Sunday, 15 February 2015
The mechanism of action of cannabis
The mechanism of action of cannabis
The active ingredient of cannabis is ∆9-tetrahydrocannabinol (∆9-THC) and it is thought to exert its effect by binding to cannabinoid CB1 receptors on pre-synaptic nerve terminals in the brain. ∆9-THC binding to CB1 receptors activates G-proteins that activate/inhibit a number of signal transduction pathways. The G-proteins directly inhibit N and P/Q-type voltage dependant calcium channels and sodium channels and indirectly inhibit A-type calcium channels via inhibition of adenylate cyclase. ∆9-THC binding and G-protein activation also activates inwardly rectifying potassium channels and the MAP kinase signalling pathway. The cumulative effect of these pathways is the euphoric feelings associated with cannabis use.
Cannabis Helping Children with Severe Epilepsy
Cannabis Helping Children with Severe Epilepsy
Dravet syndrome is a severe myoclonic epilepsy whose onset occurs in infancy. Those with Dravet may have upwards of 100 seizures per day. The most intense episodes can last for 15 minutes to up to an hour. There is no known cure. The best available treatment is to minimize seizures, which are precipitated by environmental stress.
The longer a person has an epileptic attack, the higher the likelihood that prolonged damage could occur. Dravet seizures are so intense and long that brain development is delayed. In severe cases, a seizure may cause cardiac arrest. Each day can vary drastically for those with Dravet. There are a variety of pharmaceutical anticonvulsants available, but none of them eliminate seizures, and all have side effects.
Recently, a group of families affected by Dravet have turned to CBD-rich cannabis as a treatment for their children. These families have formed a Facebook group with close to 200 members that allows members to provide support, compare notes, and to share experiences. Some had initial reservations about using cannabis on their children, but were eager to try alternatives to conventional pharmaceuticals. The prospect of less- psychoactive cannabis piqued their interest, especially in light of the anticonvulsant and anti-inflammatory properties of CBD.
Suzie Engelhardt, mother of Regan (age 7), said that pharmaceutical medications left her daughter “like a zombie” and did not properly control seizures. Jason David, whose son Jayden is 5 and was featured on “Weed Wars”, reported that his son was having 100-300 myoclonic seizures per day despite taking 12 different pharmaceutical drugs. Rebecca Hamilton Brown’s son Cooper is 14 and has been using cannabis since last year. Brown describes her son as “highly functional” as a result, and explains, “parents of children with Dravet often get to a point of feeling scared and desperate… they tend to be open to alternatives.”
All of the families have reported improvement in their children’s health after using CBD cannabis. Cooper Brown is virtually seizure free since he has been using 3:1 CBD/THC oil capsules. His mother reports that his overall mood is much improved and his appetite has increased. Rebecca says that even though Cooper is not completely seizure free, the CBD cannabis regimen has “improved the frequency and severity of [his] seizures”.
After experimenting with different strains and CBD ratios, Regan Engelhardt’s daily seizure frequency fell from 50 seizures per night down to five. Before cannabis, her seizures dramatically altered her ability to walk, sleep, eat, or drink (she had been hospitalized for dehydration as a result). According to her mother, the pharmaceutical medications delayed her ability to walk until the age of 2 and left her “catatonic.” Currently, Regan’s cannabis medicine has allowed her to be weaned off one pharmaceutical medication, has increased focus, and is able to sleep through the night. “You see so much more light back in her eyes” her mother Suzie says. “Just a couple of weeks ago I wondered if she would ever come back.”
Jayden David has made vast improvements as well. His father reports that his walking is better (Jayden was previously non-ambulatory). He can now swim, an activity he adores, without having a seizure. Jason says that Jayden’s eye contact is “100 times better” and his “comprehension has greatly increased”.
All of the families interviewed have been using CBD strains with varying ratios and forms. Each has had to use trial and error to find what is most beneficial for their child. Jason David says that he “has to play doctor” for his son by experimenting with countless CBD/THC ratios for Jayden, finally settling on a CBD glycerin tincture. It has been a constant struggle to pin down the right strain and keep a steady supply for his son, despite living in California.
Maintaining a reliable supply is invaluable to families. “You see results” says Suzie Engelhardt, “and you want to keep it that way.” All the families have faced similar challenges and have to cope with the ebb and flow of plant material for their child’s treatment.
