Medical Marijuana Approved By Sweden

Medicinal cannabis would now be available as a prescription in Sweden after Sativex, a cannabis-based mouth spray, was approved by the Medical Products Agency for the treatment of multiple sclerosis (MS).

“This is great news for those who can’t get any relief from the most common drugs,” Jan Hillert, an MS researcher at Karolinska Institute and said the institute is planning to closely monitor prescriptions for Sativex to ensure against abuse.

The cannabis-based mouth spray does not result in a “high” as the cannabinoids included — a near 1:1 mix of tetrahydrocannabinol (THC) and cannabidiol (CBD) — are not administered in large enough doses, according to both the agency and Sativex manufacturer GW Pharmaceuticals, which grows medicinal cannabis and prepares the extract in Britain.

Sativex spray is used sublingually (under the tongue), has been shown by a series of medical studies to be successful for alleviating multiple sclerosis (MS) symptoms.
“Evidence generated from clinical trials shows that Sativex® has a positive impact on spasticity in multiple sclerosis, while alleviating associated symptoms including pain, bladder or sleep disturbance,” GW Pharmaceuticals said in a press release. “By relieving the symptoms of MS, Sativex® can improve patients’ quality of life and allow them greater independence in performing their daily activities.”

The cannabis spray is already available as a prescription medication in the United Kingdom, Germany, Spain, Denmark, Canada and New Zealand, according to GW.

THC May Block Spread Of Cancer Forms Causing Herpes Viruses

According to a report by University of South Florida College of Medicine scientists, delta-9 tetrahydrocannabinol or THC may block the spread of several forms of cancer causing herpes viruses. The findings could lead to the creation of antiviral drugs based on THC nonpsychoactive derivatives.

The gamma herpes viruses include Kaposi’s Sarcoma Associated Herpes virus that is linked with an increased risk of cancer that is particularly prevalent in AIDS patients. Once an individual gets infected, the viruses could remain dormant for long periods within white blood cells before they burst out and begin replicating. This virus reactivation enhances the number of cells infected thereby increasing the chances that the cells will become cancerous.

Led by virologist Peter Medveczky, MD, the team found that this sudden reactivation was prevented if infected cells were grown in the presence of THC, the marijuana compound. It was revealed that cells infected with a mouse gamma herpes virus survive when cultured in the laboratory along with the cannabinoid compound – further evidence that THC prevents viral reactivation. It was also revealed that THC acts specifically on gamma herpes viruses and the chemical had no effect on herpes simplex-1, another related virus.
Dr. Medveczky, a professor in the Department of Medical Microbiology and Immunology, said that small THC concentrations were more potent and selective against gamma herpes viruses than the commonly used antiviral drugs acyclovir, gancicyclovir, and foscamet.
THC selectively inhibits the spread of gamma herpes viruses by targeting a gene these viruses all share called ORF50, the USF researchers suggested.

Dr. Medveczky emphasized that more studies are needed. “We have not evaluated the effect of THC in an animal model yet so we do not recommend people start using pot to prevent or treat cancers.”

In fact, Dr. Meveczky said, THC has also been shown to suppress the immune system so smoking marijuana could “do more harm than good” to patients whose immune systems are often already weakened.

Reference:
University of South Florida College of Medicine

Marijuana Reduces Memory Impairment

Scientists from the Ohio State University have found out that specific elements of marijuana could be good for the aging brain by minimizing inflammation there and possibly even stimulating the formation of new brain cells.

It was also suggested by the research that the development of a legal drug that includes specific properties similar to those in marijuana might help prevent or delay the onset of Alzheimer’s disease. Chronic inflammation in the brain is believed to contribute to memory impairment though the exact cause of Alzheimer’s disease remains unknown.

Properties of any new drug would resemble those of tetrahydrocannabinol, or THC, the main psychoactive substance in the cannabis plant, but would not share its high-producing effects.

“It’s not that everything immoral is good for the brain. It’s just that there are some substances that millions of people for thousands of years have used in billions of doses, and we’re noticing there’s a little signal above all the noise,” said Gary Wenk, professor of psychology at Ohio State and principal investigator on the research.

The most recent research on rats indicated that at least three receptors in the brain are activated by the synthetic drug, which is similar to marijuana. These receptors are proteins with the endocannabinoid system of the brain that is involved in memory as well as physiological processes associated with appetite, mood, and pain response.

