11/29/16

Marijuana & Adverse Health Effects

© David Castillo Dominici | 123rf.com

© David Castillo Dominici | 123rf.com

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

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

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

Effect

Overall Level of Confidence

Addiction to marijuana or other substances

High

Diminished lifetime achievement

High

Motor vehicle accidents

High

Symptoms of chronic bronchitis

High

Abnormal brain development

Medium

Progressive use of other drugs

Medium

Schizophrenia

Medium

Depression or anxiety

Medium

Lung cancer

Low

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

08/10/15

Marijuana Peek-a-Boo

© antonprado | stockfresh.com

© antonprado | stockfresh.com

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

04/6/15

Regulate Marijuana Like Alcohol?

© smithore |stockfresh.com

© smithore |stockfresh.com

Paul Gaita of The Fix reported that on February 20th, 2015 two bills were introduced in the House of Representatives that were aimed at legalizing marijuana for recreational purposes and taxing it like tobacco and alcohol. The Regulate Marijuana Like Alcohol Act was introduced by: Rep. Jared Polis of Colorado. The Marijuana Tax Revenue Act was introduced by: Rep.. Earl Blumenauer from Oregon.  Polis and Blumenauer previously introduced similar bills in the past, but they failed to secure approval.

Polis was quoted as saying the legislation was important as the country moves toward a presidential election in 2016. “We don’t know if the next president will have the same hands-off approach that Barack Obama and Eric Holder eventually found their way towards.” Economist Jeff Miron, an advocate for legalization of marijuana, worried that a new president could order the new Attorney General to enforce federal prohibition, regardless of state law.

Tim Devaney, for The Hill, quoted Blumenauer as saying that: “A lot of people are recognizing that it’s insane to shuffle billions of dollars to Mexican drug cartels when we could just be taxing it.” His bill would initially tax recreational marijuana at 10%, gradually raising the rate to 25%. Medical marijuana would not be taxed at the federal level. Blumenauer estimated the federal government could make $10 billion dollars annually through marijuana taxes and the savings in not locking people up for possession of marijuana. “The federal prohibition of marijuana has been a failure, wasting tax dollars and ruining countless lives.”

Matt Ferner, for the Huffington Post, noted the bills would not force states to legalize marijuana. Rather, they would provide a regulatory framework for states that do decide to legalize it. Despite the four states and the District of Columbia who have made recreational marijuana use legal, “the sale, possession, production and distribution of marijuana all remain illegal under federal law.” Existing jurisprudence (Gonzales v. Raich 2005) holds that federal law trumps state law when it comes to marijuana. Only because of the current “hands off” guidance from the current administration has this legalization movement been able to move forward.

Congressman Blumenauer said, “It’s imperative the federal government become a full partner in building a workable and safe framework.” You can review a copy of the “Regulate Marijuana Like Alcohol Act” here. You can review a copy of the “Marijuana Tax Revenue Act” here. The summary of the “Regulate Marijuana Like Alcohol Act” made the following points.

  • It directs the Attorney General to remove marijuana “in any form” from ALL schedules of controlled substances under the Controlled Substances Act.
  • It will revise the definition of “felony drug offense” to exclude conduct relating to marijuana; and eliminate marijuana from “provisions setting forth penalties applicable to prohibited conduct” under the Act.
  • It prohibits the shipment of marijuana from outside the United States into any jurisdiction in the U.S. where its possession, use or sale is prohibited.
  • It will grant the FDA the same authorities with respect to marijuana as it currently has for alcohol. Functions currently under the Drug Enforcement Administration would be transferred to the Bureau of Alcohol, Tobacco, Firearms and Explosives, which will be renamed as: the Bureau of Alcohol, Tobacco, Marijuana, Firearms and Explosives. The Alcohol and Tobacco Tax and Trade Bureau will be renamed as Alcohol, Tobacco and Marijuana Tax and Trade Bureau.

There are several points to raise about the above proposed legislation and statements made by Polis and Blumenauer in support of them. First is Blumenauer’s assertion of a $10 billion dollar annual income for the federal government. If the states are to be allowed to decide to legalize recreational marijuana, how can an annual federal income even be estimated with any accuracy? Federal savings on incarcerations for marijuana possession would only be in federal facilities. Were the savings projections based on ONLY individuals incarcerated in federal prisons for marijuana possession?

Colorado does have a promising new tax income base with marijuana. The state reported that in January of 2015, its total income from all marijuana taxes, licenses and fees for fiscal year 2014-2015 to date was $61,372,000. Would the proposed federal increase in marijuana tax at 10% to 25% be added to the existing tax of states like Colorado? Colorado currently has 2.9% retail and medical marijuana sales tax, 10% retail marijuana special sales tax, 15% marijuana excise tax, and retail/medical marijuana application and license fees. Additional taxes would drive up the price and promote even greater price inequities between legal and black market marijuana, which is already a problem in both Colorado and Washington.

This doesn’t seem to be a way to simply divert income from the Mexican drug cartels into the state and federal treasuries.  A future post, “The Economics of Heroin,” will indicate that instead of planting marijuana, the cartels are simply having their drug farmers plant opium poppies. And if cartel marijuana is cheaper than the state approved kind, it will still have a market.

Marijuana is currently a Schedule I Controlled Substance, according to the DEA. That means it is considered to have no currently accepted medical use and a high potential for abuse. While its harm potential is lower than many other drugs, including alcohol, completely removing it from classification in the Controlled Substance Act is an unrealistic expectation. Reclassifying it into a lower Schedule would increase its availability for research—and legitimize its medical use.

The potential harm and benefit of marijuana could be looked at in future research. With what we already know about the harmful effects of alcohol on the human body, would we want to remove all restraint on marijuana at the federal level before we know more about it? Isn’t it likely that similar to tobacco, we could see an increasing consensus of the public health problems with widespread marijuana use and then look to institute a similar public health program to address them? How many countless lives would be ruined if marijuana was regulated as alcohol is currently?

There also seems to be a hidden trap in making the proposed changes on the federal level by the “Regulate Marijuana Like Marijuana Act.” While the legislation may not force states to legalize marijuana, if existing jurisprudence, such as Gonzales v. Raich 2005, has been used to hold that federal law trumps state law when it comes to marijuana, could the “Regulate Marijuana Like Alcohol Act” be used to undermine and challenge any existing state laws with more restrictive laws on marijuana than the federal government? No, I don’t think we should regulate marijuana like we do alcohol.