Marijuana's THCA relieves nausea

Nonpsychoactive THCA from unheated marijuana reduced nausea in lab animals more effectively than THC (from heated marijuana), legalize! How many dealers sell THCA? None. Support dispensary rights.

Br J Pharmacol. 2013 Jul 25. doi: 10.1111/bph.12316. [Epub ahead of print]

Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus.

Rock E, Kopstick R, Limebeer C, Parker L.

Source

Department of Psychology, University of Guelph, Guelph, ON, Canada.

Abstract

BACKGROUD AND PURPOSE:

We evaluated the anti-emetic and anti-nausea properties of the acid precursor of Δ9 -tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and to determine its mechanism of action in these animal models.

EXPERIMENTAL APPROACH:

We investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping (nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea, AN) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 (CB1 ) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist).

KEY RESULTS:

In rats, THCA (0.05 and/or 0.5 mg/kg) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-HT1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg/kg) reduced LiCl-induced vomiting; an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg/kg) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples.

CONCLUSIONS AND IMPLICATIONS:

THCA potently reduced conditioned gaping in rats and vomiting in S. murinus; effects that were blocked by SR.. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting.

via Tetrahydrocannabinolic acid reduces nausea-in... [Br J Pharmacol. 2013] - PubMed - NCBI.

Marijuana increases positivity

A just-published study found that THC from marijuana increased activity for positive emotional content. Marijuana enhances happiness which could explain the enormous drop in suicides, especially among young adult men, in medical marijuana states.

Eur Neuropsychopharmacol. 2013 Aug 5. pii: S0924-977X(13)00195-8. doi: 10.1016/j.euroneuro.2013.06.009. [Epub ahead of print]

The endocannabinoid system and emotional processing: A pharmacological fMRI study with ∆9-tetrahydrocannabinol.

Bossong MG, van Hell HH, Jager G, Kahn RS, Ramsey NF, Jansma JM. Abstract

Various psychiatric disorders such as major depression are associated with abnormalities in emotional processing. Evidence indicating involvement of the endocannabinoid system in emotional processing, and thus potentially in related abnormalities, is increasing. In the present study, we examined the role of the endocannabinoid system in processing of stimuli with a positive and negative emotional content in healthy volunteers. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist ∆9-tetrahydrocannabinol (THC) on brain function related to emotional processing in 11 healthy subjects. Performance and brain activity during matching of stimuli with a negative ('fearful faces') or a positive content ('happy faces') were assessed after placebo and THC administration. After THC administration, performance accuracy was decreased for stimuli with a negative but not for stimuli with a positive emotional content. Our task activated a network of brain regions including amygdala, orbital frontal gyrus, hippocampus, parietal gyrus, prefrontal cortex, and regions in the occipital cortex. THC interacted with emotional content, as activity in this network was reduced for negative content, while activity for positive content was increased. These results indicate that THC administration reduces the negative bias in emotional processing. This adds human evidence to support the hypothesis that the endocannabinoid system is involved in modulation of emotional processing. Our findings also suggest a possible role for the endocannabinoid system in abnormal emotional processing, and may thus be relevant for psychiatric disorders such as major depression.

via The endocannabinoid system and emot... [Eur Neuropsychopharmacol. 2013] - PubMed - NCBI.

Marijuana Use Reduces Obesity » Marijuana Gateway to Health

Marijuana use is significantly protective against obesity as well as the harmful illnesses that accompany the syndrome. This is because THC and other cannabinoids work as systemic biological health regulators, the are key to our ability to survive and thrive. We really do need to encourage more adults to use marijuana in some form to improve their health and guard against degenerative illnesses. Science continues to affirm this position.                       Med Hypotheses. 2013 Feb 11. Cannabis and Δ9-tetrahydrocannabinol THC for weight loss?Le Foll B, Trigo JM, et al.Abstract: Obesity is one of the highest preventable causes of morbidity and mortality in the developed world [1]. It has been well known for a long time that exposure to cannabis produces an increase of appetite a phenomenon referred to as the ‘munchies’. This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile [2]. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ9-tetrahydrocannabinol THC present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.via Cannabis and Δ9-tetrahydrocannabinol THC … [Med Hypotheses. 2013] – PubMed – NCBI. via Marijuana Use Reduces Obesity » Marijuana Gateway to Health.

