01/30/24

Continue to Keep Marijuana Medical in PA

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Medical marijuana has been available in Pennsylvania since February of 2018. Fortunately, progress to the legalization of recreational marijuana has not occurred yet. I’ve been urging for almost six years that we wait for the research into the risks and benefits of marijuana use can be reliably researched. Here are three recently published research articles to reflect on that suggest going ‘full Colorado’ in Pennsylvania may not be a good idea.

In August of 2023, The British Medical Journal (BMJ) published “Balancing risks and benefits of cannabis use” by Solmi et al. Their research was an umbrella review of 101 meta-analyses that have reported on the safety of cannabis, cannabinoids or cannabis-based medicines. According to the 2019 Global Burden of Disease Study, Solmi et al said more than 23.8 million people have cannabis use disorder (CUD). In the U.S., the prevalence of CUD was estimated at around 6.3% in a lifetime. In Europe, around 15% of people aged 15 to 35 reported using cannabis in the past year.

In Europe, over the past decade, self-reported use of cannabis within the past month has increased by almost 25% in people aged 15-34 years, and more than 80% in people who are 55-64 years. Cannabis or products containing tetrahydrocannabinol (cannabinoids) are widely available and have increasingly high tetrahydrocannabinol content. For instance, in Europe, tetrahydrocannabinol content increased from 6.9% to 10.6% from 2010 to 2019. Evidence has suggested that cannabis may be harmful, for mental and physical health, as well as driving safety, across observational studies but also in experimental settings. Conversely, more than a decade ago, cannabidiol was proposed as a candidate drug for the treatment of neurological disorders such as treatment-resistant childhood epilepsy. Furthermore, it has been proposed that this substance might be useful for anxiety and sleep disorders, and even as an adjuvant treatment for psychosis. Moreover, cannabis-based medications (ie, medications that contain cannabis components) have been investigated as putative treatments for several different conditions and symptoms.

There was converging evidence of an increased risk of psychosis in adolescents and adults, and with psychosis relapse in people with a psychotic disorder. There was an association between cannabis and general psychiatric symptoms such as depression and mania; and detrimental effects on memory, verbal delayed recall, verbal learning and visual immediate recall. “Across different clinical and non-clinical populations, observational evidence suggests an association between cannabis use and motor vehicle accidents.” There was also evidence of an association with somnolence (drowsiness) with cannabinoids and cannabidiol. Cannabis-based medicines were associated with visual impairment, disorientation, dizziness, sedation and vertigo.

In addition to the association of cannabis and psychosis, cannabis use is associated with a worse outcome after onset, including poorer cognition, lower adherence to antipsychotics and a higher risk of relapse. “In other words, use of cannabis when no psychotic disorder has already occurred increases the risk of its onset, and using cannabis after its onset, worsens clinical outcomes.” Mood disorders have their peak of onset close to that for cannabis use, raising concern because of the associations noted in this study between cannabis and depression, mania and suicide attempt. High THC content cannabis is thought to serve at a gateway to other substances, especially in younger people.

With regard to the therapeutic potential of cannabis-based medicines, cannabidiol was beneficial in reducing seizures in certain forms of epilepsy. They were also beneficial for pain and spasticity in multiple sclerosis, as well as for chronic pain in various conditions. In patients with chronic pain, the effects of prolonged use of cannabinoids needs to be tested “because current findings only come from short term randomized controlled trials.” Active comparisons between cannabidiol and available options for epilepsy, cannabis-based medicines and other pain medications, other treatments for muscle spasticity in multiple sclerosis are needed with a focus on efficacy and safety to inform future guidelines.

In conclusion, Solmi et al said converging and convincing evidence supported the association of marijuana use with poor mental health and cognition and the increased risk of car crashes. Cannabis use should be avoided in adolescents and young adults when neurodevelopment is still occurring, when mental health disorders begin and cognition is important for optimizing academic performance and learning. Cannabidiol could be considered as a potential treatment option in epilepsy. Cannabis-based medicines could be considered for chronic pain across different conditions, and for nausea and vomiting and for sleep in cancer.

Law and public health policy makers and researchers should consider this evidence synthesis when making policy decisions on cannabinoids use regulation, and when planning a future epidemiological or experimental research agenda, with particular attention to the tetrahydrocannabinol content of cannabinoids. Future guidelines are needed to translate current findings into clinical practice.

The 2022 National Survey on Drug Use and Health (NSDUH) released in November of 2023, 22% of people 12 or older reported using marijuana in various ways (smoking, vaping, dabbing, eating or drinking, lotion or cream, taking pills or some other way). The percentage was highest among young adults, 18 to 25 (38.2% or 13.3 million people), followed by adults over 26 (20.6%, 45.7 million people), then adolescents 12 to 17 (11.5%, 2.9 million people). Among people 12 or older in 2022, 6.7% or 19 million people, has a CUD (cannabis use disorder) in the past year. The percentage of young adults 18 to 25 with CUD was 16.5% or 5.7 million people. Adolescents aged 12 to 17 with CUD was 5.1%, or 1.3 million people. These figures were higher than the data reported in the following article, “Cannabis-Related Disorders and toxic Effects,” perhaps reflecting more recent data.

In December on 2023, The New England Journal of Medicine published “Cannabis-Related Disorders and Toxic Effects” by Daniel Gorelick. The article reviewed the seven cannabis-related disorders defined in the DSM-5-TR. The author said worldwide, an estimated 209 million persons between 15 and 64 used cannabis in 2020. In the U.S., an estimated 52.4 million people 12 and older used cannabis in 2021, representing 18.7% of that age group. And 16.2 million persons met the diagnostic criteria for CUD.

