Marijuana Saves Lives http://marijuanasaveslives.org The Truth About Medical Marijuana Sat, 19 Jun 2010 04:57:02 +0000 en hourly 1 http://wordpress.org/?v=3.0 Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation http://marijuanasaveslives.org/cannabinoids-endocannabinoids-and-related-analogs-in-inflammation-4/ http://marijuanasaveslives.org/cannabinoids-endocannabinoids-and-related-analogs-in-inflammation-4/#comments Fri, 18 Jun 2010 20:00:58 +0000 Brett http://marijuanasaveslives.org/?p=703 This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process. ]]> http://marijuanasaveslives.org/cannabinoids-endocannabinoids-and-related-analogs-in-inflammation-4/feed/ 0 THC Prevents MDMA Neurotoxicity in Mice. http://marijuanasaveslives.org/thc-prevents-mdma-neurotoxicity-in-mice/ http://marijuanasaveslives.org/thc-prevents-mdma-neurotoxicity-in-mice/#comments Fri, 18 Jun 2010 20:00:03 +0000 Brett http://marijuanasaveslives.org/?p=701 The majority of MDMA (ecstasy) recreational users also consume cannabis. Despite the rewarding effects that both drugs have, they induce several opposite pharmacological responses. MDMA causes hyperthermia, oxidative stress and neuronal damage, especially at warm ambient temperature. However, THC, the main psychoactive compound of cannabis, produces hypothermic, anti-inflammatory and antioxidant effects. Therefore, THC may have a neuroprotective effect against MDMA-induced neurotoxicity. Mice receiving a neurotoxic regimen of MDMA (20 mg/kg x 4) were pretreated with THC (3 mg/kg x 4) at room (21 degrees C) and at warm (26 degrees C) temperature, and body temperature, striatal glial activation and DA terminal loss were assessed. To find out the mechanisms by which THC may prevent MDMA hyperthermia and neurotoxicity, the same procedure was carried out in animals pretreated with the CB(1) receptor antagonist AM251 and the CB(2) receptor antagonist AM630, as well as in CB(1), CB(2) and CB(1)/CB(2) deficient mice. THC prevented MDMA-induced-hyperthermia and glial activation in animals housed at both room and warm temperature. Surprisingly, MDMA-induced DA terminal loss was only observed in animals housed at warm but not at room temperature, and this neurotoxic effect was reversed by THC administration. However, THC did not prevent MDMA-induced hyperthermia, glial activation, and DA terminal loss in animals treated with the CB(1) receptor antagonist AM251, neither in CB(1) and CB(1)/CB(2) knockout mice. On the other hand, THC prevented MDMA-induced hyperthermia and DA terminal loss, but only partially suppressed glial activation in animals treated with the CB(2) cannabinoid antagonist and in CB(2) knockout animals. Our results indicate that THC protects against MDMA neurotoxicity, and suggest that these neuroprotective actions are primarily mediated by the reduction of hyperthermia through the activation of CB(1) receptor, although CB(2) receptors may also contribute to attenuate neuroinflammation in this process.

]]> http://marijuanasaveslives.org/thc-prevents-mdma-neurotoxicity-in-mice/feed/ 0 Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor. http://marijuanasaveslives.org/cannabinoid-receptor-1-binding-activity-and-quantitative-analysis-of-cannabis-sativa-l-smoke-and-vapor-2/ http://marijuanasaveslives.org/cannabinoid-receptor-1-binding-activity-and-quantitative-analysis-of-cannabis-sativa-l-smoke-and-vapor-2/#comments Fri, 18 Jun 2010 19:59:05 +0000 Brett http://marijuanasaveslives.org/?p=699 Cannabis sativa L. (cannabis) extracts, vapor produced by the Volcano vaporizer and smoke made from burning cannabis joints were analyzed by GC-flame ionization detecter (FID), GC-MS and HPLC. Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. Cannabinoids plus other components such as terpenoids and pyrolytic by-products were identified and quantified in all samples. Cannabis vapor and smoke was tested for cannabinoid receptor 1 (CB1) binding activity and compared to pure Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan vapor (>1.0 mg/g) were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. The major components in Bedrocan smoke (>1.0 mg/g) were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. There was no statistically significant difference between CB1 binding of pure Delta(9)-THC compared to cannabis smoke and vapor at an equivalent concentration of Delta(9)-THC.

