04/25/17

Pesticides, Fungi and Pot

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 The marijuana website The Cannabist has an archived page on marijuana pesticides with fourteen articles published between December 4, 2015 and July 29, 2016.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?

04/4/17

CBD and the DEA

As 2016 drew to a close, the DEA announced its decision to classify cannabis extracts separately under the federal government’s Schedule I category. As Victoria Kim reported for The Fix, the ruling sent ripples of panic through the marijuana industry, playing on fears of what is ahead as our country grew closer to a Donald Trump presidency. While the DEA sees the change as marking a clear distinction between cannabis and it extracts, the marijuana industry sees it as saying that those who sell CBD oil are in violation of federal law. However, according to the DEA, the decision was made to more closely align U.S. policy with the United Nations, which already treats cannabis and its extracts separately.

Writing for Leafly, Bruce Barcott described the DEA announcement as an attempt “to criminalize the status of cannabidiol (CBD).” Hundreds of thousands of people around the country who rely on CBD products will be forced find CBD on the black market, according to the CEO of Women Grow. She said the rule “has the potential to inflict substantial harm to a legitimate industry that has been operating legally worldwide for over a decade.” The executive director of the Cannabis Business Alliance said it creates “unfair barriers for companies with cannabidiol in their products.”

Cloaked in the guise of a bureaucratic technicality, DEA Administrator Chuck Rosenberg made an aggressive bid to wrap CBD into the Controlled Substances Act as a federally illegal Schedule I drug.

In an article he wrote for Leafly on the day of the DEA announcement, Barcott noted where the acting administrator for the DEA said the new code would allow the DEA to track quantities of marijuana extract separately from marijuana. The changes bring U.S. regulations into compliance with international drug-control treaties and present no major change in the law. “Rather it serves to clarify and reinforce the DEA’s position on all cannabis extracts, including CBD oil.” All marijuana extracts will continue to be treated as Schedule I controlled substances.

So what is the uproar if the DEA is merely bringing U.S. regulations in line with international regulations—if marijuana extracts were already Schedule I controlled substances? Barcott said the new rule clarifies the DEA’s position after the 2014 farm bill allowed certain states to grow hemp and blocked federal law enforcement from interfering with state agencies, hemp growers and agricultural research. Hemp-derived CBD oil is available nationwide on web sites and through mail order services. “Those operations survive on the assumption that cannabidiol products below the legal threshold for THC percentage in hemp (0.3 percent or less) are technically legal.” Barcott suggested the rule now says you can grow hemp, but if you try to extract CBD oil from it, the DEA considers that a federal crime.

First, hemp-based CBD products do not have the therapeutic benefits they claim to have. Writing for High Times, Mike Adams noted in his 2014 article, “The Difference Between Hemp Oil and High-CBD Strains,” that while CBD was still illegal in most of the U.S., its rise as “the rock star of the medical marijuana industry” provided the opportunity for some hemp businesses to “market a variation of knockoff CBD treatments that they claim have the same healing power as popular strains such as Charlotte’s Web.” These so-called “knockoff CBD treatments,” while technically similar to medical marijuana strains with CBD, “do not provide the same health benefits as high-CBD cannabis strains.”

However, after patients began submitting complaints about some of these products, including “Real Scientific Hemp Oil,” claiming they were making them sick, a research firm dedicated to cannabidiol education – called Project CBD – launched a full-blown investigation into the matter. After six months, the organization emerged with a 30-page report entitled “Hemp Oil Hustlers: A Project CBD Special Report on Medical Marijuana Inc., HempMeds and Kannaway,” which began as a curious look into an umbrella penny stock company, but transformed into a dissection of the hemp oil industry and its sometimes shady business practices.

Project CBD published a report in 2014 that investigated hemp oil products. The introduction of the report said that Project CBD did not believe that industrial hemp was an optimal source of CBD. On page 13 of the report is a quote from a press release of the Hemp Industries Association. The quote clearly indicates its position:

It is important for America farmers and processors of hemp to understand that most CBD in products mislabeled as ‘hemp oil’ is a co-product of large-scale hemp stalk and fiber processing facilities in Europe where the fiber is the primary material produced at a large scale. CBD is not a product or component of hemp seeds, and labeling to that effect is misleading and motivated by the desire to take advantage of the legal grey area under federal law. Hemp seed oil does not contain any significant quantity of CBD.