Cannabis use disorder occurs in all age groups but is primarily a disease of young adults. The median age at onset is 22 years (interquartile range, 19 to 29). In the United States, the percentage of 18-to-25-year-old persons with current (past-year) cannabis use disorder in 2021 was 14.4%. Younger age at initiation of cannabis use is associated with faster development of cannabis use disorder and more severe cannabis use disorder.

The major risk factors for developing CUD are the frequency and duration of cannabis use. And the core feature is loss of control, reflected in persistent use despite adverse consequences. The potency and amount of cannabis are also risk factors, but they have not been well studied because of the difficulty in quantifying the amount and potency of the THC content of products. “The potency of cannabis has doubled over the past 2 decades, according to analyses of samples seized by U.S. law enforcement, which may contribute to the increased risk of cannabis use disorder and cannabis-induced psychosis.” The risk of CUD increases with the frequency of use: 3.5% prevalence of CUD with yearly use (less than 12 days per year); 8.0% with monthly use (up to 4 days per month); 16.8% with weekly use (up to 5 days per week); and 36% with daily or near daily use.

Several clinical and sociodemographic factors are associated with an increased risk of cannabis use disorder, including the use of other psychoactive substances such as alcohol and tobacco; having had adverse childhood experiences (such as physical, emotional, or sexual abuse); having a history of a psychiatric disorder or conduct problems as a child or adolescent; depressed mood, anxiety, or abnormal regulation of negative mood; stressful life events (such as job loss, financial difficulties, and divorce); and parental cannabis use. These significant associations do not necessarily indicate a direct causal influence on cannabis use disorder, because many of these factors are also highly associated with both cannabis use and frequent cannabis use.

Gorelick told Medical Xpress almost 50% of people with CUD have another diagnosable psychiatric disorder such as major depression, PTSD or generalized anxiety disorder. He said: “There is a lot of misinformation in the public sphere about cannabis and its effects on psychological health with many assuming that this drug is safe to use with no side effects.” About 1 in 10 people who use cannabis will become addicted and if you start using before the age of 18 the risk rises to one in six. Cannabis use accounts for 10% of all drug-related emergency room visits and is associated with a 30 to 40 percent increased risk of car accidents.

He concluded that CUD and heavy or long-term cannabis use have clear adverse effects on physical and psychological health. He thought research on the endocannabinoid system is needed to better explain the pathophysiology of these effects and to develop treatments. In other words, continue to keep marijuana medical in PA until we have reliable research to determine whether or not recreational marijuana should be legalized. So far, it’s not looking to be a wise move.

For more information on marijuana and the concerns with legalization, search for “marijuana” or “cannabis” on this website or see, PREPARING to Legalize Cannabis.” For more information on marijuana legalization in Pennsylvania, see “Keep Marijuana Medical in PA,” “Waiting Before Pennsylvania Goes ‘Full Colorado’” and others.

01/9/24

Dimming the Experience of Pleasure and Addiction

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Neuroscience News reported on a recent study led by researchers from the National Institute on Drug Abuse (NIDA) and other federal agencies that found the brain’s ‘salience network’ was only activated when drugs were taken intravenously or smoked, but not ingested orally. “When drugs enter the brain quickly, such as through injection or smoking, they are more addictive than when they enter the brain more slowly, such as when they are taken orally.” The study suggests there’s new information on what may be behind the difference.

Nora Volkow, senior author of the study said, “We’ve known for a long time that the faster a drug enters the brain, the more addictive it is – but we haven’t known exactly why.” Using new imaging technology, the researchers believe they may now have an understanding of why this is. “Understanding the brain mechanisms that underlie addiction is crucial for informing prevention interventions, developing new therapies for substance use disorders, and addressing the overdose crisis.”

The researchers conducted a double-blind, randomized, counterbalanced clinical trial that used simultaneous PET/fMRI imaging. There were twenty adults who participated in the trial. Over three separate sessions, they received either a small dose of placebo or methylphenidate (Ritalin), orally or intravenously. After the participants received the study drug or placebo, the researchers looked at the differences in dopamine levels (through PET imaging) and brain activity (through fMRI imaging). The participants also reported their subjective experience of euphoria in response to the drug.

Consistent with previous research, the PET scan showed when participants received the methylphenidate orally, their dopamine rate peaked more than an hour after administration. However, participants who received methylphenidate intravenously, peaked within 5 to 10 minutes of administration. The fMRI of the participants indicated the ventromedial prefrontal cortex (where we process risk and fear) was less active after both oral and intravenous drug use. “However, two brain regions, the dorsal anterior cingulate cortex [associated with learning and self-control] and the insula [linked with salience detection and addiction], which are part of the brain’s salience network, were activated only after receiving the injection of methylphenidate, the more addictive route of drug administration.” The same areas of the brain were not activated after taking methylphenidate orally.

The salience network of the brain attributes value to things in our environment. It is important for recognizing and translating internal bodily sensations, like the euphoric effects of drugs. “This research adds to a growing body of evidence documenting the important role that the salience network appears to play in substance use and addiction.” Interestingly, other studies have shown when people experience damage to their insula (part of the brain’s salience network), they may have a complete remission of their addiction.

After receiving the drug intravenously, researchers noticed that the activity and connectivity of the salience network, observed via fMRI imaging, very closely paralleled almost every participant’s subjective experience of feeling high. When the imaging showed increased activity in this part of the brain, participants’ reports of feeling high increased.

When the imaging showed decreasing activity in the salience network, participants’ reports of feeling high decreased. Researchers theorize that the network identified in this study is relevant not just for the chemical action of the drug, but also the conscious experience of drug reward.

The authors indicated a next step would be to see whether inhibiting the salience network when someone takes a drug effectively blocks the feeling of being high. This would further support the salience network as a target for the treatment of substance use disorders. The lead author of the study said, “I’ve been doing imaging research for over a decade now, and I have never seen such consistent and clear fMRI results across all participants in one of our studies.”

