08/2/22

The Future of Marijuana Legalization in Pennsylvania

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The World Drug Report for 2021 reported that roughly 200 million people used cannabis in 2019, roughly 4% of the global population. North America has the highest number of cannabis users, with an estimated 14.5% of its population use in 2019. The percentage of THC (∆9-THC), the main psychoactive ingredient in cannabis, rose from around 4% in 1995 to 16% in 2019. Although THC is responsible for the development of mental health disorders in long-term, heavy cannabis users, the percentage of adolescents who view regular cannabis use as harmful has decreased by as much as 40% during the same time period. While the potency of cannabis has increased four-fold since 1995, fewer young people see it as harmful.

Such a mismatch between the perception and the reality of the risk posed by more potent cannabis could increase the negative impact of the drug on young generations. Scientific evidence has demonstrated the harm to health caused by regular use of cannabis, particularly in young people. Evidence from surveys suggests a link between a low perception of risk and higher rates of usage. This is the case not only in Europe and the United States, but also in other parts of the world.Aggressive marketing of cannabis products with a high Δ9-THC content by private firms and promotion through social-media channels can make the problem worse. Products now on sale include cannabis flower, pre-rolled joints, vaporizers, concentrates and edibles. The potency of those products varies and can be unpredictable – some jurisdictions where cannabis use is legalized set no limit on THC content – and may be a public health concern.

(See the following charts from the World Drug Report for 2021)

In 2020, 14.6% of high-school students reported past-month use of cannabis. There was a significant increase in the daily or near-daily use of cannabis in the past two years (20919 and 2020). The daily or near-daily use of marijuana was estimated at 4.1% among high-school students in 2020, compared with almost 1% in 1991. In the past few years, the debate about medical marijuana and measures allowing for the non-medical use of cannabis in the United States have led adolescents to perceive cannabis as less harmful than was true in the past.

In the United States, the decreasing perception of risk from occasional or regular use of cannabis is considered to be a spillover effect as debates over measures allowing the medical and non-medical use of cannabis in the states considering those measures extend to other states, and the result of an increase in regular cannabis use, which comes to be perceived as less risky among users, as well as media coverage of the medical use of various cannabis products in many states containing claims of the medical benefits of cannabis products, including those of CBD.

Not only are there concerns for increases in mental health disorders among youth, there are other concerns with how cannabis effects young adults. Cannabis use among adolescents was found to be related to impaired cognition; showing delayed effects on self-control, working memory and concurrent effects on delayed memory recall and perceptual reasoning (ability to think and reason using pictures or visual information). So, exactly what are the risks when individuals, particularly adolescents and young adults, use marijuana? A meta-analysis published in The Lancet Psychiatry suggested the equivalent of one joint can induce psychotic and other psychiatric symptoms in healthy adults with no history of a major mental illness.

In “Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis,” the researchers their findings highlighted the acute risks of cannabis use, as “medical, societal, and political interest in cannabinoids continues to grow.” Significantly, they concluded that CBD (the second most common cannabinoid in cannabis) did not induce psychiatric symptoms; and the evidence that it moderated the induction of psychiatric symptoms was inconclusive. These effects were larger with intravenous administration than with inhaled.

Commenting on the results for Medscape, senior investigator Oliver Howes said “As clinicians, we need to be aware that the medical use of marijuana comes with a risk of inducing psychiatric symptoms, even in people with no vulnerability, and this needs to be factored into decisions to prescribe and to monitor.” Even if the symptoms are short-lived, people need to be aware of them because not only van they be distressing, but they can also affect decision-making and behavior. With regard to the failure of the researchers to find evidence that CBD moderates the psychotic effects of THC, Howes said, “I think it’s fair to conclude there’s a lack of consistent evidence that CBD is protecting against THC’s effect.” The mean age of the subjects ranged from early to late 20s.

An editorial of the study by Carsten Hjorthøj and Christine Merrild Posselt said the finding that low doses of THC can induce psychotic symptoms was “extremely worrying,” because they were similar to those found in medical marijuana. They also said there was no clear evidence that concurrent administration of CBD reduces symptoms induced by THC. “The authors failed to find any clear evidence that concurrent administration of cannabidiol (CBD) reduced these symptoms. Indeed, such an ameliorating effect was observed in only one of four included studies.”

This growing scientific consensus is not reflected in the mainstream public discourses, which have a major effect on the political agenda to decriminalise or legalise cannabis. It also appears that, in many places (eg, several US states), the first thing to be legalised is medicinal cannabis followed by increasing decriminalisation and sometimes complete legalisation of cannabis. It is thus of utmost importance that the public and politicians are informed of the most up-to-date evidence on cannabis. Adding to the state of this evidence is the systematic review and meta-analysis by Guy Hindley and colleagues in The Lancet Psychiatry. The authors demonstrate that Δ9-tetrahydrocannabinol (THC) leads to an increase in total symptoms, which was assessed in nine studies, with ten independent samples, involving 196 participants: standardised mean change in scores (assessed with the Brief Psychiatric Rating Scale and the Positive or Negative Syndrome Scale) 1·10 (95% CI 0·92–1·28, p<0·0001). The effect sizes were also large for other symptoms (including general psychiatric symptoms), and were induced even with low doses of THC, somewhat similar to the doses often seen in medicinal cannabis, which we find extremely important and worrying.

The significance of the above research findings should not be lost on Pennsylvania citizens and politicians. As the availability of cannabis increases in the state, as the potency of THC in that marijuana increases, we will see a corresponding increase of psychosis and other mental health-related problems among regular users. This is the future of marijuana legalization in Pennsylvania.

Medical marijuana has been legal in Pennsylvania since April 6, 2016. The first dispensary opened in the Pittsburgh area in Butler PA, on February 1, 2018. But medical marijuana dispensaries continue to spring up like “weeds.” The Weedmaps website indicated there were 39 dispensaries in the Pittsburgh area. Nineteen advertised they provided Curbside pickup.

John Fetterman, the current lieutenant governor of Pennsylvania, is running for the office of U.S. Senator and wants to see Pennsylvania “go full Colorado.” Its governor, Tom Wolf, has publicly supported the legalization of recreational marijuana. There has been legislation proposed by two state senators, the Adult-Use Cannabis Act, to legalize recreational marijuana in the state. See “Should Pennsylvania Go ‘Full Colorado’ With Marijuana?” Part 1 and Part 2.

08/19/16

Head-in-the-Sand

© andreykuzim | 123rf.com

© andreykuzim | 123rf.com

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.

chartHowever, 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.

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.