Tag: CBD

04/20/21

The Business of Legalizing Marijuana in PA

Brass big marijuana coin with cannabis leaf near business inscription.

In the midst of our national political news, there was an announcement by John Fetterman, the Lieutenant Governor of Pennsylvania, that he is formally exploring a run for the U.S. Senate in 2022. According to Marijuana Moment, legalizing weed is a central part of his political platform. Fetterman said: “We’re going to get there. There’s never going to be a time when that’s not true. It’s inevitable. They know it, I know it, everyone knows it.” He even placed a marijuana flag on the balcony of his office in the Pennsylvania Capitol building as lawmakers were sworn in ahead of the 2021 legislative session.

If he decides to run, this will be his second try for the U.S. Senate. In 2016 Fetterman lost in the Democratic primary, but earned 20 percent of the vote in a four-way race. Two years later, he ran for Pennsylvania Lieutenant Governor and won. Weeks after taking office, he began a listening tour through all 67 counties of the state “to engage with Pennsylvanians about legalizing marijuana.” He said: “We want full legalization. I mean, that’s really the net goal.”

Given Fetterman’s commitment to full legalization, which means legalizing marijuana for recreational use, Pennsylvanians should know more about the potential consequences of this proposed marijuana legalization. If HB 2050 is passed, adults 21 and over could possess any amount of cannabis. Public consumption is prohibited. Adults 21 and older could cultivate 50 square feet of mature, flowering cannabis plants within a private residence. And adults could gift up to one ounce from cannabis grown in their private residences.

Going “full Colorado,” as Fetterman has called it has had negative consequences in Colorado, with the crime rate increasing 11 times faster than the rest of the nation since legalization, according to the Colorado Department of Public Safety. SAM, Smart Approaches to Marijuana, reported the number of drivers intoxicated with marijuana and involved in fatal accidents increased 88% from 2013 to 2015. The proportion of Colorado youth who reported marijuana use in the past 30 days was higher than the national average. Fuller discussion of these facts and more can be found in, “Should Pennsylvania Go ‘Full Colorado’ With Marijuana?” Part 1 and Part 2. Also see, “From The Frying Pan Into the Fire With Recreational Marijuana in PA.”

There are also concerns with the potential consequences with high-potency marijuana. Today’s cannabis is much more powerful than it was in the past. The U.S. Surgeon General published an advisory on Marijuana Use and the Developing Brain. Citing a study published in Biological Psychiatry, “Changes in Cannabis Potency over the Last Two Decades,” he said the THC concentration in commonly cultivated marijuana plants increased three-fold from 1995 through 2014, 4% to 12%. Researchers of a different study of legal cannabis sold in Washington State dispensaries found that the median THC levels varied from 17.7% to 23.2%.

Concentrated THC products, known as “dabs,” “wax,” “budder,” are becoming more widely available to recreational users and were found in yet another study, “To Dab or Not to Dab,” to range from 23.7% to 75.9% THC. The authors also cited published case reports that showed significant psychosis, neurotoxicity and cardiotoxicity with dabs. They described three males in their teens or twenties who used some form of dab. Two of the subjects had paranoia-like symptoms and one subject had seizure-like activity. Analysis of the dab sample used by one of the subjects was 20.5% THC without any detectable level of cannabidiol (CBD). The Surgeon General said the risks of physical dependence and other negative consequences increase with exposure to high concentrations of THC. “Higher doses of THC are more likely to produce anxiety, agitation, paranoia, and psychosis.”

A systematic review and meta-analysis published in the Lancet found that acute administration of THC induced increased positive (psychotic), negative (i.e., poor rapport) and general (depression) psychiatric symptoms.  “These findings demonstrate that the acute administration of THC induces positive, negative, and general psychiatric symptoms with large effect sizes.” However, CBD did not induce psychiatric symptoms and there was inconclusive evidence that it moderated the initiation of psychiatric symptoms by THC.

These findings highlight the acute risks of cannabis use, which are highly relevant as medical, societal, and political interest in cannabinoids continues to grow.

In addition to mental health concerns with the legalization of marijuana, there are physical health concerns. Marijuana smoke contains some of the same toxic combustion products in tobacco smoke, which raises the possibility that exposure to some smoke-related toxicants could have adverse effects on the health of heavy cannabis users.

In another Lancet study, the plasma and urine levels of exclusive marijuana smokers, exclusive tobacco smokers, dual users of both substances and non-smokers were compared. Participants were classified as marijuana or tobacco smokers based upon self-report and detection of nicotine or THC metabolites in their plasma or urine. Marijuana smoking was independently associated with smoke-related toxicants including acrylamide and acrylonitrile metabolites, which are known to be toxic at high levels. But levels were lower when compared with those associated with tobacco smoking. Researchers also found elevated levels of an acrolein metabolite that may identify adults at risk of cardiovascular disease. The senior author of the study told Science Tech Daily:

Marijuana use is on the rise in the United States with a growing number of states legalizing it for medical and nonmedical purposes — including five additional states in the 2020 election. The increase has renewed concerns about the potential health effects of marijuana smoke, which is known to contain some of the same toxic combustion products found in tobacco smoke.

