent.[12] The largest and most recent genome-wide association study (GWAS) failed to find any particular locus that exerts a large effect reinforcing the idea that no single gene is responsible for bipolar disorder in most cases.[43] Polymorphisms in BDNF, DRD4, DAO, and TPH1 have been frequently associated with bipolar disorder and were initially successful in a meta-analysis, but failed after correction for multiple testing.[44] On the other hand, two polymorphisms in TPH1 were identified as being associated with bipolar disorder.[45]
Due to the inconsistent findings in GWAS, multiple studies have undertaken the approach of analyzing SNPs in biological pathways. Signaling pathways traditionally associated with bipolar disorder that have been supported by these studies include CRH signaling, cardiac β-adrenergic signaling, Phospholipase C signaling, glutamate receptor signaling,[46] cardiac hypertrophy signaling, Wnt signaling, Notch signaling,[47] and endothelin 1 signaling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the dorsolateral prefrontal cortex portion of the brain in post-mortem studies, CACNA1C, GNG2, and ITPR2.[48]
Findings point strongly to heterogeneity, with different genes being implicated in different families.[49] Robust and replicable genome-wide significant associations showed several common single nucleotide polymorphisms, including variants within the genes CACNA1C, ODZ4, and NCAN.[35][43]
Advanced paternal age has been linked to a somewhat increased chance of bipolar disorder in offspring, consistent with a hypothesis of increased new genetic mutations.[50]
Environmental
Although the first genetic linkage finding for mania was in 1969,[42] the linkage studies have been inconsistent.[12] The largest and most recent genome-wide association study (GWAS) failed to find any particular locus that exerts a large effect reinforcing the idea that no single gene is responsible for bipolar disorder in most cases.[43] Polymorphisms in BDNF, DRD4, DAO, and TPH1 have been frequently associated with bipolar disorder and were initially successful in a meta-analysis, but failed after correction for multiple testing.[44] On the other hand, two polymorphisms in TPH1 were identified as being associated with bipolar disorder.[45]
Due to the inconsistent findings in GWAS, multiple studies have undertaken the approach of analyzing SNPs in biological pathways. Signaling pathways traditionally associated with bipolar disorder that have been supported by these studies include CRH signaling, cardiac β-adrenergic signaling, Phospholipase C signaling, glutamate receptor signaling,[46] cardiac hypertrophy signaling, Wnt signaling, Notch signaling,[47] and endothelin 1 signaling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the dorsolateral prefrontal cortex portion of the brain in post-mortem studies, CACNA1C, GNG2, and ITPR2.[48]
Findings point strongly to heterogeneity, with different genes being implicated in different families.[49] Robust and replicable genome-wide significant associations showed several common single nucleotide polymorphisms, including variants within the genes CACNA1C, ODZ4, and NCAN.[35][43]
Advanced paternal age has been linked to a somewhat increased chance of bipolar disorder in offspring, consistent with a hypothesis of increased new genetic mutations.[50]
Environmental
Psychological, Neurological & Neurochemical
Less commonly, bipolar disorder or a bipolar-like disorder may occur as a result of or in association with a neurological condition or injury. Conditions like these and injuries include (but are not limited to) stroke, traumatic brain injury, HIV infection, multiple sclerosis, porphyria, and rarely temporal lobe epilepsy.[55]
Abnormalities in the structure and/or function of certain brain circuits could underlie bipolar. Meta-analyses of structural MRI studies in bipolar disorder report decreased volume in the left rostral anterior cingulate cortex(ACC), fronto-insular cortex, ventral prefrontal cortex, and claustrum. Increases have been reported in the volume of the lateral ventricles, globus pallidus, subgenual anterior cingulate, and amygdala as well as in the rates of deep white matter hyperintensities.[56][57][58][59] Functional MRI findings suggest that abnormal modulation between ventral prefrontal and limbic regions, especially the amygdala, likely contributes to poor emotional regulation and mood symptoms.[60] Pharmacological treatment of mania increases ventral prefrontal cortex (vPFC) activity, normalizing it relative to controls, suggesting that vPFC hypoactivity is an indicator of mood state. On the other hand, pretreatment hyperactivity in the amygdala is reduced post treatment but still increased relative to controls, suggesting that it is a trait marker.[61]
initial manic episodes are associated with both increased oxidative stress parameters and activated antioxidant defenses, which may be related to dysfunctions on energy metabolism and neuroplasticity pathways.