]]> http://marijuanasaveslives.org/cannabinoid-receptor-1-binding-activity-and-quantitative-analysis-of-cannabis-sativa-l-smoke-and-vapor-2/feed/ 0 Delta9-tetrahydrocannabinol (Delta9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia. [Comparative Study, Journal Article, Research Support, Non-U.S. Gov't] http://marijuanasaveslives.org/delta9-tetrahydrocannabinol-delta9-thc-prevents-cerebral-infarction-via-hypothalamic-independent-hypothermia-comparative-study-journal-article-research-support-non-u-s-govt/ http://marijuanasaveslives.org/delta9-tetrahydrocannabinol-delta9-thc-prevents-cerebral-infarction-via-hypothalamic-independent-hypothermia-comparative-study-journal-article-research-support-non-u-s-govt/#comments Fri, 18 Jun 2010 19:57:57 +0000 Brett http://marijuanasaveslives.org/?p=697 Delta(9)-tetrahydrocannabinol (Delta(9)-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB(1) receptor. In this study, Delta(9)-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Delta(9)-THC was completely abolished by SR141716, cannabinoid CB(1) receptor antagonist, and by warming the animals to 31 degrees C. Delta(9)-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 degrees C. At 24 h after cerebral ischemia, Delta(9)-THC significantly increased the expression level of CB(1) receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 degrees C during 4 h cerebral ischemia did not increase the expression of CB(1) receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Delta(9)-THC is mediated by a temperature-dependent mechanism via the CB(1) receptor. In addition, warming to 31 degrees C might attenuate both the neuroprotective and hypothermic effects of Delta(9)-THC through inhibiting the increase in CB(1) receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Delta(9)-THC.

