Medicinal Uses of Marijuana and Cannabinoids
Franjo Grotenhermena and Kirsten Muller-Vahl
In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex, THC:CBD D 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabisbased medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.
Source : Plant Sciences
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Emerging Evidence for Cannabis' Role in Opioid Use Disorder
Beth Wiese and Adrianne R. Wilson-Poe
Introduction: The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose deaths are at an all-time high, and relapse remains pervasive.
Discussion: Although there are a number of FDA-approved opioid replacement therapies and maintenance medications to help ease the severity of opioid withdrawal symptoms and aid in relapse prevention, these medications are not risk free nor are they successful for all patients. Furthermore, there are legal and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone or buprenorphine, and the demand for these services far outweighs the supply and access. To fill the gap between efficacious OUD treatments and the widespread prevalence of misuse, relapse, and overdose, the development of novel, alternative, or adjunct OUD treatment therapies is highly warranted. In this article, we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight knowledge gaps and discuss cannabis' potential to prevent opioid misuse (as an analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the likelihood of relapse.
Conclusion: The compelling nature of these data and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct or alternative treatment for OUD.
Source : Cannabis and Cannabinoid Research
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Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression
Rameshprabu Nallathambi, Moran Mazuz, Dvory Namdar, Michal Shik, Diana Namintzer, Ajjampura C. Vinayaka, Aurel Ion,
Adi Faigenboim, Ahmad Nasser, Ido Laish, Fred M. Konikoff, and Hinanit Koltai
Introduction: Colorectal cancer remains the third most common cancer diagnosis and fourth leading cause of cancer-related mortality worldwide. Purified cannabinoids have been reported to prevent proliferation, metastasis, and induce apoptosis in a variety of cancer cell types. However, the active compounds from Cannabis sativa flowers and their interactions remain elusive.
Research Aim: This study was aimed to specify the cytotoxic effect of C. sativa-derived extracts on colon cancer cells and adenomatous polyps by identification of active compound(s) and characterization of their interaction.
Materials and Methods: Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography and gas chromatograph/mass spectrometry and their cytotoxic activity was determined using alamarBlue-based assay (Resazurin) and tetrazolium dye-based assay (XTT) on cancer and normal colon cell lines and on dysplastic adenomatous polyp cells. Annexin V Assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle, and RNA sequencing was used to determine gene expression.
Results: The unheated cannabis extracts (C2F), fraction 7 (F7), and fraction 3 (F3) had cytotoxic activity on colon cancer cells, but reduced activity on normal colon cell lines. Moreover, synergistic interaction was found between F7 and F3 and the latter contains mainly cannabigerolic acid. The F7 and F7+F3 cytotoxic activity involved cell apoptosis and cell cycle arrest in S or G0/G1 phases, respectively. RNA profiling identified 2283 differentially expressed genes in F7+F3 treatment, among them genes related to the Wnt signaling pathway and apoptosis-related genes. Moreover, F7, F3, and F7+F3 treatments induced cell death of polyp cells.
Conclusions:C. sativa compounds interact synergistically for cytotoxic activity against colon cancer cells and induce cell cycle arrest, apoptotic cell death, and distinct gene expression. F3, F7, and F7+F3 are also active on adenomatous polyps, suggesting possible future therapeutic value.
Source : Cannabis and Cannabinoid Research
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Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells
- Sindiswa T. Lukhele and
- Lesetja R. Motadi
Background Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies. In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.
Methods To achieve our aim, phytochemical screening, MTT assay, cell growth analysis, flow cytometry, morphology analysis, Western blot, caspase 3/7 assay, and ATP measurement assay were conducted.
Results Results obtained indicate that both cannabidiol and Cannabis sativa extracts were able to halt cell proliferation in all cell lines at varying concentrations. They further revealed that apoptosis was induced by cannabidiol as shown by increased subG0/G1 and apoptosis through annexin V. Apoptosis was confirmed by overexpression of p53, caspase 3 and bax. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels.
Conclusions In conclusion, these data suggest that cannabidiol rather than Cannabis sativa crude extracts prevent cell growth and induce cell death in cervical cancer cell lines.
Source : BMC Complementary and Alternative Medicine
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Cannabis Taxonomy: The ‘Sativa’ Vs. ‘Indica’ Debate
by Robert C. Clarke, Mark D. Merlin, PhD
Marijuana and hemp (Cannabis) and the closely related hop genus (Humulus) are the only widely known genera included in the small, but economically valuable, Cannabaceae family. Swedish botanist Carl Linnaeus, the “father of modern taxonomy,” first published the scientific name Cannabis sativa in his seminal Species Plantarum of 1753. The Latin nameCannabis derives from Greek (kannabis) and may have been originally derived from Scythian. The term sativa simply means “cultivated” and describes the common hemp plant that was widely grown across Europe in Linnaeus’ time. We, the authors, consider C. sativa to be native to western Eurasia and especially Europe, where, for millennia, the plant has been grown for its strong fibers and nutritious seeds, and from where it was introduced to the New World multiple times during early European colonization. Cannabis sativa plants also produce very small amounts of the compound delta-9-tetrahydrocannabinol (THC), the medically valuable and primary psychoactive cannabinoid found only in Cannabis. Since C. sativa evolved within the geographical limits of western Eurasia, it represents only a small portion of the genetic diversity seen in the genus Cannabis worldwide.1
Continue Reading at Source : HerbalGram, American Botanical council
Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid
- Francesca Borrelli†¶,
- Ester Pagano†¶,
- Barbara Romano¶,
- Stefania Panzera,
- Francesco Maiello1,
- Diana Coppola1,
- Luciano De Petrocellis2,¶,
- Lorena Buono2,¶,
- Pierangelo Orlando3,¶§ and
- Angelo A. Izzo*,¶
Cannabigerol (CBG) is a safe non-psychotropic Cannabis-derived cannabinoid (CB), which interacts with specific targets involved in carcinogenesis. Specifically, CBG potently blocks transient receptor potential (TRP) M8 (TRPM8), activates TRPA1, TRPV1 and TRPV2 channels, blocks 5-hydroxytryptamine receptor 1A (5-HT1A) receptors and inhibits the reuptake of endocannabinoids. Here, we investigated whether CBG protects against colon tumourigenesis. Cell growth was evaluated in colorectal cancer (CRC) cells using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide and 3-amino-7-dimethylamino-2-methylphenazine hydrochloride assays; apoptosis was examined by histology and by assessing caspase 3/7 activity; reactive oxygen species (ROS) production by a fluorescent probe; CB receptors, TRP and CCAAT/enhancer-binding protein homologous protein (CHOP) messenger RNA (mRNA) expression were quantified by reverse transcription–polymerase chain reaction; small hairpin RNA-vector silencing of TRPM8 was performed by electroporation. The in vivoantineoplastic effect of CBG was assessed using mouse models of colon cancer. CRC cells expressed TRPM8, CB1, CB2, 5-HT1A receptors, TRPA1, TRPV1 and TRPV2 mRNA. CBG promoted apoptosis, stimulated ROS production, upregulated CHOP mRNA and reduced cell growth in CRC cells. CBG effect on cell growth was independent from TRPA1, TRPV1 and TRPV2 channels activation, was further increased by a CB2 receptor antagonist, and mimicked by other TRPM8 channel blockers but not by a 5-HT1A antagonist. Furthermore, the effect of CBG on cell growth and on CHOP mRNA expression was reduced in TRPM8 silenced cells. In vivo, CBG inhibited the growth of xenograft tumours as well as chemically induced colon carcinogenesis. CBG hampers colon cancer progression in vivo and selectively inhibits the growth of CRC cells, an effect shared by other TRPM8 antagonists. CBG should be considered translationally in CRC prevention and cure.