So the hue-and-cry about the DEA’s clarification means that the loophole opened by the 2014 farm bill for hemp CBD products has been closed. Retailers selling “knockoff CBD treatments” of questionable medicinal value will now have to stop selling these products or face possible federal prosecution. This is a good thing. But what about the new 7350 drug code proposed by the DEA?

In the Federal Register, vol. 81, no. 240, under “Why a New Code Number is Needed,” it was noted that U.N. conventions on international drug control treated cannabis extracts differently from marijuana and THC. So creating a new drug code for marijuana extracts would allow for more appropriate accounting of these materials consistent with existing treaty provisions. The existing schedules contained in DEA regulations include marijuana as a Schedule I drug (drug code 7360). This listing includes “any material, compound, mixture, or preparation, which contains any quantity of the substance, or which contains any of its salts, isomers, and salts of isomers that are possible within the specific chemical designation.”

Until now, the DEA has used the 7360 drug code for all marijuana extracts. The proposed rule change recommends that a new drug code, 7350, should be used for marijuana extracts. Marijuana extracts “will continue to be treated as Schedule I controlled substances.” In other words, they were always Schedule I substances.

The Single Convention on Narcotic Drugs and 1971 Convention on Psychotropic Substances are international treaties that provide for the international control of marijuana. The schedules under the Single Convention prohibit the production and supply of specific drugs as well as drugs with similar effects—except for drugs under license for specific purposes, such as medical treatment and research. Many of the provisions of the Controlled Substances Act (CSA) under which the DEA operates were drafted to comply with these Conventions. Both the CSA and the Single Convention list drugs in four schedules, but their classification schemes mean different things. For one, drugs can be in more than one schedule under the Single Convention.

In the Single Convention, the most stringent controls are in Schedule IV; and all Schedule IV drugs are also listed in Schedule I. So placing a drug into both Schedule I and Schedule IV “imposes the most stringent controls under the Single Convention.” Cannabis or marijuana falls into three listings within the Single Convention. Cannabis is the flowering or fruiting tops of the cannabis plant (with the resin not extracted). Cannabis resin is the separated resin, crude or purified, obtained from the cannabis plant. Then there are the extracts and tinctures of cannabis.

The Single Convention placed “cannabis” and “cannabis resin” under both Schedule I and IV of the Convention, the most stringent level of control under the Convention. While “cannabis resin” is extracted from “cannabis,” the Single Convention specifically controls “extracts” separately. Extracts of cannabis are controlled only under Schedule I of the Convention, which is a lower level of control than “cannabis resin.”

Cannabis resin and cannabis (marijuana) will continue under the drug code for marijuana (drug code 7360). The DEA changes will distinguish cannabis extracts from cannabis resin, by defining “marijuana extract” to exclude material referenced as “cannabis resin” under the Single Convention. The new code number created by the DEA is as follows:

Marihuana Extract—7350 ‘‘Meaning an extract containing one or more cannabinoids that has been derived from any plant of the genus Cannabis, other than the separated resin (whether crude or purified) obtained from the plant.’’

Not only does this distinction bring U.S., CSA regulations in line with the Single Convention, it creates a category for medicinal cannabis extracts to be scheduled differently from the recreational cannabis products that fall within the “7360” drug code. Cannabis resin products such as shatter, wax, honey, budder and others will remain classified as 7360—along with the flowering or fruiting tops of the cannabis plant that are rolled into joints or smoked in pipes. But cannabis or marijuana extracts, coded with the 7350 drug code, could be reclassified into a lower CSA Schedule. As the science of CBD research demonstrates the medicinal efficacy of CBD more clearly and consistently, this could be done without rescheduling cannabis bud and flower or cannabis resin. No wonder companies selling marijuana and hemp-based CBD products don’t like the new DEA ruling.

03/3/17

Shatter and Psychosis

Dr. Kiri Simms is an emergency psychiatrist in Victoria, British Columbia. Two years ago she saw her first patient with marijuana-induced psychosis. The person was very young and very disconnected from reality. “She was very, very ill.” Shatter, a butane hash oil product, was the only drug she used. In the past, most people did not become psychotic with marijuana use alone, Dr. Simms said. “That has changed with these butane hash oil products.”

