04/25/17

Pesticides, Fungi and Pot

© Eric Limon | 123rf.com

In 2015, two Colorado marijuana users sued the state’s largest marijuana grower, claiming it used a dangerous agricultural fungicide on its pot plants. The fungicide, Eagle 20, contains the chemical myclobutanil, which becomes poisonous when ignited. The allegations were that while Eagle 20 is approved for certain edible products, it is not approved for smokable products like marijuana and tobacco. The lawsuit said: “Persons who smoke cannabis that has been sprayed with Eagle 20 inhale … poisonous hydrogen cyanide.” The company, LivWell, maintained its plants are safe.

The two individuals alleged they were not aware of LivWell’s use of Eagle 20 on their cannabis when they bought it. Had they known, they would not have smoked LivWell’s cannabis. They were asking for a monetary reimbursement for their unused product and were also demanding that LivWell stop using the Eagle 20 fungicide on its cannabis. The plaintiff’s lawyer said that to his knowledge, this was the first product liability action filed against the legal marijuana industry. LivWell’s owner said: “Testing of our finished product by an independent, state-licensed lab approved by the City of Denver showed that our products are safe – as we have always maintained.”

In the end, the lawsuit was dismissed. The Denver judge who heard the case said the plaintiffs couldn’t sue because they were not actually harmed. They bought and then consumed the pot without any repercussions. The written opinion noted there were no allegations that the cannabis did not perform as it was supposed to; and both consumers smoked it without harm. LivWell’s owner said this had been a ploy intended to smear the company’s name. “The people behind this case do not want the commercial cannabis industry to succeed and will try anything to bring down the industry.”

Setting aside the rhetoric from the lawyers on both sides of the dismissed lawsuit and LivWell’s owner, the use of pesticides on marijuana is a growing concern for the industry. The marijuana website The Cannabist has an archived page on marijuana pesticides with fourteen articles published between December 4, 2015 and July 29, 2016. Their titles range from: “Check Your Stash: Are you consuming pesticide-peppered pot? Full recall list” to “State releases hundreds of recalled pot batches after they tested pesticide-free.”

Ricardo Baca and others, writing for The Cannabist, said Denver’s Department of Environmental Health has issued 26 recalls of marijuana and pot products since September of 2015. The Colorado Marijuana Enforcement Division has issued 26 recalls in the form of administrative holds between February and July of 2016. The recalls originated from an executive order issued by the governor of Colorado in November of 2015. Within the order, the governor said: “Until scientific assessment establishes which additional pesticides can be safely applied to marijuana, marijuana contaminated by an Off-Label Pesticide shall constitute a threat to the public safety.”

At the core of legal cannabis’ pesticide problem in Colorado is the state’s lack of a pesticide certification for marijuana testing labs. So while cannabis testing facilities are certified by the state’s health department to test for potency and contaminants, the Colorado Department of Public Health and Environment is still working with other agencies, labs and industry to develop proficiency standards and testing certification requirements for pesticide tests.

Reporting originally for The Denver Post, David Migoya and Ricardo Baca, noted how The Post revealed in its own testing that a number of marijuana-infused products contained high levels of pesticides that shouldn’t be used on cannabis. The Catch-22 is that there is no pesticide specifically approved for use with marijuana, because pesticide chemicals are regulated by the EPA. And since cannabis is illegal under federal law, there are no federal standards. “As a result, there have been no tests to show how pesticides used on marijuana could affect consumers or whether their use is safe.” Colorado state agriculture officials have allowed certain pesticides to be used on marijuana as long as it does not violate the restrictions of the product’s label.

Ron Kammerzell, a senior director in the Colorado Department of Revenue, which oversees the state Marijuana Enforcement Division (MED), said the state’s responsibility was to make sure the marijuana is safe for the consumer and not contaminated by pesticides. The top priority is to keep pesticide-contaminated products from getting to consumers. He added that pesticides were a challenging area fro testing, so they wanted to be sure they did it right. “Once we have mandatory testing for pesticides, that will be a game-changer in terms of making sure that we’re minimizing these types of contaminations.” Kammerzell hopes to have the state’s pesticide testing certification program implemented sometime in 2017.

Writing for Slate, Rachel Gross noted how cannabis vendors are pitching healthier, organic marijuana to their customers. “Like wine aficionados, certain weed smokers have always had a reputation for being connoisseurs.” The U.S. legal cannabis industry was projected to bring in almost $7 billion in 2016. The founder of Clean Green, a marijuana-certifying program, said: “These are sophisticated buyers, the same people who are buying organic food and organic coffee.” The industry is becoming more industrialized and corporate and the fear is that industrial pot is laced with pesticides.

Consider the gram of weed you can buy, right now, in the four states (Washington, Oregon, Colorado, and Alaska) and Washington, D.C., where recreational marijuana is legal (or the 24 states where it’s available for medical purposes). Before it was sealed in that baggie, it was a plant. That plant likely got sprayed with fungus-, insect-, and disease-killing chemicals. Before it was a plant, it was a seedling. That seedling may have sat in soil that had been fumigated with even more pesticides. And before that seedling got planted, the grow room that would one day be its home was probably bug-bombed and lined with pest strips, which are laced with chemicals that linger in enclosed spaces.

Thanks to the series of recalls, like those noted above in Colorado, consumers are becoming more aware of the pesticide issues in the marijuana industry. The Oregonian found abnormally high levels of pesticides in nearly half the products sold in state dispensaries. “Those pesticides included a common roach killer, half a dozen human carcinogens, and a fungicide [myclobutanil] that allegedly turned into hydrogen cyanide when heated.” The dose is the issue. Even a toxic substance like hydrogen cyanide could be harmless in a small enough dose. Oregon is working closely with the state of Washington and Colorado to coordinate which pesticides should be tested for in cannabis.

Researchers at UC Davis recently announced a study that found medical marijuana contained “multiple bacterial and fungal pathogens that may cause serious and even fatal infections.” Smoking, vaping or inhaling aerosolized marijuana may pose a serious health risk to individuals, especially those with impaired immune systems. George Thompson, one of the study’s authors, noted where patients with impaired immune systems are routinely advised to avoid exposure to plants and certain raw foods because of the risk of infection. “But at the same time, they are increasingly turning to medical marijuana to help them with symptom control. Because microorganisms known to cause serious infections in immunocompromised patients were found to be common on marijuana, we strongly advise patients to avoid it.”

They publically voiced their concerns in a letter to the editor of the journal Clinical Microbiology and Infection. There is a copy of the letter here. The news media also picked up on the study. Claudia Black, writing for The Sacramento Bee, said the uneasy news comes as a majority of states have eased laws on medical and recreational marijuana, and a majority of U.S. doctors support the use of medical marijuana for symptoms such as pain, nausea and loss of appetite during chemotherapy and other treatments. George Thompson was quoted as saying it was a big oversight to not warn patients with compromised immune systems to avoid marijuana. “It’s basically dead vegetative material and always covered in fungi.”

The study gathered marijuana from 20 Northern California growers and dispensaries. The analysis of marijuana for the study was done by Steep Hill Labs, a cannabis testing company. “The analysis found numerous types of bacteria and fungi, including organic pathogens that can lead to a particularly deadly infection known as Mucor.” There is a misconception that if it is from a dispensary, the marijuana must be safe. But that’s not the case, according to Joseph Tuscano, another one of the researchers. “This is potentially a direct inoculation into the lungs of these contaminated organisms, especially if you use a bong or vaporization technique.” You can watch a CBS Sacramento news video on the study posted on YouTube here.

So it’s not just that the anti-pot people are out to sink the industry. Its customers are concerned about the presence of pesticides in their pot. Researchers are finding that some marijuana contains common bacteria and fungi that poses a danger to individuals with compromised immune systems. The marijuana industry is going through some serious growing pains. But the question begs to be asked, did the states that legalized recreational and medical marijuana run ahead of the regulatory and bureaucratic changes needed to support it?

02/20/17

Listening to Marijuana Research

© Mohammed Anwarul Kabir Choudhury

Would it surprise you to know that only .6% of all participants in medical marijuana programs are getting any ongoing medical oversight? Williams et al. assessed medical marijuana programs for Health Affairs according to seven components of traditional medical care and pharmaceutical regulation. The authors found that of the initial 23 states and the District of Columbia who had approved medical marijuana, 14 programs were nonmedical, according to those standards. These fourteen programs collectively enrolled 99.4% of all nationwide participants in medical marijuana programs.