Source : Journal Carcinogenesis
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Therapeutic Potential of Cannabinoids in Counteracting Chemotherapy-induced Adverse Effects: An Exploratory Review
- Sattar Ostadhadi1,
- Mahdieh Rahmatollahi1,
- Ahmad-Reza Dehpour1,2 and
- Reza Rahimian1,*
Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.
Source : Phytotherapy Research
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Cannabis induces a clinical response in patients with Crohn's disease: a prospective placebo-controlled study.
Naftali T1, Bar-Lev Schleider L, Dotan I, Lansky EP, Sklerovsky Benjaminov F, Konikoff FM.
BACKGROUND & AIMS:The marijuana plant Cannabis sativa has been reported to produce beneficial effects for patients with inflammatory bowel diseases, but this has not been investigated in controlled trials. We performed a prospective trial to determine whether cannabis can induce remission in patients with Crohn's disease.
METHODS:We studied 21 patients (mean age, 40 ± 14 y; 13 men) with Crohn's Disease Activity Index (CDAI) scores greater than 200 who did not respond to therapy with steroids, immunomodulators, or anti-tumor necrosis factor-α agents. Patients were assigned randomly to groups given cannabis, twice daily, in the form of cigarettes containing 115 mg of Δ9-tetrahydrocannabinol (THC) or placebo containing cannabis flowers from which the THC had been extracted. Disease activity and laboratory tests were assessed during 8 weeks of treatment and 2 weeks thereafter.
RESULTS:Complete remission (CDAI score, <150) was achieved by 5 of 11 subjects in the cannabis group (45%) and 1 of 10 in the placebo group (10%; P = .43). A clinical response (decrease in CDAI score of >100) was observed in 10 of 11 subjects in the cannabis group (90%; from 330 ± 105 to 152 ± 109) and 4 of 10 in the placebo group (40%; from 373 ± 94 to 306 ± 143; P = .028). Three patients in the cannabis group were weaned from steroid dependency. Subjects receiving cannabis reported improved appetite and sleep, with no significant side effects.
CONCLUSIONS:Although the primary end point of the study (induction of remission) was not achieved, a short course (8 weeks) of THC-rich cannabis produced significant clinical, steroid-free benefits to 10 of 11 patients with active Crohn's disease, compared with placebo, without side effects. Further studies, with larger patient groups and a nonsmoking mode of intake, are warranted
Source : Clin Gastroenterol Hepatol.
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Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain
Barth Wilsey, MD, Thomas D. Marcotte, PhD, Associate Professor, Reena Deutsch, PhD, Statistician, Ben Gouaux,Research Associate, Staci Sakai, Research Associate, and Haylee Donaghe, Research Associate
We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain.
Source : Journal Pain
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RIA neuroscience study points to possible use of medical marijuana for depression
Scientists at the University at Buffalo’s Research Institute on Addictions (RIA) are studying chronic stress and depression, with a focus on endocannabinoids, which are brain chemicals similar to substances in marijuana.
The findings raise the possibility that components of marijuana may be useful in reducing depression that results from chronic stress.
“In the animal models we studied, we saw that chronic stress reduced the production of endocannabinoids, leading to depression-like behavior,” says RIA senior research scientist Samir Haj-Dahmane, PhD.
Endocannabinoids are naturally produced chemical compounds in the brain that affect motor control, cognition, emotions and behavior. As the name suggests, they are similar to the chemicals found in marijuana (Cannabis sativa) and its active ingredient, delta-9-tetrahydrocannabinol (THC).
“Chronic stress is one of the major causes of depression,” Haj-Dahmane says. “Using compounds derived from cannabis — marijuana — to restore normal endocannabinoid function could potentially help stabilize moods and ease depression.”
He cautions this is preliminary research. “Our research thus far has used animal models; there is still a long way to go before we know whether this can be effective in humans,” he says. “However, we have seen that some people who suffer from post-traumatic stress disorder have reported relief using marijuana.”
Haj-Dahmane says the next step in the research is to see if using a marijuana extract, cannabidiol (CBD), restores normal behaviors in the animals without leading to dependence on the drug.
The study, co-authored by Roh-Yu Shen, PhD, RIA senior research scientist, was funded by a grant from the National Institute of Mental Health. It appeared in the fall issue of the Journal of Neuroscience.
Medical marijuana remains a controversial issue. Although 23 states and the District of Columbia have approved its use to provide relief for health problems such as glaucoma, nerve pain, epilepsy, multiple sclerosis and nausea from chemotherapy, some experts are concerned that medical use of marijuana may normalize attitudes about the drug and lead people — especially youth — to believe it is completely safe.
Source : University of Buffalo
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Media Leaping to Extremely Faulty Conclusions from Study on the Effects of Marijuana on the Brain
Uh oh -- new study looks at brain imaging of marijuana consumers, but it's impossible to draw conclusions.
A new study identifying minor differences in the brain imaging of habitual marijuana consumers compared to non-users may be ideal for stimulating sensational headlines (e.g., “Regular pot smokers have shrunken brains, study says,” Los Angeles Times, November 10), but tells us little in regard to whether pot poses actual health risks.
Specifically, an MRI scan revealed less gray matter in the orbital frontal cortex of pot-smoking subjects compared to those who had never used the drug. Researchers also identified increased connectivity between certain regions of the brain in regular marijuana users compared with non-users.