Marijuana's cannabinoids protect the brain from Alzheimer's disease

Here is more evidence that THC and CBD, cannabinoids from marijuana, can effectively protect us from the damage that leads to the development of Alzheimer's disease as well as other neurological ailments. The cannabinoid THC stimulates both the CB1 and CB2 receptors, but the cannabinoid CBD steers THC away from the CB1 receptor and over to the CB2 receptors, thus possibly activating the neuroprotective effects described in this study. With the trillion dollar threat that Alzheimer's disease poses to our national health care budget, isn't it critical that we recruit more adults to use some form of marijuana? Tell you friends and family that the most effective thing they can do to protect themselves from Alzheimer's disease is to start using cannabis--either smoking or vaporizing a small amount a few times a week, or taking some drops of a cannabis tincture before bedtime or eating a low-dose edible. What we want to do is increase the regular consumption of cannabinoids in our society because the evidence is in: using some form of marijuana regularly lowers our risks for developing numerous, serious illnesses. J Alzheimers Dis. 2013 Jan 1;354:847-58. doi: 10.3233/JAD-130137.CB2 Cannabinoid Receptor Agonist Ameliorates Alzheimer-Like Phenotype in AβPP/PS1 Mice.Aso E, Juvés S, Maldonado R, Ferrer I.SourceInstitut de Neuropatologia, Servei d'Anatomia Patològica, Abstract: The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double AβPP/PS1 transgenic mice, a genetic model of Alzheimer's disease. This effect was more pronounced when administered at the pre-symptomatic rather than the early symptomatic stage. The cognitive improvement was associated with decreased microglial reactivity and reduced expression of pro-inflammatory cytokines IL-1β, IL-6, TNFα, and IFNγ. In addition, JWH-133 reduced the expression of active p38 and SAPK/JNK, increased the expression of inactive GSK3β, and lowered tau hyperphosphorylation at Thr181 in the vicinity of amyloid-β plaques. Moreover, JWH-133 produced a decrease in the expression of hydroxynonenal adducts, and enhanced the expression of SOD1 and SOD2 around plaques. In contrast, the chronic treatment with JWH-133 failed to modify the amyloid-β production or deposition in cortex and hippocampus. In conclusion, the present study lends support to the idea that stimulation of CB2 receptors ameliorates several altered parameters in Alzheimer's disease such as impaired memory and learning, neuroinflammation, oxidative stress damage and oxidative stress responses, selected tau kinases, and tau hyperphosphorylation around plaques.

via CB2 Cannabinoid Receptor Agonist Ameliorate... [J Alzheimers Dis. 2013] - PubMed - NCBI.

THC from marijuana is an anticancer drug

How long will this government-perpetrated fraud that there is no such thing as medical marijuana endure in the face of an overwhelming tsunami of science which proves that marijuana delivers health-building and protecting cannabinoids which fight disease and enhance our vitality? Promote adult marijuana use! From the following report, "THC has shown therapeutic potential as an anticancer drug." J Drug Target. 2013 Jun 18. [Epub ahead of print]

Preparation and characterization of Δ9-tetrahydrocannabinol-loaded biodegradable polymeric microparticles and their antitumoral efficacy on cancer cell lines.

de la Ossa DH, Gil-Alegre ME, Ligresti A, Aberturas MD, Molpeceres J, Torres AI, Di Marzo V.

Source

Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University of Madrid , Madrid , Spain .

Abstract

Abstract: Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer, AIDS and multiple sclerosis), analgesics, and in the treatment of multiple sclerosis and cancer, among other conditions. However, despite their high clinical potential, only few dosage forms are available to date. In this paper, the development of Δ9-tetrahydrocannabinol (THC) biodegradable microspheres as an alternative delivery system for cannabinoid parenteral administration is proposed. Tetrahydrocannabinol was encapsulated into biodegradable microspheres by the oil-in-water (o/w) emulsion solvent evaporation method. Several formulations were prepared using different drug:polymer ratios. The influence of antioxidant (α-tocopherol acetate) concentration on the release of THC from the microparticles was studied. Elevated process yield and entrapment efficiencies were achieved. The in vitro drug release studies showed that the encapsulated drug was released over a two week period. As THC has shown therapeutic potential as anticancer drug, the efficacy of the microspheres was tested on different cancer cell lines. Interestingly, the microspheres were able to inhibit cancer cell proliferation during the nine-day study period. All the above results suggest that the use of biodegradable microspheres would be a suitable alternative delivery system for THC administration.

via Preparation and characterization of Δ9-tetrahy... [J Drug Target. 2013] - PubMed - NCBI.