Manic and depressive episodes tend to be characterized by ventral versus dorsal dysfunction in the ventral prefrontal cortex. During attentional tasks and resting, mania is associated with decreased Orbitofrontal cortex activity, while depression is associated with increased resting metabolism. Consistent with affective disorders due to lesions, mania and depression are lateralized in ventral prefrontal cortex (vPFC) dysfunction, with depression primarily being associated with the left vPFC, and mania the right vPFC. Abnormal vPFC activity, along with amygdala hyperactivity is found during euthymia as well as in healthy relatives of those with bipolar, indicating possible trait features.[62]
Euthymic bipolar people show decreased activity in the lingual gyrus, while people who are manic demonstrate decreased activity in the inferior frontal cortex, while no differences were found in people with bipolar depression.[63] People with bipolar have increased activation of left hemisphere ventral limbic areas and decreased activation of right hemisphere cortical structures related to cognition.[64]
One proposed model for bipolar suggests that hypersensitivity of reward circuits consisting of fronto-striatal circuits causes mania and hyposensitivity of these circuits cause depression.[65]
Euthymic bipolar people show decreased activity in the lingual gyrus, while people who are manic demonstrate decreased activity in the inferior frontal cortex, while no differences were found in people with bipolar depression.[63] People with bipolar have increased activation of left hemisphere ventral limbic areas and decreased activation of right hemisphere cortical structures related to cognition.[64]
One proposed model for bipolar suggests that hypersensitivity of reward circuits consisting of fronto-striatal circuits causes mania and hyposensitivity of these circuits cause depression.[65]
According to the "kindling" hypothesis, when people who are genetically predisposed toward bipolar disorder experience stressful events, the stress threshold at which mood changes occur becomes progressively lower, until the episodes eventually start (and recur) spontaneously. There is evidence supporting an association between early-life stress and dysfunction of the hypothalamic-pituitary-adrenal axis (HPA axis) leading to its over activation, which may play a role in the pathogenesis of bipolar disorder.[66][67]
Some of the brain components which have been proposed to play a role are the mitochondria[38] and a sodium ATPase pump.[68] Circadian rhythms and regulation of the hormone melatonin also seem to be altered.[69]
Some of the brain components which have been proposed to play a role are the mitochondria[38] and a sodium ATPase pump.[68] Circadian rhythms and regulation of the hormone melatonin also seem to be altered.[69]
Dopamine, a known neurotransmitter responsible for mood cycling, has been shown to have increased transmission during the manic phase.[14][70] The dopamine hypothesis states that the increase in dopamine results in secondary homeostatic down regulation of key systems and receptors such as an increase in dopamine mediated G protein-coupled receptors. This results in decreased dopamine transmission characteristic of the depressive phase.[14] The depressive phase ends with homeostatic up regulation potentially restarting the cycle over again.[71]
Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.[72] The increase in GABA is possibly caused by a disturbance in early development causing a disturbance of cell migration and the formation of normal lamination, the layering of brain structures commonly associated with the cerebral cortex.[73]
Medications used to treat bipolar may exert their effect by modulating intracellular signaling, such as through depleting myo-inositol levels, inhibition of cAMP signaling, and through altering G coupled proteins.[74] Consistent with this, elevated levels of Gαi, Gαs, and Gαq/11 have been reported in brain and blood samples, along with increased protein kinase A expression and sensitivity.[75] ( Cannabis is a regulatory system, As ALL above mentioned factors, are ALL apart of the Endo-cannabinoid system, regulating directly and/or indirectly. Through the Endo-cannabinoids system, cannabinoids couple directly to G proteins influencing Glutamate, GABA, cAMP signaling AND most interestingly also the Kinase protein which job is to modulate gene expression giving cannabinoids one potential means to correct the problem at the core). Diagram to the Left. <
Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of serotonin, are present in the cerebrospinal fluid of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α2 adrenergic receptors as well as increased cell counts in the locus ceruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found.[76] One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder.[77] Tyrosine depletion was found to reduce the effects of methamphetamine in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania.[78]
Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.[72] The increase in GABA is possibly caused by a disturbance in early development causing a disturbance of cell migration and the formation of normal lamination, the layering of brain structures commonly associated with the cerebral cortex.[73]