So precisely what do these findings tell us in regard to pot use and health? Not much. Since the study design is not longitudinal, investigators cannot determine whether these differences are caused by subject’s cannabis use, whether these differences existed prior to subjects’ ever trying cannabis, or whether these differences persist when users’ cannabis consumption ceases.
Most importantly, investigators in this study failed to determine whether any of these differences are positively associated with any measurable adverse performance outcomes, such as cognitive performance or quality of life. It may be that these cannabis users are functioning in their daily lives in a manner that is indistinguishable from controls, in which case the imaging differences may hold little if any real-world significance. (In fact, one of the paper’s authors acknowledged, “[C]hronic users appear to be doing fine.”)
Authors’ comments in regard to marijuana-using subjects' IQs also need to be taken with a grain of salt. Researchers noted that marijuana users in the study possessed, on average, lower IQs than those in the non-using group, a finding they acknowledged may be linked to a variety of factors other than pot use. This outcome would hardly be surprising. A review of a highly publicized 2012 study purporting to link adolescent pot use to lower IQ later in life determined that once economic variables were factored into the assessment, cannabis’ actual effect on intelligent quotient was likely to be “zero.” The findings of a previous longitudinal study from Canada that tracked the IQs of a group of marijuana users and non-users from birth similarly concluded, “[M]arijuana does not have a long-term negative impact on global intelligence.”
Even if we are to accept the findings of this latest paper at face value, such concerns are hardly a justification for cannabis’ continued criminalization. Ultimately, if we are truly concerned about pot’s potential impact on the brain, and in particular how it may impact the developing brains of young people, the obvious public policy response is to regulate the substance in a manner that better restricts adolescents’ access to it and provides them with evidence-based information in regard to its potential risks. This is the policy we have employed for alcohol and tobacco, two substances that possess known risks far greater than those posed by cannabis, and they have been successful, as adolescent alcohol and tobacco use now stand at historic lows. It's high time we as a society employ a similarly principled policy for cannabis.
Source : Alternet
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Unconvincing Study Links Cannabis Use to Cardiovascular Complications
by Ashley Lindstrom
On April 23, 2014, the Journal of the American Heart Association (JAHA) published an article titled “Cannabis Use: Signal of Increasing Risk of Cardiovascular Disorders.”1
The authors of the JAHA article worked with the French Addictovigilance Network (FAN) to analyze cases in which cardiovascular complications were reported to the network alongside cannabis (Cannabis sativa, Cannabaceae) use for the years 2006 through 2010. (FAN was “created in the 1990s with the aim of achieving reliable surveillance of abuse and pharmacodependence cases related to drug abuse.”1) According to the study, healthcare providers in France have a “legal obligation to report to their regional addictovigilance center all serious cases defined as one of the following criteria of seriousness: leading to temporary or permanent functional incapacity or disability, to inpatient hospitalization or prolongation of existing hospitalization, to congenital anomalies, or to an immediate vital risk or death.”1
During the five years investigated, a total of 9,936 reports were filed with FAN for all drugs. Of those, 1,979 cases were cannabis related. From there, only 35 involved cardiovascular complications and cannabis use, nine of which were fatal. (As a result, based on these somewhat limited data, part of the authors’ conclusion is that a death rate of 25.6% exists in cases of cardiovascular complications related to cannabis.1) Inclusion criteria were adequate documentation with outcome chronology; however, cases with insufficient patient management and toxicological information also were admitted, as noted below. Research was funded by the French InterMinisterial Mission for the Fight Against Drugs and Addiction and the French Drug Agency.1
The various shortcomings of the study — many of which will be elucidated herein — signal the need for critical analysis of the data and even skepticism toward the validity of the authors’ conclusions.
As noted by the JAHA authors, cardiovascular diseases (CVDs) are the world’s leading causes of death. Well-known risk factors include age, tobacco and/or alcohol use, obesity, physical inactivity, and high blood pressure and/or cholesterol. According to the World Health Organization, behavioral risk factors such as tobacco and/or alcohol use, poor diet, and physical inactivity are to blame for 80% of incidences of coronary heart disease and cerebrovascular disease.2 Other concerns include genetics (familial history of CVD), sex (pre-menopausal women have a lower risk), secondhand-smoke exposure, kidney disease, low birth weight, and intake of substances such as caffeine or pharmaceuticals such as sildenafil (the active ingredient in Viagra®).
Cannabis has been posited as a potential trigger for coronary events. According to a 2002 Journal of Clinical Pharmacology article, “THC [tetrahydrocannabinol] acutely causes a substantial increase in heart rate (as high as 50%-60%) that is dose dependent and is generally associated with a modest increase in blood pressure, whether smoked in marijuana cigarettes or administered intravenously. Maximal heart rate increase occurs 10-15 minutes after peak plasma THC concentration.”3 Tolerance develops to the acute effects.2
Conversely, in several recent studies4-6 cannabinoids have exhibited potential cardioprotective properties, according to Jahan Marcu, PhD, multidisciplinary scientific advisory board vice-chair of Americans for Safe Access, a medical cannabis patient advocacy organization (email, May 4, 2014). “Cannabis-based medicine and cannabinoids are being developed to treat ischemia and other pathologies due to heart attacks,” said Dr. Marcu. “Cannabinoids protect the heart from damage, stimulate repair mechanisms of cardiac tissues, and are being developed to reduce brain damage from heart attacks.”
While the possibility exists that individuals with cardiovascular risks could be adversely affected by cannabis intake, a study of 65,171 subjects over the course of 49 years showed no significant difference in mortality rate between cannabis users and non-users.7
The mean age of the JAHA subjects was 34.3; 30 of the patients were men; 21 of the patients were tobacco smokers; and no associated substances were declared in 11 cases. (As previously stated, both men and tobacco smokers are at a higher risk for CVD.) Seven patients had a familial cardiovascular history and nine had personal cardiovascular history, adding up to 16 — a total of 46% of the subjects.1
In seven of the nine fatal case reports, patients had either already collapsed or were found dead and more than likely would not have been able to contribute relevant details to their medical files — including vital information about associated substances for which they may not have been tested. No case descriptions or toxicology information were presented for the other two fatalities. Fatal cases for which patient management information was not available totaled five.
Patients’ exposure to cannabis was broken down into three categories: actual, recent, and regular/daily. In eight of the nine fatal cases, exposure was actual, defined as “one or more uses in the past 12 months,” while recent refers to one to nine uses in the past 30 days. In the article, several case descriptions seem to disagree with reported exposure. In one fatal 2009 case, exposure was classified as actual when the case description reports the presence of cannabinoids “at a dose compatible with recent intoxication.” The case description for a 2010 case states that the deceased was under the influence of cannabis, but exposure is listed as actual. Another fatal 2010 case classifies exposure as actual, though the case description notes “[c]hronic exposure to cannabis.”