One of the study’s coauthors, Dr. Silvia Martins said: “When you’re allowing someone to have access to a certain product as a medication, it needs to be overseen by good medical practices and medical rules.” And that is necessarily based on a clear understanding of the risks and benefits of any medicinal product.

With that in mind, the MIND project at McLean Hospital in Boston is researching medical marijuana (MMJ).  MIND stands for: Marijuana Investigations for Neuroscientific Discovery. Currently MIND is conducting a longitudinal study of MMJ. The first phase of the MIND project assesses subjects at baseline, before beginning their MMJ treatment. They then track their use of marijuana (MJ) and are in touch with researchers biweekly. Follow up visits occur every three months for two years in order to assess the potential impact of MMJ on cognitive function and related brain and quality of life measures.

The second phase is an FDA-approved clinical trial of high-CBD sublingual tincture for treating anxiety. A third and final phase will examine the clinical state and cognition in veterans who are using cannabinoids to treat various conditions, including PTSD, insomnia and pain. The MIND website noted how policy has gone too far ahead of science, so there is little data available on the impact of MMJ on cognitive functioning.

Given the considerable difficulty with cognitive function and disrupted mood experienced by patients with severe medical disorders, the addition of MJ, which has shown promise in alleviating a range of symptoms, could potentially improve cognitive performance. Equally critical, data showing a loss or impairment of cognitive function following the use of MMJ could inform alternative courses of treatment, staggered dosing, and ultimately prevent unjustified exposure to harm. As the number of states who have passed MMJ laws continues to grow, the ‘need to know’ has never been more important, relevant or timely, and has significant implications for public health policy.

Staci Gruber, who is the director of the MIND project, has been doing research into the effects of MJ since the early 1990s and has documented some interesting neurological effects from MJ. She led a 2013 study that found there were differences in the brain’s white matter and impulsivity between teenagers and young adults smoked an average of 25.5 joints of MJ per week and a control group who did not smoke MJ. Their research suggested that in some individuals who begin smoking MJ at an early age, differences in brain function and structure emerge during development. The study sample was small and it was not clear if the brain changes resulted from MJ use or predated MJ use. The changes could have occurred as the result of either chronic MJ use or reflect a delay in brain development in MJ smokers.

These data represent the first report of significant alterations in frontal white matter fiber tract integrity that are associated with self-report measures of impulsivity in chronic, heavy MJ smokers, and appear to be related to age of onset of MJ use. . . . Future investigations should include additional measures of behavioral impulsivity and their relationship to age of onset of MJ use to more fully explore the potential neurodevelopmental aspects of white matter changes in MJ smokers. Findings from this study suggest that changes in white matter microstructure may be predictive or associated with increased impulsivity, and may ultimately contribute to the initiation of MJ use or the inability to discontinue use.

A follow up study done by Gruber and others was published that same year, 2013. The study confirmed that heavy MJ smokers had lower levels of white matter in the corpus callosum region of the brain; and that earlier age of MJ use was associated with these lower levels of white matter. MJ smokers also had higher levels of impulsivity.

Taken together, these findings reinforce the idea that early onset of MJ use negatively impacts white matter development and is associated with behavioral impulsivity, a combination that may have enduring negative effects, particularly on the developing brain. Data from this study highlight the importance of early identification of MJ use among emerging adults and the need for efforts aimed at delaying or preventing the onset of MJ use.

Then a third study by Gruber and her research team at MIND published in the March 2016 issue of the Journal of Studies on Alcohol and Drugs found that MJ smokers had poorer executive brain function than the control group. The difference seemed to be primarily the result of early onset of MJ use, before the age of 16. The differences remained even after the frequency and amounts of MJ used were controlled. Additionally, the early MJ use and the greater amounts of MJ used predicted poorer performance and errors on the Wisconsin Card Sorting Test (WCST), which is used to assess abstract thinking. “The WCST is also considered a measure of executive function because of its reported sensitivity to frontal lobe dysfunction.”

These findings underscore the impact of early onset of marijuana use on executive function impairment independent of increased frequency and magnitude of use. In addition, poorer performance on the WCST may serve as a neuropsychological marker for heavy marijuana users. These results highlight the need for additional research to identify predictors associated with early marijuana use, as exposure to marijuana during a period of developmental vulnerability may result in negative cognitive consequences.

STAT News highlighted Dr. Gruber’s research with MIND in an August 2016 article. She commented there on the commitment of some of her research participants, how they drive two to three hours to be part of the MIND study. “They’re really committed. They really want to know what effect this will have on them.”

After reviewing some of the comments on the STAT article, it seemed to me that several of the pro marijuana readers either missed or ignored a few of her comments in the article. One of her comments was: “There’s a lot we don’t know about long-term effects, and that’s what I’m here to find out.” In a second remark Gruber pointed out that the cannabinoids she studies aren’t the ones that get you high. “But whether you’re for medical marijuana or against it, what we really need is information.”

SAMA (Science and Management of Addictions) president, Kim Bracket, said Staci Gruber has a talent for translating scientific information so that non-scientists can understand. This leads to a third and telling comment by Gruber in the article: “In science, you can have all the findings in the world, but if you can’t communicate them, what good are they?” So far, I think she is communicating her findings clearly and concisely to scientists and non-scientists, legalization activists and opponents to legalization. And we need to continue to listen to what she says.

11/29/16

Marijuana & Adverse Health Effects

© David Castillo Dominici | 123rf.com

© David Castillo Dominici | 123rf.com

In the 2016 election there was another political milestone met besides the presidential election of Donald Trump—four more states voted to legalize recreational marijuana. California, Maine, Massachusetts, and Nevada joined Alaska, Colorado, Oregon, Washington and the District of Columbia. However, the public use of marijuana—recreational or medical—is still not permitted anywhere. Arkansas, Florida and North Dakota approved medical marijuana initiatives and Montana loosened restrictions on an existing medical marijuana law. The executive director of the Drug Policy Alliance was quoted in The Washington Post as saying: “The end of marijuana prohibition nationally, and even internationally, is fast approaching.”

Given the election of Donald Trump and the international position on marijuana, this may be more optimism than reality. Within the U.S. there has been clear momentum towards legalization of some kind, as there are now eight states and the District of Columbia where recreational marijuana is legal; and 28 states and the District of Columbia where medical marijuana is permitted. However, because of the ongoing federal classification of marijuana as a Schedule I drug, reliable research into the benefits and adverse health effects from marijuana use is hard to come by. The public needs to be more aware of the scientific research into the potential adverse effects and medical benefits from marijuana as the U.S. continues to move toward a complicated, patchwork quilt of varied state laws and regulations regarding marijuana.

A good place to start is with an article written by the current director of the National Institute on Drug Abuse (NIDA), Dr. Nora Volkow and three others, “Adverse Health Effects of Marijuana Use.” Volkow et al. reviewed the current state of the scientific findings on the adverse health effects related to the recreational use of marijuana. Their review focused on the areas where the evidence was the strongest. In a table summarizing their confidence in the evidence for adverse effects of marijuana on health and wellbeing, they gave the following assessment of marijuana use, particularly with heavy or long-term use that starts in adolescence.

Effect

Overall Level of Confidence

Addiction to marijuana or other substances

High

Diminished lifetime achievement

High

Motor vehicle accidents

High

Symptoms of chronic bronchitis

High

Abnormal brain development

Medium

Progressive use of other drugs

Medium

Schizophrenia

Medium

Depression or anxiety

Medium

Lung cancer

Low

Long-term marijuana use can lead to addiction; there’s no real doubt. About 9% of those who experiment with marijuana will develop dependence, according to the criteria for dependence in the DSM-IV. This increases to one in six (16.7%) among those who started using marijuana as teens. Daily smokers have a 25% to 50% risk of developing an addiction to marijuana. There is also a cannabis withdrawal syndrome, with symptoms such as: irritability, sleep difficulties, dysphoria (a state of being unhappy or unwell), cravings, and anxiety.

Since the brain remains in a state of active development until around the age of 21, individuals under 21 who use marijuana are more vulnerable to adverse long-term effects from marijuana use. Adults who smoked marijuana regularly during adolescence have impaired neural connectivity (fewer fibers) in certain brain regions.

The impairments in brain connectivity associated with exposure to marijuana in adolescence are consistent with … findings indicating that the cannabinoid system plays a prominent role in synapse formation during brain development.