All of the families interviewed live in medical cannabis states (California, Michigan, and Washington) with functioning analytical labs. The parents interviewed report that dispensaries’ supply of CBD medicine is problematic, if they carry CBD medicine at all. Suzie Engelhardt called over 100 dispensaries seeking plant material with above a 3:1 CBD/THC ratio, even having to resort to looking for CBD medicine on Craigslist!
None of the families have noted any criticism of their decision to use cannabis for their children. Rather, the public has been supportive and understand Dravet families simply want to do anything that will help affected children. As Brown puts it, “my kid is [virtually] seizure free, how can you argue with that?” Luckily these families have mutual support and the encouragement of the medical cannabis community. The next step is to ensure reliable access to CBD medicine.
Pharmacological actions of non-psychotropic cannabinoids
Pharmacological actions of non-psychotropic cannabinoids
Connecticut bill would allow medical marijuana use for ill children
Connecticut bill would allow medical marijuana use for ill children
Cyndimae Meehan, 12 years old, was suffering as many as 2,000 seizures a day from a severe form of epilepsy known as Dravet’s syndrome.
The condition, which she developed at 10 months old (one day after she had been vaccinated, though the connection is unknown) jerks her body violently, over and over. The only thing that has helped has been marijuana, which she consumes in oil form.
The youngest of four children, Cyndimae and her mother, Susan Meehan, moved to Maine to take advantage of that state’s medical marijuana program, which, unlike Connecticut’s, allows patients under 18 to use cannabis.
For Meehan, it’s an important issue for the many children with severe epileptic disorders, many of whom don’t live to adulthood.
Meehan has asked her state legislator, state Rep. Kevin Ryan, D-Montville, to propose a bill that would give children under 18 access to prescribed medical marijuana. His proposed House Bill 5892 is titled “An Act Concerning the Palliative Use of Marijuana for Children.”
“I’m trying to be supportive with her and the needs of her child,” Ryan said, but he said he was unsure about the fate of the bill, which would have to go through a hearing in the Public Health Committee.
Meehan said state Sen. Joseph Crisco, D-Woodbridge, vice chairman of the committee, also has expressed support. Crisco could not be reached.
Cyndimae’s journey has been long and torturous. She had tried 23 anti-epileptic drugs, some of which had severe side effects, Meehan said, leaving the girl “near comatose at times.” A special anti-epileptic diet — high in fats, low in carbohydrates — worked well but only for a couple of years. She then had a vagal-nerve stimulator implanted, which reduced the number of seizures she endured by 90 percent — still not enough to allow Cyndimae to live a normal life.
By the end of 2013, “she was just losing ground,” Meehan said. She could barely eat or walk. “We were losing her fast,” she said.
So Meehan moved with her daughter to Dixfield, Maine, leaving her husband and three older children at their home in the Oakdale section of Montville. Her husband is a firefighter/EMT in Rhode Island. Susan was a cultural educator for the Mohegan tribe, of which the Meehans are members.
In Maine, a state that Meehan said has been “attracting refugee families” seeking medical marijuana, Cyndimae and her mother live with a medical marijuana caregiver, who is allowed to grow cannabis plants under state law. Meehan grows the plants for her daughter and, using 190-proof alcohol, which draws the oil out of the plant, creates tinctures high in a cannabinoid called THC-A. It’s then diluted in coconut oil, which Cyndimae drinks.
That forms Cyndimae’s maintenance dose, but at times she also needs a “rescue formulation” of “very potent active THC,” which is applied directly to her gum line or rectally. “It’s unbelievable,” Meehan said. The seizure “stops within 15 to 20 seconds. It’s pretty phenomenal.”
“She still has some seizures,” Meehan said, but went from Jan. 21 to Feb. 7 “with absolutely no seizures, which was a huge run for her.”
Meehan said she’s also fighting to allow medical marijuana in hospitals, where it is not allowed.
When Connecticut passed its medical marijuana program in 2012, Meehan said she was “ecstatic” until she saw the 18-year-old age limitation, which left her “devastated … crushed.” Epilepsy is one of 11 conditions for which prescribed marijuana is allowed in the state.
Meehan says getting the age limit changed in Connecticut is “my first big future accomplishment.” She also wants expansion of the four-plant limit that registered medical marijuana patients may grow in this state without penalty.
“I’m very hopeful that they’ll see the common sense of allowing pediatric patients to use it,” she said of legislators in Connecticut, which she said is one of just a few states with such an age restriction.
