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Member since: 2002
Number of posts: 27,075
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Cannabis was used to illustrate 4 features of synergistic plant medical action not obtained by isolating and synthetically reproducing a naturally-occurring multi-molecular interaction. There are over a hundred different cannabinoids in the cannabis plant - which were discovered before we knew we had an endocannabinoid regulatory system in the human body. Some plants other than cannabis do act upon endocannabinoids, however.
At present, the only phytocannabinoid that has been discovered to also exist in plants other than Cannabis is β-caryophyllene, which is among the most abundant plant essential oil components.
...‘This type of synergism may play a role in the widely held (but not experimentally based) view that in some cases plants are better drugs than the natural products isolated from them’. Support derives from studies in which cannabis extracts demonstrated effects two to four times greater than THC (Carlini et al., 1974); unidentified THC antagonists and synergists were claimed (Fairbairn and Pickens, 1981), anticonvulsant activity was observed beyond the cannabinoid fraction (Wilkinson et al., 2003), and extracts of THC and CBD modulated effects in hippocampal neurones distinctly from pure compounds (Ryan et al., 2006). Older literature also presented refutations: no observed differences were noted by humans ingesting or smoking pure THC versus herbal cannabis (Wachtel et al., 2002); pure THC seemed to account for all tetrad-type effects in mice (Varvel et al., 2005); and smoked cannabis with varying CBD or CBC content failed to yield subjective differences combined with THC (Ilan et al., 2005). Explanations include that the cannabis employed by Wachtel yielded 2.11% THC, but with only 0.3% cannabinol (CBN) and 0.05% CBD (Russo and McPartland, 2003), and Ilan's admission that CBN and CBD content might be too low to modulate THC. Another factor is apparent in that terpenoid yields from vaporization of street cannabis were 4.3–8.5 times of those from US National Institute on Drug Abuse cannabis (Bloor et al., 2008). It is undisputed that the black market cannabis in the UK (Potter et al., 2008), Continental Europe (King et al., 2005) and the USA (Mehmedic et al., 2010) has become almost exclusively a high-THC preparation to the almost total exclusion of other phytocannabinoids. If – as many consumers and experts maintain (Clarke, 2010) – there are biochemical, pharmacological and phenomenological distinctions between available cannabis ‘strains’, such phenomena are most likely related to relative terpenoid contents and ratios. This treatise will assess additional evidence for putative synergistic phytocannabinoid-terpenoid effects exclusive of THC, to ascertain whether this botanical may fulfil its promise as, ‘a neglected pharmacological treasure trove’ (Mechoulam, 2005).
...Phytocannabinoids are exclusively produced in cannabis (vide infra for exception), but their evolutionary and ecological raisons d'ętre were obscure until recently. THC production is maximized with increased light energy (Potter, 2009). It has been known for some time that CBG and CBC are mildly antifungal (ElSohly et al., 1982), as are THC and CBD against a cannabis pathogen (McPartland, 1984). More pertinent, however, is the mechanical stickiness of the trichomes, capable of trapping insects with all six legs (Potter, 2009). Tetrahydrocannabinolic acid (THCA) and cannabichromenic acid (Morimoto et al., 2007), as well as cannabidiolic acid and cannabigerolic acid (CBGA; Shoyama et al., 2008) produce necrosis in plant cells. Normally, the cannabinoid acids are sequestered in trichomes away from the flower tissues. Any trichome breakage at senescence may contribute to natural pruning of lower fan leaves that otherwise utilize energy that the plant preferentially diverts to the flower, in continued efforts to affect fertilization, generally in vain when subject to human horticulture for pharmaceutical production. THCA and CBGA have also proven to be insecticidal in their own right (Sirikantaramas et al., 2005).
THC (Table 1) is the most common phytocannabinoid in cannabis drug chemotypes, and is produced in the plant via an allele co-dominant with CBD (de Meijer et al., 2003). THC is a partial agonist at CB1 and cannabinoid receptor 2 (CB2) analogous to AEA, and underlying many of its activities as a psychoactive agent, analgesic, muscle relaxant and antispasmodic (Pacher et al., 2006). Additionally, it is a bronchodilator (Williams et al., 1976), neuroprotective antioxidant (Hampson et al., 1998), antipruritic agent in cholestatic jaundice (Neff et al., 2002) and has 20 times the anti-inflammatory power of aspirin and twice that of hydrocortisone (Evans, 1991). THC is likely to avoid potential pitfalls of either COX-1 or COX-2 inhibition, as such activity is only noted at concentrations far above those attained therapeutically (Stott et al., 2005).