While regular use of marijuana is associated with anxiety and depression, causality has not been established. Marijuana is also regularly linked to psychosis, especially among people with a predisposition. Heavy marijuana use, greater drug potency, and exposure at a young age can all negatively effect the experience of psychosis or schizophrenia, accelerating the time of a first psychotic episode by 2 to 6 years.

Because marijuana use impairs critical cognitive functions during acute intoxication and for days after use, many students may be functioning below their natural capabilities for long periods of time. “The evidence suggests that such use results in measurable and long-lasting cognitive impairments, particularly among those who started to use marijuana in early adolescence.” A failure to learn at school, even for short or sporadic periods of time because of acute intoxication, will interfere with the capacity to achieve educational goals. This seems to explain the association between marijuana use and poor grades.

Heavy marijuana use has been linked to lower income, greater need for socioeconomic assistance, unemployment’s, criminal behavior, and lower satisfaction with life.

There is also a relationship between THC levels in blood and performance in controlled driving-simulation studies. These studies have been a good predictor of real-world driving ability. “Recent marijuana smoking and blood THC levels of 2 to 5 mg per milliliter are associated with substantial driving impairment.” The overall risk of involvement in an accident increases by a factor of 2 when someone drives soon after using marijuana. Not surprisingly, combining marijuana and alcohol seems to result in greater risks than the use of either drug alone.

The authors noted that most of the long-term effects of marijuana use in the article have been seen among heavy or long-term users. Yet the presence of multiple confounding factors, including the frequent use of marijuana with other drugs, detracts from their ability to establish causality.

They also noted there is a need to improve our knowledge on the potential medical benefits of the marijuana plant. A report by the Institute of Medicine sees the benefits for stimulating appetite and in combating chemotherapy-induced nausea and vomiting, severe pain and decreasing intraocular pressure in the treatment of glaucoma. “Nevertheless, the report stresses the importance of focusing research efforts on the therapeutic potential of synthetic or pharmaceutically pure cannabinoids.” With all of its problems, the existing structure for the approval of new medicines through the FDA is better than the current lack of any safety and regulatory apparatus with medical marijuana. The ongoing failure to confirm or refute the plethora of health and medicinal claims with marijuana use is progressively taking us back to the days of patent medicine claims in state-by-state approval. In conclusion they summarized the results of their review of the literature on adverse effect from marijuana use as follows:

Marijuana, like other drugs of abuse, can result in addiction. During intoxication, marijuana can interfere with cognitive functions (e.g. memory and perception of time) and motor function (e.g. coordination), and these effects can have detrimental consequences (e.g. motor-vehicle accidents). Repeated marijuana use during adolescence may result in long-lasting changes in brain function that can jeopardize educational, professional, and social achievements. . . . . As policy shifts toward legalization of marijuana, it is reasonable and probably prudent to hypothesize that its use will increase and that, by extension, so will the number of persons for whom there will be negative health consequences.

A German review study by Hoch et al., “Risk Associated with the Non-Medical Use of Cannabis,” also sought to summarize the current state of knowledge regarding the physical and mental adverse effects of intensive recreational cannabis use. They came to conclusions similar to the Volkow et al. study. Hoch et al. noted the potential for addiction and withdrawal, mild negative effects on learning capacity, neurocognitive impairments with adolescents, an increased risk of psychosis, and others. “Further research is required to clarify the causal nature of the links between cannabis consumption patterns and adverse events.”

Empirical data have now clearly shown that starting early in life and regularly using high amounts of cannabis for a long period of time increases the risk of various mental and physical disorders and endangers age-appropriate development. Because many studies have failed to control properly for confounding variables, it still cannot be stated beyond doubt that there is a causal connection between cannabis consumption patterns and cognitive damage or the development of comorbid psychic or somatic disorders. The worldwide increase in the THC content of cannabis may increase the health risks, particularly for adolescent users. Further research is required to determine why some people are more affected than others by the unfavorable consequences.

On the other hand, another long-term study of chronic marijuana use among young adult men by Bechtold et al., was published  in the journal, Psychology of Addictive Behavior. The study used data from The Pittsburgh Youth Study, a longitudinal study that followed seventh grade students until they were 36. The study found that chronic marijuana users were no more likely than other groups to experience several physical or mental health problems, including early onset psychosis and heart problems. Some limitations in applying the findings of this study would include the fact that participants were only followed until the age of 36, perhaps too early for many of the health problems to become evident. Another difference was that the heaviest use category for marijuana was “more than 3 times per week,” while Volkow et al. seems to have been looking at daily or almost daily use.

In a postscript addition to the above studies, a 2016 study by Columbia researchers found evidence of a compromised dopamine system in heavy marijuana users. Dopamine levels were lower in the striatum, an area in the brain involved in working memory, impulsive behavior and attention. Previous studies have found addiction to other drugs of abuse, like cocaine and heroin, have similar effects on dopamine release. This was the first such evidence for marijuana.

A press release by the Columbia University Medical Center quoted the lead author as stating that in light of the increasing use and acceptance of marijuana, especially by young people, it is important to look more closely at the potentially addictive effects of cannabis on key regions of the brain. The study was small, with 11 adults who were severely dependent upon marijuana and 12 matched healthy controls. The average age of onset among the marijuana users was 16, with dependence occurring by 20. In the month before the study, all users in the study had smoked daily.

“Compared with controls, the cannabis users had significantly lower dopamine release in the striatum, including subregions involved in associative and sensorimotor learning.” The investigators also explored the relationship between dopamine release in the striatum and cognitive performance on learning and working memory tasks. The bottom line was that long-term, heavy marijuana use could impair the dopaminergic system, which in turn could have a series of negative effects on learning and behavior.

I talked with someone who had been to California a few weeks after the 2016 election when recreational marijuana use was legalized. She reported how employees of her hotel were gathering outside on their break to smoke pot, similar to what cigarette smokers do. If legal recreational use becomes more widespread in the U.S., the adverse physical and mental adverse effects from heavy, regular use will also become more evident. Then marijuana use will take a place beside alcohol use and tobacco use as a public health problem.

07/29/16

Be Careful of Where You’re Going

© : J�rg St�ber | 123rf.com

© : J�rg St�ber | 123rf.com

On July 9, 2015 eight Senators sent a letter to the Department of Health and Human Services (HHS), Office of National Drug Control Policy (ONDCP), and the Drug Enforcement Administration (DEA) asking for information on their efforts to facilitate scientific research into the benefits of medical marijuana. The Senators asked for answers to a series of questions, stating that relevant federal agencies had to play a leadership role in coordinating and facilitating research into medical marijuana. This began a process culminating in the administrators of the three agencies sending a detailed reply to their questions in an April 4, 2016 response … 26 pages long. And so speculation began that the DEA would decide whether or not to change the controlled substance status of marijuana “in the first half of 2016.”

This was part of the inquiry made by the Senators’ letter, in noting the need to remove “extraneous regulatory barriers for researchers who wish to perform scientific studies on the sue of marijuana for various diseases.” They pointed to the need of the federal government to make a concerted effort to understand how marijuana works and what the appropriate doses and methods of treatment are, “like any prescribed medicine.” Within Appendix C of the HHS, ONDCP, DEA response, was the following graphic and text delineating the process to schedule or re-schedule any drug.

DEAThe Controlled Substance Act requires eight factors as part of its scientific review: 1) the actual or relative potential for abuse; 2) the scientific evidence of its pharmacological effect; 3) the state of current scientific knowledge regarding the substance; 4) the history and current pattern of abuse; 5) the scope, duration and significance of abuse; 6) the risk to the public health; 7) the psychic or physiological dependence liability; and 8) the immediate precursor of a substance already controlled.

Writing for the Huffington Post in April 2016, Matt Ferner noted the FDA completed its review of the medical evidence of the safety and effectiveness of marijuana, and forwarded it to the DEA. But the FDA recommendations are still not public. In the Washington Post, Christopher Ingraham interviewed John Hudak of the Brookings Institution, who said the small amount of researchers currently working with marijuana is not due to the government turning down applications to do the research. Rather, it is a function of the application process itself. “People just aren’t applying because of all the headaches involved. . . . It’s a huge disincentive for the academic community.”

The bureaucratic hurdles also mean that colleges and universities are often hesitant to fund marijuana research for fear of running afoul of complex federal regulations. One ongoing study on the use of marijuana to treat veterans with PTSD has been struggling to get off the ground for more than five years, for instance.