Dr. Simms said she’s seeing an increased severity and intensity of symptoms with some people at her emergency department (ED). In the past year, she estimated she’s treated ten people who had used shatter and whose problems were severe enough to require a stay in psychiatric intensive care or on one of their inpatient wards. People are often surprised they experienced psychotic symptoms from using marijuana products, she said.

It used to be that people did not become psychotic from marijuana use alone. Infrequently, individuals with a family history of schizophrenia might have a psychotic experience after smoking marijuana, but not any more. It’s not like the old days, where symptoms would pass in a few hours or days. Now Dr. Simms said they are seeing people who sometimes take weeks and occasionally months for their psychotic symptoms to clear.

The above discussion was in an interview she did with Greg Craigie the host of the CBC radio program, On the Island. You can read excerpts or follow a link to hear the full interview here. Craigie followed the Simms interview with one he did with Rebecca Jessemen, the senior policy advisor for the Canadian Centre of Substance Abuse. She said they were really concerned with minimizing the risk of harm with youth, as marijuana legalization moves closer in Canada. “That includes key messages such as delaying initiation of use, reducing frequency of use, and reducing the quantity of use… Part of that is quantity in terms of concentration too.”

Not surprisingly, the interview and web story prompted several mostly negative Facebook comments rejecting a link between shatter and psychosis. Accusations were made of this being false news, that CBC was spreading anti-cannabis propaganda, etc. You can read an article about Craigie’s interview with Rebecca Jessemen here. But this is not fake news. There is a clear, known association of marijuana use and psychotic episodes. And with higher THC content in a marijuana product, the risk of a psychotic episode increases.

Do people react differently to the same dose of THC? Does cannabidiol (CBD) reduce the psychotic effects of THC? There was an experiment done at the Institute of Psychiatry at King’s College, London that looked at the relationship of the effects of the two main cannabinoids in cannabis, THC and CBD. You can watch a video of a reporter participating in the experiment here.

She was given pure THC and a mixture of THC and CBD. On the THC and CBD mixture, the reporter said she seemed flippant; on pure THC, she just didn’t care. The 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.”

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.” “It’s horrible. It’s like being at a funeral . . . Worse . . . It’s just so depressing. You want to top [kill] yourself.”

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; changes that would be associated with schizophrenic psychosis. She scored fourteen. The effects on the reporter were temporary and would not be long lasting. But the video clearly shows how higher concentrations of THC can induce temporary psychotic symptoms in normal individuals.

In a NPR interview, Dr. Nora Volkow, the director of the National Institute for Drug Abuse (NIDA) said while no one would question that marijuana can trigger temporary symptoms of psychosis in some people, it is not clear whether cannabis alone can trigger schizophrenia. “You can have a psychotic episode from the use of marijuana without it turning into schizophrenia. . . . It’s very distressing, but you’ll get out of it.” While drugs like marijuana and methamphetamine can lead to experiencing symptoms like paranoia and disorganized thinking, that’s very different from schizophrenia.

Dr. Volkow suggested the studies show that people with schizophrenia tend to smoke pot. People with an emerging schizophrenic disorder maybe “trying to self-medicate because they just don’t feel right.” Volkow believes if someone has a vulnerability to schizophrenia smoking it could trigger a psychotic episode. Without the predisposition, “you can smoke all the marijuana you want and it will make no difference.” Volkow did acknowledge the dramatic increase in people showing up in the emergency department with a temporary psychotic episode could be related to “a much more potent marijuana.”

But not everyone has the same opinion; that there is a clear distinction between schizophrenia and marijuana-induced psychosis. Sir Robin Murray, a psychiatrist at King’s College in London said 20 years ago he would tell patients that cannabis was safe. “It’s only after you see all the patients that go psychotic that you realize—it’s not safe.”

Krista Lisdahl, a clinical neuropsychologist, said that if marijuana is causing schizophrenia, this happens during an individual’s early years of development. There hasn’t been an increase in the number of people with schizophrenia; the number still hovers around 1%. However, studies do show that the earlier someone starts using marijuana, the more likely they will develop a psychiatric disorder in general.