Meehan said having cannabis available to treat severe illnesses like Cyndimae’s is important for afflicted children, many of whom “will never live to see adulthood. … We’ve had more friends lose their children waiting for legalized marijuana in other states.”
As for Cyndimae, “I don’t think [she] would be alive right now,” if it wasn’t for marijuana.
Cyndimae’s doctor, Dustin Sulak of Falmouth, Maine, said she has thrived on cannabis and is “an incredible case for a lot of reasons: How she’s developed since she’s stopped seizing … It’s like an explosion of health bursting out of her.”
She’s grown by several inches and developed in other ways as well. “Now she’s coloring, painting inside the lines,” which wasn’t possible for her before, he said.
“There’s very little human research” of medical marijuana’s efficacy “and even less on children,” Sulak said. “In my practice right now, I have about 40 cases and we’re having good results with about half of them,” Sulak said. All 40 “have failed conventional seizure treatments.”
The other unusual factor in Cyndimae’s treatment is that she is not using CBD, the chemical in marijuana “which is what all the news buzz is about. A lot of the stories out of Colorado have demonized THC and glorified CBD.” But Cyndimae’s case shows medicine should be “looking for medicine in the whole plant.”
The raw form of THC-A that Cyndimae uses is “non-psychoactive so it doesn’t get her stoned at all,” he said. But there’s still a “very minimal understanding of how it works,” he said.
The Dravet Syndrome Foundation, which is based in West Haven, has only issued a position paper on CBD, calling for more research, not on THC.
The pediatric community has been cautious about medical marijuana. The American Academy of Pediatrics recently issued a policy saying it should only be used when there is no other treatment option and only for severely ill children.
However, the AAP recommended taking marijuana off the federal Schedule 1 list of narcotics so that it can be studied more easily.
Cyndimae has been “one of the best examples of success,” Sulak said, “because she’s also been able to stop several of the medications” she’s used, relying now only on cannabis.
He said those on CBD “start reporting things like better cognition, better alertness,” which is the “opposite of other seizure medicines,” Sulak said. “The other thing is there’s simply nothing else to try.”
How Banks Are Transforming Canada's Cannabis Industry
How Banks Are Transforming Canada's Cannabis Industry
(NPR News)
Marijuana is now legal in one form or another in 23 U.S. states. But possessing and selling it is still a federal crime. That's one big reason the banking industry has largely ignored this emerging market. Steve Henn from NPR's Planet Money team wanted to explore what the business would look like without a banking boycott.
Marijuana is now legal in one form or another in 23 U.S. states. But possessing and selling it is still a federal crime. That's one big reason the banking industry has largely ignored this emerging market. Steve Henn from NPR's Planet Money team wanted to explore what the business would look like without a banking boycott.
STEVE HENN, BYLINE: A couple of weeks ago, I found myself in this tiny, little airplane. It was so small, my head hit the ceiling.
UNIDENTIFIED MAN: Good morning, folks. Welcome aboard. Sorry about the delay today. We're going to try to get deiced here just as quick as we can and get out of here.
HENN: I was on this plane because I was headed north to Canada. I was flying with Brendan Kennedy. Now, imagine if Alex P. Keaton woke up one morning and decided that he was going to devote the rest of his life to creating a marijuana industry. That is Kennedy. He's a Yale School of Management grad who runs a private equity company that's devoted to buying and building marijuana businesses. And together we were headed north to see his latest project in Nanaimo, British Columbia. He says Nanaimo is a pot producer's paradise.
BRENDAN KENNEDY: Amazing. You know, one of the reasons we picked it was because of the support of the local community, the local city council, the local mayor and the local chamber of commerce. They have a group here called the Nanaimo Economic Development Corporation.
HENN: Nanaimo has just about 80,000 people. Its economy was dominated by lumber and fishing, but recently it created a special zoned area for marijuana businesses. The biggest draw, though, is that medical marijuana is completely legal here in Canada, and Kennedy is building his business with the help of the banking industry.
KENNEDY: I've been to cannabis grows around the world, and most of them have a safe in their building. And if you go to, you know - I've been to the dispensaries in California where there is a million dollars in a room, and that's really uncomfortable. You know, we don't have any of those problems in Canada.
HENN: Unlike marijuana businesses in the U.S., Kennedy has a bank account and he can accept credit cards. But that is just the beginning of how banking has transformed this industry here. Kennedy and his competitors can also borrow millions. And as we pull up to his project, you can see what that means.