While there is less of a risk of cardiovascular disease when smoking marijuana than tobacco, there is a clear risk of experiencing psychiatric symptoms of psychosis and depression. This occurs as a result of the psychoactive substance in the cannabis plant, THC. However, another of the 66 chemicals (cannabinoids) in cannabis, cannabidiol (CBD), does not induce psychiatric symptoms. This distinction is crucial when considering whether or not to broaden the existing use of medical marijuana in Pennsylvania to include recreational use.

The FDA has approved only one CBD product Epidiolex, a prescription drug to treat two rare, severe forms of epilepsy. It is also illegal to market CBD by adding it to a food or drink; or currently to label it as a dietary supplement. According to Marijuana Moment, the FDA is in the process of developing regulations for hemp-derived cannabidiol products and is actively exploring ways to permit lawful sales of CBD as a dietary supplement. In 2019 the World Health Organization (WHO) said hemp-derived CBD did not contain more than .2 percent THC and was not under international control.

In a 2017 report to the WHO, the Expert Committee on Drug Dependence said in humans, “CBD exhibit no effects indicative of any abuse or dependence potential.” It is generally well tolerated and has a good safety profile. Reported adverse effects were thought to be a result of interactions between CBD and patients’ existing medications. “CBD has been demonstrated as an effective treatment of epilepsy in several clinical trials. . . There is also preliminary evidence that CBD may be a useful treatment for a number of other medical conditions.”

 

The evidence that CBD may be a useful treatment for a number of other medical conditions is not as scientifically sound as the research for treating epilepsy. For most indications, there is only pre-clinical evidence. Consistent with its properties, the range of conditions for which CBD has been assessed is diverse. Why can’t there be changes in how CBD from cannabis is scheduled and regulated to facilitate further research into these preliminary findings? The following table in the WHO report represents a review of the various therapeutic applications for CBD found in “Cannabidiol: State of the art and new challenges for therapeutic applications.”

 

The WHO commented that since CBD was not considered a drug of abuse (as was THC) and at the same time was legal and not regulated, a market for CBD-based products for medical purposes (such as CBD oil, tinctures and vapors) has rapidly expanded. It flourishes “in a no man’s land with potential health dangers for patients and all end-users.” The WHO cautioned that the lack of regulation with these products cannot guarantee the patient “the quality of the product itself, the effective dosage of CBD that is fundamental for its therapeutic effectiveness, the purity and the absence of chemical or microbiological contaminations, thus raising critical public safety concerns.”

Regulatory changes with regard to CBD are needed in the U.S. At the end of December 2020, the FDA announced it had issued five more warning letters to companies selling CBD products in ways that violated the Federal Food, Drug and Cosmetic Act (FD&C Act). “All five warning letters address the illegal marketing of unapproved CBD products claiming to treat medical conditions. In addition, they address violations relating to the addition of CBD to food, and the impermissible marketing of CBD products as dietary supplements.” Under the FD&C Act, any product intended to diagnose, cure, treat or prevent a disease and any product intended to affect the structure or function of the body of humans or animals, is considered to be a drug.

In “FDA is Committed to Sound, Science-based Policy on CBD,” the FDA said the Agriculture and Improvement Act of 2018, the Farm Bill, removed cannabis and cannabis derivatives that are very low in THC from the definition of marijuana in the Controlled Substances Act while specifically preserving the FDA’s responsibility over such products. If a product is being marketed as a drug, meaning it is intended to have a therapeutic effect as in treating a disease, then it is regulated as a drug. Over the past several years the FDA has issued several warning letters to companies for marketing unapproved new drugs claiming to contain CBD, including for uses such as treating cancer or Alzheimer’s disease. “These products were not approved by the FDA for the diagnosis, cure, mitigation, treatment, or prevention of any disease.”

Legislative action is needed, but not to legalize recreational marijuana. An official distinction between THC and CBD should be made that permits research into the therapeutic potential of CBD, while keeping THC as a controlled substance at a less restrictive Schedule. Marijuana was listed as a Schedule I Controlled Substance in 1970. This has hampered the scientific investigation of the therapeutic benefits of CBD as well as the potential harms (or lack thereof) from THC to be done.

There is enough evidence of the therapeutic potential of CBD to research the above-noted therapeutic benefits and we desperately need legislation that permits this. There is also evidence that high levels of THC can be a catalyst to the emergence of psychotic symptoms in some users—and we need to protect those users from this danger. The science is clear enough to stop the push towards legalizing recreational marijuana in Pennsylvania while we permit the scientists to do their research into the potential benefits of CBD and the adverse effects of THC. Activists and those in favor of legalizing recreational marijuana like Lieutenant Governor Fetterman are really seeking to legalize THC, a psychoactive chemical in cannabis with serious adverse effects and significant profit potential for some. We need to clearly see this.

04/4/17

CBD and the DEA

© arnoldvanrooij

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.

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.”

08/3/15

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.

06/15/15

Let’s Not Get Ahead of Ourselves

© iqoncept | stockfresh.com
© 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 CBD is to test it.”

There was an experiment at the Institute of Psychiatry at Kings 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.