A report by DAWN (Drug Abuse Warning Network) found that ED visits due to marijuana increased by 52% between 2004 and 2011. This was lower than the increase in ED visits for anti-anxiety and insomnia medications (124%), narcotic pain relievers (153%), antipsychotics (71%), and stimulants like ADHD medications (292%). Nevertheless, Sir Robin Murray said the data strengthens the case of an association between cannabis and the risk for schizophrenia. A study in The Lancet which he published suggested marijuana with around 15% THC could increase the risk of schizophrenia 5 times. “We think about 5 percent of people will go psychotic instead of 1 percent.”

Our findings show the importance of raising public awareness of the risk associated with use of high-potency cannabis, especially when such varieties of cannabis are becoming more available. The worldwide trend of liberalisation of the legal constraints on the use of cannabis further emphasises the urgent need to develop public education to inform young people about the risks of high-potency cannabis.

A 2014 article in Frontiers in Psychiatry, “Gone to Pot,” reviewed the emerging evidence of a connection between cannabis and psychosis/psychotic disorders, including schizophrenia. The review was comprehensive and suggested cannabis may be a component in the emergence of psychosis. But the precise nature of these associations remains unclear. However, the relationship has been evident since the mid 1800s. One of the earliest studies of marijuana and psychosis was done by the French psychiatrist Jacques-Joseph Moreau, and reported in his 1845 book, Hashish and Mental Illness. Moreau said hashish (cannabis resin) could precipitate:

… acute psychotic reactions, generally lasting but a few hours, but occasionally as long as a week; the reaction seemed dose-related and its main features included paranoid ideation, illusions, hallucinations, delusions, depersonalization, confusion, restlessness, and excitement. There can be delirium, disorientation, and marked clouding of consciousness.

Consistent with the YouTube video of the King’s College experiment linked above, cannabis extract and THC alone have been shown to produce a range of transient symptoms similar to the positive symptoms of schizophrenia: “suspiciousness, paranoid and grandiose delusions, conceptual disorganization, fragmented thinking, and perceptual alterations. Additionally, cannabis and THC also result in depersonalization, derealization, alterations in sensory perception, and feelings of unreality.” A double-blind, randomized, placebo-controlled study by D’Souza et al. found that THC produced transient positive psychotic symptoms. A similar study replicated these findings in healthy individuals with a lower THC dose than D’Souza et al.

Several studies suggest a “window of opportunity” hypothesis, meaning there is a critical period during early adolescence “where the brain is particularly susceptible to the psychosis-inducing effects of cannabis.” The premise suggests cannabis may affect the brain during a critical period of development and maturation. Cannabis could disrupt one or more of these maturation processes.

By disrupting the endocannabinoid system and interfering with neurodevelopmental processes, exogenous [from outside of an organism] cannabinoids may provide a biologically plausible mechanism by which exposure to cannabinoids during adolescence may increase the risk for the development of schizophrenia.

While there has been a notable increase in the rates of cannabis use over the past four decades, there has not been an increase in the prevalence of schizophrenia. The authors admit these results are difficult to explain in the context of their review showing how “the relationship between cannabinoids and psychosis fulfills many but not all of the traditional criteria for causality.” One possible explanation is that schizophrenia rates are lagging behind increased rates of cannabis consumption. In other words, we need to look for a future increase of schizophrenia rates with a cannabis connection.

Given the evidence presented above, it is likely that cannabis is an important component cause in the development of psychotic disorders. This causal role is apparantly magnified when cannabis exposure occurs at an earlier age, in greater quantities, and over a longer time-course. Further, as was discussed in this review, specific populations (i.e., those with a genetic vulnerability or a history of childhood abuse) may be particularly susceptible to the causal effects of cannabis. In conclusion the authors said:

Acute exposure to both natural and synthetic cannabinoids can produce a full range of transient symptoms, cognitive deficits, and psychophysiological abnormalities that bear a striking resemblance to some of the features of schizophrenia. Also clear is that, in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Finally, exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. However, it should be remembered that the majority of individuals who consume cannabis do not experience any kind of psychosis.