Many other cardiac risk factors are not mentioned among the data and do not seem to be considered by the authors, including the subjects’ physical inactivity, kidney disease, history of substance abuse, stress level, exposure to secondhand smoke, blood lipid disorder(s), caffeine intake (usually not considered a cardiac risk factor), et al.
Several sources for this article highlighted the fact that cannabis is most frequently smoked along with tobacco in France (a country with a relatively high per-capita tobacco-smoking population8), thereby cautioning that the cases in which cannabis is the sole “associated substance” in this article should be considered with a considerable degree of skepticism where toxicology testing does not confirm that a subject was in fact tobacco-free.
“There’s a tendency for folks who are of the…drugs-are-bad kind of mindset that leads to a gross over-interpretation and a tendency to not just cherry-pick…but to just completely turn things inside out,” said William Dolphin, publications director of Americans for Safe Access (personal communication, May 2, 2014). “This study comes [from people] who are looking at negative outcomes, and fair enough — that’s the lens that they’re interpreting it through,” said Dolphin, adding, “You tend to find what you look for and there are all kinds of that kind of observational bias that get through to the media and then the media take it and amplify it.”
“Now, the caveat to all of that — and it’s a serious concern — is that the elevated heart rate, the vasodilation can be problematic for some people,” explained Dolphin. “If you’ve got a heart problem, you shouldn’t be using Viagra, you shouldn’t be engaging in really strenuous exercise, and maybe you shouldn’t be going near the cannabis — IF you know it creates that effect in you.”
Skewed and poor-quality cannabis studies, whether their outcomes are positive or negative, highlight the need for research of high methodological quality in this area. Despite a long history of relatively safe use, legitimate concerns regarding the effects of cannabis and its many unique compounds demand robust and critical study, particularly as more people have access to legal medicinal and recreational cannabis. In the United States, the erroneous view that cannabis is a highly dangerous substance with no redeeming medicinal value perpetuates its frequently-criticized Drug Enforcement Agency Schedule I classification, which in turn makes it more difficult to attain approval for medical research. That the American Heart Association allowed such an inadequate cannabis study to be published under its auspices is troubling. When correlation is spun as causation and resultant media coverage is uncritical and misleading, scientific and public health progress is hindered.
Source : American Botanical Council - Herbalgram
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Cannabis and Schizophrenia
by Lindsay Stafford Mader
The proposition that cannabis causes schizophrenia has existed since at least the early days of the anti-marijuana movement in America, as illustrated in the 1936 film Reefer Madness, in which a character descends into psychosis after smoking a joint.1 The cannabis-schizophrenia connection intensified during the “War on Drugs,” which produced propaganda linking the herb to schizophrenia, as well as cancer and brain damage.2 Fast-forward more than seven decades since the film, and the academic and mainstream media continue to refer to cannabis’s ability to cause and increase the risk of developing this serious mental illness.3,4
The link between cannabis (Cannabis sativa, Cannabaceae) and schizophrenia, however, is much more complex and much less certain. Cannabis and the brain have an interesting and unique relationship, part of which remains a mystery to researchers even today. After more than two decades of scientific analysis, researchers know that the human body contains receptors that bind with tetrahydrocannabinol (THC) and other cannabinoids from the cannabis plant, and also has neurotransmitters that activate these receptors in much the same way. The body's receptors include the CB1 and CB2 receptors, and the endogenous cannabinoids, referred to as endocannabinoids, including anandamide and 2-AG.5,6
Although this intricate endocannabinoid system of receptors and neurotransmitters — as well as the exact role played by the cannabis plant — is not yet fully understood, it clearly is involved in numerous physiological and pathological processes that are essential to human health. As Ester Fride and Ethan Russo, MD, wrote in the neuropsychiatry chapter of the 2005 book Endocannabinoids: The Brain and Body’s Marijuana and Beyond (CRC Press), “Endocannabinoids serve a modulatory function in many neurochemical and psychopharmacological processes, and deficiencies or excesses in any of these may produce manifestations of psychopathology.”5
Even more perplexing to scientists is the severe brain disorder called schizophrenia, which affects about 24 million people worldwide — approximately one percent of the population. According to the PsychCentral mental health web resource, “In spite of advances in the understanding of its causes, course, and treatment, schizophrenia continues to confound both health professionals and the public. It is easier for the average person to cope with the idea of cancer than it is to understand the odd behavior, hallucinations, or strange ideas of the person with schizophrenia.”7
Medical researchers believe that schizophrenia is tied to a genetic link as incidence among those with afflicted family members is increased by about nine percent.8 It is also thought that schizophrenia might be caused by the malfunction of a gene that creates important brain chemicals, as well as possible environmental triggers, and/or an imbalance of the neurotransmitters dopamine and glutamate. Scans of schizophrenia patients’ brains have revealed that they have larger center-brain ventricles and less gray matter, and post-mortem brain analyses have shown differences in schizophrenics’ brain cell characteristics — perhaps occurring during abnormal fetal brain development. Schizophrenia presents itself through a variety of symptoms, including hallucinations, delusions, thought and movement disorders, monotonous voice, and motionless face when speaking (referred to as “positive” symptoms), as well as social withdrawal, inability to make decisions, lack of emotion and motivation, etc. (referred to as “negative” symptoms and “cognitive deficits”).
While a fair amount of scientific research has examined the relationship between cannabis and schizophrenia, most of this consists of laboratory, animal, epidemiological, or post-mortem human studies. Recognizing the “tremendous amount” of preclinical research on cannabis and schizophrenia, Martin Lee — author of the 2012 book Smoke Signals: A Social History of Marijuana – Medical, Recreational, and Scientific — noted the ethical implications of studying cannabis in humans.
“You’re not going to get experiments in the United States where the federal government will approve a researcher or a scientist giving marijuana to a schizophrenic, but you could do a survey of schizophrenics,” said Lee (oral communication, March 15, 2013).
Cannabis is well known to cause physiological and psychological side effects in almost all people who use it, particularly varieties that contain higher levels of THC. Thus, the concept that cannabis causes negative mental experiences is not ridiculous; anecdotal reports of momentary post-cannabis psychosis and hallucinations have been shared for quite some time.2
While the psychological side effects of cannabis can be similar to the symptoms experienced by diagnosed schizophrenics — such as visual illusions, paranoia, mood alterations, and memory deficits9 — cannabis-produced symptoms typically disappear after three to five hours.10
Still, the allegation persists that cannabis can cause schizophrenia, a disease in which psychotic symptoms typically last throughout a patient’s life. When experts discuss this cannabis-schizophrenia relationship, they make sure to differentiate between cannabis’s impact on healthy populations and cannabis’s impact on diagnosed schizophrenic patients and individuals with risk factors for developing schizophrenia.9 This important detail is often not provided in media reports on the topic.