“When we’re young, we reproduce neurons and our memory works fine. When we age, the process slows down, so we have a decrease in new cell formation in normal aging. You need those cells to come back and help form new memories, and we found that this THC-like agent can influence creation of those cells,” said Yannick Marchalant, a study coauthor and research assistant professor of psychology at Ohio State.

Marchalant described the research in a poster presentation recently at the Society for Neuroscience meeting in Washington, D.C.

“Could people smoke marijuana to prevent Alzheimer’s disease if the disease is in their family? We’re not saying that, but it might actually work. What we are saying is it appears that a safe, legal substance that mimics those important properties of marijuana can work on receptors in the brain to prevent memory impairments in aging. So that’s really hopeful,” Wenk said.

“The end goal is not to recommend the use of THC in humans to reduce Alzheimer’s,” Marchalant said. “We need to find exactly which receptors are most crucial, and ideally lead to the development of drugs that specifically activate those receptors. We hope a compound can be found that can target both inflammation and neurogenesis, which would be the most efficient way to produce the best effects.”

The research was supported by the National Institutes of Health and co-authors on the presentation are Holly Brothers and Lauren Burgess, both of Ohio State’s Department of Psychology.

Reference:
Ohio State University

Agitation In Alzheimer’s Patients Reduced By Synthetic Marijuana

A synthetic version of the active ingredient in marijuana, dronabinol, minimizes agitation in patients with Alzheimer’s disease according to results from a Phase II, multi-center study. It was also concluded by the researchers that minimized agitation could contribute to the relief of caregiver burden linked with the condition.

The findings were presented at the American Society of Consultant Pharmacists’ 34th annual meeting.

‘Our results show dronabinol is an effective treatment for behavioral agitation in patients with Alzheimer’s and may ultimately help reduce the stress often experienced by caregivers,’ said geriatrician Joel S. Ross, M.D. a member of the teaching faculty at Monmouth Medical Center and the lead investigator in the study.

‘While difficult for the patient, the effects of agitation can greatly impact the emotional and physical health of family members and caregivers. By reducing patients’ agitation, caregivers are able to focus more time and energy on their patients’ overall wellbeing.’

Agitation is the most common behavioral management problem in Alzheimer’s patients and could lead to a variety of symptoms ranging from physical and/or verbal abusive postures, physically non-aggressive conduct including pacing and restlessness.

Marketed as Marinol, Dronabinol is synthetic delta-9-tetrahydrocannabinol (delta-9-THC). Delta-9-THC also is a naturally occurring component of Cannabis sativa L (marijuana). The U.S. Food and Drug Administration (FDA) have approved Dronabinol for the treatment of anorexia in patients with HIV/AIDS and for the treatment of nausea and vomiting associated with cancer chemotherapy.

Reference:
1Zajicek, J. The Lancet, Nov. 8, 2003: vol 263;pp 1517-1526

Cannabinoids Treat Lung Cancer

According to a study, Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo.

The primary cannabinoid of marijuana, Δ9-Tetrahydrocannabinol (THC), has been shown to either inhibit or potentiate tumor growth, depending on the cancer type and its pathogenesis. Little is known about activity of cannabinoids such as THC on epidermal growth factor receptor-over expressing lung cancers that are often highly aggressive and resistant to chemotherapy.

In the study, the researchers characterized the effects of THC on the EGF-induced growth and metastasis of human non-small cell lung cancer using the cell lines A549 and SW-1573 as in vitro models. It was found that these cells express cannabinoid receptors CB1 and CB2, known targets for THC action. It was also found that THC inhibited EGF-induced growth, chemotaxis, and chemoinvasion. The signaling studies indicated that THC could act by inhibiting the EGF-induced phosphorylation of ERK1/2, JNK1/2 and AKT. The primary cannabinoid of marijuana was also responsible for inducing phosphorylation of focal adhesion kinase at tyrosine 397.

Additionally, there was significant inhibition of the subcutaneous tumor growth and lung metastasis of A549 cells in THC-treated animals as compared to vehicle-treated controls in vivo studies. Tumor samples from animals treated with THC revealed anti-proliferative and anti-angiogenic effects of THC.

The study suggested that cannabinoids such as THC must be explored as novel therapeutic molecules to control the growth and metastasis of certain lung cancers.