So the On the Island interview with Dr. Simms was not an example of fake news or anti-marijuana fear mongering. While the dangers of cannabis use don’t approach those portrayed in the classic cult film Reefer Madness, there is growing evidence of a risk of psychotic symptoms with higher levels of THC in marijuana products like shatter. And there is an increased risk of psychosis later in life for a subgroup of adolescents who use marijuana. The evidence is not conclusive at this time, but can we afford to just wait-and-see if wide spread recreational marijuana use conclusively causes the adverse effects discussed above before taking regulatory action?

02/20/17

Listening to Marijuana Research

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.

01/20/17

Marijuana Use and the Heart

Research was presented in November of 2016 at the American Heart Association’s Scientific Sessions that connected marijuana use and a heart muscle problem that can mimic the symptoms of a heart attack. “Stress cardiomyopathy is a sudden, usually temporary, weakening of the heart muscle that reduces the heart’s ability to pump, leading to chest pain, shortness of breath, dizziness and sometimes fainting.” Younger marijuana male users were twice as likely as non-users to experience this heart condition, which usually occurs in older women. They were also significantly more likely to go into cardiac arrest and need an implanted defibrillator to detect and correct the dangerously abnormal heart rhythms.

None of the people in the study who had used marijuana died after they were admitted to the hospital; so this study did not link marijuana use to sudden death. But some reports, discussed below, do report such a link. Nevertheless, one of the study’s co-authors said the link between smoking marijuana and stress cardiomyopathy in younger patients suggests the need for further investigation, especially with the growing legalization of recreational and medical marijuana in the U.S. “If you are using marijuana and develop symptoms such as chest pain and shortness of breath, you should be evaluated by a healthcare provider to make sure you aren’t having stress cardiomyopathy or another heart problem.” See the article on Live Science and the press release from the American Heart Association for more information.

The above heart condition is a rare occurrence, as is sudden cardiac death with marijuana use, but the incidence rate is not zero. Thomas, Kloner and Rezkalla published an article in the January 2014 issue of The American Journal of Cardiology describing a series of marijuana-related heart problems. Thomas et al. noted that published reports describe a temporal relationship between marijuana use and developing heart problems such as: acute myocardial infarction (a heart attack), cardiomyopathy, and sudden cardiac death. Careful evaluation of the cardiovascular effects of marijuana are complicated by the fact that it is often combined with other drugs, such as alcohol or tobacco.

The mechanism underlying the association between marijuana use and myocardial infarction is currently unknown. But it seems possible cannabis has a negative effect on coronary microcirculation. One reviewed report demonstrated how marijuana use made a 34-year-old man susceptible to ventricular tachycardia. After he stopped his marijuana use, his coronary flow returned to normal. A 2010 case study by Karabulut and Cakmak in Kardiologia Polska documented the existence of slow coronary flow in an individual who consumed marijuana regularly over a long period of time.

In “Triggering Myocardial Infarction by Marijuana,” Mittleman et al. interviewed 3,882 individuals an average of four days after the onset of myocardial infarction. The risk of myocardial infarction was 4.8 times higher in the sixty minutes after marijuana use. The risk rapidly decreased afterwards. They were less likely to have a history of angina or hypertension. Showing the presence of the above noted complicating factors, they also tended to be current cigarette smokers and obese.

Thomas, Kloner and Rezkalla noted where most case reports described relatively young patients in their 20s or 30s with normal coronary arteries or minimal atherosclerosis. This suggested that marijuana does not lead to or accelerate atherosclerotic damage in healthy adults and might explain the rarity of reports of marijuana-associated myocardial infarction despite the widespread use of the drug.

Marijuana use may also precipitate the development of myocardial infarction in patients with coronary artery disease. After myocardial infarction, mortality is signiifcantly higher in marijuana users than in the general population. In a study of 1,913 adults after hospitalization for myocardial infarction, Mukamal et al found a 4.2-fold increased risk for mortality in marijuana users who reported consuming the drug more than once per week before the onset of the infarction compared with nonusers.