CBD is the most common phytocannabinoid in fibre (hemp) plants, and second most prevalent in some drug chemotypes. It has proven extremely versatile pharmacologically (Table 1) (Pertwee, 2004; Mechoulam et al., 2007), displaying the unusual ability to antagonize CB1 at a low nM level in the presence of THC, despite having little binding affinity (Thomas et al., 2007), and supporting its modulatory effect on THC-associated adverse events such as anxiety, tachycardia, hunger and sedation in rats and humans (Nicholson et al., 2004; Murillo-Rodriguez et al., 2006; Russo and Guy, 2006). CBD is an analgesic (Costa et al., 2007), is a neuroprotective antioxidant more potent than ascorbate or tocopherol (Hampson et al., 1998), without COX inhibition (Stott et al., 2005), acts as a TRPV1 agonist analogous to capsaicin but without noxious effect (Bisogno et al., 2001), while also inhibiting uptake of AEA and weakly inhibiting its hydrolysis. CBD is an antagonist on GPR55, and also on GPR18, possibly supporting a therapeutic role in disorders of cell migration, notably endometriosis (McHugh et al., 2010). CBD is anticonvulsant (Carlini and Cunha, 1981; Jones et al., 2010), anti-nausea (Parker et al., 2002), cytotoxic in breast cancer (Ligresti et al., 2006) and many other cell lines while being cyto-preservative for normal cells (Parolaro and Massi, 2008), antagonizes tumour necrosis factor-alpha (TNF-α in a rodent model of rheumatoid arthritis (Malfait et al., 2000), enhances adenosine receptor A2A signalling via inhibition of an adenosine transporter (Carrier et al., 2006), and prevents prion accumulation and neuronal toxicity (Dirikoc et al., 2007). A CBD extract showed greater anti-hyperalgesia over pure compound in a rat model with decreased allodynia, improved thermal perception and nerve growth factor levels and decreased oxidative damage (Comelli et al., 2009). CBD also displayed powerful activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 0.5–2 µg·mL−1 (Appendino et al., 2008). In 2005, it was demonstrated that CBD has agonistic activity at 5-hydroxytryptamine (5-HT)1A at 16 µM (Russo et al., 2005), and that despite the high concentration, may underlie its anti-anxiety activity (Resstel et al., 2009; Soares Vde et al., 2010), reduction of stroke risk (Mishima et al., 2005), anti-nausea effects (Rock et al., 2009) and ability to affect improvement in cognition in a mouse model of hepatic encephalopathy (Magen et al., 2009). A recent study has demonstrated that CBD 30 mg·kg−1 i.p. reduced immobility time in the forced swim test compared to imipramine (P < 0.01), an effect blocked by pre-treatment with the 5-HT1A antagonist WAY100635 (Zanelati et al., 2010), supporting a prospective role for CBD as an antidepressant. CBD also inhibits synthesis of lipids in sebocytes, and produces apoptosis at higher doses in a model of acne (vide infra). One example of CBD antagonism to THC would be the recent observation of lymphopenia in rats (CBD 5 mg·kg−1) mediated by possible CB2 inverse agonism (Ignatowska-Jankowska et al., 2009), an effect not reported in humans even at doses of pure CBD up to 800 mg (Crippa et al., 2010), possibly due to marked interspecies differences in CB2 sequences and signal transduction. CBD proved to be a critical factor in the ability of nabiximols oromucosal extract in successfully treating intractable cancer pain patients unresponsive to opioids (30% reduction in pain from baseline), as a high-THC extract devoid of CBD failed to distinguish from placebo (Johnson et al., 2010). This may represent true synergy if the THC–CBD combination were shown to provide a larger effect than a summation of those from the compounds separately (Berenbaum, 1989).
Posted by RainDog | Wed Mar 12, 2014, 01:21 AM (0 replies)
A panel at the recent CPAC convention turned into an argument for legalization. So, the left and the right are in agreement that marijuana laws need to change. Are Republicans ignoring the will of their base?
All the more reason for Democrats to make this an issue on state ballots in 2014, imo.
In recent years, American public opinion has shifted rapidly in favor of legalizing marijuana. The percentage of adults who support it has gone from 12 percent in 1969 to 58 percent as of last fall, according to Gallup; in the past decade alone, support for legalization has increased by 24 percentage points. The shift has powered a wave of political victories for marijuana advocates, from the 20 states where medical marijuana is now legal to the unprecedented ballot measures legalizing the drug in Colorado and Washington in 2012. Three more states expect to put pot to a popular vote this year, with referenda on medical marijuana in Florida and full legalization in Oregon and Alaska.