Reference:
Oncogene 10: 339-346

Marijuana The Reliever Of Pain

A team from Canada has found that three puffs of cannabis (also known as marijuana) a day could be helpful for people with chronic nerve pain because of surgery or injury to feel less pain and sleep better.

“It’s been known anecdotally,” says researcher Mark Ware, MD, assistant professor of anesthesia and family medicine at McGill University in Montreal. “About 10% to 15% of patients attending a chronic pain clinic use cannabis as part of their pain [control] strategy,” Ware remarked.

The study of Ware is more scientific in nature as it was a clinical trial in which his team compared placebo with three different cannabis doses. The study “adds to the trickle of evidence that cannabis may help some of the patients who are struggling [with pain] at present,” Henry McQuay, DM, an emeritus fellow at Balliol College, Oxford University, England, writes in a commentary accompanying the study.

Twenty-one men and women, with an average age of 45 years, were evaluated by Ware and his team. All of the 21 people had chronic nerve pain (or neuropathic pain). Three different potencies of marijuana were tried by the team of Ware and the highest of all concentrations was at 9.4% tetrahydrocannabinol (THC) herbal cannabis, the other two being 2.5% and 6% THC.

“Each person was in the study for two months, and used all four strengths [including placebo],” Ware says.

The participants were allowed to continue on their routine pain medications and all took a single puff of marijuana three times a day for five days for each of the doses and the placebo. Participants rated their pain on a scale of zero to 10, with 10 being the worst after each of the five-day trials.

Ware said the highest dose (9.4%) offered relief and reduced their pain down to 5.4, compared to 6.1 from placebo. “We’ve shown again that cannabis is analgesic,” Ware says. “Clearly, it has medical value.”

The research is published in CMAJ, the Canadian Medical Association Journal.

How Marijuana Works?

As soon as a user of marijuana smokes a cigarette filled with it or ingest marijuana in any other form, THC (Tetrahydrocannabinol, the primary ingredient of marijuana) and other chemicals make an entry into their body. Both THC and chemicals make their way into the human body through the bloodstream and then move to the brain and thereafter the remaining of the body.

When marijuana smoke is inhaled, THC goes directly to the lungs that lined with tiny air sacs (alveoli) where exchange of gases takes place. These air sacs have a significant surface area, which is about 90 times greater than of the human skin, which makes it easy for marijuana ingredients to enter the human body after the smoke of marijuana is absorbed by the lungs in a matter of just few seconds.

When eaten, marijuana enters the human body to find its place in the stomach where it is absorbed by blood. Thereafter, marijuana is carried by the blood to the liver and the remaining body. It is important to note here that THC is slowly absorbed by the stomach when compared to the lungs and therefore the THC levels are lower and effects last longer when marijuana is eaten.

Medical Marijuana And Pruritus

Pruritus or itching is a common symptom associated with many skin diseases, and is also considered as a secondary symptom of numerous serious complications like liver disease and renal failure. Unlike other skin sensations, pruritus is usually a result of CNS activities and typically goes untreated by standard medical therapies.

A review of the scientific literature revealed three clinical trials investigating the use of cannabinoids in the treatment of pruritus. Investigators from the University Of Miami Department Of Medicine, writing in the August 2002 issue of the American Journal of Gastroentrology, reported successful treatment of pruritus with 5 mg of THC in three patients with cholestatic liver disease. Subjects had failed to respond to standard medications prior to cannabinoid therapy and had lost their ability to work. Following evening cannabinoid administration, all three patients reported a decrease in pruritus and “marked improvement” in sleep and were eventually able to return to work. It was also found that the resolution of depression was also reported in two out of three subjects. “Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus,” investigators concluded.

In 2003, British researchers reported in the issue of the journal Inflammation Research that the peripheral administration of the synthetic cannabinoid agonist HU-211 significantly minimized experimentally-induced itch in 12 subjects.

Most recently, researchers at Wroclaw, Poland’s University of Medicine, Department of Dermatology, reported that the application of an endocannabinoid-based topical cream minimized remic pruritus and xerosis (abnormal dryness of the skin) in hemodialysis patients. Three weeks of twice-daily application of this cream “completely eliminated” pruritus in 38 percent of trial subjects and “significantly reduced” itching in others.

Some dermatology experts, in light of these encouraging preliminary results, now believe that cannabinoids and the cannabinoid system may represent “promising new avenues for managing itch more effectively.”