]]> http://marijuanasaveslives.org/delta9-tetrahydrocannabinol-delta9-thc-prevents-cerebral-infarction-via-hypothalamic-independent-hypothermia-comparative-study-journal-article-research-support-non-u-s-govt/feed/ 0 Cannabinoid CB2 receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model http://marijuanasaveslives.org/cannabinoid-cb2-receptor-activation-decreases-cerebral-infarction-in-a-mouse-focal-ischemiareperfusion-model/ http://marijuanasaveslives.org/cannabinoid-cb2-receptor-activation-decreases-cerebral-infarction-in-a-mouse-focal-ischemiareperfusion-model/#comments Fri, 18 Jun 2010 19:57:05 +0000 Brett http://marijuanasaveslives.org/?p=695 Cannabinoid CB2 Receptor (CB2) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB2 agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB2 agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB2 agonists significantly decreased cerebral infarction (30%) and improved motor function (P < 0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P < 0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB2 agonists administered either at 1 h before or after MCAO (P < 0.05). CB2 activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia. ]]> http://marijuanasaveslives.org/cannabinoid-cb2-receptor-activation-decreases-cerebral-infarction-in-a-mouse-focal-ischemiareperfusion-model/feed/ 0 Δ9-Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors http://marijuanasaveslives.org/%ce%b49-tetrahydrocannabinol-thc-and-am-404-protect-against-cerebral-ischaemia-in-gerbils-through-a-mechanism-involving-cannabinoid-and-opioid-receptors/ http://marijuanasaveslives.org/%ce%b49-tetrahydrocannabinol-thc-and-am-404-protect-against-cerebral-ischaemia-in-gerbils-through-a-mechanism-involving-cannabinoid-and-opioid-receptors/#comments Fri, 18 Jun 2010 19:56:11 +0000 Brett http://marijuanasaveslives.org/?p=693
Background and purpose:
It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage. In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB1) agonist, Δ9-tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil.
Experimental approach:
The effects of AM 404 (0.015–2 mg kg−1) and THC (0.05–2 mg kg−1), given 5 min after ischaemia, were measured from 1 h to 7 days in terms of electroencephalographic (EEG) total spectral power, spontaneous motor activity, memory function, rectal temperature and hippocampal CA1 neuronal count.
Key results:
Over the dose range tested, AM 404 (2 mg kg−1) and THC (1 mg kg−1) completely reversed the ischaemia-induced behavioural, EEG and histological damage. Only THC (1 and 2 mg kg−1) induced a decrease of body temperature. Pretreatment with the selective CB1 receptor antagonist, AM 251 (1 mg kg−1) and the opioid antagonist, naloxone (2 mg kg−1) reversed the protective effect induced by both AM 404 and THC while the TRPV1 vanilloid antagonist, capsazepine (0.01 mg kg−1), was ineffective.
Conclusions and implications:
Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB1 and opioid receptors. Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.
]]> http://marijuanasaveslives.org/%ce%b49-tetrahydrocannabinol-thc-and-am-404-protect-against-cerebral-ischaemia-in-gerbils-through-a-mechanism-involving-cannabinoid-and-opioid-receptors/feed/ 0 Role of cannabinoids and endocannabinoids in cerebral ischemia http://marijuanasaveslives.org/role-of-cannabinoids-and-endocannabinoids-in-cerebral-ischemia/ http://marijuanasaveslives.org/role-of-cannabinoids-and-endocannabinoids-in-cerebral-ischemia/#comments Fri, 18 Jun 2010 19:54:45 +0000 Brett http://marijuanasaveslives.org/?p=691 The human costs of stroke are very large and growing; it is the third largest cause of death in the United States and survivors are often faced with loss of ability to function independently. There is a large need for therapeutic approaches that act to protect neurons from the injury produced by ischemia and reperfusion. The goal of this review is to introduce and discuss the available data that endogenous cannabinoid signaling is altered during ischemia and that it contributes to the consequences of ischemia-induced injury. Overall, the available data suggest that inhibition of CB1 receptor activation together with increased CB2 receptor activation produces beneficial effects. ]]> http://marijuanasaveslives.org/role-of-cannabinoids-and-endocannabinoids-in-cerebral-ischemia/feed/ 0 Clinical investigation of delta-9-tetrahydrocannabinol (THC) as an alternative therapy for overactive bladders in spinal cord injury (SCI) patients. http://marijuanasaveslives.org/clinical-investigation-of-delta-9-tetrahydrocannabinol-thc-as-an-alternative-therapy-for-overactive-bladders-in-spinal-cord-injury-sci-patients/ http://marijuanasaveslives.org/clinical-investigation-of-delta-9-tetrahydrocannabinol-thc-as-an-alternative-therapy-for-overactive-bladders-in-spinal-cord-injury-sci-patients/#comments Fri, 18 Jun 2010 19:53:15 +0000 Brett http://marijuanasaveslives.org/?p=689 We are presenting the preliminary results of a pilot study. THC was administered over a period of 6 weeks. In 15 patients with spastic spinal cord injury the effect of THC on the overactive bladder has been investigated. The effect of THC was compared with urodynamic and clinical parameters, first without any bladder medication and after 6 weeks medication with THC. There are no data of invasive investigation in literature up till now.
Patients and methods:
THC was administered for 6 weeks in two different groups orally as Dronabinol (Marinol®) in 9 patients and rectally as THC-Hemisuccinate suppositories (THC-HS-supp) in 6 patients in several individual dosages per day. An urodynamic investigation, urine analysis and urine bacteriology was performed at the beginning of the study (without any bladder medication and without any spasmolytic therapy) and in the end after 6 weeks treatment. On the last day of medication all patients have been administered either 10 mg Dronabilon or 10 mg THC-HS-supp 2 h before the urodynamic investigation (relating to the group they were in).
Investigated parameters: first desire to void (FDV), maximum cystometric capacity (MCC), intravesical pressure (IVP), bladder compliance (CPL), post void residual urine volume (RV), volume at first detrusor contraction (VFC).
Results:
The dronabinol group showed an increase of the CPL from mean 34.3 ml/cm H2O (9 – 100) to mean 52.2 ml/cm H2O (11 – 200). All other parameters have not been changed essentially.
The THC-HS-supp group showed a trend with increase of MCC from mean 227 ml (143 – 323) to mean 278 ml (121 – 322) (p value = 0.075), and an increase of the VFC from mean 191.3 ml (121 – 322) to mean 224.6 ml (96 – 407), CPL increased from mean 21.3 ml/cm H2O (6 – 60) to mean 40 ml/cm H2O (10 – 120) significantly
(p value = 0.028). All other parameters have not been changed essentially.
Conclusion:
These preliminary results indicate a reduction of the overactivity of the detrusor of the bladder especially in the THC-HS-supp group with potential therapeutic consequences. The different results between oral and rectal application may demonstrate their different bioavailability.

]]> http://marijuanasaveslives.org/clinical-investigation-of-delta-9-tetrahydrocannabinol-thc-as-an-alternative-therapy-for-overactive-bladders-in-spinal-cord-injury-sci-patients/feed/ 0 The treatment of spasticity with D9-tetrahydrocannabinol (D9-THC) in patients with spinal cord injury http://marijuanasaveslives.org/the-treatment-of-spasticity-with-d9-tetrahydrocannabinol-d9-thc-in-patients-with-spinal-cord-injury/ http://marijuanasaveslives.org/the-treatment-of-spasticity-with-d9-tetrahydrocannabinol-d9-thc-in-patients-with-spinal-cord-injury/#comments Fri, 18 Jun 2010 19:52:15 +0000 Brett http://marijuanasaveslives.org/?p=687 Introduction:
Spasticity is a common complaint after traumatic SCI. &#61508;9–THC the main psychoactive cannabinoid of cannabis has been shown to have beneficial effects in the treatment of spasticity of different origin. The aim of the study was to assess the effectiveness and safety of &#61508;9–THC (Dronabinol, Marinol® capsules) and THC-hemisuccinate suppositories (THC-HS) for the treatment of spasticity in patients with SCI as a homogeneous population of patients. We are presenting the results of spasticity as partial results of a finished study with a wide spectrum of other investigations.