Manza et al, the study reported in Neuroscience and discussed above, said: “Together, these findings provide insight into how the salience network is critically linked to the pathophysiology of substance use disorder.” Among the considerations to note in the study, participants were naïve to stimulant drugs. The participants were also administered methylphenidate in a laboratory environment, which tends to inhibit the results. For example, other studies have shown adult males will drink significantly more alcohol when they are exposed to a simulated bar environment relative to a neutral laboratory setting. Manza et al further said:

Notably, our study identified two distinct circuits similar to the pattern of brain lesions leading to clinical remission of addiction. Patients who suffered stroke lesions to brain regions that had positive functional connectivity with dACC [dorsal anterior cinugulate] and insula (where we observed activation with fast dopamine increases), and lesions to brain regions that had negative functional connectivity with ventromedial prefrontal cortex (where we observed deactivation both with slow and fast dopamine increases) led to remission. Therefore, both studies support interventions to inhibit the dACC and insula and interventions to stimulate the ventromedial prefrontal cortex as strategies for the treatment of substance use disorder. Indeed, the dACC is being tested as a neuromodulation target to combat compulsive drug use with preliminary findings showing decreases in cocaine self-administration, cue-induced alcohol craving, and heavy drinking days. Critically, in the latter study, successful stimulation effects were associated with decreased connectivity between dACC and caudate. A key next step is to evaluate if inhibition of this circuit during drug administration blocks the subjective experience of drug reward, which could open new avenues to treat substance use disorders.

The Reward Pathway and Addiction

The significance of the above-described study demonstrating the importance of fast or slow dopamine increases in the develop of a substance use disorder can be understood by reviewing Carleton Erickson’s description of the Reward Pathway of the brain in his book, The Science of Addiction. Erickson capitalizes the word “Addiction” to represent when addiction progresses to the stage of physical dependence.

Drugs produce “Addiction” in the mesolimbic dopamine system (MDS), the pleasure pathway located in the middle of the brain. It is believed that addiction problems develop when the function of these MDS neurotransmitter systems are disrupted due to genetic problems, long-term exposure to a drug, or a combination of these with environmental influences. The MDS generates signals in the part of the brain known as the ventral tegmental area (VTA), which releases dopamine (DA) into the nucleus accumbens (NAc). This release of DA into the NAc causes the feelings of pleasure, but not only from drugs. Other areas of the brain, like the basal ganglia, create a lasting record or memory that associates the good feelings with the from the drug use with the circumstances and environment in which they occur. See the figure below.

Release of DA in the NAc produces the sensation of pleasure. The anticipation of obtaining the drugs activates the limbic pathways in a way that leads to chemical dependence, to Addiction. This is why the above discussed study is significant and as the researchers speculated, opens “new avenues to treat substance use disorders.” But there is a potential problem with inhibiting connectivity between the dACC and insula in the treatment of substance use disorder as suggested.

In Never Enough, the neuroscientist Judith Grisel explained when activity in the mesolimbic pathway is prevented, the person is unable to experience pleasure. If activity in the mesolimbic pathway was prevented before a person used drugs, she said they’d “think the drugs were a complete waste of money.”

This might look like a cure, but … it is ethically problematic. Such an intervention would prevent pleasure from all sources, including things like food and sex. Most of the world has prohibited this sort of surgical intervention, although some nations, including China and the Soviet Union, are reportedly reducing relapse rates by employing this strategy. However, it doesn’t work all that well for seasoned addicts who use mainly to avoid unpleasant symptoms associated with withdrawal rather than seeking a high.

Addicts who are clearly suffering from their addiction are generally not willing to voluntarily undergo a procedure that would produce this form of anhedonia, a global deficit in their experience of pleasure. Most would rather go to prison or suffer other severe consequences, because then they could still experience transient pleasures. “Without dopamine in the nucleus accumbens, nothing, a letter from a friend, an especially beautiful sunset or piece of music, or even chocolate, would alleviate a persistently bleak existence.”

The research of Manza et al, reported by Neuroscience and discussed above is interesting. And when it’s replicated, it will become even more important to our growing knowledge of addiction. I would hope as we pursue the association of dopamine and addiction, that future research won’t dim the person’s experience of pleasure as it tries to cure their addiction.

12/19/23

Health Effects of Vaping

Photo by Itay Kabalo on Unsplash

The American Heart Association recently published a scientific statement on the use of e-cigarettes, “Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products.” It describes the latest usage trends, the current scientific evidence about e-cigarettes and identifies current health impacts. It noted that vaping and e-cigarette use has grown exponentially over the past ten years, particularly among youth and young adults. They have been touted as safer alternatives to tobacco cigarettes, and even as potential tobacco-cessation products. However, e-cigarettes in 2019 led to more than 2,800 hospitalizations.

The CDC reported that as of February 18, 2020, a total of 2,807 hospitalized EVALI (e-cigarette or vaping product use-associated lung injury) cases or deaths were reported. Laboratory data showed that vitamin E acetate, an additive in some THC-containing products, was strongly linked to the EVALI outbreak. The CDC and FDA recommended that people not use THC-containing ENDS—electronic nicotine delivery system. After the identification of the primary cause of EVALI, and a significant decline in EVALI cases, the CDC stopped collecting data from states as of February 2020, the beginning of the COVID pandemic.

By 2019 in the U.S., 27.5% of high school students said they used e-cigarettes or ENDS. These products are the most commonly used tobacco products among youth, a growing number of whom reported never smoking combustible cigarettes. Data from the National Youth Tobacco Survey (NYTS) indicated current use in the past 30 days of ENDS increased from 1.5% in 2011 to 20.8% in 2018, an estimated 3.1 million students. Among middle school students, current e-cigarette use increased from .6% in 2011 to 4.9% in 2018, an estimated 570,000 students. See the following figure from “Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products.”