There was an unconfirmed rumor by an “anonymous” DEA attorney that the DEA planned to reschedule marijuana as a Schedule II controlled substance and make medical marijuana legal with a doctor’s prescription in all 50 states. This is simply not true. Rescheduling would merely make it easier to get permission to do research with marijuana, not make it legal for doctors in all 50 states to prescribe marijuana. If that were the case, why can’t doctors prescribe cocaine legally? It is a Schedule II Controlled Subtance. Writing for The Fix, McCarton Ackerman noted the skepticism about the validity of the source.

In response to the rumors, DEA staff coordinator Russ Baer would not confirm the rumored rescheduling by August 1st in an interview with aNewDomain. Baer pointed out the complexity of what is referred to as “medical marijuana.” While THC and CBD are the two main cannabinoids, there are an estimated 480 compounds in cannabis. “What is under-reported right now is how complex the marijuana plant is.”

Baer said the DEA wants to remove the roadblocks to further research into the effectiveness of medical marijuana. However, he said the DEA doesn’t support decisions made on anecdotal evidence.

We want there to be research on marijuana and its component parts, there needs to be (more) studies about both the benefits and the adverse effects about marijuana. . . . We want to know more about cannabis— we need rigorous scientific research — the DEA stands behind the scientific process.

He added that safe medical cannabis requires rigorous peer-reviewed studies. He singled out current research into the benefits of cannabinol (CBD). “We are told by NIDA, also, that there are medical studies out there also preliminarily indicate CBD is beneficial.” But the opioid crisis has captured most of the DEA’s attention. “Marijuana is important, but our efforts are mainly focused on the nation’s growing opioid crisis. . . . We’re focusing on fentanyl, fentanyl compounds and on preventing the deaths caused by opioid addiction.”

A June 24th article by Kate O’Keeffe for the Wall Street Journal said Baer didn’t expect an answer by June 30th, but the agency was in the final stages of deciding whether to reschedule marijuana. He added that a decision is expected sometime soon.

On July 13, 2016 Dr. Douglas Throckmorton of the FDA appeared before the Judiciary Subcommittee on Crime and Terrorism. In his written statement to the committee, he reiterated its standing 2006 recommendation that marijuana remain as a Schedule I controlled substance because of a high potential for abuse; no currently-accepted medical use; and that it lacks accepted safety for use under medical supervision. However, “DEA is currently in the process of evaluating a number of other Citizen Petitions regarding the scheduling of marijuana.”

He noted there are three drugs approved for human use that contain active ingredients present in or similar to those in botanical marijuana: Marinol Capsules, Syndros and Cesamet Capsules. These products have undergone the FDA’s approval process and have been determined to be safe and effective for their respective indications. The future of medical marijuana lies in “classical drug development.”

If there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives. Isolated cannabinoids will provide more reliable effects than crude plant mixtures. Therefore, the purpose of clinical trials of smoked marijuana would not be to develop marijuana as a licensed drug but rather to serve as a first step toward the development of nonsmoked rapid-onset cannabinoid delivery systems.

Throckmorton pointed to three Fast Track designations for Savitex (April 2014), Epidiolex (June 2014) and a CBD formulation of Insys Therapeutics to treat Dravet syndrome (February 2015). All three are drugs derived from marijuana.He said the FDA is working with researchers who are conducting studies on the development of potential new drugs derived from marijuana.

FDA encourages and supports medical research into the safety and effectiveness of marijuana products through adequate and well-controlled clinical trials conducted under an IND [Investigational New Drug] and consistent with DEA requirements for research on Schedule I substances. FDA has provided scientific advice to representatives from several states considering support for medical research of marijuana and its derivatives, including CBD, to help ensure that their research is rigorous and appropriate.

Another date floated on the rumor pond for a DEA decision on rescheduling marijuana was August 1st, which is fast approaching. Will there be an answer? Who knows? According to Russ Baer, the DEA is not bound to give its answer within some artificially determined timeframe. So I suggest those anxious for an announcement by the DEA (senators and marijuana activists alike) apply a mash up of a famous Yogi-ism here: “Marijuana ain’t re-scheduled till it’s rescheduled.” Perhaps the DEA is just trying to be careful in its decision making process about the rescheduling. Yogi Berra has some further words of wisdom to apply there: “You’ve got to be very careful if you don’t know where you are going, because you might not get there.”

08/10/15

Marijuana Peek-a-Boo

© antonprado | stockfresh.com

© antonprado | stockfresh.com

On Friday, July 10th, the House of Representatives passed H.R. 6, the 21st Century Cures Act (244-183). The bill is now in the Senate for consideration. There had been an amendment proposed that would have rescheduled marijuana and its derivatives under a new 1-R schedule, which would have facilitated research. Marijuana could then have been rescheduled further, after that research was completed and further reclassification was warranted. The National Institute of Health (NIH) and the Drug Enforcement Agency (DEA) were also directed in the amendment to study the benefits and risks of medical marijuana. But the bipartisan amendment was defeated. The irony is that both critics and supporters of legalizing marijuana put forth the failed amendment.

Reporting for the Washington Post, Aaron Davis said that House Republicans have consistently defended their opposition to marijuana laws, saying there is no evidence that such action would do anything “but destroy the brains of the nation’s adolescents.” But the lack of evidence can be traced to Congressional resistance to fund federal agencies to do objective testing on the effects of marijuana. This “Catch 22” led to the support of the amendment by critics and supporters of legalization.

Maryland Representative Andy Harris, a doctor and outspoken critic of legalization over the past two years, co-sponsored the amendment. Before the House Rules Committee sidelined the amendment, he said: “We need science to clearly determine whether marijuana has medicinal benefits and, if so, what is the best way to gain those benefits.”  Harris reportedly doesn’t think that research will find medical benefits, but another Republican, H. Morgan Griffith of Virginia, thinks there are limited circumstances in which marijuana has medical benefits. He said: “This amendment would have answered the question one way or the other. I think it would have shown it is a valuable medical substance, but now we don’t have the evidence.”

The failed effort put advocates for marijuana legislation in the odd position of having to praise Harris, who had become a nemesis of their cause. Michael Collins, the policy manager for the pro-marijuana Drug Policy Alliance, said: “To Mr. Harris’s credit, he thinks there are benefits to researching marijuana, whether you support it or not.” Opponents to legalization of marijuana also see research as a logical step forward. Sue Rusche, head of the National Families in Action, a drug prevention organization, said: “Right now we really don’t know what you’re getting. What we need is research to show us what level of CBD and THC should be given and what’s safe.”

Back in January of 2014, President Obama said it was up to Congress, not his administration, to reschedule marijuana. Steven Nelson, reporting for US News and World Report, said that marijuana advocates said that wasn’t entirely accurate. Representative Earl Blumenauer from Oregon said the law actually permits the current administration to reclassify marijuana. “I don’t dispute that Congress could and should make the change, but it’s also something the administration could do in a matter of days and I hope they will consider it.” Rep. Blumenauer is one of 17 cosponsors of other legislation aimed at reclassifying marijuana, the “Regulate Marijuana Like Alcohol Act.” There has been no action reported on the bill at this point. Govtrack.us said the bill had a 3% chance of getting past committee, and a 1% chance of being enacted. Blumenauer has introduced “The Marijuana Tax Act,” also listed as having a 1% chance of being enacted by Govtrack.us.

Tom Angell, chairman of the group, Marijuana Majority, said it was unfortunate that President Obama “passed the buck” to Congress on marijuana. Dan Riffle, the director of federal policies for the Marijuana Policy Project, said that rescheduling marijuana “is not a ‘job for Congress,’ as the president says.” Riffle said that scheduling decisions are handled by the DEA. In June of 2014, Anna Edney for Bloomberg Business reported that the FDA had been asked by the DEA to review marijuana’s status. This is the third time since 2001. In 2001 and 2006 the FDA recommended that marijuana remain a Schedule 1 Controlled Substance.

Douglas Throckmorton, the Deputy Director for Regulatory Programs at the FDA, acknowledged the FDA was once again conducting an analysis, but could not say when the FDA would complete its analysis or whether it would recommend a change. His testimony before a House subcommittee described the FDA’s role in potentially approving marijuana as a prescription drug.  Dr. Throckmorton affirmed the FDA’s belief that its drug approval process was “the best way to ensure that safe and effective new medicines from marijuana are available as soon as possible for the largest numbers of patients.” He added that it was important to apply these scientific standards to the development and assessment of any alleged therapeutic uses of marijuana.