What opposition remains is concentrated among Republicans. According to Gallup, only about a third of Democrats and independents now oppose legalization, compared to nearly two-thirds of Republicans. Opponents of legalization are also disproportionately elderly. The situation closely parallels the party's predicament on gay marriage, which most Republicans still oppose even as widening majorities of the broader public support it.
It adds up to a quandary for the GOP: Should it embrace the unpopular position still disproportionately favored by its members and risk marginalization as a result? Or will the burgeoning conservative voices in favor of legalization win out? Simply put, do Republicans want to be on the losing side of yet another culture war?
...The tide, (Beach, producer for Morning in America) believes, could still turn back against legalization—if the opponents' dark predictions come true and states like Colorado and Washington experience serious consequences from their embrace of marijuana. "The beauty of America is that the states can experiment with this and we will see what happens," Beach said. "But I am afraid of the effects it's going to have on society."
Yes. So far it's caused 37 fake deaths, cited by a police chief more than a month after the hoax was revealed, CNN correspondents giggling on air, sales of Girl Scout Cookies,1 million to Colorado tax coffers, and the exodus of families from Texas, New Jersey, Utah, Florida, South Carolina, Virginia, New York, and other states without legal marijuana laws to seek help for family members who might benefit from cannabis oil for various medical conditions.
Posted by RainDog | Fri Mar 7, 2014, 05:42 PM (3 replies)
The Washington D.C. city council just voted to decriminalize according to MPP.
Posted by RainDog | Tue Mar 4, 2014, 03:13 PM (7 replies)
...and members of the BLO (Barbie Liberation Front!)
Posted by RainDog | Mon Mar 3, 2014, 09:08 PM (3 replies)
The National Black Caucus of State Legs. represents more than 650 legislators from 45 states.
Members of the National Black Caucus of State Legislators recently resolved at their Annual Legislative Conference in favor of decriminalizing marijuana.
“Whereas state and local governments could potentially stand to save billions of dollars that they currently spend regulating marijuana use by decriminalizing the recreational use of marijuana, therefore be it resolved that the National Black Caucus of State Legislators recognizes the decision of the Administration to not challenge the choice made by citizens of these states, and urges the continued respect of state law, and encourages other states to consider decriminalization,” the Caucus resolved.
It added, “ NBCSL supports the states’ authority to make a determination as to what age, at or above 18, qualifies as a “legal adult” who may purchase, possess, or consume marijuana … urges the federal government to reduce the penalties associated with the use and simple possession of marijuana.”
The 2014 resolution is LJE-14-40: Supporting States’ Rights to Decriminalize Marijuana Use.
Posted by RainDog | Sun Mar 2, 2014, 07:58 AM (0 replies)
Their proposal is a lot like CO's.
Alaska voters will decide this summer whether America's Last Frontier will become the third U.S. state to legalize the sale and recreational use of marijuana for adults under a proposal that officially qualified on Wednesday for a statewide ballot.
Alaska Lieutenant Governor Mead Treadwell formally certified that a petition campaign for the measure had gathered more than 36,000 valid signatures from registered voters, nearly 6,000 more than legally required to qualify.
The marijuana initiative, and a separate measure to raise the state's minimum wage by $2 an hour to $9.75 by January 2016, will be placed on the state's primary election ballot on August 17.
Passage of the marijuana initiative would permit adults 21 and older to possess up to one ounce (28 grams) of marijuana for private personal use and to grow as many as six cannabis plants for their own consumption.
Posted by RainDog | Fri Feb 28, 2014, 06:34 PM (0 replies)
Published on: Thu, Feb 20 2014 by Philip M. Gattone, President & CEO, Epilepsy Foundation, and Warren Lammert, Chair, Epilepsy Foundation Board of Directors, with Commentary from Orrin Devinsky, M.D., Professor of Neurology, Neurosurgery and Psychiatry, Director, NYU Comprehensive Epilepsy Center Member of Epilepsy Foundation National Board of Directors
As parents and as advocates, we feel an urgency to respond and take action on an issue that has been brought to the Epilepsy Foundation from individuals we serve across the country-- the use of marijuana to treat epilepsy. We write this with advice and support from Nathan Fountain, Chairman of our Professional Advisory Board, and with advice and support from a range of other leading epilepsy professionals and board members.
2.3 million Americans live with epilepsy, a neurological condition that includes recurring seizures. More than 1 million of them live with uncontrolled seizures. Some of these people may be helped by surgery or other non-drug treatments, but for many, no answers have been found yet. People with uncontrolled seizures live with the continual risk of serious injuries and loss of life.