Medications used to treat bipolar may exert their effect by modulating intracellular signaling, such as through depleting myo-inositol levels, inhibition of cAMP signaling, and through altering G coupled proteins.[74] Consistent with this, elevated levels of Gαi, Gαs, and Gαq/11 have been reported in brain and blood samples, along with increased protein kinase A expression and sensitivity.[75] ( Cannabis is a regulatory system, As ALL above mentioned factors, are ALL apart of the Endo-cannabinoid system, regulating directly and/or indirectly. Through the Endo-cannabinoids system, cannabinoids couple directly to G proteins influencing Glutamate, GABA, cAMP signaling AND most interestingly also the Kinase protein which job is to modulate gene expression giving cannabinoids one potential means to correct the problem at the core). Diagram to the Left. <
Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of serotonin, are present in the cerebrospinal fluid of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α2 adrenergic receptors as well as increased cell counts in the locus ceruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found.[76] One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder.[77] Tyrosine depletion was found to reduce the effects of methamphetamine in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania.[78]
~ How Cannabis Aids ~
Cannabis Aiding in inflammation, Serotonin & Dopamine Levels
Cannabis Aiding in inflammation, Serotonin & Dopamine Levels
Increased attention has been directed toward understanding the role of the endocannabinoid system in mood regulation. Clinical studies have reported benefits of cannabis on mood disorders Cannabis, present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. Present studies are aimed to directly investigate the effects of CBD in an animal model of mania induced episodes related to bipolar.
.Also, the possibility of interaction among receptor subtypes including a putative CB3R and vanilloid receptors, which has likewise been demonstrated operating in a plethora of cannabimimetic responses, may underlie ambivalent effects on mood modulation.
.Also, the possibility of interaction among receptor subtypes including a putative CB3R and vanilloid receptors, which has likewise been demonstrated operating in a plethora of cannabimimetic responses, may underlie ambivalent effects on mood modulation.
Oxidative stress & Free Radicals
Cannabis Aiding in the Suppression of Damaging proteins eg. Glutamate
Cannabis Aiding in the Suppression of Damaging proteins eg. Glutamate
CBD can inhibit glutamate toxicity and offers anti-convulsant and mood-stabilizing benefits, which are similar to the benefits of conventional therapeutic drugs such as valproate and lithium that are indicated for bipolar disorder. In open-label human clinical trials, CBD has significantly reduced psychotic symptoms and normalized motor functions in psychiatric patients. These benefits can be useful to treat manic episodes in bipolar disorder patients.
Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (−)Δ9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-d-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-d-aspartate receptor-induced toxicity has been shown to be calcium dependent, partly mediated by voltage sensitive calcium channels ( Ion system Is regulated by the endo-cannabinoid system(ie Calcium Channels) G coupled cannabinoids block the calcium ion channels inhibiting the production of above mentioned receptor producing inflammatories ). hybridization studies revealed a detectable CB1 in situ signal within the CeA and strong expression in the basolateral amygdala (BLA) of wild-type (WT), but not CB1 knockout (KO; Crn1−/−), mice (Figures 1A–1C). The presence of CB1 mRNA in the majority of BLA neurons, which project glutamatergic afferents to the CeAL, suggested that BLA-CeA glutamatergic terminals might express CB1 receptor protein (Figure 1C). Therefore, we employed a new high-affinity anti-CB1 antibody to probe the localization of CB1 receptors in the CeA (Yoshida et al., 2011). Using this antibody, CB1 receptors were clearly detected at high levels in both the CeAL and CeAM of WT, but not Crn1−/− mice (Figures 1D–1F). Additionally, electron microscopic (EM) examination revealed CB1 receptor expression in presynaptic boutons forming asymmetric synapses onto dendritic shafts and spines within the CeAL (Figures 1G1, 1G2, and 1I). The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent (meaning cannabis alone without the receptors, Is responsible for the neuroprotection, although the endo-cannabinoid system does play a significant roll in neuroprotective, neurogenesis & neuroplasticity properties, making it a double whammy, ie. 1 manner is in enhancing potassium ion channels which is a necessary by-product of synaptic firing). Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or α-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.
In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) also at a rate doubled, CBD (30 or 60 mg/kg) prevented the D-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the D-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). CBD protects against d-AMPH-induced oxidative protein.