One of the considerations with establishing the safety and efficacy of a drug is a manufacturer’s ability to demonstrate an ability to consistently manufacture a high-quality drug product. This presents a special challenge with botanically derived drugs like marijuana, including the consistency of lot-to-lot potency. Another consideration is the need to identify a method of consistently providing a specific drug dose. Citing a report from the Institute of Medicine (IOM), Throckmorton noted problems associated with getting consistent dosing from smoked products such as marijuana. The IOM recommended that clinical trials involving marijuana be conducted to find a safe, alternative delivery system.

If there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives. Isolated cannabinoids will provide more reliable effects than crude plant mixtures. Therefore, the purpose of clinical trials of smoked marijuana would not be to develop marijuana as a licensed drug but rather to serve as a first step toward the development of nonsmoked rapid-onset cannabinoid delivery systems.

Throckmorton then cited two drugs approved for human use that contain active ingredients that are present or similar to those in botanical marijuana: Marinol and Cesamet.

These products have undergone FDA’s rigorous approval process and have been determined to be safe and effective for their respective indications, and reflect the views of the IOM that the future of marijuana as a potential medicine lies in classical pharmacological drug development. As a result, patients who need medication can have confidence that any approved drug will be safe and effective for its indicated uses.

So here’s what I’m thinking. When the 21st Century Cures Act is reviewed by the Senate, it needs a provision that will add the changes proposed by the Griffth-Harris-Blumenauer-Farr amendment. This would bring future research into medical marijuana under the authority of the FDA. Effective regulations for the safety and efficacy of medical marijuana can be developed. All states, those who have already approved the use of medical marijuana and those in the future who may approve it, would benefit from the standardization of FDA regulation. The existing problems with medical marijuana (see “Let’s Not Get Ahead of Ourselves”) such as biological and chemical contaminants, accurate labeling, overmedication, and consistent dosing in products could be worked out. The at times outrageous claims for exactly what marijuana DOES medically treat can be examined systematically and scientifically.

But I’m also thinking that isn’t what some legalization advocates want, because it will take time; and the momentum towards recreational marijuana legalization could be lost.  The best path to legalization is to let the political infighting in Congress and federal agencies like the FDA and the DEA continue to neutralize any federal regulation of medical marijuana while marijuana activists continue their state-by-state battle.  If I wanted to develop a strategy for national legalization of marijuana, I’d suggest the following.

The strategy for eventual national legalization of recreational marijuana is to eat the elephant one bite at a time. Keep the battles going state-by-state and keep the federal government out of the fight. Legislatures within the states where medical marijuana is not yet approved should hear about the income and health benefits of legalizing medical marijuana, but not the existing problems where it has been approved. Information on the different kinds of cannabinoids in marijuana and their varying medical benefits—some greater than others—needs to be suppressed. Let them think the medical benefits are all or nothing with marijuana and not contingent upon specific cannabinoids within marijuana. The known health problems from smoking marijuana should be minimized or ridiculed. If I wanted a sound national policy toward medical marijuana, I’d look for the following developments.

The best strategy to slow and perhaps stop the growth of state-by-state legalization of recreational marijuana is to be proactive about the legalization of medical marijuana at the federal level. Quality research that showed the medical benefits of specific cannabinoids, like CBD and THC, the psychoactive cannabinoid in marijuana needs to be done. A more efficient delivery system for medical marijuana than smoking an herbal product of varying potency, with possible biological and chemical contaminants could be developed. The sideshow of existing medical marijuana “treatment” as an excuse to legally medicate (and overmedicate) with THC to get high would stop. Individuals who could benefit from legitimate medicinal marijuana products would get the help they need. And the recreational advocates couldn’t hide behind the medical marijuana movement anymore.

08/3/15

Is the Cart Before the Horse?

11088571_sSenators Dianne Feinstein and Charles Grassley wrote a brief article for Time that highlighted the effectiveness of CBD oil, a product derived from cannabis, in treating the debilitating seizures of a little girl. Her father, an ER doctor, said it took just 36 hours to see profound changes. However, CBD (cannabidiol) oil is not approved by the FDA; and there is no guarantee that the formulation of each batch will be the same. A one-month supply can cost up to $2,500; and the girl’s parents are forced to pay $100 per bottle if they want to verify the contents. “Simply put, we need to know more about CBD, and the only way to gain that knowledge is to remove barriers to research.”

The Time article has a 16-minute video linked, which reviews the issue in more detail and mentions some of the problems with the current state of regulation and research into medical marijuana. I’ve written several other articles on the legalization of marijuana and have a concern that the current practice of state-by-state approval is creating greater problems for the legitimate use of medicinal cannabis products; problems that must be addressed by federal action. The potential for CBD products should be fast tracked to confirm their medicinal use.

Currently, medical marijuana products are typically high in THC, the psychoactive cannabinoid in marijuana, and low in CBD. Compared to CBD, THC has limited medical benefits. But it is the only “therapeutic” agent in the vast majority of medical marijuana products. It seems this crucial and basic understanding of medical marijuana is not widely known or understood. It may be that many “medical” marijuana users don’t care. But it begs the following question—is the current process of state-by-state approval just a “smoke screen?” Is what is actually happening with medical marijuana just the first stage of national legalization of recreational marijuana use?

There is real, legitimate potential for the use of cannabis-based medicines. But they should pass through the same FDA gauntlet that other medicines have, even though the process itself in not perfect. It was put in place because of past abuses and the resulting dangers to public consumers from other so-called miracle cures. Let’s not ignore the past and repeat its mistakes.

The June 23/30 2015 issue of JAMA, The Journal of the American Medical Association, contained several articles related to medical marijuana. Three of them are reviewed below. They address both the potential benefits and consequences with medical marijuana. One article raises the concern embodied in the title of this article: are we putting the cart before the horse in rushing to approve medical marijuana without taking the time to scientifically assess its pros and cons?

Vandrey et al. in a JAMA research letter reported on edible cannabis products that they purchased from three randomly selected dispensaries in three cities: Los Angeles, San Francisco, and Seattle. Of the 75 different products purchased from 47 different brands, only 17% were accurately labeled with respect to their THC content. Twenty-three percent were underlabeled (contained more THC than claimed on the label); and 60% were overlabeled (contained less THC than claimed on the label). Some of the overlabled products contained negligible amounts of THC.

The non-THC content of tested products was generally low. Forty-four products (59%) contained detectable levels of CBD. But only 13 had their CBD content labeled. Four products were overlabeled and nine were underlabeled.

Whiting et al. did a systematic review and meta-analysis, “Cannabinoids for Medical Use,” of randomized clinical trials of cannabinoids for various conditions: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity from multiple sclerosis or paraplegia, depression anxiety disorder, sleep disorder, psychosis, glaucoma or Tourette syndrome. They used a methodology designed to reduce the risk of publication bias in their analyses.

The study concluded there was moderate-quality evidence for the use of cannabinoids (smoked THC and nabiximols) to treat chronic pain and spasticity. There was low-quality evidence to support using cannabinoids for nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders and Tourette syndrome. There was very low quality evidence for improvement in anxiety as assessed by a public speaking test. There was some evidence that cannabinoids (mainly nabiximols) were associated with an improvement in sleep. There was no evidence showing that cannabinoids helped in the treatment of depression or glaucoma.

Cannabinoids were also found to be associated with increased risk of short-term adverse events such as: dizziness, dry mouth, nausea, fatigue, drowsiness, euphoria, vomiting, disorientation, confusion, loss of balance and hallucination. The two studies that assessed the association between psychosis and cannabis found no difference in mental health outcomes, but they were judged to be at high risk of bias. There were no identified studies of long-term adverse events of cannabinoids, even when the searches were extended to lower levels of evidence than established in the initial methodology.

Doctors D”Souza and Ranganathan wrote an editorial for the same issue of JAMA, “Medical Marijuana: Is the Cart Before the Horse?” They raised the same concern Whitling et al. found, namely that for most of the indications that qualify by state law for medical marijuana, the supporting evidence for its use is of poor quality. “For most qualifying conditions, approval has relied on low-quality scientific evidence, anecdotal reports, individual testimonials, legislative initiatives, and public opinion.” So state and federal governments should support and encourage research so that high quality research on medical marijuana can be done for the conditions for which the existing evidence is insufficient or of poor quality.