Reports of marijuana use and sudden death are rarer than those of myocardial infarction, but nevertheless still evident. Most patients were abusing other drugs along with marijuana, precluding an accurate conclusion about the role played by marijuana in the cause of death. Yet there was a case report in the December 2001 issues of Forensic Science International by Bachs and Morland, “Acute cardiovascular fatalities following cannabis use,” of six possible cases of acute cardiovascular death in young adults, who had very recent cannabis use. This was confirmed by the presence of THC in post mortem blood samples; no other drugs were present. The article abstract noted where similar cases have been reported, but the toxicology reports were absent or limited to just urine samples.

The authors also speculated on the underlying mechanisms to these adverse effects. They acknowledged that currently relatively little is known about the underlying mechanisms at this point in time. Yet they noted several features of marijuana use that may explain the potential for an adverse effect on patients with known coronary artery disease. For example, marijuana is known to increase heart rate.

Supporting these findings, the American College of Cardiology described the following effects of marijuana on the cardiovascular system. In “Marijuana and Coronary Heart Disease,” the cardiovascular effects of marijuana included: elevated systolic and diastolic blood pressure, tachycardia,elevated sympathetic stimulation, decreased time to angina, increased risk of myocardial infarction for one hour after marijuana use.

A 2006 study based on data from The Coronary Artery Risk Development in Young Adults (CARDIA) study showed that marijuana use was associated with increased appetite, high caloric diet, and acute increase in blood pressure. “Although marijuana was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors … which all have long-term detrimental effects on health.”

There seems to be a consensus with the following remarks by Thomas, Kloner and Rezkalla to cardiologists and their patients alike:

In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects.

01/10/17

Marijuana Makes You Nauseous?

Live Science reported on a study published in the August 31, 2016 issue of The Lancet that found more people are using marijuana and they are using it more often. In 2014, 13.4% of people said they had used marijuana in the previous year, an increase of 3% since 2002. The percentage of people who reported daily or near daily use rose from 1.9% to 3.5%. At the same time concerns about the risks associated with marijuana use dropped. In 2002, 50.4% of adults thought there was a great risk with marijuana use. That fell to 33.3% by 2014. But the perception of lowered risks may be premature.

The authors of the Compton et al. study thought the combination of increased marijuana use and a decreasing perception of the harm suggested there was a need for education regarding the risks of smoking marijuana. One of these health risks is for a medical condition called cannabinoid hyperemesis syndrome, or CHS. It is caused by heavy, long-term use of various forms of marijuana. Its symptoms include cyclic episodes of nausea and vomiting; some people have severe abdominal pain. A CBS Evening News report described a man who struggled with symptoms of CHS for two years before it was correctly diagnosed. Oddly, hot showers or baths seem to provide symptom relief.

CHS was first reported in 2004 by Allen et al. The ten patients were all cyclical vomiters and chronic marijuana users. Nine of the ten also had the abnormal bathing behavior of multiple hot showers or baths. The symptoms of nausea, vomiting and abdominal pain would all settle within minutes of taking a hot bath or shower. Symptoms resolved with abstaining from marijuana use in seven of the ten patients. Three of the abstaining patients resumed marijuana use and relapsed within months.

High Times described CHS as a rare form of cannabinoid toxicity that developed in chronic smokers. The author suggested with CHS, there was generally daily use in excess of three to fives times for several years. CHS is often mistaken for cyclic vomiting syndrome (CVS), because the symptoms are similar. But CVS is not caused by marijuana use. CHS is easily cured by abstaining from cannabis use.

This should not, by any means, hurt marijuana’s reputation for being the safest recreational drug around, but people need to be aware of the syndrome’s existence. If you know anyone with these symptoms tell him or her go to a doctor and stop smoking.

A 2011 review article by Galli et al., “Cannabinoid Hyperemesis Syndrome,” observed how the recognition of CHS coincided with the increased use of cannabis. Their review gave an overview of cannabinoid pharmacology that focused on the properties that seem to contributes to CHS. They also gave a clinical description of CHS and a proposed a method for clinical evaluation, which included differential diagnosis and treatment modalities.

Patients are typically young adults with a long history of cannabis use. They present with recurrent episodes of nausea, vomiting and dehydration with frequent visits to emergency departments. In almost all cases, there was a delay of several years between their chronic marijuana use and the onset of symptoms. One study reported an average duration of 16.3 years of cannabis use before the onset of symptoms. But there have been reports where the time lag was equal to or less than three years.