Acute Δ9-tetrahydrocannabinol blocks gastric... [Eur J Pharmacol. 2013] - PubMed - NCBI

THC blocks stomach damage from NSAIDs (nonsteroidal anti-inflammatory drugs) with doses that do not cause mind-altering effects. Marijuana, it's not just about getting high anymore!. Eur J Pharmacol. 2013 Jun 11. pii: S0014-29991300461-5. doi: 10.1016/j.ejphar.2013.06.001. [Epub ahead of print]Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.Kinsey SG, Cole EC.SourceDepartment of Psychology, West Virginia University, Morgantown, WV USA. Electronic address: sgkinsey@mail.wvu.edu.AbstractNonsteroidal anti-inflammatory drugs NSAIDs, which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening. Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol THC, the primary psychoactive component of marijuana, have yet to be investigated. Male C57BL/6J mice were fasted, administered vehicle or Δ9-THC .01-50mg/kg; oral or intraperitoneal, and then treated with the NSAID diclofenac sodium 100mg/kg, p.o. to induce gastric lesions. In separate groups of mice, the cannabimimetic behavioral effects of Δ9-THC given via each route of administration were compared using a battery of tests, consisting of assessment of locomotor activity, nociception in the tail withdrawal test, catalepsy in the bar test, and hypothermia. Δ9-THC dose-dependently attenuated diclofenac-induced gastric hemorrhagic streaks through both p.o. and i.p. routes of administration ED50 95% confidence interval=0.64 0.26-1.55 mg/kg and 0.06 0.01-0.34 mg/kg, respectively. Δ9-THC given i.p. was 2-3 orders of magnitude more potent in reducing diclofenac-induced gastric ulcers than in producing locomotor immobility, antinociception, hypothermia, and catalepsy, while the potency of ratio of p.o. Δ9-THC between each behavior measure was 7-18. These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.

via Acute Δ9-tetrahydrocannabinol blocks gastric... [Eur J Pharmacol. 2013] - PubMed - NCBI.

zp8497586rq

Acute Δ9-tetrahydrocannabinol blocks gastric... [Eur J Pharmacol. 2013] - PubMed - NCBI

THC blocks stomach damage from NSAIDs (nonsteroidal anti-inflammatory drugs) with doses that do not cause mind-altering effects. Marijuana, it's not just about getting high anymore!. Eur J Pharmacol. 2013 Jun 11. pii: S0014-29991300461-5. doi: 10.1016/j.ejphar.2013.06.001. [Epub ahead of print]Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.Kinsey SG, Cole EC.SourceDepartment of Psychology, West Virginia University, Morgantown, WV USA. Electronic address: sgkinsey@mail.wvu.edu.AbstractNonsteroidal anti-inflammatory drugs NSAIDs, which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening. Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol THC, the primary psychoactive component of marijuana, have yet to be investigated. Male C57BL/6J mice were fasted, administered vehicle or Δ9-THC .01-50mg/kg; oral or intraperitoneal, and then treated with the NSAID diclofenac sodium 100mg/kg, p.o. to induce gastric lesions. In separate groups of mice, the cannabimimetic behavioral effects of Δ9-THC given via each route of administration were compared using a battery of tests, consisting of assessment of locomotor activity, nociception in the tail withdrawal test, catalepsy in the bar test, and hypothermia. Δ9-THC dose-dependently attenuated diclofenac-induced gastric hemorrhagic streaks through both p.o. and i.p. routes of administration ED50 95% confidence interval=0.64 0.26-1.55 mg/kg and 0.06 0.01-0.34 mg/kg, respectively. Δ9-THC given i.p. was 2-3 orders of magnitude more potent in reducing diclofenac-induced gastric ulcers than in producing locomotor immobility, antinociception, hypothermia, and catalepsy, while the potency of ratio of p.o. Δ9-THC between each behavior measure was 7-18. These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.

via Acute Δ9-tetrahydrocannabinol blocks gastric... [Eur J Pharmacol. 2013] - PubMed - NCBI.

THC could be a chemotherapeutic agent for treating stomach cancer

Cannabinoids, such as THC, which activate the CB1 and CB2 cannabinoid receptors are more effective against stomach cancer than the main chemotherapy treatment. Using marijuana protects us from so many cancers and other illnesses, aren't you mad that it's still illegal? Anticancer Res. 2013 Jun;33(6):2541-7.

Cannabinoid Receptor Agonist as an Alternative Drug in 5-Fluorouracil-resistant Gastric Cancer Cells.

Xian XS, Park H, Choi MG, Park JM.

Source

Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505, Banpo-Dong, Seocho-Gu, Seoul, 137-070, Korea. parkjerry@catholic.ac.kr.