“I don’t think we should say cannabis induces schizophrenia, and so we should discourage people from using cannabis because they’ll become psychotics,” said Andrea Giuffrida, PhD, an associate professor of pharmacology at the University of Texas Health Science Center in San Antonio, who researches this topic (oral communication, March 25, 2013). “Maybe some of them have a higher risk, but not the entire population.”
Researchers and proponents of the argument that cannabis does not cause schizophrenia in the general population often cite epidemiological data that shows a significant increase in cannabis usage during the last several decades while the rates of schizophrenia have remained largely static. As stated by the authors of a recent article titled, “Cannabis and Psychosis: What Causes What?,” “Most people who use cannabis do not develop schizophrenia, and many people diagnosed with schizophrenia have never used cannabis.”9
“As marijuana usage has increased in culture in the last 50 years, you haven’t seen that increase in schizophrenia,” said Lee. “If it was causing schizophrenia, you would probably see an increase, so the causal thing is just not there.”
But according to psychiatrists Patricia Gerbarg, MD, who has a clinical practice in New York City, and Richard Brown, MD, a professor at Columbia University, the lack of correlation could be explained in other ways. “For example,” they said, “improvements in prenatal nutrition and healthcare are more likely to lower the incidence of schizophrenia…. Also, there may appear to be a lack of increase in schizophrenia because of a lack of increase in the diagnosis of schizophrenia, which could be due to the many changes in diagnostic categories since the 1970s. Many cases that would previously have been diagnosed as schizophrenia, would now be diagnosed as Asperger’s or bipolar disorder” (email, March 16, 2013).
Some epidemiological surveys have shown that schizophrenic patients abuse cannabis more than any other illegal drug and also have cannabis usage rates higher than healthy population rates, which has been used as an argument that cannabis possibly causes or increases the chance of developing schizophrenia in otherwise healthy populations.11 But according to Dr. Giuffrida, this is just a correlation, which, he points out, cannot establish causality. He additionally noted the hypothesis that schizophrenic patients might use cannabis more because they are attempting to self-medicate.
“Whether they smoke more because they are schizophrenic or they are schizophrenic because they smoke more cannabis, we don’t know the direction of the connection,” he explained.
Further, a Swedish survey published in 1987 of almost 50,000 male participants conducted over the course of 15 years found that those who self-reported heavy cannabis use were 50 times more likely to be diagnosed with schizophrenia.12 But when these findings were reanalyzed and adjusted to account for other risk factors, the increased likelihood dropped to 6.7 times, and many of the participants who reported cannabis use also reported the use of other drugs that have the ability to precipitate psychosis.13
In examining the connection between cannabis and schizophrenia, researchers also study brain morphology. In a 2012 paper in the European Archives of Psychiatry and Clinical Neuroscience, a team of researchers from Germany and England analyzed 16 neuroimaging studies. The authors concluded that there is “no convincing evidence” that cannabis-related brain alterations happen before the onset of schizophrenia.11 In fact, essentially none of the changes seen in the brains of schizophrenic patients using cannabis were observed in healthy individuals who used cannabis.
Some journals and other sources report that young people are especially vulnerable for developing cannabis-induced schizophrenia. A large-scale survey conducted in 2005 by Henquet et al. suggested that ingesting cannabis at a young age (14 to 24 years) was associated with an increased chance of developing psychotic symptoms,14,15 but this data did not analyze the risk of developing full schizophrenia, and those with predisposed risks for psychosis were more likely to develop psychotic symptoms. According to an expert peer reviewer of this article, while extra caution is always advised in adolescents, there is still no evidence that permanent, schizophrenia-related de novo damage is done to young, healthy individuals.
“The work of Henquet is very interesting,” added Dr. Giuffrida, “but the assessment of cannabis use is based on an interview and consequently is not as precise as a study where cannabis is administered in a controlled fashion. I do believe we need more experiments before establishing a causal relation between cannabis exposure and schizophrenia development in the healthy population.”
At-Risk and Diagnosed Populations
Most researchers agree that because schizophrenia likely is brought on by a variety of “component causes,” one of which could include cannabis use, a healthy person with no risk factors is very unlikely to develop the disease from cannabis use alone.9,11,14 The situation is different, however, for individuals with predisposed risks.
Those at risk for developing schizophrenia include individuals with schizophrenic family members or those who exhibit symptoms of the prodromal stage (a precursor to a more full set of symptoms or disease), which typically consist of increased isolation and decreased motivation and appear a year before true schizophrenia symptoms.11 Interestingly, recent research suggests that a mutation in the AKT1 gene also might put an individual at increased risk for developing cannabis-associated schizophrenia.16 These at-risk groups are cautioned against using cannabis as epidemiological evidence and survey data show that they have worse psychotic-disorder outcomes when cannabis is a factor.15
The aforementioned 2012 brain morphology literature review by Malchow et al. found just three studies on high-risk individuals, in which an “additional effect of cannabis use on brain structure” was suggested.11 These studies found that cannabis use was associated with a bilateral volume loss of the thalamus, a region of the brain that integrates and processes sensory and cognitive functions; increased thinning of the cortex, the largest region of the brain; and an increased volume of the brain’s fluid-filled cavities known as ventricles. (The latter of these studies, however, analyzed cannabis and alcohol in high-risk subjects.)
The review authors conclude that there is “some weak evidence that cannabis abuse could affect brain structures in high-risk subjects, but replication of these findings is needed. The results of the identified neuroimaging studies are heterogeneous and inconclusive,” for various reasons, including differing definitions of regional volume boundaries and differing volume extraction methods (when measuring content of the brain), as well as differing MRI techniques.11
For patients who have been diagnosed with schizophrenia, the implications for using cannabis are somewhat better understood. Although few human clinical trials on cannabis and schizophrenics have been performed, epidemiological data and survey evidence indicate — and most experts agree — that ingesting cannabis can aggravate schizophrenia symptoms and/or increase their frequency.13 The few human studies found cannabis products (i.e., hashish, THC) to exacerbate symptoms, although these were temporary effects. According to Endocannabinoid’s neuropsychiatry chapter, “Taken together, most studies confirm the vulnerability hypothesis for cannabis use and schizophrenia. Thus, schizophrenia patients should probably not use cannabis because a psychotic episode can be induced in someone with a preexisting disorder and, indeed, increased hospitalization rates and symptom exacerbation have been demonstrated.”5
Malchow et al. noted that most brain imaging studies on cannabis and schizophrenia examined individuals with first-episode or recent-onset schizophrenia.11 Some of this research suggested that schizophrenic patients who used cannabis had subtle brain abnormalities, increased ventricle volumes, thinning of various cortical regions, decreased gray and white matter volume, and “altered brain structure in particular regions … with a high density of CB1 receptors.” The authors noted, however, that anti-psychotic medication has been strongly associated with reduced gray matter and that many of the studies included “comorbid patients consuming other substances than cannabis, for example, amphetamines, cocaine, and sometimes alcohol, making it difficult to focus on the effect of cannabis alone.”