CHS is a recurrent disorder, with symptom-free periods. There are three phases: pre-emetic, hyperemetic, and recovery. The pre-emetic phase can last for months or years. Patients have early morning nausea, a fear of vomiting and abdominal discomfort. They maintain normal eating patterns and may even increase their marijuana use because its reported relief of nausea.

The hyperemetic phase has spasms of intense and persistent nausea and vomiting, which has been described as “overwhelming and incapacitating.” Patients vomit profusely, often without warning—up to five times per hour. There can be weight loss. Most patients have diffuse, but relatively mild abdominal pain. They are found to be dehydrated, but hemodynamically stable. The tests and work ups done at EDs are inconclusive in the majority of cases.

During this phase, patients take numerous hot showers throughout the day. As this seems to be the only measure that brings some symptom relief, it rapidly becomes a compulsive behavior. The precise mechanism for this relief is not known. It typically lasts for 24 to 48 hours, but the risk of relapse is high if the patient resumes cannabis use.

The recovery phase can last for days, weeks or months. It’s associated with relative wellness and eating patterns. “Weight is regained and bathing returns to regular frequency.”

Patients with CHS usually are misdiagnosed for a considerable length of time. One problem is that it is often confused with cyclic vomiting syndrome (CVS). “Confusion also exists in the medical literature secondary to a failure to recognize chronic marijuana use as a source of vomiting.” Although there is a close similarity of conditions, there are also significant differences.

A 2015 study by Kim et al. looked at the prevalence of patients presenting for cyclic vomiting in Colorado before and after the liberalization of medical marijuana in 2009. A secondary objective was to describe the odds of marijuana use among cyclic vomiting visits during these same time periods. The prevalence of CVS increased from 42 per 113,262 Ed visits to 87 per 125,095 ED visits after marijuana liberalization. Patients with CVS post liberalization were more likely to have documented marijuana use than patients in the pre liberalization period.

The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both.

The study said it does not demonstrate causation of CHS. But it does demonstrate a preliminary association “and should serve as the foundation for future prospective studies on the association between marijuana and cyclic vomiting, the eventual establishment of formal diagnostic criteria for CHS.” Foremost among the interventions for symptomatic treatment should be counseling toward abstinence from marijuana use. The authors saw their study as a crucial first step towards establishing a formal diagnosis of cannabinoid hyperemesis syndrome.

High Times seemed to minimize the present concerns with CHS by referring to it as “a very rare syndrome” that is easily cured. CHS does not reverse marijuana’s reputation as “the safest recreational drug around” at this point. But remember that even High Times agreed the cure for CHS is to stop using cannabis. We are just entering into a time of not only increased marijuana use, but also increased daily or near daily marijuana use. As this trend grows into a population of chronic, heavy marijuana users, the safety profile for marijuana will likely change; and it seems that CHS will be part of that decreasing safety profile.

11/29/16

Marijuana & Adverse Health Effects

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.

08/19/16

Head-in-the-Sand

Within the U.S. the legalization of medical and recreational marijuana has rapidly increased over the past few years, but not without some disturbing trends. One of these is the rise in THC potency within cannabis. The 2016 World Drug Report (2016 WDR) indicated that cannabis THC potency in the U.S. has been increasing over the past thirty years. It went from less than 3.4% in 1993 to 8.8% in 2008. Bloomberg reported that more recent data suggests that THC potency in cannabis increased to 12.6% in marijuana seized by authorities in 2013. In states where recreational marijuana is legal, such as Colorado and Washington, some samples have reached as high as 30%, with the average around 17%, according to the 2016 WDR.

Mehmedic et al. published an article in the September 2010 edition of the Journal of Forensic Sciences that also concluded the increasing potency of THC in cannabis. While there was the above noted increase of THC in cannabis seized by authorities, the CBD concentration increased only slightly, from .3% to .4%. The cannabinoid with the greatest known medical potential in marijuana is CBD, not THC. The researchers concluded not only was cannabis more potent, the market share for higher-potency products was increasing. “The question now becomes: What are the effects of the availability of high-potency products on cannabis users?”