Abstract

Fluorouracil is the main chemotherapeutic drug used for gastrointestinal cancers, which suffers the important problem of treatment resistance. There is little information whether cannabinoid agonists can be used as an alternative drug for fluorouracil-resistant gastric cancer cells. In this study, we investigated the effects of a cannabinoid agonist, WIN-55,212-2, on 5-fluorouracil (5-FU)-resistant human gastric cancer cells, to examine whether the cannabinoid agonist may be an alternative therapy. Survival of the 5-FU-resistant gastric cancer cell line, SNU-620-5FU/1000, was not significantly reduced even by a high dose of 5-FU treatment. However, WIN-55,212-2 inhibited the proliferation of SNU-620-5FU/1000 and enhanced their apoptosis, as indicated by an increase of apoptotic cell proportion, activated caspase-3 and Poly (ADP-ribose) polymerase cleavage. Furthermore, WIN-55,212-2 reduced phospho-extracellular-signal-regulated kinases (ERK) 1/2, phospho-Akt (protein kinase B), B-cell lymphoma-2 (BCL2) and BCL2-associated X (BAX) protein expression in 5-FU-resistant gastric cancer cells. These results indicate that a cannabinoid agonist may, indeed, be an alternative chemotherapeutic agent for 5-FU-resistant gastric cancer.

KEYWORDS:

Gastric cancer, apoptosis, cannabinoids, drug resistance, fluorouracil

via Cannabinoid Receptor Agonist as an Alternativ... [Anticancer Res. 2013] - PubMed - NCBI.

Cannabinoids fight pancreatic cancer

Cannabinoids which work via the CB1 and CB2 receptor, as does THC from marijuana, interfere with pancreatic cancer's cellular metabolism, causing the cancer cells to die off. The following abstract is quite technical but what you need to consider is the final line which reports that cannabinoids killed off and stunted the growth of pancreatic cancer cells. Cell Death Dis. 2013 Jun 13;4:e664. doi: 10.1038/cddis.2013.151.Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells.Dando I, Donadelli M, Costanzo C, Dalla Pozza E, D'Alessandro A, Zolla L, Palmieri M.SourceDepartment of Life and Reproduction Sciences, Biochemistry Section, University of Verona, Verona, Italy. Abstract: The anti-tumoral effects of cannabinoids have been described in different tumor systems, including pancreatic adenocarcinoma, but their mechanism of action remains unclear. We used cannabinoids specific for the CB1 ACPA and CB2 GW receptors and metabolomic analyses to unravel the potential pathways mediating cannabinoid-dependent inhibition of pancreatic cancer cell growth. Panc1 cells treated with cannabinoids show elevated AMPK activation induced by a ROS-dependent increase of AMP/ATP ratio. ROS promote nuclear translocation of GAPDH, which is further amplified by AMPK, thereby attenuating glycolysis. Furthermore, ROS determine the accumulation of NADH, suggestive of a blockage in the respiratory chain, which in turn inhibits the Krebs cycle. Concomitantly, inhibition of Akt/c-Myc pathway leads to decreased activity of both the pyruvate kinase isoform M2 PKM2, further downregulating glycolysis, and glutamine uptake. Altogether, these alterations of pancreatic cancer cell metabolism mediated by cannabinoids result in a strong induction of autophagy and in the inhibition of cell growth.

via Cannabinoids inhibit energetic metabolism and... [Cell Death Dis. 2013] - PubMed - NCBI.

Medical marijuana ingredient prevents brain damage

The words “marijuana” and “brain damage” usually go in that order in medical literature. An Israeli researcher has flipped them around, finding that THC, the active ingredient in marijuana, may arrest some forms of brain damage in mice.The loco weed already is favored by those who suffer from chronic diseases, not to mention fans of Cypress Hill, Bob Marley and the Grateful Dead.But pharmacologist Josef Sarne of Tel Aviv University found that a minuscule amount of tetrahydrocannabinol may protect the brain after injuries from seizures, toxic drug exposure or a lack of oxygen. via Medical marijuana ingredient prevents brain damage in mice - latimes.com.