They also noted how there are inconsistencies from state to state in how conditions are qualified for medical marijuana use. One example noted was that posttraumatic stress disorder was approved as a qualifying condition in some, but not all states. Unlike most FDA-approved drugs, marijuana has over 400 compounds; and there isn’t a uniform composition of the cannabis preparations. “Given the variable composition, patients will have to experiment with different strains and doses to achieve the desired effects,” a process known as titrating. The patient is looking for the personal Goldilocks dose—not too high and not too low.

While the acute adverse effects are known, the effects of repeated exposure, as would occur with medical marijuana needs further study. The risk of addiction, and a smaller risk of psychotic disorder were discussed. The interaction of marijuana with other drugs concurrently prescribed needs further study. They suggested that medical marijuana be added to monitoring databases along with opioids and benzodiazepines, so doctors would have a more complete understanding of the medication profile of their patients.

The human endocannabinoid system is involved in a variety of physiological processes such as appetite, pain-sensation, mood and memory. And there are two known cannabinoid receptors, CB1 and CB2. THC is a direct “fit” with the CB1 receptor, while another cannabinoid, cannabinol fits with CB2. The receptors are predominantly found in the brain (CB1) and the immune system (CB2). Cannabidiol (CBD) does not directly fit with either receptor, but has powerful indirect effects that are still being studied. See this graphic representation of the human endocannabinoid system.

“Emerging evidence suggests that the endocannabinoid system is critical in brain development and maturation processes, especially during adolescence and early adulthood.” This ongoing development of the system during adolescence then raises questions on what age exposure to medical marijuana is justifiable. Brain development continues until the age of 25. “Changes in the endocannabinoid system have been linked to affective, behavioral, cognitive and neurochemical consequences that last into adulthood.”

In conclusion, if the states’ initiative to legalize medical marijuana is merely a veiled step toward allowing access to recreational marijuana, then the medical community should be left out of the process, and instead marijuana should be decriminalized. Conversely, if the goal is to make marijuana available for medical purposes, then it is unclear why the approval process should be different from that used for other medications. Evidence justifying marijuana use for various medical conditions will require the conduct of adequately powered, doubleblind, randomized, placebo/active controlled clinical trials to test its short- and long-term efficacy and safety. The federal government and states should support medical marijuana research. Since medical marijuana is not a life-saving intervention, it may be prudent to wait before widely adopting its use until high-quality evidence is available to guide the development of a rational approval process. Perhaps it is time to place the horse back in front of the cart.

07/27/15

Clearing Away the Medical Marijuana Smoke

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© lunamarina | stockfresh.com

There have been some studies that demonstrate potential medicinal benefits of marijuana use, but they often don’t meet the clinical trial standards used by the FDA to approve medications for human consumption. With the state-by-state movement to legalize marijuana progressing, there is a need for quality scientific research into the potential medical benefits of marijuana. Although marijuana has been used recreationally and medicinally for centuries, the mechanics of how it works are not clearly understood. This is partly because there are over 400 different chemicals in cannabis. THC, the psychoactive ingredient in cannabis, was just isolated in the 1960s. What follows are reviews of some articles that look at the benefits and the concerns with medical marijuana.

Marijuana has been used as a folk medicine as far back in time as five thousand years ago. The first medical use likely occurred in Central Asia and spread from there to China and India. The Chinese emperor Shen-Nung is known to have prescribed it in 2800 BC.  Between 2000 and 1400 BC it came to India, and from there to Egypt, Syria and Persia. The Greeks and Romans valued marijuana as hemp for ropes. Europeans ate its seeds and used its fibers to make paper. An urban legend falsely held that the U.S. Constitution, Declaration of Independence, and Bill of Rights were written on hemp paper. All three were actually written on parchment.

An Irish doctor, W. B. O’Shaughnessy, working in Calcutta in the 1830s, wrote a paper on the medical uses of cannabis, which were strikingly similar to those known today—vomiting, convulsions and spasticity. By 1854, the medical use of cannabis was listed in the US Dispensatory. Nineteenth-century physicians had cannabis tinctures and extracts for ailments from insomnia and headaches to anorexia and sexual dysfunction. “Cannabis-containing remedies were also used for pain, whooping cough, asthma, and insomnia and were compounded into extracts, tinctures, cigarettes, and plasters.”

The above short history on the history of medical marijuana was taken from an article by J. Michael Bostwick, “Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana.” He noted how the term medical marijuana refers to botanical cannabis, which contains hundreds of compounds—including the two most often used medicinally, THC and cannabidiol. Synthetic cannabinoids are produced in a laboratory. Botanical cannabis attracts the notoriety and controversy—because it is the same substance used recreationally by “stoners” to get high.

Bostwick noted how the recreational and medical marijuana use of marijuana is not always distinct, which has medical implications for both seasoned and naïve users. For example, naïve users may decide to stop using medical marijuana because of the psychoactive effects of the THC. Although most users will experience a mild euphoria, a few experience dysphoria, anxiety and even paranoia.

As cannabis strains are bred that amplify THC content and diminish counteracting cannabidiol, highs become more intense but so do degrees of anxiety that can rise to the level of panic and psychosis, particularly in naive users and unfamiliar stressful situations.

The Bostwick article reviewed the often-blurred relationship between medical and recreational users. He discussed a Canadian study that found medical cannabis use often followed recreational use; and that most medical users continued using marijuana recreationally.  Another study of 4100 Californians found that medical users preferred inhaling their medication. Smoked cannabis has a more rapid response and is easier to titrate so that users get the analgesic effects without the higher levels favored by recreational users seeking the high. Given some of the medical problems from smoking marijuana, using vaporizers or nasal sprays may be an effective alternative delivery system.

Doctor Robert DuPont, in his book The Selfish Brain: Learning from Addiction, referred to marijuana as “a crude drug, a complex chemical slush.” Marijuana and hashish contain over 420 different chemicals, falling into 18 different chemical families. THC and cannabidiol (CBD), are only two of sixty-one cannabinoids, chemicals found only in the marijuana plant. THC is highly soluble in fats, and this quickly passes the blood-brain barrier. The factor, plus the fact that it is insoluble in water, means that it is trapped in bodily organs like the brain and reproductive glands, remaining there of days or even weeks afterwards.

Grant et al. reviewed evidence on the medicinal usefulness of marijuana in “Medical Marijuana: Clearing Away the Smoke.” They noted that most of the studies on the efficacy and safety of cannabinoids for pain and spasticity have occurred since the year 2000. A series of randomized studies at the University of California Center for Medicinal Cannabis Research (CMCR) found that cannabis significantly reduced pain intensity. A significantly greater proportion of individuals reported at least 30% reduction in pain on cannabis; the threshold of decreased pain intensity generally associated with improved quality of life. Medium doses of 3.5% THC cannabis cigarettes were as effective as higher dose (7% THC).

Oral preparations of synthetic THC (dronabinol, Marinol) and a synthetic THC analogue (nabilone, Cesamet) are legally available. Studies suggest that dronabinol significantly reduces pain. The effects on spasticity are mixed: “there may be no observable change in examiner-rated muscle tone, but patients report significant relief.” There has been less research done with nabilone, but there have been reports of modest analgesia. Dronabinol and nabilone are FDA-approved for control of acute and delayed nausea and vomiting from cancer chemotherapy.

Alternative delivery systems for cannabis include vape-pens, sublingual devices, and others that use a metered spray device. The advantages to such systems seem to be the use of known cannabinoid concentrations, predetermined dosing portions, and time-out systems that may help prevent overuse.

There are side effects, which are dose-related in terms of severity. Grant et al. reported that they seem to decline over time and are of mild to moderate severity. “Reviews suggest the most frequent side effects are dizziness or lightheadedness (30%-60%), dry mouth (10%-25%), fatigue (5%-40%), muscle weakness (10%-25%), myalgia [muscle pain] (25%), and palpitations (20%).” There is little data on a timeline of adverse or therapeutic effects. There have been concerns that rapid tolerance to adverse effects may indicate a corresponding tolerance to beneficial effects. But studies of oral sprays in multiple sclerosis report that you can reduce the incidence and severity of adverse effects by downward self-titration without loss of analgesia.