A partial explanation for the increased potency in legal commercial markets like Colorado is the popularity of edible cannabis products made with cannabis extract-based concentrates such as oil, “wax,” or “shatter.” The THC potency of these extracts can be up to 80-90 percent. In 2014, edible products accounted for an estimated 35% of retail sales of recreational marijuana in Colorado. This makes it difficult to determine the dose or amount of THC ingested in an edible, leading to potential over-intoxication. “With edible products, the slower onset and longer duration of intoxication could increase the risk of over-intoxication, especially for new or inexperienced users.”

One way of regulating this concern has been to implement stringent labeling and packaging requirements. Washington and Colorado require edibles to have a 10mg serving size of THC. Alaska and Oregon have drafted legislation to set the serving size at a maximum of 5 mg of THC. The increasing potency has not been the only concern within states where marijuana is now legal.

Since the legalization of recreational marijuana in Colorado and Washington, incidents of accidental ingestion of cannabis among young children have been increasing. The Washington Poison Control center reported the number of cannabis exposure calls for people under 20 doubled from 2010 to 2014. In Colorado, within one year of legalization there was a 29% increase in the number of marijuana-related ER visits and a 38% increase in the number of cannabis-related hospitalizations.

More people using marijuana recreationally means an increase in the number of individuals driving under the influence of marijuana. The 2016 WDR said studies suggested that although cannabis seemed to be less hazardous than alcohol with regard to driving impairment, it is much more dangerous when used in combination with alcohol. In both Colorado and Washington there have been increases in the percentages of crashes and fatal crashes of drivers who tested positive for marijuana from 2012 to 2015.

Not surprisingly, the number of arrests and court cases with cannabis-related offences dropped substantially in state that have legalized marijuana. But data on other marijuana-related offences such as citations or warnings for public consumption were not readily available. See the following chart taken from the 2016 WDR.

However, there has been a ripple effect of drug concerns in the states adjacent to states where recreational marijuana is legal. In December of 2014, Nebraska and Oklahoma sued Colorado, requesting that the U.S. Supreme Court reverse Colorado’s decision to legalize marijuana, as it had led to an increase in trafficking marijuana in these neighboring jurisdictions. Attorneys for Colorado and the Obama administration asked the Supreme Court not take up the lawsuit. But as it turned out, the Court was also reluctant to take on the dispute as well.

The Supreme Court justices spent more than a year pondering whether to take the case. The proposed lawsuit was scheduled and re-scheduled five times for a closed-door conference, where the justices would debate the merits of taking the case.

In March of 2016 the Supreme Court declined by a vote of 6-2 to hear their complaint against Colorado. But the vote did not rule out future challenges. The Colorado Attorney General said that while the state has had several legal victories in federal lawsuits surrounding Amendment 64 legalizing recreational marijuana, Nebraska and Oklahoma’s concerns will not disappear. Doug Peterson, the Nebraska Attorney General was quoted by the Denver Post as saying: “The Court’s decision does not bar additional challenges to Colorado’s scheme in federal district court.” The Oklahoma Attorney General, Scott Pruitt said:

The fact remains — Colorado marijuana continues to flow into Oklahoma, in direct violation of federal and state law. Colorado should do the right thing and stop refusing to take reasonable steps to prevent the flow of marijuana outside of its border. And the Obama administration should do its job under the Constitution and enforce the Controlled Substances Act. Until they do, Oklahoma will continue to utilize every law enforcement tool available to it to ensure that the flow of illegal drugs into our state is stopped.

The federal government cannot continue to sit on the sidelines while recreational marijuana laws take hold state-by-state. The medical potential needs to be scientifically delineated and a step towards that is rescheduling marijuana as a Schedule II controlled Substance. The adverse effects of increased THC potency should be investigated, monitored and ultimately regulated. The collateral harm in neighboring states where marijuana is not legal should be dealt with cooperatively between states or result in federally mediated changes. Continuing a head-in-the-sand approach at the federal level is no longer a viable option.

The United Nations Office on Drugs and Crime (UNODC) publishes a yearly report giving a global overview of the supply and demand of various drugs and their impact on health. This is one of a series of articles discussing information from the 2016 World Drug Report.

07/27/15

Clearing Away the Medical Marijuana Smoke

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 (CBD). 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.”

04/20/15

Medical Reform or Medicinal Con?

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.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag Archives: Marijuana