THC from Marijuana Protects the Brain from Injury

Once again we see that using (even very small amounts of) marijuana improves our health by shielding the brain from the damage that follows a head injury. These same actions protect the brain from the age-related changes that lead to Alzheimer's disease and other forms of dementia. We need to recruit more people to use marijuana on a regular basis to lower our national health-care expenditures. Marijuana use is good for you! Tell someone today! Long-term behavioral and biochemical effects of an ultra-low dose of Δ9-tetrahydrocannabinol THC: neuroprotection and ERK signaling Miriam Fishbein, Sahar Gov, Fadi Assaf, Mikhal Gafni, Ora Keren, Yosef Sarne                                                                              Abstract: We have previously reported that a single injection of an ultra-low dose of delta-9-tetrahydrocannabinol THC; the psychoactive ingredient of marijuana protected the brain from pentylenentetrazole PTZ-induced cognitive deficits when applied 1–7 days before or 1–3 days after the insult. In the present study we expanded the protective profile of THC by showing that it protected mice from cognitive deficits that were induced by a variety of other neuronal insults, including pentobarbital-induced deep anesthesia, repeated treatment with 3,4 methylenedioxymethamphetamine MDMA; “ecstasy” and exposure to carbon monoxide. The protective effect of THC lasted for at least 7 weeks. The same ultra-low dose of THC 0.002 mg/kg, a dose that is 3–4 orders of magnitude lower than the doses that produce the known acute effects of the drug in mice induced long-lasting 7 weeks modifications of extracellular signal–regulated kinase ERK activity in the hippocampus, frontal cortex and cerebellum of the mice. The alterations in ERK activity paralleled changes in its activating enzyme MEK and its inactivating enzyme MKP-1. Furthermore, a single treatment with the low dose of THC elevated the level of pCREB phosphorylated cAMP response element–binding protein in the hippocampus and the level of BDNF brain-derived neurotrophic factor in the frontal cortex. These long-lasting effects indicate that a single treatment with an ultra-low dose of THC can modify brain plasticity and induce long-term behavioral and developmental effects in the brain.

via Long-term behavioral and biochemical effects of an ultra-low dose of Δ9-tetrahydrocannabinol THC: neuroprotection and ERK signaling - Springer.

Marijuana protects the brain from alcohol damage

Here is evidence that using marijuana shields the brain from a significant amount of the damage that alcohol causes. If you are drinking, you should probably be toking. Also recall that a recent study concluded that: "There is no safe threshold for alcohol consumption with regards to cancer," and recall that ample evidence shows that using marijuana causes cancer cells to die off thus lowering the risk for everything from lung to head and neck to bladder cancers as well as lymphoma. Prohibition is carcinogenic. White Matter Integrity in Adolescents with Histories of Marijuana Use and Binge Drinking  J. Jacobus,a,b T. McQueeny,g S. Bava,b,c B. C. Schweinsburg,e,f L.R. Frank,d T. T. Yang,c and S. F. Tapertb,c, Abstract: Structural brain abnormalities have been observed in adolescents with alcohol use disorders but less is known about neuropathological brain characteristics of teens with subdiagnostic binge drinking or the common pattern of binge drinking combined with marijuana use. The goal of this study was to examine white matter integrity in adolescents with histories of binge drinking and marijuana use.Diffusion tensor imaging DTI was conducted with 42 adolescents ages 16−19 classified as controls, binge drinkers, or binge drinkers who are also heavy marijuana users. Tract based spatial analysis identified shared fiber structure across individuals and facilitated voxelwise comparisons of fractional anisotropy FA and mean diffusivity MD between groups.Significant between group differences were found in FA in eight white matter regions ps ≤ .016 between the binge drink-only group and controls, including superior corona radiata, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and superior longitudinal fasciculus. Interestingly, in 4 of these same regions, binge drinkers who are also heavy marijuana users had higher FA than binge drinkers who did not use marijuana ps < .05. MD did not differ between groups. Findings are largely consistent with research suggesting less neuropathology in adolescents without histories of substance use. However, binge drinkers who also use marijuana did not show as consistent a divergence from non-users as did the binge drink-only group. Detection of white matter alterations may have implications in identifying early cognitive dysfunction in substance using adolescents.Keywords: Adolescence, Brain Imaging, Marijuana Abuse, Alcohol Abuse, White Matter, Diffusion Tensor Imaging

via White Matter Integrity in Adolescents with Histories of Marijuana Use and Binge Drinking.