Data from the 2019 NYTS indicated 25.5% of 12th graders reported current e-cigarette use compared to 11% in 2017. Current THC (cannabis) vaping increased in 12th graders from 4.9% in 2017 to 14.0% in 2019, 4.3% to 12.6% with 10th graders, and 1.6% to 3.9% with 8th graders. The prevalence of ENDS use among youth remained stable despite the pandemic. Data from 2020 showed ENDS use declined to 19.6% among high school students and to 4.7% among middle school students. “Whether this is an artifact of the great societal disruptions from the global pandemic or represents a decreased trend remains to be seen.”

Because of the rapid evolution of ENDS, it is important to examine prevalence rates with other vaping products besides e-cigarettes such as e-hookahs (e-waterpipes). E-hookahs are a new category of vaping devices, introduced in 2014 and recently patented by Philip Morris [the tobacco company], that are marketed as healthier alternatives to traditional hookah fruit-flavored tobacco smoking. Findings from the nationally represented PATH study (Population Assessment of Tobacco and Health; 2014–2015) in children 12 to 17 years of age indicated that 7.7% were identified as ever-users of e-hookahs compared with 14.26% who were ever-users of ENDS products.

Studies in the U.S. indicate a rapid increase in ever and current ENDS use among adults since 2010, “with the vast majority of users being current or former cigarette smokers.” Recent analysis of NHIS (National Health Interview Survey) data from 2014 to 2018 showed young adults 18 to 24 years of age are using ENDS at high rates. Current use increased from 5.1% to 7.6%. There were large increases among never-smokers (1.5% to 4.6%) and former smokers (10.4% to 36.5%).

See “Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products” for a detailed discussion of the acute health effects and toxicity of e-cigarettes and vaping products.

Chronic Health Effects and Toxicity of E-Cigarettes and Vaping Products

E-cigarettes were created in China in the early 2000s and introduced to the US market in 2007. The basic mechanism heats or atomizes a liquid solution or e-liquid that generally contains a humectant (a substance used to keep things moist), nicotine and flavoring agents. The e-liquid formulations can contain other drugs beside nicotine, including THC, methamphetamine and methadone. The FDA attempted to stop the importation of these products, recognizing they could be used as drug-delivery devices. But a 2010 court ruling, Smoking Everywhere, Inc. vs US Food and Drug Administration deemed e-cigarettes should be considered tobacco products, and fall under the 2009 Family Smoking Prevention and Tobacco Control Act.

E-cigarettes and vaping were introduced in the US 16 years ago, and only saw widespread adoption in the past ten years. “We do not yet know the long-term health effects of these products.” Tobacco use was not recognized as a major preventable cause of death until many years after cigarette smoking became widespread. An increasing incidence of lung cancer was not noted until 1930. Definite scientific evidence associating cigarette smoking and lung cancer was not reported until the 1950s.

In 1964, the US Surgeon General report on tobacco and health attributed the increase in lung cancer to cigarette smoking. Only then did cigarette smoking per capita begin to decline. With the delayed development of chronic disease from smoking, lung cancer deaths did not begin to fall accordingly until decades after the 1964 report.

See the following figure taken from “Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products.”

In 2018 an evidence-based summary of the health concerns with ENDS found no available evidence that ENDS use was associated with coronary heart disease, stroke, and peripheral artery disease. There was insufficient evidence that ENDS use was associated with long-term effects on heart rate, blood pressure and cardiac function. There was also no available evidence on whether ENDS use causes respiratory diseases in humans. There was only moderate evidence ENDS use is associated with increased asthma problems, and limited evidence of adverse effects of ENDS exposure on the respiratory system.

There have been few studies of the chronic cardiovascular effects of ENDS because they have only been available for the past 16 years! Assuming similar time delays for the appearance of chronic disease from cigarettes and for ENDS, “epidemiological increases in disease prevalence would not be expected to be observed for years.”

Vaping devices have not been shown to be safe for long-term use. The short- and long-term toxicities of inhaling aerosols generated from liquids containing vegetable glycerin, propylene glycol, nicotine, or flavors are unknown. Inhaling aerosols generated from THC- or CBD-containing liquids, which often contain additional chemical components, also have unknown health effects. Thus, elucidating their long-term respiratory, cardiac, and cancer health effects is a public health priority.

E-Cigarette and Vaping Products as Cigarette-Cessation Products

The Cochrane Review found that nicotine e-cigarettes can be effective in helping people stop smoking for at least six months. They were found to be more effective than nicotine replacement therapy and cessation with e-cigarettes without nicotine. And yet, they strongly discouraged those who have never smoked from using e-cigarettes, especially young people. “This is because they are a relatively new product and we don’t yet know the long-term health effects.”

“Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products” said in the Cochrane Review adverse events were higher at 12 weeks to 6 months in ENDS users when compared to no support or behavioral support only. One study compared e-cigarettes with varenicline (Chantix), finding e-cigarettes were less effective than varenicline. Four of 27 e-cigarette users versus 13 of 27 varenicline users stopped smoking. The main study results assessed smoking cessation and not complete product cessation. “This could mean that participants who quit smoking continued ENDS use.”

Another study compared nicotine ENDS plus a nicotine patch (NRT) with NRT alone and NRT plus nicotine-free ENDS. The patch alone has a 2% abstinence rate. The patch and nicotine-free ENDS had a 4% abstinence rate and the nicotine patch and nicotine ENDS had a 7% abstinence rate. “No current ENDS products have FDA approval as a tobacco-cessation aid. There is only low to moderate confidence of improved cessation with nicotine-containing ENDS products compared with NRT or behavioral interventions.”