“The results of these neuroimaging studies are again heterogeneous and remain inconclusive,” they wrote.
Researchers are beginning to understand that the connection between cannabis and schizophrenic individuals might lie in the human body’s mysterious and powerful endocannabinoid system. According to the authors of a 2008 article in Expert Review of Neurotherapeutics, “There are several lines of evidence suggesting that, at least in a subgroup of patients, alterations in the endocannabinoid system may contribute to the pathogenesis of schizophrenia.”15
Human studies have shown schizophrenics to have increased levels of anandamide and endocannabinoid-like molecules such as palmitylethanolamide, and these patients with higher levels of anandamide typically experience fewer psychotic symptoms.15 Additionally, frequent cannabis usage was found to decrease cerebral spinal fluid levels of anandamide, suggesting a possible explanation for why some schizophrenic patients sometimes have negative experiences after ingesting cannabis. Authors of additional studies have found a possible connection between lower levels of the endocannabinoid 2-AG and schizophrenia progression, as well as impaired endocannabinoid signaling associated with acute psychotic episodes.
“My preferred hypothesis is that frequent and intense cannabis smoking [reduces] an endogenous protective mechanism, mediated by anandamide, resulting in an increased risk for precipitation of psychosis,” said Daniele Piomelli, PhD, PharmD, a professor of anatomy and neurobiology at the University of California at Irvine (email, March 22, 2013). “Please note that anandamide is not the only endocannabinoid present in the brain and that this theory does not rule out the possibility that other endocannabinoids (e.g., 2-AG) might be pro-psychotic.”
In explaining why cannabis and endocannabinoids might not act in the same way, Dr. Giuffrida pointed to the different pharmacologic profiles of THC and anandamide. “For example, when you smoke cannabis and take in THC, you activate all the cannabinoid receptors in the brain. But when you elevate anandamide, the elevation does not happen all over the brain but happens in specific brain areas.”
Interestingly, the CB1 receptor is expressed in high levels in the prefrontal cortex — the region of the brain responsible for cognitive and emotional functions and thought to be the “primary dysfunctional area” in schizophrenia — as well as in other brain areas relevant to schizophrenia, such as the basal ganglia, hippocampus, and the anterior cingulate cortex.8,15 Some post-mortem studies have found schizophrenic patients’ brains to have even-further increased binding levels of the CB1 receptor.
“But again,” said Dr. Giuffrida, “whether this is a contributing factor to develop schizophrenia is unknown at this time.”
Dr. Giuffrida reiterated that cannabis can sometimes help certain schizophrenia symptoms, which might explain why some patients might self-medicate with the herb.
“We know that, in schizophrenic patients, cannabis intake can make positive symptoms worse. But, on the other side, there is some work showing that the cannabinoids have a beneficial effect on the negative symptoms of schizophrenia, so they make people interact more with each other. But what happens with marijuana, especially if you are a psychotic individual, the more you use cannabis, the worse your symptoms become over time. So it can be helpful in the beginning, but definitely not in the long run.”
Therapeutic Role of CBD
While THC, the compound in cannabis responsible for the euphoric “high,” is known to increase the severity of psychotic symptoms in schizophrenia patients, another cannabinoid in cannabis — the non-psychoactive cannabidiol (CBD) — has been shown to be therapeutic for schizophrenia symptoms.
Based on CBD’s known anti-anxiety activity, researchers conducted a small pilot study on CBD in 42 patients with paranoid schizophrenia in 2012. This Phase II, double-blind, four-week trial compared CBD treatment with the antipsychotic drug amisulpride and found that CBD improved symptoms as well as the pharmaceutical — and that it produced fewer negative side effects.17
“It’s a small study so we have to see if the data is replicated in larger groups of people,” said Dr. Giuffrida, noting that CBD “is definitely one of the most exciting areas in the cannabinoid field.” He explained that although CBD’s activity within the brain is not yet completely understood, this compound is pharmacologically different from THC in that it does not bind to the CB1 receptor in the brain, whereas THC does. Additionally, he said some animal and human studies show that CBD boosts levels of the endocannabinoid anandamide, and elevated anandamide seems to have a beneficial effect on schizophrenia.
“These results suggest that the inhibition of anandamide activation may contribute to the anti-psychotic effect of cannabidiol,” said Dr. Giuffrida, “which possibly represents a completely new mechanism of treatment for schizophrenia.”
While CBD presents an exciting possibility as a novel schizophrenia treatment, additional research must be conducted to validate early studies. Likewise, more human research on cannabis’s impact on schizophrenia would greatly broaden scientists’ and medical professionals’ understanding of this interesting and complex relationship. Based on the available evidence — which includes epidemiological studies, surveys, brain morphology analyses, and a few human studies — most experts accept that cannabis intake could have negative impact on individuals who have schizophrenia and that those vulnerable to developing schizophrenia can have psychotic episodes if they ingest high doses of cannabis.
“So there definitely is something there,” said Dr. Guiffrida. “However, this is probably one of the components that may contribute to schizophrenia. It is not the cause of schizophrenia. And so I don’t think we have yet enough evidence to say that cannabis causes schizophrenia, and this is particularly true for the healthy population.”
1. George A. Hirliman Productions. Reefer Madness [film]. Director, Louis Gasnier. 1936.
2. Lee M. Smoke Signals: A Social History of Marijuana—Medical, Recreational, and Scientific. New York, NY: Scribner; 2012.
3. Collingwood J. Cannabis may cause schizophrenia-like brain changes. PsychCentral. Available at: http://psychcentral.com/lib/2012/cannabis-may-cause-schizophrenia-like-brain-changes/. Accessed March 18, 2013.