CBD protects pig brains--new hope for politicians

CBD protects pig brains in a model of stroke. Cannabinoids, such as THC and CBD, protect the brain. Neuropharmacology. 2013 Aug;71C:282-291. doi: 10.1016/j.neuropharm.2013.03.027. Epub 2013 Apr 12.Mechanisms of cannabidiol neuroprotection in hypoxic-ischemic newborn pigs: Role of 5HT1A and CB2 receptors.Pazos MR, Mohammed N, Lafuente H, Santos M, Martínez-Pinilla E, Moreno E, Valdizan E, Romero J, Pazos A, Franco R, Hillard CJ, Alvarez FJ, Martínez-Orgado J.SourceExperimental Unit, Pediatric Department, University Hospital Puerta de Hierro Majadahonda, 28222 Madrid, Spain.AbstractThe mechanisms underlying the neuroprotective effects of cannabidiol CBD were studied in vivo using a hypoxic-ischemic HI brain injury model in newborn pigs. One- to two-day-old piglets were exposed to HI for 30 min by interrupting carotid blood flow and reducing the fraction of inspired oxygen to 10%. Thirty minutes after HI, the piglets were treated with vehicle HV or 1 mg/kg CBD, alone HC or in combination with 1 mg/kg of a CB2 receptor antagonist AM630 or a serotonin 5HT1A receptor antagonist WAY100635. HI decreased the number of viable neurons and affected the amplitude-integrated EEG background activity as well as different prognostic proton-magnetic-resonance-spectroscopy H±-MRS-detectable biomarkers lactate/N-acetylaspartate and N-acetylaspartate/choline ratios. HI brain damage was also associated with increases in excitotoxicity increased glutamate/N-acetylaspartate ratio, oxidative stress decreased glutathione/creatine ratio and increased protein carbonylation and inflammation increased brain IL-1 levels. CBD administration after HI prevented all these alterations, although this CBD-mediated neuroprotection was reversed by co-administration of either WAY100635 or AM630, suggesting the involvement of CB2 and 5HT1A receptors. The involvement of CB2 receptors was not dependent on a CBD-mediated increase in endocannabinoids. Finally, bioluminescence resonance energy transfer studies indicated that CB2 and 5HT1A receptors may form heteromers in living HEK-293T cells. In conclusion, our findings demonstrate that CBD exerts robust neuroprotective effects in vivo in HI piglets, modulating excitotoxicity, oxidative stress and inflammation, and that both CB2 and 5HT1A receptors are implicated in these effects.

via Mechanisms of cannabidiol neuroprotection ... [Neuropharmacology. 2013] - PubMed - NCBI.

Marijuana use fights diabetes and lowers waist fat

The irrational opponents of marijuana legalization are having a harder and harder time of making the case that using it is harmful when we see that marijuana smokers suffer from less obesity and have significant protection from developing diabetes. Therefore, encouraging adult use of marijuana will work to lower our national health-care costs. Am J Med. 2013 May 9. The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults. Penner EA, Buettner H, Mittleman MA.SourceUniversity of Nebraska College of Medicine, Omaha; Department of Epidemiology, Harvard School of Public Health, Boston, Mass.AbstractBACKGROUND:There are limited data regarding the relationship between cannabinoids and metabolic processes. Epidemiologic studies have found lower prevalence rates of obesity and diabetes mellitus in marijuana users compared with people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes. To date, no study has investigated the relationship between marijuana use and fasting insulin, glucose, and insulin resistance.METHODS:We included 4657 adult men and women from the National Health and Nutrition Examination Survey from 2005 to 2010. Marijuana use was assessed by self-report in a private room. Fasting insulin and glucose were measured via blood samples after a 9-hour fast, and homeostasis model assessment of insulin resistance HOMA-IR was calculated to evaluate insulin resistance. Associations were estimated using multiple linear regression, accounting for survey design and adjusting for potential confounders.RESULTS:Of the participants in our study sample, 579 were current marijuana users and 1975 were past users. In multivariable adjusted models, current marijuana use was associated with 16% lower fasting insulin levels 95% confidence interval [CI], -26, -6 and 17% lower HOMA-IR 95% CI, -27, -6. We found significant associations between marijuana use and smaller waist circumferences. Among current users, we found no significant dose-response.CONCLUSIONS:We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.

via The Impact of Marijuana Use on Glucose, Insulin, an... [Am J Med. 2013] - PubMed - NCBI.

Bladder Cancer Risk Lower in Pot Smokers - Renal and Urology News

Stephan ChoMay 06, 2013                                                        Bladder Cancer Risk Lower in Pot Smokers                                  SAN DIEGO—For the first time, a study has found that cannabis use may be associated with a decreased risk of bladder cancer, researchers reported at the American Urological Association 2013 annual meeting.In a study of nearly 82,000 men, bladder cancer developed in 279 over an 11-year period. Subjects who smoked marijuana, but not tobacco, had a significant 45% decreased risk of bladder cancer compared with those who did not, after adjusting for age, body mass index, and race and ethnicity, according to lead investigator Anil A. Thomas, MD, a researcher with Southern California Permanent Medical Group in Los Angeles. Men who smoked tobacco, but not marijuana, had a significant 52% increased risk, a finding that is consistent with numerous previous studies. Men who smoked both had a 28% increased risk.Of the 82,000 men, 41% reported ever using marijuana and 57% reported tobacco use; 27% reported used both tobacco and marijuana.

via Bladder Cancer Risk Lower in Pot Smokers - Renal and Urology News.