There are additional adverse effects, including some psychiatric side effects, especially with cannabis having high concentration of THC. See the original article for more specifics. The longer-term health risks of medicinal cannabis are unclear; most of the current evidence is based upon non-medical use. Some medical professionals indicate that effective medicinal use of cannabis requires significantly less marijuana than is typically consumed by recreational users.

In “The Current Status of Medical Marijuana in the United States,” Doctor Gerald McKenna noted how the majority of medical marijuana users in Hawaii claim they have chronic pain. He said a main problem in getting the medical profession to support the use of medical marijuana is that it is not widely used medicinally in a non-smoking form. “Authorizing use by inhalation of a drug with an unknown number of co-drugs contained in the same raw form is not supportable.” He said that supporting the use of medical marijuana by inhalation because users prefer it is akin to supporting the inhalation of any other drug taken orally. His impression is that medical marijuana laws have been passed “to bypass the illegality of marijuana.”

He did recommend removing marijuana from Schedule I controlled substance so research could be done more easily. “Until that research is done, stating that marijuana is useful for treating chronic pain, anxiety, post-traumatic stress disorder, depression, and other health conditions remains anecdotal and conjectural.”

It has become clear that the federal government needs to modify its resistance to reclassifying marijuana’s Schedule I Controlled Substance status to allow more quality research into its use and to fund that research. Otherwise, the current circus of inconsistent regulations from state to state, and unverified claims about the medicinal benefits of marijuana will have us back in the days of patent medicines, as far as marijuana is concerned. Further reflections on medical marijuana can be found in: “Let’s not Get Ahead of Ourselves,” “Is the Cart Before the Horse?” and “Marijuana Peek-a-Boo.”

06/15/15

Let’s Not Get Ahead of Ourselves

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© iqoncept | stockfresh.com

At the 249th annual meeting of the American Chemical Society, Andy LaFrate, the president and director of research of Charas Scientific presented the results his lab found on its analysis of marijuana. Average potencies are around 20% THC. He said that they have seen potency values approaching 30% THC. “As far as potency goes, it’s been surprising how strong a lot of the marijuana is.” But an unexpected consequence of that breeding for higher THC potency has been the lowering of CBD levels in many marijuana strains. CBD is the cannabinoid often touted for its therapeutic value. And unlike THC, CBD does not get people high.

There’s a lot of homogeneity whether you’re talking medical or retail level . . . One plant might have green leaves and another purple, and the absolute amount of cannabinoids might change, which relates to strength. But the ratio of THC to CBD to other cannabinoids isn’t changing a whole lot.

LaFrate said in a video, “Marijuana Testing Yields Fascinating Results,” that a lot of the time the CBD concentration is very low, sometimes too low for their equipment to detect.  The lack of CBD means that many of the hundreds of strains of marijuana actually are very similar, chemically. A lot of the medicinal benefits attributed to THC are actually from CBD, one of the 85 different cannabinoids that can be isolated from cannabis. Some of the most well known ones with known or presumed medicinal properties are reviewed in this crash course, Cannabinoid Profiles , by SC Laboratories and Weedmaps. The video makes the potential for medical marijuana sound exciting and almost limitless. But one thing seemed to be said over and over again—more research needs to be done.

LaFrate also looked for biological and chemical contaminants in the marijuana they tested and the results were surprising. “You’ll see a marijuana bud that looks beautiful. And then we run it through a biological assay, and we see that it’s covered in fungi.” He was startled to find just how dirty a lot of it was. Marijuana is a natural product, so there will be some microbial growth on it, said LaFrate. So the questions become: What’s a safe threshold? And which contaminants do we need to be concerned about?

Contaminant testing is not mandatory yet, but should be soon in Colorado. LaFrate noted that many samples had fungi or bacteria. Some marijuana products tested have butane, used to strip and concentrate THC from the plant. Other samples had heavy metals. He added that when you’re dealing with something like marijuana that’s been under prohibition for the last eighty years, scientific testing gives the consumer confidence that this is something that is safe. It seems that the state-by-state approval strategy of medical marijuana dating back to California has contributed to this issue with contaminants.

Not only can there be purity and contaminant concerns with cannabis, but the majority of the available varieties of cannabis are high in THC, the primary psychoactive ingredient, and low in CBD, the primary medicinal ingredient. Weedmaps provides a graphic of the eight known cannabinoids “that effect you most” with information on the claimed medicinal properties of the eight cannabinoids. A quick look shows that THC, “the most abundant and widely known” cannabinoid in marijuana has limited medicinal properties: it is an analgesic, it reduces vomiting and nausea, it suppresses muscle spasms and it is an appetite stimulant. The only medicinal property unique to THC in the chart is its appetite stimulant properties.

In contrast, cannabidiol (CBD) “may hold the most promise for many serious conditions.” And it’s the second most common in marijuana. In the CBD video found in Cannabinoid Profiles, Josh Wurzer, the Laboratory Director for SC Laboratories said when SC Laboratories began testing marijuana strains a few years ago, most plants were high in THC, typically 10% to 20%, with 1 to 1½ percent CBD. Now they are seeing strains with between 8 and 15 percent CBD and a concurrent 5 or 6 percent of THC. The higher CBD content occurs through the activation of a recessive gene in the cannabis plants. Wurzer said cannabis breeders have to find plants with the high CBD gene locked away and breed them. “The only way you can know if it is high in CBDa is to test it.”

There was an experiment at the Institute of Psychiatry at King College, London, that looked at the relationship of the effects of the two main ingredients in cannabis, THC and CBD. You can see a video of a reporter participating in the experiment here. Her mixture of THC and CBD left her with the giggles: “No matter how hard I tried to take the experiment seriously, it all seems hilarious.” But with pure THC, it was a different story. “It’s horrible. It’s like being at a funeral . . . Worse . . . It’s just so depressing. You want to top [kill] yourself.”

On THC and CBD mixture, she said she seemed flippant; on pure THC, she just didn’t care. With pure THC, she was suspicious, introverted; “weird.” Every question seemed to have a double meaning. She felt morbid. “It’s like a panic attack.” The researchers used the Positive and Negative Syndrome Scale (PNASS), a standard test to measure changes in psychotic symptoms. On the PNASS sub scale used, changes above four was clinically significant; what would be associated with schizophrenic psychosis. She scored fourteen. The effects were temporary.

The suggestion is that high levels of THC “can play havoc with your mind.” Individuals with no history of mental illness and no predisposition to schizophrenia don’t seem to be at long-term risk of THC triggering this reaction. But is seems that CBD has a counteractive effect on the paranoid and psychotic effects of THC. Here is a link to several studies on the positive effects of CBD on schizophrenia found on Project CBD.

There is also an SC Lab/Weedmaps video on the problem with overmedicating with cannabis. The pro medicinal marijuana panel noted that there is a tendency to overmedicate because of the largely nontoxic effects of cannabis. “It’s really safe to take a large dose. And you don’t get a lot of hangovers.” But you do get psychotoxicity (perceived harm).  Bonni Goldstein, MD, the CannaCenters Medical Director said she recommends a process of titrating up—starting with a low dose and waiting to see what the effects are before you add more.

A second panel member, Mike Corral, the co-founder and agricultural Director of W.A.M.M (WO/Men’s Alliance for Medical Marijuana), said that in talking to researchers, medically effective doses are measured in micrograms; a gram should medically last as much as a week. “Invariably, we see people smoking, three, four, five, six, seven grams a day. We come from a stoner culture.” He said that he had no problem with people getting stoned, but that wasn’t medical use. He also thought there should be full legalization to separate the recreational and medicinal users.

Another panel member, Michael Backes, the Founder/Director of Cornerstone Research Collective, said: “Just because something has a drug safety profile that’s favorable, like cannabis does, doesn’t mean there aren’t potentially some issues.”  He noted that one of things they learned from a cannabis pain study is that there was a “sweet spot” of dosage for cannabis, “and you don’t want to go past it.” The graphic within the video read: “Just as a patient who underdoses, one who overdoses will not have their symptoms relieved, therefore exceeding the ‘sweetspot’ is a waste of medicine.”

He said people have to respect their dose more. You could use cannabis in an overdosage for years, with little changes that you don’t notice, because they accumulate over time. Although cannabis is a very nontoxic substance, it is pharmacologically active, “and you’ve got to respect it.” He noted that 10% of individuals will develop a dependency issue, and then he wondered how you counsel people who you know are doing too much. “And how do you convince them “Hey, it’s time to back off?’”