There are few empirically tested prevention and cessation programs for youth ENDS use. Using novel technology—text messages, social media—that have been used extensively to advertise ENDS products to youth, as wells as educational efforts targeting parents and health educators, and other methods have been shown to promote smoking cessation among youth. But further work is needed to develop and test effective interventions.

Conclusion

ENDS products have undeniably been increasing in popularity, particularly among young adults and teens, in the past decade. The constituents of these products often include nicotine, which is well established to have negative health effects and strong addictive properties. Other ingredients, particularly in flavored products, have known health risks. Because ENDS products are not regulated as classic therapeutic drugs or devices, there are no dedicated long-term safety studies. Critical questions remain unanswered about the short-term and, in particular, long-term health effects of ENDS products. Because the products have only recently gained widespread use, decades of prospective or retrospective data are not yet available to examine the long-term health effects of cigarettes. Early analysis suggests some utility of ENDS as a smoking cessation product; however, any benefit needs to be juxtaposed with a clear understanding of the health risks of the ENDS products themselves and the risks of product availability leading to nonsmokers initiating ENDS use.

11/28/23

Counterfeit Pills, Snapchat and Overdose Deaths

Image by Hasty Words from Pixabay

WPVI-TV, channel 6 in Philadelphia told a story about a new legal battle over drugs available on social media. More than 60 families are suing Snapchat, arguing the overdose deaths of their children were due to the social media app. They are demanding changes to protect their children, claiming they died after buying illegal drugs sold by dealers on the app. One parent said, “Snapchat is the largest open-air drug market we have in the United States when it comes to our kids.”

CNN reported the number of drug overdose deaths is still increasing, but seems to be slowing. New estimates from the CDC estimates were 112,024 people died from a drug overdose in the 12-month period ending in May of 2023. This was a 2.5% increase over the 12-month period ending in May of 2022 (109,261). Dr. Katherine Keyes, a professor of epidemiology, said, “There were extraordinary increases in 2020 and 2021 that have started to flatten out in 2022 – now going into 2023. They’re not declining yet. But the pace of the increase is certainly slowing.”

However, certain states have seen steep increases in overdose deaths in comparison to national totals. For example, overdose deaths in Washington increased more than 37%, from 2,373 to 3,254. Fentanyl and other synthetic opioids were involved in most overdose deaths, followed by psychostimulants like methamphetamine. Washington’s dramatic increase in overdose deaths may have been fueled by the availability of counterfeit pills, which we will look at below.

A CDC report said more than 1 million people died between 1999 from and 2021 of a drug overdose. Synthetic opioids other than methadone seem to be the main driver of drug overdose deaths. “Nearly 88% of opioid-involved overdose deaths involved synthetic opioids.” Opioid were involved in 75.4% of all drug overdose deaths.

A NCHS data brief released in December of 2022 indicated drug overdose deaths were stable from 2006 through 2013, but then increased from 13.8 per 100,000 in 2013 to 32.4 in 2021. From 2020 to 2021, the rate increased 14% from 28.3 to 32.4 per 100,000. For each year from 2001 through 2021, the rate for males was higher than females. Notice from the following figure the dramatic increase in overdose deaths that begins in 2019, the year before the COVID pandemic.

Despite the concerns of parents with Snapchat making it easy for dealers to connect with teenagers seeking drugs, there were four other age groups with higher rates of overdose deaths.  Among adults aged 25 and older, the rate of drug overdose deaths was higher in 2021 compared to 2020. The rates were highest for adults aged 35-44 (53.4 and 62.0 per 100,000 respectively) and lowest for people 65 and older. See Figure 2 below.

The drug overdose deaths involving synthetic opioids other than methadone (fentanyl, fentanyl analogs, and tramadol) increased at different rates from 2001 through 2021. Natural and semisynthetic opioid overdose deaths (i.e., oxycodone and hydrocodone) increased from 1.2 to 3.5 per 100,000 in 2010 and then leveled off, reaching 4.0 per 100,000 in 2020 and 2021. The rate of overdose death involving methadone increased from 0.5 in 2001 to 1.8 in 2006. Then it decreased through 2019 to 0.8, and remained stable through 2021 (1.1). “Of the drugs examined, only drug overdose deaths involving heroin had a lower rate in 2021 than in 2020 (2.8 and 4.1, respectively).” See figure 4 below.

Overdose deaths from cocaine and stimulants were also on the rise. Cocaine-related overdose deaths was a bit of a roller coaster ride, increasing from 1.3 per 100,000 in 2001 to 2.5 in 2006, then decreasing to 1.5 in 2001, and then increasing to 7.1 in 2021. “The rate in 2021 was 22% higher than in 2020 (6.0).” The rate of overdose deaths involving psychostimulants (i.e., amphetamine, methamphetamine and methylphenidate) increased from 0.2 in 2001 to 0.5 in 2005, remaining stable through 2008. Then it increased from 0.4 in 2008 to 10.0 in 2021. The rate in 2021 was 33% higher than the rate in 2020 (7.5). See Figure 5 below.

Drug overdose deaths have risen fivefold over the past 20 years. The rate for males increased from 39.5 to 45.1 and the rate for females increased from 17.1 to 19.6, from 2020 to 2021. For both sexes, the highest rates were for adult between 35 and 44. The rates of drug overdose deaths involving opioids and stimulants increased from 2020 to 2021.