4. Schwarz A. Drowned in a stream of prescriptions. New York Times. February 2, 2013. Available at: www.nytimes.com/2013/02/03/us/concerns-about-adhd-practices-and-amphetamine-addiction.html?pagewanted=all&_r=0. Accessed March 18, 2013.
5. Onaivi E, Sugiura T, Marzo V, eds. Endocannabinoids: The Brain and Body’s Marijuana and Beyond. Boca Raton, FL: CRC Press; 2005.
6. Sulak D. Introduction to the endocannabinoid system. NORML website. Available at: http://norml.org/library/item/introduction-to-the-endocannabinoid-system. Accessed April 2, 2013.
7. Bengston M. Schizophrenia and psychosis. PsychCentral. Reviewed June 17, 2012. Available at: http://psychcentral.com/disorders/schizophrenia/. Accessed March 18, 2013.
8. What causes schizophrenia? National Institute of Mental Health website. Available at: www.nimh.nih.gov/health/publications/schizophrenia/what-causes-schizophrenia.shtml. Accessed March 18, 2013.
9. Castle DJ. Cannabis and psychosis: what causes what? F1000 Med Rep. 2013;5:1.
10. Cannabis/Marijuana (∆ 9 -Tetrahydrocannabinol, THC). Drugs and Human Performance Fact Sheets. National Highway Traffic Safety Administration website. Available at: www.nhtsa.gov/People/injury/research/job185drugs/cannabis.htm. Accessed April 2, 2013.
11. Malchow B, Hasan A, Fusar-Poli P, Schmitt A, Falkai P, Wobrock T. Cannabis abuse and brain morphology in schizophrenia: a review of the available evidence. Eur Arch Psychiatry Clin Neurosci. 2013;263(1):3-13.
12. Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and schizophrenia: a longitudinal study of Swedish conscripts. Lancet. 1987;2(8574):1483-1486.
13. Sewell RA, Skosnik PD, Garcia-Sosa I, Ranganathan M, D’Souza DC. Behavioral, cognitive and psychophysiological effects of cannabinoids: relevance to psychosis and schizophrenia. Revista Brasilerira de Psiquiatria. 2010;32:Suppl 1.
14. D’Souza D, Sewell RA, Ranganathan M. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci. 2009;259(7):413-431.
15. Müller-Vahl KR, Emrich HM. Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia. Expert Rev Neurother. 2008 Jul;8(7):1037-1048.
16. Di Forti, Iyegbe C, Sallis H, et al. Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. Biological Psychiatry. 2010;72(10):811-816.
17. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar 20;2:e94.
Source : American Botanical Council
Link to Full Abstract
Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology
Lisa M. Eubanks,† Claude J. Rogers,† Albert E. Beuscher, IV,‡ George F. Koob,§ Arthur J. Olson,‡ Tobin J. Dickerson,† and Kim D. Janda
Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients as well as reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.
Source : Mol Pharm.
Link to Full Article
Lower Bladder cancer Risk Seen in Marijuana Users
Marijuana users had a small but statistically lower risk of bladder cancer compared with people who smoked tobacco or did not smoke, a large retrospective cohort study showed.
The overall cohort had a bladder cancer risk of <1%. Nonetheless, cannabis (marijuana) users had an incidence of 0.3% compared with 0.4% among nonusers. The difference represented a 45% reduction in the hazard ratio (HR) for bladder cancer.
The magnitude of risk reduction appeared to increase with the frequency of cannabis use, Anil A. Thomas, MD, reported at the American Urological Association meeting in San Diego, California, in May.
“The full effects of cannabis use are not known, and Kaiser Permanente does not promote nor condone the use of cannabis,” said Thomas, an endourology fellow at Kaiser Permanente Los Angeles Medical Center. “However, our findings demonstrated a reduced incidence of bladder cancer among cannabis users, which could lead to further investigational studies to determine if cannabinoids, the active components of cannabis, have biologic activity against bladder cancer. Future research may eventually lead to the development of new targeted therapies for patients with bladder cancer.”
Bladder cancer is the fourth most common cancer in men, and tobacco use is a recognized risk factor for developing the disease. Whether that risk extends to cannabis use had not been examined in large epidemiologic studies. To address the issue, Thomas and colleagues analyzed records from the California Men’s Health Study (CMHS), a multiethnic cohort study that focuses primarily on prostate cancer, but also on the etiology of other cancers and non-cancerous conditions.
The bladder cancer study involved 84,170 men from the Northern and Southern Kaiser Permanente health regions participating in the CMHS. After excluding 680 men with a history of bladder cancer, investigators analyzed data for the remaining participants.
According to self-reported information provided by the participants, a total of 71% of the men were smokers (41% cannabis, 57% tobacco and, included in those numbers, 27% both substances). Meanwhile, 29% used neither cannabis nor tobacco. During follow-up for as long as 11 years, 279 study participants (0.3%) developed bladder cancer. Cannabis users accounted for 89 (0.3%) cancers and nonusers (including tobacco users) for 190 cancers (0.4%, P <.0001).
An analysis adjusted for age race/ethnicity, and body mass index showed that exclusive tobacco use was associated with a bladder cancer HR of 1.52 compared with nonusers (P <.007). In contrast, exclusive cannabis use was associated with a reduced risk of bladder cancer (HR=0.55; P =.0484). Men who reported use of tobacco and cannabis had a bladder cancer HR of 1.28, which was not statistically different from that of nonusers (P =.1480).
In another adjusted analysis, men who reported using cannabis once or twice had no reduction in bladder cancer risk (HR=1.07; P =.760), whereas men who reported use in excess of 500 times had a bladder HR of .66, which still did not achieve statistical significance (P =.175).
“While a cause-and-effect relationship has not been established, cannabis use may be inversely associated with bladder cancer risk in this population,” Thomas said. “Additional research is needed to determine if there is indeed a biological effect of cannabis to prevent or delay the development of bladder cancer.”
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Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III
Tripathi B Rajavashisth1,2, Magda Shaheen3, Keith C Norris3, Deyu Pan3, Satyesh K Sinha1, Juan Ortega1, Theodore C Friedman1
1Division of Endocrinology, Metabolism, and Molecular Medicine, Los Angeles, California, USA
2Omics Biotechnology, Inc, Lawndale, California, USA
3Office of Research, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
To determine the association between diabetes mellitus (DM) and marijuana use.
Data from the National Health and Nutrition Examination Survey (NHANES III, 1988–1994) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention.