Serotonin
Cannabis Regulating Serotonin Levels Aiding in Mood Swings
Cannabis Regulating Serotonin Levels Aiding in Mood Swings
A study investigated the anti-depressive action of CBD in an experimental animal model (AKA olfactory bulbectomy mouse model) of depression (OBX). The results suggest that cannabidiol exerted rapid and sustained antidepressant action in the depressed animals by significantly augmenting cortical serotonin and glutamate levels in a dose-dependent manner. Receptor studies have shown that the action was exerted via a 5-HT1A receptor-dependent mechanism, which represents novel drug functionality. After prolonged CBD administration notable adaptive changes were documented in pre and post-synaptic 5-HT1A receptor action. ( all the while making notable adaptive changes in prolonged correction).
Cannabinoids influence mood perceptions and exert anti-depressant action by acting as an agonist in central CB1 receptors creating functional cannabinoid–5-HT interaction. First, the dorsal raphe (DR), the principal source of forebrain 5-HT, expresses the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) and CB1R mRNA, second CB1Rs are abundantly expressed in the prefrontal cortex (PFC) (Marsicano and Lutz, 1999; Moldrich and Wenger, 2000), which sends excitatory afferents to the DR, coursing from the medial PFC (mPFC) (Jankowski and Sesack, 2004). Furthermore, upregulation in PFC CB1R density, likely a compensatory feedback, was observed in suicidal depressives(suggesting a need for cannabinoids) (Hungund et al., 2004). Imaging studies revealed that cannabis alters PFC regional cerebral blood flow by arterial dialation and increase metabolic activity. The degree was correlated with subjective effects, and the pattern was consistent with CB1R localization (Volkow et al., 1991; Matthew et al., 2002). Third, CB1R agonism alters 5-HT1A and 5HT2A receptor-mediated behavioral responses (Hill et al., 2006) and inhibits 5-HT reuptake 5-HT is believed to be responsible for mood control and implicated in antidepressant-like actions. Research evidences have pointed out the action of CBD in the serotonin (5-HT) system and related neurons. Administration of CB1R agonists such as phytocannabinoids into the ventromedial prefrontal cortex of the brain has resulted in enhanced 5-HT neuronal activity and CB1R-dependent antidepressant-like effects in the experimental animals. This study clearly shows the dose-dependent antidepressant benefit of CBD, which can be particularly useful for the treatment of mood disorders, including bipolar disorder.
Dopamine
Cannabis Regulating Tonic & Phasic Dopamin
Cannabis Regulating Tonic & Phasic Dopamin
"A long-held misconception was that cannabinoids, such as Δ9-tetrahydrocannabinol, fail to increase dopamine concentrations in the same manner as other drugs of abuse, BUT cannabinoids can UP-REGULATE & DOWN"
Cannabinoids modulate mesolimbic dopamine; cannabinoid receptors, CB 1 R; can modify dopamine transmission trough trans-synaptic mechanisms, involving gamma-aminobutyric acid (GABA)-ergic and glutamatergic synapses, as well as by converging signal transduction cascades of the cannabinoid and dopamine receptors. The dopamine and endocannabinoid systems exert a mutual control on each other.
CANNABINOIDS INCREASE TONIC DOPAMINE LEVELS
the existence of an overwhelming body of neurochemical evidence (Ng Cheong Ton et al. 1988; Chen et al. 1990, 1991, 1993; Tanda et al. 1997; Malone and Taylor 1999) unequivocally shows that cannabinoids do, indeed, increase dopamine concentrations in the nucleus accumbens. It should be noted, however, that genetic factors partially determine the magnitude of cannabinoid-induced increases in accumbal dopamine concentration these cannabinoid-induced increases in nucleus accumbens dopamine are most prominently observed in the shell region of the nucleus accumbens and occur in a cannabinoid CB1 receptor-dependent manner.
the existence of an overwhelming body of neurochemical evidence (Ng Cheong Ton et al. 1988; Chen et al. 1990, 1991, 1993; Tanda et al. 1997; Malone and Taylor 1999) unequivocally shows that cannabinoids do, indeed, increase dopamine concentrations in the nucleus accumbens. It should be noted, however, that genetic factors partially determine the magnitude of cannabinoid-induced increases in accumbal dopamine concentration these cannabinoid-induced increases in nucleus accumbens dopamine are most prominently observed in the shell region of the nucleus accumbens and occur in a cannabinoid CB1 receptor-dependent manner.