Counterfeit Pills

One disturbing trend that seems to be driving that increase in overdose deaths is the evidence of counterfeit pill use in the U.S. In a September CDC Morbidity and Mortality Report (MMWR), the CDC said these pills are not manufactured by pharmaceutical companies, but are made to look like legitimate drugs, frequently oxycodone and alprazolam (Xanax). Counterfeit pills often contain illicitly manufactured fentanyls and illicit benzodiazepines like bromazolam, etizolam and fluaprazolam. They increase the risk of overdose by exposing individual users to drugs they did not intend to use and did not know they were in the pills they were buying.

The overall increase of overdose deaths with evidence of counterfeit pill use increased from 2% to 4.7%, driven by an increase from 4.7% to 14.7% in Western states. More than half of overdose deaths with evidence of counterfeit pills (55.8%) occurred in Western states such as Washington. See the following table reproduced from data in Table 1 of the above CDC MMWR report.

The report had these key findings. First, the overall percentage of overdose deaths with evidence of counterfeit pills remained under 6%, but more than doubled from 2.0% in the third quarter of 2019 (July-September) to 4.7% in the fourth quarter of 2021 (October-December). The percentage more than tripled in Western states. Second, the percentage of deaths with evidence of counterfeit pills using illegally manufactured fentanyl (IMF) was more than double the percentage of deaths without evidence of counterfeit pill use.

Evidence of counterfeit pill use more than tripled in western jurisdictions, indicating IMFs, which are frequently present in counterfeit pills, are infiltrating drug markets in western U.S. states. Historically, white-powder IMFs have been less prevalent in western states because of difficulty mixing with predominantly black tar heroin prevalent in that region. The highest percentages of deaths with evidence of counterfeit oxycodone use (both alone and with counterfeit alprazolam) were in western jurisdictions, whereas nearly one half of deaths with evidence of counterfeit alprazolam use only were in southern jurisdictions. This finding suggests that exposure to different types of counterfeit pills and drugs might vary by region. Prevention and education materials that incorporate local drug seizure data and information about regional drug markets might be particularly effective at highlighting relevant counterfeit pill types and reducing deaths.

Those who died from counterfeit pills were significantly younger and more often Hispanic. Counterfeit pills have been marketed towards younger persons, where they may also exhibit more risk-taking behaviors than do older persons. The higher percentage of Hispanic persons could reflect the has implications for access to and use of prevention messaging materials and harm reduction services. “It is important to ensure that prevention messaging and harm reduction outreach are tailored to younger persons and the Hispanic population to address potential engagement, language, or other barriers.”

The DEA reported their lab testing revealed that 4 out of 10 counterfeit pills contain at least 2 mg of fentanyl, a potentially lethal dose. Criminal networks are mass producing counterfeit pills and marketing them as legitimate prescription pills. They’re often sold on social media and e-commerce platforms, which make them widely available to anyone. In 2021, the DEA seized 20 million fake pills, more than the 2 previous years combined. They’ve been identified in all 50 states.

In “Overdosing,” I wrote of the overdose problem as it existed in 2016, before fentanyl, counterfeit pills and Snapchat had become part of the problem. There I referred to “Melanie,” the first person I worked with who eventually became a heroin overdose statistic in the late 1980s. In that article is a map of Pennsylvania showing the drug-related overdose deaths by county in 2014. Philadelphia County even then had the most reported deaths, followed by Allegheny County, where I live. Legislation allowing first responders to carry naloxone to reverse an overdose had just been passed. Let’s continue to fight against the everchanging and adapting drug trade and never forget those who were taken too soon by overdose like Melanie.

11/7/23

Emerging Threat with Captagon

Bekaa Valley, Lebanon; photo by Maya Babti on Unsplash

The Hamas-Israeli conflict currently dominates the news of what’s happening in the Middle East. There’s even been speculation that Hezbollah could join Hamas in it fight against Israel. However, there is a quieter, nonmilitary struggle coming out of Syria with the potential to spread havoc on a wide scale beyond the Middle East—the fight against the drug captagon. While the drug is not widely known outside the Middle East, CNN said it has become a “financial lifeline” to the Assad regime of Syria to the tune of an estimated $57 billion in 2022. Captagon smuggling is worth approximately three times the combined trade of the Mexican drug cartels.

Captagon or fenethylline was first synthesized by the German company Degussa Pharma Gruppe in 1961. It was used as a milder alternative to amphetamine and related compounds in the treatment of what we now refer to ADHD until it was listed as a Schedule I controlled substance in the U.S. in 1981. It became illegal in most countries when the World Health Organization listed it under the Convention on Psychotropic Substances in 1986. It is a synthetic drug of the phenethylamine family, which also contains amphetamine, methamphetamine and MDMA (known as ecstasy).

Counterfeit “Captagon” tablets containing other amphetamine derivatives that are easier to produce are pressed and stamped to look like Captagon pills. These knockoffs often contain a mixture of amphetamines, caffeine and various fillers and are sometimes referred to as “captagon” with a lower case “c.”

The BBC reported there have been an increasing number of drug busts involving captagon across the Middle East, with the Persian Gulf region being its main destination. Police in the United Arab Emirates seized 13 tons of captagon pills (worth $1 billion), smuggled in furniture. In 2020, 14 tons of captagon (worth over $1 billion) were seized in Italy. In 2022, Saudi Arabia seized 46 million captagon pills smuggled in a shipment of flour at a warehouse in the capital Riyadh. CNN said millions more pills have been intercepted since.

Captagon has become a bargaining chip for Syria, as it tries to normalize ties with neighboring Arab states. Although Syria’s neighbors are now in talks to normalize relations with Syria and President Bashar al-Assad, Saudi Arabia is still not on board because it is the biggest market for Syrian drugs. According to New Lines Institute, the Syrian regime has leveraged its agency over the captagon trade, suggesting they could reduce captagon trafficking “as a good will gesture.” Syrian state media regularly reports how the interior ministry is cracking down on captagon and other narcotics.