The Epilepsy Foundation supports the rights of patients and families living with seizures and epilepsy to access physician directed care, including medical marijuana. Nothing should stand in the way of patients gaining access to potentially life-saving treatment. If a patient and their healthcare professionals feel that the potential benefits of medical marijuana for uncontrolled epilepsy outweigh the risks, then families need to have that legal option now -- not in five years or ten years. For people living with severe uncontrolled epilepsy, time is not on their side. This is a very important, difficult, and personal decision that should be made by a patient and family working with their healthcare team.
The Epilepsy Foundation calls for an end to Drug Enforcement Administration (DEA) restrictions that limit clinical trials and research into medical marijuana for epilepsy. We applaud recent decisions that have allowed clinical trials of Cannabidiol (CBD) oil, to begin in several states. Certain components of medical marijuana, including CBD, have shown effectiveness in animal studies, and there have been encouraging anecdotal reports from patients. But further research and unbiased clinical trials are needed to establish whether and in what forms medical marijuana is or is not effective and safe. Restrictions on the use of medical marijuana continue to stand in the way of this research.
Posted by RainDog | Mon Feb 24, 2014, 02:32 PM (1 replies)
Kleiman, the author of the article further down this page, was an advisor for Washington State's marijuana laws and is a professor of Public Policy at UCLA.
Mark Kleiman continues to insist that I am “talking through hat” on the subject of rescheduling marijuana, but the reason he gives for saying so has changed. At first he claimed I had exaggerated the impact of rescheduling, which was weird, since the post he was criticizing said nothing about the impact of rescheduling, focusing instead on the question of whether the Obama administration has the authority to reclassify marijuana without new legislation from Congress. As Kleiman conceded, the answer to that question is yes, although President Obama suggested otherwise in a CNN interview. In any case, Kleiman was clearly wrong to say that the “practical effect” of moving marijuana out of Schedule I would be “identically zero”—or, as he put it on Twitter, that “rescheduling does nothing.” He has since retreated from that position without acknowledging that he has ceded any ground. Now he says rescheduling marijuana would be “mostly pointless” and/or that its effects would be “ mostly symbolic.” These clams are more defensible, although advocates of rescheduling might nevertheless take issue with them (especially the first one).
...Which brings us to the letter that Rep. Earl Blumenauer (D-Ore.) and 17 other members of Congress sent the president last week. Blumenauer et al. argue that marijuana does not meet the criteria for Schedule I and urge Obama to “instruct Attorney General Holder to delist or classify marijuana in a more appropriate way, at the very least eliminating it from Schedule I or II.” Kleiman says these legislators do not understand the law either, but it is not clear why he says that. “It’s not as simple as someone saying, ‘Gee, I’d like to reschedule cannabis this morning,’” Kleiman writes, since the CSA lays out a process to follow, including consultation with the Department of Health and Human Services. That is true, but I do not see where Blumenauer et al. claim otherwise. Although rescheduling would not happen instantly, even beginning the process could help advance the debate about marijuana prohibition by calling attention to the questionable distinctions drawn by our drug laws.
Kleiman emphasizes that the attorney general’s rescheduling power is “not arbitrary.” That’s true in the sense that his power is constrained by the statute in certain ways. For example, the CSA’s reference to treaty obligations seems to preclude removing marijuana from the schedules entirely. But as Alex Kreit notes, the CSA gives the attorney general (and therefore the DEA) a great deal of discretion in interpreting and applying the scheduling criteria, since it leaves key terms such as “potential for abuse” and “accepted medical use” undefined. The DEA has bent over backward to justify keeping marijuana on Schedule I, and nothing in the statute requires it to do that.
The current impasse is because of an entrenched bureaucracy that has views akin to creationists in its denial of reality. To wit:
The DEA says marijuana meets the second criterion—no currently accepted medical use—not because the drug is ineffective at treating symptoms such as nausea, pain, and muscle spasms (in fact, the Obama administration concedes the medical utility of cannabinoids) but because such uses have not gained wide enough acceptance within the medical community. Given the subjectivity of that judgment, it amounts to saying that marijuana has no accepted medical use because the DEA deems medical use of marijuana unaccceptable. The agency likewise does not accept that marijuana can be used safely, although it obviously can, as Obama conceded when he observed that alcohol is more dangerous.