References:
[1] Neff et al. 2002. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. American Journal of Gastroenterology 97: 2117-2119.
[2] Dvorak et al. 2003. Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin (PDF). Inflammation Research 25: 238-245.
[3] Dvorak et al. 2003. Cannabinoid agonists attenuate capsaicin-induced responses in human skin. Pain 102: 283-288.
[4] Szepietowski et al. 2005. Efficacy and tolerance of the cream containing structured physiological lipid endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerologic Croatica (Croatia) 13: 97-103.
[5] Paus et al. 2006. Frontiers in pruritus research: scratching the brain for more effective itch therapy. Journal of Clinical Investigation 116: 1174-1185.

Cannabinoids Effective In Treating Parkinson’s Disease

Researchers have found that Delta9-tetrahydrocannabinol and cannabidiol (CBD), two plant-derived cannabinoids, are neuroprotective in an animal model of Parkinson’s disease (PD), presumably because of their antioxidant properties.

The neuroprotective effects of a series of cannabinoid-based compounds with more selectivity for different elements of the cannabinoid signaling system in rats with unilateral lesions of nigrostriatal dopaminergic neurons caused by local application of 6-hydroxydopamine were evaluated for the research purposes.

The CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA), the CB2 receptor agonist HU-308, the non-selective agonist WIN55, 212-2, and the inhibitors of the endocannabinoid inactivation AM404 and UCM707 were used and all of them administered i.p. Daily administration of ACEA or WIN55, 212-2 did not reverse 6-hydroxydopamine-induced dopamine (DA) depletion in the lesioned side, whereas HU-308 produced a minor recovery supporting a likely involvement of CB2 but not CB1 receptors.

AM404 produced a significant recovery of 6-hydroxydopamine-induced DA depletion and tyrosine hydroxylase deficit in the lesioned side, possibly caused by the antioxidant properties of AM404. The AM404 properties are derived from the presence of a phenolic group in its structure, rather than by the capability of AM404 to block the endocannabinoid transporter as another transporter inhibitor devoid of antioxidant properties, UCM707, did not produce the same effect.

The researchers also evaluated the timing for the effect of CBD in offering 6-hydroxydopamine-induced DA depletion when it was administered immediately after the lesion. However, it failed to do that when treatment was initiated a week later. Moreover, the effect of CBD implied an upregulation of mRNA levels for Cu, Zn-superoxide dismutase, a key enzyme in endogenous defenses against oxidative stress.

In short, the results indicate that those cannabinoids having antioxidant cannabinoid receptor-independent properties offer neuroprotection against the progressive degeneration of nigrostriatal dopaminergic neurons occurring in PD. Furthermore, the activation of CB2 (but not CB1) receptors, or other additional mechanisms, may also contribute to some extent to the potential of cannabinoids in Parkinson’s disease.

The study was conducted by García-Arencibia M, González S, de Lago E, Ramos JA, Mechoulam R, Fernández-Ruiz J. from Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, 28040-Madrid, Spain.

Reference:
Brain Res., 2007 Feb 23;1134(1):162-70

Neurons may be guarded by marijuana

A marijuana chemical could protect against brain damage from a stroke, according to a report in Proceedings of the National Academy of Sciences. Cannabidiol, the compound, in the test tube sops up damaging oxygen-free radicals more effectively than vitamins C and E, two of the most powerful known dietary antioxidants.

It is widely known that marijuana and its psychoactive component tetrahydrocannabinol (THC) inhibit the activity of certain brain regions. Aidan Hampson, working jointly with colleagues at the National Institute of Mental Health and elsewhere, set out for testing whether the inhibitory effects of THC might also prevent the toxic overstimulation of brain cells that results when the brain cells become starved for oxygen and sugar, and are then unable to pump out the neurotransmitter glutamate.

A stroke was simulated by researchers via bathing a petri dish full of neurons in the neurotransmitter glutamate that is toxic at high doses. Half as many neurons died when purified THC was added. It was first assumed by the researchers that THC was binding to the cannabinoid receptor but they found that THC still protected the cells when they added another chemical that blocks the receptor. “It shouldn’t have protected the neurons, but it worked just as well,” Hampson says.

THC was mopping up free radicals, such as hydrogen peroxide, that are spewed out by over-stimulated neurons, a fact that was noticed after further testing. It was also revealed that cannabidiol, a marijuana component similar to THC but lacking its psychoactive effects, provided the same antioxidant benefits.

Reference:
Proceedings of the National Academy of Sciences