CANNABINOIDS INCREASE PHASIC DOPAMINE EVENTS
The majority of the aforementioned neurochemical studies measured changes in tonic dopamine levels using in vivo microdialysis. To assess whether cannabinoids increase phasic dopamine release events, Cheer et al. (2004) measured nucleus accumbens dopamine concentrationsthe cannabinoids Δ9-tetrahydrocannabinol and WIN55,212-2 increased the frequency of phasic dopamine events detected in the nucleus accumbens shell. Δ9-tetrahydrocannabinol and WIN55,212-2 both increased the frequency of bursts in addition to the number of impulses occurring during each burst of dopaminergic neural activity (Gessa et al. 1998).
The majority of the aforementioned neurochemical studies measured changes in tonic dopamine levels using in vivo microdialysis. To assess whether cannabinoids increase phasic dopamine release events, Cheer et al. (2004) measured nucleus accumbens dopamine concentrationsthe cannabinoids Δ9-tetrahydrocannabinol and WIN55,212-2 increased the frequency of phasic dopamine events detected in the nucleus accumbens shell. Δ9-tetrahydrocannabinol and WIN55,212-2 both increased the frequency of bursts in addition to the number of impulses occurring during each burst of dopaminergic neural activity (Gessa et al. 1998).
MECHANISM
2-AG is a bodily Cannabinoid (cannabinoids) which can be supplemented by plant derived cannabinoids (phyto-cannabinoids), which have the mimicking function of cannabinoids and there own healing properties over & above.
|
cannabinoids increase nucleus accumbens dopamine concentrations, in part, by binding to the dopamine transporter and thereby decreasing uptake into presynaptic terminals (Hershkowitz and Szechtman 1979; Poddar and Dewey cannabinoids might also directly stimulate dopamine neurons;
A microcircuit within the ventral tegmental area showing GABAergic and glutamatergic terminals synapsing onto a dopamine neuron. (A) Under typical conditions, ventral tegmental area dopamine neurons are inhibited via activation of GABAB receptors on the dopaminergic neuron. (B) When animals are presented with motivational salient stimuli (e.g., a drug-associated cue), dopamine neurons fire in high-frequency bursts. Consequently, intracellular calcium levels increase, which results in the activation of endocannabinoid synthesizing enzymes (e.g., diacylglycerol lipase, DGL). As a result, 2-arachydonoylglycerol (2-AG) is synthesized and released into the extrasynaptic space. By retrogradely activating Gi/o-coupled cannabinoid CB1 receptors on GABAergic terminals, GABA release is suppressed. This GABA suppression results in disinhibition of the dopamine neuron, which presumably promotes the occurrence of phasic dopamine events.
|
Neuroprotection in Acute & Chronic Neurodegeneration
This effect of delta9-THC appeared to be irreversible since interruption of the daily administration of this cannabinoid after the 2-week period did not lead to the re-initiation of the 6-hydroxydopamine-induced neurodegeneration. In addition, the fact that the same neuroprotective effect was also produced by cannabidiol (CBD), another plant-derived cannabinoid with negligible affinity for cannabinoid CB1 receptors, suggests that the antioxidant properties of both compounds, which are cannabinoid receptor-independent, might be involved in these in vivo effects, although an alternative might be that the neuroprotection exerted by both compounds might be due to their anti-inflammatory potential. As a second objective, we examined whether cannabinoids also provide neuroprotection against the in vitro toxicity of 6-hydroxydopamine. We found that the non-selective cannabinoid agonist HU-210 increased cell survival in cultures of mouse cerebellar granule cells exposed to this toxin. However, this effect was significantly lesser when the cannabinoid was directly added to neuronal cultures than when these cultures were exposed to conditioned medium obtained from mixed glial cell cultures treated with HU-210, suggesting that the cannabinoid exerted its major protective effect by regulating glial influence to neurons.
Clinical Studies
Study - Apr. 2006 - Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug
Study - April 2016, - Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors
Study - October 2007, - Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex
Study - 2005 Jun - Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro:
Study - April 2016, - Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors
Study - October 2007, - Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex
Study - 2005 Jun - Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro:
Patents
1989 ~ Antiinflammatory and antimicrobial compounds and compositions
United States Patent 4837228.
US6630507 Autoimmune/Neurological Disorders; Cannabiniods as antioxidants & neuroprotectants
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
1989 ~ Antiinflammatory and antimicrobial compounds and compositions
United States Patent 4837228.
US6630507 Autoimmune/Neurological Disorders; Cannabiniods as antioxidants & neuroprotectants
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