New Lines Institute published a 55-page report “The Captagon Threat,” that investigated the available information about captagon trade efforts to expand its market beyond the Persian Gulf region. Recent seizures point to southern Europe and North Africa as “new transit points and sites of interest.” It remains unclear whether these are intended transit areas for other markets, or if they are emerging as new consumer markets. “Regions beyond are also potentially at risk for increased captagon trafficking from Syria and neighboring states.” See the following map from New Lines Institute.

Captagon production in Syria has shifted from smaller outfits to industrial, containerized operations in rebel-held areas held by the regime of President Bashar al-Assad. Parts of the Syrian government are key drivers for the captagon trade. After the international economic isolation that occurred as a result of the 2011 civil war in Syria, captagon smuggling helped turn Syria into a narco-state. The BBC said at the height of the civil war armed groups supplied the drug to fighters in order to boost their courage and keep them awake. The growth of the captagon industry led the US to introduce the 2022 US Captagon Act, which linked the trade to Syria and called it a “transnational security threat;” but the legislation was never enacted. See the following map from New Lines Institute.

Elements of the Syrian government are key drivers of the captagon trade, with ministerial-level complicity in production and smuggling, using the trade as a means for political and economic survival amid international sanctions. The Syrian government appears to use local alliance structures with other armed groups such as Hezbollah for technical and logistical support in captagon production and trafficking.

Al-Assad and the Syrian government denies that it profits from the drug trade, and Hezbollah denies any ties to it. Nevertheless, in March of 2023, the U.S. and the European Union imposed sanctions on a list of people that included two of President Assad’s cousins suspected of involvement in the captagon trade, as well as prominent businessmen and militia leaders. The militia leaders are associated with drug smuggling and production. One is known as the ‘king of captagon’ and is associated with Hezbollah. Another uses his militia headquarters to facilitate captagon production.

The Assad regime, Hizballah, and other Iranian-backed militia all facilitate the captagon industry, and in doing so fuel regional instability and creating a growing addiction crisis across the region.

The BBC reported a soldier said many soldiers became drug dealers to supplement their incomes. He said they were not allowed to go to the factory. “They would pick a meeting place and we would buy from Hezbollah. We would receive the goods and co-ordinate with the Fourth Division to facilitate our movement.”

The Fourth Division, an elite Syrian army unit tasked with protecting the government from internal and external threats, is heavily involved in the captagon trade. Since 2018, it has been led by Maher al-Assad, the younger brother of President Assad. A former officer who defected from the Syrian army said it because of difficult financial conditions that many members of the Fourth Division have resorted to smuggling. “So the cars of the Fourth Division’s officers started to be used to carry extremists, weapons, drugs, since it was the only body able to move across checkpoints in Syria.”

In “The Captagon Threat,” New Lines Institute said there was some evidence that the Fourth Division was cooperating with loyal elements of Syria’s industries over protection, smuggling and distribution of captagon in and outside of Syria. “These elements appear to be using military or commercial vehicles to transport captagon from distribution centers at militia headquarters and checkpoints under the guise of security missions or business activities.” There is also some evidence that Fourth Division officials use a series of state-owned ports in the Latakia and Tartus region to dispatch captagon shipments.  The Fourth Division’s 42nd Brigade has allegedly been used to guard a captagon manufacturing center close to the Syrian-Jordanian border.

Hezbollah’s fighters played a crucial role in helping the Syrian government turn the tide in the civil war and now have a presence throughout the country. They have been repeatedly accused of involvement in drug trafficking, but have always denied it. A Syrian journalist said, “Hezbollah is involved but is very careful not to have its members playing key roles in transporting and smuggling the merchandise.” However, Hezbollah has a known history of controlling Lebanese cannabis production and smuggling it out of the southern Bekaa Valley. In 2016, the UN estimated that Lebanon was the third-largest cannabis producing country in the world.

Hezbollah’s technical expertise in drug smuggling, along with the number of potential partner criminal organizations in the Middle East, Europe, and North Africa, has aided the Syrian government’s efforts to run an industrial-sized captagon market. The relationship builds upon a dynamic that has existed since the Lebanese civil war, where Syrian political, military, and intelligence officials collaborated with Hezbollah in cannabis cultivation and production, activities that led the U.S. Department of State to designate Syria as a narco-state until the Pax Syriana era.

This expertise and its partner organizations has meant Hezbollah could support smuggling efforts, helping dispatch captagon shipments from Lebanese ports in Tripoli and Beirut. Hezbollah has protected transit routes between Syria and Lebanon, and uses its political leverage and security networks within Lebanon to facilitate uninterrupted illicit commerce. Hezbollah fighters have been seen assisting the Fourth Division in controlling and securing key areas of captagon production and smuggling at key checkpoints along the Damascus-Amman highway and other smuggling routes. They have also been seen visiting captagon factories in Syria.

Yet given Hezbollah’s political imperative to preserve its conservative image, particularly amid increasing domestic backlash with political protests and anti-corruption calls, Hezbollah Secretary-General Hassan Nasrallah and other political leaders have publicly denied direct involvement in the narcotics trade, shifting blame to local tribal leaders and political barons with proven ties to the captagon trade and to Syria.

Aljazeera recently reported on the role captagon is playing in Syria and President Bashar al-Assad’s attempt to return to the Arab fold. Al-Assad, of course, denies any organized governmental efforts to profit from the drug. So, it came as no surprise in May of 2023 that he did not discuss the drug trade during the Arab League’s 32nd summit in Jeddah, Saudi Arabia. Following a meeting of foreign ministers after the summit, Syria agreed to address drug trafficking and within days an air raid on Syrian soil killed a reputed Syrian drug kingpin.