The study included participants of the NHANES III, a nationally representative sample of the US population. The total analytic sample was 10 896 adults. The study included four groups (n=10 896): non-marijuana users (61.0%), past marijuana users (30.7%), light (one to four times/month) (5.0%) and heavy (more than five times/month) current marijuana users (3.3%). DM was defined based on self-report or abnormal glycaemic parameters. We analysed data related to demographics, body mass index, smoking status, alcohol use, total serum cholesterol, high-density lipoprotein, triglyceride, serum 25-hydroxy vitamin D, plasma haemoglobin A1c, fasting plasma glucose level and the serum levels of C reactive protein and four additional inflammatory markers as related to marijuana use.
Main outcome measures
OR for DM associated with marijuana use adjusted for potential confounding variables (ie, odds of DM in marijuana users compared with non-marijuana users).
Marijuana users had a lower age-adjusted prevalence of DM compared to non-marijuana users (OR 0.42, 95% CI 0.33 to 0.55; p<0.0001). The prevalence of elevated C reactive protein (>0.5 mg/dl) was significantly higher (p<0.0001) among non-marijuana users (18.9%) than among past (12.7%) or current light (15.8%) or heavy (9.2%) users. In a robust multivariate model controlling for socio-demographic factors, laboratory values and comorbidity, the lower odds of DM among marijuana users was significant (adjusted OR 0.36, 95% CI 0.24 to 0.55; p<0.0001).
Marijuana use was independently associated with a lower prevalence of DM. Further studies are needed to show a direct effect of marijuana on DM.
Source : BMJ
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The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults
Elizabeth A. Penner, BS Hannah Buettner, BA Murray A. Mittleman, MD, DrPH
Department of Epidemiology, Harvard School of Public Health, Boston, Mass
Cardiovascular Epidemiology Research Unit, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Mass
Requests for reprints should be addressed to Murray A. Mittleman, MD, DrPH, 375 Longwood Ave, Boston, MA 02215.
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.
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.
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.
We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR, and smaller waist circumference.
Source : The American Journal of Medicine
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Smoked Cannabis Reduces Some Symptoms of Multiple Sclerosis
A clinical study of 30 adult patients with multiple sclerosis (MS) at the University of California, San Diego School of Medicine has shown that smoked cannabis may be an effective treatment for spasticity – a common and disabling symptom of this neurological disease.The placebo-controlled trial also resulted in reduced perception of pain, although participants also reported short-term, adverse cognitive effects and increased fatigue. The study will be published in the Canadian Medical Association Journal on May 14.
Principal investigator Jody Corey-Bloom, MD, PhD, professor of neurosciences and director of the Multiple Sclerosis Center at UC San Diego, and colleagues randomly assigned participants to either the intervention group (which smoked cannabis once daily for three days) or the control group (which smoked identical placebo cigarettes, also once a day for three days). After an 11-day interval, the participants crossed over to the other group.
“We found that smoked cannabis was superior to placebo in reducing symptoms and pain in patients with treatment-resistant spasticity, or excessive muscle contractions,” said Corey-Bloom.
Earlier reports suggested that the active compounds of medical marijuana were potentially effective in treating neurologic conditions, but most studies focused on orally administered cannabinoids. There were also anecdotal reports of MS patients that endorsed smoking marijuana to relieve symptoms of spasticity.
However, this trial used a more objective measurement, a modified Ashford scale which graded the intensity of muscle tone by measuring such things as resistance in range of motion and rigidity. The secondary outcome, pain, was measured using a visual analogue scale. The researchers also looked at physical performance (using a timed walk) and cognitive function and – at the end of each visit – asked patients to assess their feeling of “highness.”
Although generally well tolerated, smoking cannabis did have mild effects on attention and concentration. The researchers noted that larger, long-terms studies are needed to confirm their findings and determine whether lower doses can result in beneficial effects with less cognitive impact.
The current study is the fifth clinical test of the possible efficacy of cannabis for clinical use reported by the University of California Center for Medicinal Cannabis Research (CMCR). Four other human studies on control of neuropathic pain also reported positive results.
“The study by Corey Bloom and her colleagues adds to a growing body of evidence that cannabis has therapeutic value for selected indications, and may be an adjunct or alternative for patients whose spasticity or pain is not optimally managed,” said Igor Grant, MD, director of the CMCR, which provided funding for the study.
Source : Newswise
Link to Source
Study: Could More Medical Pot Reduce Prescription Pill Deaths?
Physicians who prescribe opioid drugs to patients with neuropathy (nerve pain) ought to consider recommending cannabis as an alternative therapy, according to a peer-reviewed paper published online this week in the Harm Reduction Journal.
“There is sufficient evidence of safety and efficacy for the use of (cannabis/cannabinoids) in the treatment of nerve pain relative to opioids,” the commentary states. “In states where medicinal cannabis is legal, physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. … Prescribing cannabis in place of opioids for neuropathic pain may reduce the morbidity and mortality rates associated with prescription pain medications and may be an effective harm reduction strategy.”
The author notes that between the years 1999 and 2006, “approximately 65,000 people died from opioid analgesic overdose.” By contrast, he writes “[N]o one has ever died from an overdose of cannabis.”
In clinical trials, inhaled cannabis has been consistently shown to reduce neuropathic pain of diverse causes in subjects unresponsive to standard pain therapies.
In November, clinical investigators at the University of California, San Francisco reported that vaporized cannabis augments the analgesic effects of opiates in subjects prescribed morphine or oxycodone. Authors of the study surmised that cannabis-specific interventions “may allow for opioid treatment at lower doses with fewer [patient] side effects.”
Neuropathy affects between five percent and 10 percent of the US population. The condition is often unresponsive to conventional analgesic medications such as opiates and non-steroidal anti-inflammatory drugs.
Source : AlterNews (5 Jan 2012)
Link to Full Study "...Prescribing cannabis in place of opioids for neuropathic pain may reduce the
morbidity and mortality rates associated with prescription pain medications and may be an
effective harm reduction strategy."
Link to Source
Antioneoplastic Activity of Cannabinoids
Lewis lung adenocarcinoma growth was retarded by the oral administration of delta-9-tetrahydrocannabinol, delta-8-tetrahydrocannabinol, and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta-9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta-8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta-9-THC, delta-8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg;, respectively), whereas CBD did not. Delta-9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 X DBA/2) F (BDF) mice hosting the L1210 murine leukemia. However, delta-9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta-8-THC and delta-9-THC showed a dose-dependent (10 -4 10 -7) inhibition (80-20%, respectively) of tritiated thymidine and 14C -uridine uptake into these cells. CBD was active only in high concentrations (10 -4)
Source : UKCIA.org direct from Journal of the National Cancer Institute, Vol. 55, No. 3, September 1975
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