zp8497586rq

Bladder Cancer Risk Lower in Pot Smokers - Renal and Urology News

Stephan ChoMay 06, 2013                                                        Bladder Cancer Risk Lower in Pot Smokers                                  SAN DIEGO—For the first time, a study has found that cannabis use may be associated with a decreased risk of bladder cancer, researchers reported at the American Urological Association 2013 annual meeting.In a study of nearly 82,000 men, bladder cancer developed in 279 over an 11-year period. Subjects who smoked marijuana, but not tobacco, had a significant 45% decreased risk of bladder cancer compared with those who did not, after adjusting for age, body mass index, and race and ethnicity, according to lead investigator Anil A. Thomas, MD, a researcher with Southern California Permanent Medical Group in Los Angeles. Men who smoked tobacco, but not marijuana, had a significant 52% increased risk, a finding that is consistent with numerous previous studies. Men who smoked both had a 28% increased risk.Of the 82,000 men, 41% reported ever using marijuana and 57% reported tobacco use; 27% reported used both tobacco and marijuana. via Bladder Cancer Risk Lower in Pot Smokers - Renal and Urology News.

Marijuana for psoriasis

When we passed the first medical marijuana laws in CA and AZ, opponents mocked the movement saying that doctors would be writing recommendations for people with psoriasis. Guess what, here is evidence that activating the CB1 receptor, as triggered by THC in marijuana, inhibits the inflammation and cell proliferation that cause the disease's miserable and disfiguring side effects. PeerJ. 2013 Feb 19; .A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytes in vitro and in situ.Ramot Y, Sugawara K, Zákány N, Tóth BI, Bíró T, Paus R.SourceDepartment of Dermatology, University of Luebeck , Luebeck , Germany ; Department of Dermatology, Hadassah-Hebrew University Medical Center , Jerusalem , Israel.          Abstract: Cannabinoid receptors CB are expressed throughout human skin epithelium. CB1 activation inhibits human hair growth and decreases proliferation of epidermal keratinocytes. Since psoriasis is a chronic hyperproliferative, inflammatory skin disease, it is conceivable that the therapeutic modulation of CB signaling, which can inhibit both proliferation and inflammation, could win a place in future psoriasis management. Given that psoriasis is characterized by up-regulation of keratins K6 and K16, we have investigated whether CB1 stimulation modulates their expression in human epidermis. Treatment of organ-cultured human skin with the CB1-specific agonist, arachidonoyl-chloro-ethanolamide ACEA, decreased K6 and K16 staining intensity in situ. At the gene and protein levels, ACEA also decreased K6 expression of cultured HaCaT keratinocytes, which show some similarities to psoriatic keratinocytes. These effects were partly antagonized by the CB1-specific antagonist, AM251. While CB1-mediated signaling also significantly inhibited human epidermal keratinocyte proliferation in situ, as shown by K6/Ki-67-double immunofluorescence, the inhibitory effect of ACEA on K6 expression in situ was independent of its anti-proliferative effect. Given recent appreciation of the role of K6 as a functionally important protein that regulates epithelial wound healing in mice, it is conceivable that the novel CB1-mediated regulation of keratin 6/16 revealed here also is relevant to wound healing. Taken together, our results suggest that cannabinoids and their receptors constitute a novel, clinically relevant control element of human K6 and K16 expression.

via A novel control of human keratin expression: cannabino... [PeerJ. 2013] - PubMed - NCBI.

THC/Marijuana fights liver cancer

First we learned that the cannabinoids produced by the cannabis plant fight and kill cancer cells now we are beginning to uncover the mechanisms by which cannabinoids target and kill cancer cells. Alcohol promotes cancer while marijuana suppresses cancer, what's wrong with this picture? I could go buy gallons and gallons of booze legally, but the government will destroy your life if you market marijuana. Cell Death Dis. 2013 May 2;4:e618. doi: 10.1038/cddis.2013.141.Involvement of PPARγ in the antitumoral action of cannabinoids on hepatocellular carcinoma.Vara D, Morell C, Rodríguez-Henche N, Diaz-Laviada I.SourceBiochemistry and Molecular Biology Unit, Department of System Biology, School of Medicine, University ofAlcala, 28871 Madrid, Spain.AbstractCannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma HCC cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol THC and JWH-015, against HepG2 and HUH-7 HCC cells. Both cannabinoids increased the activity and intracellular level of PPARγ mRNA and protein, which was abolished by the PPARγ inhibitor GW9662. Moreover, genetic ablation with small interfering RNA siRNA, as well as pharmacological inhibition of PPARγ decreased the cannabinoid-induced cell death and apoptosis. Likewise, GW9662 totally blocked the antitumoral action of cannabinoids in xenograft-induced HCC tumors in mice. In addition, PPARγ knockdown with siRNA caused accumulation of the autophagy markers LC3-II and p62, suggesting that PPARγ is necessary for the autophagy flux promoted by cannabinoids. Interestingly, downregulation of the endoplasmic reticulum stress-related protein tribbles homolog 3 TRIB3 markedly reduced PPARγ expression and induced p62 accumulation, which was counteracted by overexpression of PPARγ in TRIB3-knocked down cells. Taken together, we demonstrate for the first time that the antiproliferative action of the cannabinoids THC and JWH-015 on HCC, in vitro and in vivo, are modulated by upregulation of PPARγ-dependent pathways.