Methods:
Phase 1: open trial, six weeks treatment of 22 patients with Dronabinol (7 drop outs)
Phase 2: open trial, six weeks treatment of 8 patients with THC-HS (1 drop out)
Phase 3: randomized, double-blind, placebo controlled clinical trial with 13 patients (Marinol&#61666;/placebo)
25 patients mean age 42.3 years with spasticity due to SCI (11 para- and 14 tetraplegics) were included. Mean time since injury was 13.4 years. Inclusion criteria for spasticity were minimum of 3 points on the Ashworth scale without therapy, negative urine drug screening, age > 18 years.
Spasticity was investigated using the modified Ashworth scale (MAS) after administration of 10 mg Dronabinol (Marinol®) or 10 mg THC-HS at day one and after one and six weeks treatment with an individual dose. Self-rating of spasticity was performed every day using a seven point scale from absent to unbearable.

Results:
Phase 1: Dronabinol (Marinol®) significantly decreased the mean spasticity sum score (± SD) (summed Ashworth scores divided by four) in 15 patients after a single dose of 10 mg (day 1) from 16.72 ± 7.60 to 7.75 ± 7.00 points (p<0.001) and after 6 weeks of treatment with an individual symptom oriented mean dose of 30 mg Dronabinol to 8.92 ± 7.14 points (p<0.05).
Phase 2: THC-HS significantly decreased the mean spasticity sum score (± SD) in 7 patients after a single dose of 10 mg (day 1) from 22.71 ± 11.68 to 9.86 ± 8.15 points (p<0,05) and after 6 weeks of treatment with an individual symptom oriented mean dose of 43 mg THC-HS to 9.21 ± 9.25 points (p<0.05).
The comparison of oral and rectal application in five patients showed no difference.
Phase 3: summed spasticity scores for the Dronabinol group (7.21 points) differed significantly from summed scores of the placebo group (12.10 points) as a treatment effect of Dronabinol during the entire 6 weeks (p=0.001).

Conclusion:
The results demonstrate a significant therapeutic effect of &#61508;9–THC (Dronabinol, Marinol ®) as well as THC-HS in patients with SCI. However the antispastic efficacy is significant the treatment often is limited by side effects.

Acknowledgement:
The research was supported by ElSohly Laboratories Inc., Oxford, Mississippi

]]> http://marijuanasaveslives.org/the-treatment-of-spasticity-with-d9-tetrahydrocannabinol-d9-thc-in-patients-with-spinal-cord-injury/feed/ 0 Are oral cannabinoids safe and effective in refractory neuropathic pain? http://marijuanasaveslives.org/are-oral-cannabinoids-safe-and-effective-in-refractory-neuropathic-pain/ http://marijuanasaveslives.org/are-oral-cannabinoids-safe-and-effective-in-refractory-neuropathic-pain/#comments Fri, 18 Jun 2010 19:51:10 +0000 Brett http://marijuanasaveslives.org/?p=685 Although cannabinoids have anti-hyperalgesic e.ects in animal models of nerve injury, there are currently very few prospective trials of the efficacy of cannabinoids in neuropathic pain in humans. This open label prospective study investigated the safety, tolerability and analgesic benefit of oral delta-9-tetrahydrocannabinol (THC) titrated to a maximal dosage of 25 mg/day in 8 consecutive patients with chronic refractory neuropathic pain. Spontaneous ongoing and paroxysmal pain, allodynia and paresthesias were assessed. The sensory and affective components of pain using the McGill pain questionnaire, quality of life, mood, anxiety and functionality were also evaluated. Seven patients suffered from side effects necessitating premature arrest of the drug in 5 of them. THC (mean dosage: 16.6±6.5 mg/day) did not induce any significant effects on ongoing and paroxysmal pain, allodynia, quality of life, anxiety/depression scores and functional impact of pain. These results do not support an overall benefit of THC in pain and quality of life in patients with refractory neuropathic pain.

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