The DEA clearly is bending over backward to keep marijuana on Schedule I, and nothing in the CSA requires it to do that. It could easily apply the CSA's criteria in a way that would make marijuana less restricted, and the decision not to do so is ultimately Obama's. He is the one who appointed the current DEA administrator, a hardline holdover from the Bush administration who is so committed to prohibitionist orthodoxy that she recoils in horror at the thought of a hemp flag flying over the Capitol and could not restrain herself from openly criticizing Obama, notionally her boss, for his scientifically uncontroversial statement about the relative hazards of marijuana and alcohol. He is the one who, despite his avowed commitment to sound science and his own statements to the contrary, allows the DEA to insist marijuana is so dangerous that it must be more tightly restricted than cocaine, morphine, oxycodone, and methamphetamine.
"It's very unfortunate that President Obama appears to want to pass the buck to Congress when it comes to marijuana laws," says Tom Angell, chairman of Marijuana Majority. "If the president truly believes what he says about marijuana, he has a moral imperative to make the law match up with his views and the views of the majority of the American people without delay. He should initiate the long overdue rescheduling of marijuana today."
Yet there is another way rescheduling could be accomplished - by directing the DEA to an interpretation of policy that implements rescheduling of marijuana to, ideally (if it's going to be scheduled at all) to Schedule V, or the least dangerous of substances within the Controlled Substances Act.
Alex Kreit, a professor at Thomas Jefferson School of Law in San Diego who studies drug policy, notes that the CSA leaves undefined phrases on which scheduling hinges. The DEA therefore "has enjoyed incredibly broad discretion to interpret and define 'potential for abuse' and other scheduling criteria," Kreit writes on the Marijuana Law, Policy & Reform blog. Just as it could adopt a less demanding definition of "accepted medical use," the DEA could take a narrower view of "abuse," which it equates with any nonmedical use. By that standard, marijuana, by far the most popular illegal drug, does indeed have a high potential for abuse. But that judgment seems peculiar if abuse is defined as problematic use, in which case potential for abuse might be measured by the percentage of users who become addicted or suffer serious harm.
In truth, as Lester Grinspoon observes, marijuana does not fit any of the schedules very well. It is not the sort of medicine the FDA is used to approving. But it clearly can be used safely, as Obama conceded when he noted that it is less dangerous than alcohol. Back in 1988, when he urged the DEA to reschedule marijuana, Administrative Law Judge Francis Young called it "one of the safest therapeutically active substances known to man." And while marijuana surely can be abused (what can't?), its potential for abuse seems lower than that of many pharmaceuticals, not to mention alcohol and tobacco, which the CSA specifically excludes from its schedules.
In light of these inconsistencies, could the DEA take marijuana off of the CSA's schedules altogether? Probably not. "I think it is very unlikely that the attorney general could remove marijuana from the schedules entirely," Kreit says. Although the CSA gives the attorney general the power to "remove a drug or other substance entirely from the schedules," it also says that "if control is required by United States obligations under international treaties, conventions, or protocols in effect on October 27, 1970, the Attorney General shall issue an order controlling such drug under the schedule he deems most appropriate."
This article notes Republicans are attacking Obama and Holder for "schizophrenic" actions related to marijuana, including Obama's claim that marijuana is no more dangerous than alcohol, and Holder's statement that states can work out their laws without federal interference as long as certain points of the law (export, association with illegal drug organizations, zoning laws, etc. are enforced.)
As a matter of law, Section 873 of the Controlled Substances Act orders the attorney general to "cooperate with local, State, tribal and Federal agencies concerning traffic in controlled substances and in suppressing the abuse of controlled substances." Most states have drug laws that track federal prohibitions. But the voters in Washington state and Colorado chose regulation over prohibition as a means of dealing with cannabis abuse; if the state regulatory systems succeed, there will be less drug abuse than if they fail.
A straightforward reading of the law would therefore seem to require the attorney general to cooperate with those state efforts rather than trying to disrupt them, if in his judgment doing so promotes the purposes of the law in controlling drug trafficking and drug abuse. It is Holder's critics who seem to be selective about which laws they want to pay attention to.
As a matter of fact, federal drug law enforcement is a relatively small part of the national drug enforcement effort; about 80 percent of the 500,000 drug offenders behind bars in the U.S. are in state prisons and local jails. The Drug Enforcement Administration has fewer than 5,000 agents worldwide; Colorado and Washington state between them have more than 22,000 state and local police.
The Justice Department could easily have shut down the licensed growers and sellers in Washington and Colorado, but it would simply not have had the capacity to control strictly illegal production in those states without the help of state and local police. Letting the reasonably regulated Colorado and Washington systems operate while going after participants in California's virtually unregulated "medical marijuana" business creates the right incentives for state officials and industry participants; if you don't want federal attention, keep things under control.
Posted by RainDog | Mon Feb 24, 2014, 12:31 PM (3 replies)