via Involvement of PPARγ in the antitumoral actio... [Cell Death Dis. 2013] - PubMed - NCBI.

THC and similar compounds suppress HIV infection and spread

Here is more evidence that using marijuana can improve the health of and increase the long-term survival of people with AIDS. THC and similar synthetic compounds block the ability of HIV to infect cells and to replicate. Recall that the Bush Sr. Administration denied medical marijuana to the numerous AIDS patients who were seeking it and ended the Compassionate Use Act rather than help the suffering. How many people died prematurely because of you old buzzard Bush? Blood drips from your mangled talons you evil vulture. Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists Servio H. Ramirez,†,1, Nancy L. Reichenbach, Shongshan Fan, Slava Rom, Steven F. Merkel, Xu Wang, Wen-zhe Ho,† and Yuri Persidsky,†,1+ Author Affiliations Department of Pathology and Laboratory Medicine and †Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania, USA ↵1.Correspondence: Dept. of Pathology and Laboratory Medicine, Temple University School of Medicine, 3401 N. Broad St., Philadelphia, PA 19140, USA. E-mail: yuri.persidsky@tuhs.temple.edu or servio.ramirez@temple.edu                                                     Abstract: Infiltrating monocytes and macrophages play a crucial role in the progression of HIV-1 infection in the CNS. Previous studies showed that activation of the CB2 can attenuate inflammatory responses and affect HIV-1 infectivity in T cells and microglia. Here, we report that CB2 agonists can also act as immunomodulators on HIV-1-infected macrophages. First, our findings indicated the presence of elevated levels of CB2 expression on monocytes/macrophages in perivascular cuffs of postmortem HIV-1 encephalitic cases. In vitro analysis by FACS of primary human monocytes revealed a step-wise increase in CB2 surface expression in monocytes, MDMs, and HIV-1-infected MDMs. We next tested the notion that up-regulation of CB2 may allow for the use of synthetic CB2 agonist to limit HIV-1 infection. Two commercially available CB2 agonists, JWH133 and GP1a, and a resorcinol-based CB2 agonist, O-1966, were evaluated. Results from measurements of HIV-1 RT activity in the culture media of 7 day-infected cells showed a significant decrease in RT activity when the CB2 agonist was present. Furthermore, CB2 activation also partially inhibited the expression of HIV-1 pol. CB2 agonists did not modulate surface expression of CXCR4 or CCR5 detected by FACS. We speculate that these findings indicate that prevention of viral entry is not a central mechanism for CB2-mediated suppression in viral replication. However, CB2 may affect the HIV-1 replication machinery. Results from a single-round infection with the pseudotyped virus revealed a marked decrease in HIV-1 LTR activation by the CB2 ligands. Together, these results indicate that CB2 may offer a means to limit HIV-1 infection in macrophages.

via Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists.

Cannabis and THC promote weight loss

Marijuana is a gateway to health! Med Hypotheses. 2013 May;80(5):564-7. doi: 10.1016/j.mehy.2013.01.019. Epub 2013 Feb 11.

Cannabis and Δ(9)-tetrahydrocannabinol (THC) for weight loss?

Le Foll B, Trigo JM, Sharkey KA, Le Strat Y.

Source

Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Addictions Program, CAMH, Toronto, Ontario, Canada; Departments of Psychiatry, Pharmacology, Family and Community Medicine, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address: bernard.lefoll@camh.ca.

Abstract

Obesity is one of the highest preventable causes of morbidity and mortality in the developed world [1]. It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the 'munchies'). This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome. This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile [2]. Despite being efficacious, Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market. We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ(9)-tetrahydrocannabinol (THC) present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.

Copyright © 2013 Elsevier Ltd. All rights reserved.

via Cannabis and Δ(9)-tetrahydrocannabinol (THC) ... [Med Hypotheses. 2013] - PubMed - NCBI.