KENNEDY: This is the main production facility here. Canadian flag - there's a 10-foot barbed wire fence.
HENN: To me, Kennedy's $25 million grow house looks a lot like a Silicon Valley server farm. It's this huge, nondescript building, basically a warehouse, that's sucking down enormous amounts of electricity.
KENNEDY: This is a transformer that, you know, could power a small neighborhood.
HENN: Inside there are more than a hundred workers. Most of them are wearing color-coded, sterile bunny suits, and they're scurrying from room to room. The smell is intense.
Holy cow. Wow.
KENNEDY: So this is...
HENN: (Laughter).
KENNEDY: ...This is a room that's about a week away from harvest.
HENN: This room is, like, 50-feet deep and 40-feet long. The light is just - it's really pretty blinding.
KENNEDY: You're right. It's bright. Our lighting engineers will tell you that this room is about 15 percent brighter than the equator at noon.
HENN: The value of the cannabis crop in this room alone is probably worth more than $100,000. And there are dozens of other rooms like this. With the help of banks and lending companies, Kennedy was able to build all of this in less than a year.
Now, to see what the marijuana industry looks like without modern banking, all you have to do is travel a couple dozen miles south, back into the U.S. Nate Loving sells weed in a legal retail shop in Washington. He says doing business without a bank is a hassle.
NATE LOVING: I've got to go get a money order for $130 for papers.
HENN: Buying inventory is an all-cash deal.
LOVING: A producer-processor brings an order. We're going to count the cash out, and then they got to leave here with a bunch of 20s. I'd like to be able to cut them a check.
HENN: And forget about small business loans. Loving raised the cash for his shop by scraping together $90,000 from friends and family. Just to the north, Kennedy's negotiating a $100,000 million loan with investment banks. He's planning to open another grow house next to his first. This one will be five to six times larger than the one he has now. Steve Henn, NPR News.
Consuming Alcohol Poses a Much Larger Risk for Driving Accidents Than Cannabis
Consuming Alcohol Poses a Much Larger Risk for Driving Accidents Than Cannabis
Drivers who test positive for the presence of THC in blood are no more likely to be involved in motor vehicle crashes than are drug-free drivers, according to a federally sponsored case-control study involving some 9,000 participants. The study, published Friday by the United States National Highway Traffic Administration (NHTSA), is the first large-scale case-control study ever conducted in the United States to assess the crash risk associated with both drugs and alcohol use by drivers.
Drivers who test positive for the presence of THC in blood are no more likely to be involved in motor vehicle crashes than are drug-free drivers, according to a federally sponsored case-control study involving some 9,000 participants. The study, published Friday by the United States National Highway Traffic Administration (NHTSA), is the first large-scale case-control study ever conducted in the United States to assess the crash risk associated with both drugs and alcohol use by drivers.
Authors reported that drivers who tested positive for any amount of THC possessed an unadjusted, elevated risk of accident of 25 percent (Odds Ratio=1.25) compared to controls (drivers who tested negative for any drug or alcohol). However, this elevated risk became insignificant (OR=1.05) after investigators adjusted for demographic variables, such as the drivers’ age and gender. After researchers controlled for both demographic variables and the presence of alcohol, THC-positive drivers’ elevated risk of accident was zero (OR=1).
By contrast, researchers reported that drivers who tested positive for low levels of alcohol possessed a statistically significant risk of accident, even after controlling for demographic variables (e.g., Drivers with a BAC of 0.03 possessed a 20 percent greater risk of motor vehicle accident [OR=1.20] compared to controls). Drivers with BAC levels of 0.05 possessed a greater than two-fold risk of accident (OR=2.07) while motorists with BAC levels of 0.08 possessed a nearly four-fold risk of accident (OR=3.93).
Marijuana-based medicine to be trialled in Scotland
Marijuana-based medicine to be trialled in Scotland
A new treatment derived from cannabis is to go on trial in Scotland in a bid to help sick children.
Doctors have been given the go-ahead to test Epidiolex, a treatment based on cannabidiol (CBD) a non-psychoactive compound found in the cannabis plant.
And medical experts are hoping the treatment – which has had success in studies on the treatment of epilepsy in the US – will help Scottish children whose seizures cannot be controlled with existing medications.
‘Many children with serious forms of epilepsy do not respond to the medications that we currently have available,’ said Dr Richard Chin, director of the Muir Maxwell Epilepsy Centre.
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