Marijuana legalization continues to move forward on a state-by-state basis, which creates problems in a number of ways. As the above information pointed out, there is not a good system of quality control and contaminant testing available yet, even in Colorado. The majority of marijuana strains available, including those for medical marijuana, appear to be high in THC (the primary psychoactive cannabinoid) and lower in CBD (the primary medicinal cannabinoid). Current dosing practices, according to a panel of pro-medical cannabis individuals, are too high for medicinal purposes and could over time, lead to health problems like “dependency issues.” A cannabis strain high in THC and low in CBD could trigger symptoms associated with schizophrenia.

Before marijuana is legalized in more states, it seems advisable to make some federal changes. First, marijuana should be reclassified as a Schedule II controlled substance. This would make the desperately needed research on the medicinal properties of cannabis easier to do. Second would be to appropriate more funds into medical marijuana research. Third would be to fund the development of marijuana strains that are much higher in CBD and lower in THC. Fourth would be using the established process of clinical trials with the FDA for confirming treatment possibilities for cannabinoids.

Legalization polls  (see this Pew Research Center poll) that distinguish recreational marijuana use from medicinal marijuana use show that more Americans in favor of legalization fall into the medicinal camp. These suggestions would be consistent with the poll’s findings. Legalizing medical marijuana without these steps puts us back to the days of patent medicine. Medical marijuana should be treated like all other substances proposed as medicinal treatments for humans. Let’s not make the mistake of treating marijuana as a special case that doesn’t need to go through the same approval process for all other proposed medical treatments.

04/20/15

Medical Reform or Medicinal Con?

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© lightwise | 123RF.com

In my home state of Pennsylvania, the legislature is considering the legalization of medical marijuana. At least one activist believes it will happen in 2015: “We have the votes for it. It’s going to happen this term.” Jon Delano of KDKA cited Jay Costa, the Democratic Senate leader, as saying the medical marijuana bill is likely to be approved this spring. Legislation has been introduced in the Senate and gone to committee. “And it is very likely over the course of the next couple of months it will pass through the Senate and make its way over to the House.”

The new governor, Tom Wolfe, has publically said he would support medical marijuana in PA: “I believe that doctors who can now prescribe some of the most potent drugs in the world should be able to prescribe medical marijuana.” The problem seems to be in the State House, which is currently holding hearings on its own legislation. Tony Romeo with CBS Philly reported that law enforcement stressed the need for strict regulatory control if medical marijuana was legalized. Republican Matt Baker, chair of the House Health Committee said:

I am very cynical and skeptical about moving forward with this. And I think there are a lot of unresolved issues, and when you talk with the medical groups and the scientific community, they’re very, very concerned about us putting on white coats and trying to play doctor here.

Polls indicate that most Americans support the legalization of medical marijuana. More than half of the US population now lives in a state where marijuana in some form (medical or recreational) is legal. But take some time to really review this compilation of surveys on marijuana legalization on PollingReport.com. Several polls by organizations like the Pew Research Center, Gallup, and CBS News show a changing trend of Americans over time to agreeing that marijuana should be legalized, when the question is put as: “Do you think the use of marijuana should be made legal, or not?” All three organizations reported results that were essentially the same as the October 2014 Gallup poll—51% said yes to legalization; 47% said no to legalization.

But now look further down at a nationwide poll by the Pew Research Center taken in February of 2014, when the question answers had more options. There the question was: “Which comes closer to your view about the use of marijuana by adults? It should be legal for personal use. It should be legal only for medicinal use. OR, It should not be legal.” The results were: 39% said marijuana should be legal for personal use; 44% said it should be legal for medicinal use; 16% said it should not be legal; 2% were unsure or refused to answer.

Then the Pew Research Center published their newest poll on legalizing marijuana on April 14, 2015. This survey reported that 53% of Americans favored legalization, while 44% opposed legalization. Millennials (18-34) had the strongest support for legalization, with 68% in favor and 29% opposed. Among those who said marijuana should be legal, 78% did not think the federal government should enforce federal laws in states that allow its use. Conversely, among those who think marijuana should be illegal, 59% said there should be federal enforcement.

The most frequently cited reasons for supporting legalization are its medicinal benefits (41%), the belief that it is no worse than other drugs (36%) and its potential for tax revenue (27%). The most frequently mentioned reasons why people oppose legalization were that it hurts society and is bad for individuals (43%), and it is a dangerous, addictive drug (30%). So it seems that the Pew Research polls suggest there is more support for the use of medicinal marijuana than recreational marijuana.

Returning now to the compilation of results on Pollingreport.com there are some further interesting results in two other polls. In a CNN/ORC Poll done in January of 2014 the legal, not legal dichotomy gets most Americans saying marijuana should be legalized. And there is support for decriminalization measures as well. However, there are two other interesting results. 88% percent of the people polled think that marijuana should be able to be legally prescribed for medical purposes by their doctor. When asked if Colorado’s legalization of recreational marijuana was a good idea, a bad idea, or if you want to wait and see what happens before deciding, 33% thought legalization was a good idea; 29% thought is was a bad idea; and 37% wanted to wait and see what happens before they decide!

A Fox News Poll taken in February of 2013 asked if you thought that most people who smoke medical marijuana truly need it for medical purposes or just want to smoke marijuana; 30% said they truly needed it; 47% thought they just wanted to smoke it; 12% said it depended upon the person; 11% were unsure. Although there aren’t many well-accepted medical uses for marijuana as this point in time, there are some.

A 2007 study in the journal Neurology showed that marijuana is effective in reducing neuropathic pain in HIV patients. Live Science also reported marijuana, when combined with opiates, led to dramatic levels of pain relief. It has been helpful in reducing stiffness and muscle spasms in MS (Multiple sclerosis). It appears useful for reducing nausea induced by chemotherapy. Medical marijuana has been touted as a treatment for glaucoma, but other drugs are more effective.

Legalizing medical marijuana now will not just legitimize its medicinal use for these generally accepted conditions, it would permit the medicinal use of marijuana whenever the individual has been given a prescription for it by a doctor. Without reliable, scientifically replicated studies of the claims for medical marijuana efficacy, we would be returning to the times of patent medicine, where medical marijuana is claimed to treat almost anything and everything. The CNN polled opinion that medical marijuana users didn’t really need it, but just wanted to smoke it would then come true.

Sensible use of medical marijuana should follow the established procedures for all medicinal substances—approval by the FDA. As the medical usefulness of marijuana for a condition is demonstrated through this process, it would then become a FDA approved medicine.  I realize that once marijuana reaches this bar of approval, it would then be available for off label use for other medical conditions. But it would also then be REGULATED like all other medical treatments. The current process of state-by-state legislative approval of marijuana for medical purposes circumvents this regulative process. It was established to protect American citizens from the fiascos of past medical treatments that turned out to be ineffective at best and harmful at worst.

Reform must start at the federal level. Given that marijuana has been a Schedule I controlled substance, its availability for the kind of medical research needed to gain FDA approval has to be increased. So a first step would be changing its status from a Schedule I controlled substance to that of Schedule II. The reclassification would make it easier to do the needed research on its legitimate medical uses. I’d suggest delaying the approval of medical marijuana in Pennsylvania and the other states where it is not yet legal until research demonstrating its medical usefulness has gone through the FDA clinical trial process. This would delay the approval of medical marijuana, but it would establish a more stable path forward for the legitimate medical use of marijuana. Debates for the off label medical use could occur alongside those now going on for other classes of FDA approved drugs such as antipsychotics and antidepressants.

Incidentally, there was a bill introduced in the U.S. Senate to reclassify marijuana from Schedule I to Schedule II, the Compassionate Access, Research Expansion and Respect States (CARERS) Act. While it is gaining support, key leaders in both parties have reservations. As the Motley Fool pointed out, the proposed loosening of federal restraints comes just as a new study of the effects of heavy marijuana use on long-term memory in adolescents was published. I hope that if ongoing research demonstrates the need for further restrictions on the medicinal use of marijuana, there would be public and legislative support for that as well.

I suspect this suggestion would not be acceptable for many medical marijuana activists because their final goal is not just the medicinal legitimization of marijuana. Acceptance of medical marijuana may be the first steppingstone towards the legalization of recreational marijuana. As the polls show, there seems to be wider support for the medical use of marijuana than for the recreational use of marijuana. So press for the medical use of marijuana now, and then recreational approval at a future date.