A director at New Lines Institute told Aljazeera how the Syrian regime had already conducted a series of “cosmetic” seizures in order to build good will with Arab governments. “They want to be seen as a country that could interdict Captagon if they are persuaded and incentivised to, particularly with sanctions relief and economic packages.” She thought they would give up traffickers that are not closely aligned to the regime, but are named as potential contributors to the drug trade. She does not believe Syrian authorities will touch any of the core backers of the trade named on the U.S. and the European Union list noted above.

I also think the regime is very much using this as their own political card in normalisation discussions, essentially owning up to the fact that they have agency over the trade and using that as a main tactic to encourage countries to pay them off in exchange for them cracking down.

The director of the SOAS Middle East Institute said she believes al-Assad was unlikely to give up captagon and other Arab states have little leverage over al-Assad to persuade him to do so. Revenue from the drug trade, which is Syria’s largest export, will require the restoration of legitimate trade. Al-Assad will demand the lifting of sanctions and the return of his territory. “The most Arab countries can hope for in this regard is that those regime elements involved in the Captagon trade might divert some of it to markets outside the Arab world so as to reduce the flow of the drug to Arab countries.”

So, begin to look for Captagon to come to a drug market near you.

10/10/23

Goodblend is Closing Its Dispensaries in PA

Medical marijuana customers in Pennsylvania received some disappointing news when Goodblend PA, a subsidiary of Parallel Cannabis, announced the company was closing its operations in the state in order to serve “patients” in other more established markets. The Northside feed and grow operation is scheduled to close by September 15th 2023 and the dispensaries, located in Erie and on Baum Boulevard in Pittsburgh will close sometime in October. A planned dispensary in Cranberry Township will never open. Trib Live reported the company said in an emailed statement, “In connection with a strategic review, we have made the decision to withdraw from the Pennsylvania market in order to serve patients in our other, more established markets.” That could be good news for PA cannabis users in the long run.

Medical marijuana was legalized in Pennsylvania is 2016 and dispensaries began to open in the state in 2018. According to the National Conference of State Legislators, as of April 24, 2023, 38 states have legalized cannabis products for medical use, and 22 states have legalized the recreational use of marijuana. But so far PA has resisted the pressure to join the 22 states who legalized recreational marijuana. I’d encourage the Commonwealth to continue to hold out while research related to the potential problems associated with marijuana use is completed and published.

In PREPARING to Legalize Cannabis, I reviewed two recent studies. One suggested cannabis use had strong associations with adverse mental health and life outcomes in teens. Another one added to the growing evidence of a causal association between cannabis use disorder (CUD) and schizophrenia that was said to be “almost certain.” Now a study published on August 29, 2023, in The Journal of the American Medical Association Network Open, by Lapham et al, found that CUD was commonly found among primary care patients in Washington State. Washington legalized recreational marijuana in 2012.

The New York Times reported that 21 percent of people in the Lapham et al study had some degree of a CUD. These findings were similar to previous research by Leung et al. They quantified the prevalence and risk of CUD as cannabis abuse (CA) or cannabis dependence (CD). Among people who used cannabis, 22% have CUD; 13% have CA (8-18%) and 13% (10-15%) have CD. The risk of developing cannabis dependence increased to 33% (22-44%) among young people who use marijuana weekly or daily.

Cannabis users need to be informed about the risks of developing CUDs and the higher risks among those who initiate early and use frequently during adolescence. Future studies are needed to examine how changes in cannabis policies may affect the risks of CUDs in the population.

The Lapham et al study in Washington State was conducted with data from Kaiser Permanente, a large health system in Washington. 5,000 patients 18 years and older were randomly selected from 108,950 eligible patients with a record of completing a cannabis screen as part of their routine primary care. They were categorized by their stated reason for using cannabis during the past 30 days: medical use only, nonmedical use only, or both. DSM-5 symptoms for CUD were used to assess severity, with 2-3 symptoms = mild, 4-5 symptoms = moderate, and 6-11 = severe.

Patients were asked about all modes of cannabis use as well as the primary mode, including inhalation (ie, smoke, vape, dab), ingestion (ie, eat, drink), application (ie, lotion, ointment), or other modes. Questions also included the frequency of past-year use and typical number of days per week and times per day of cannabis use.

Among cannabis users, 42.4% reported medical use only; 25.1% reported nonmedical use only; and 32.5% reported both recreational and medical use. The prevalence of CUD was 21.3% and interestingly did not differ depending of their reasons for use (i.e., medical use only). The most prevalent CUD symptoms for all groups were tolerance, uncontrolled escalation of use and craving. Patients with nonmedical use only or both reasons for use were more likely to report “withdrawal, use in hazardous situations, continued use despite consequences, time spent on use, interference with obligations, and activities given up.” Patients who reported any nonmedical use were at the greatest risk of moderate to severe CUD, with the lowest risk was among patients reporting medical use only. Lapham et al concluded:

In this study, CUD was common (21%) among primary care patients who use cannabis in a state with legal recreational use, with patients using for nonmedical reasons most at risk of moderate to severe CUD. As legal recreational cannabis use among adults continues to increase across the US, the results here underscore the importance of assessing patient cannabis use and CUD symptoms in medical settings.

So, as legal recreational marijuana use increases across the US, there is a corresponding call to assess people’s cannabis use and symptoms of CUD into standard medical care and practice. Research is also coalescing around a causative connection between using marijuana and schizophrenia. Teenaged use of marijuana leads to future adverse health and life outcomes. But there is a problem between the rapid pace of marijuana legalization and state and federal policy changes. These policy changes are happening faster than the scientific research can be done on the medical benefits and adverse consequences of marijuana.

In October of 2022 President Biden asked the Secretary of Health and Human Services (HHS) and the Attorney General to review how marijuana is scheduled under federal law. He also pardoned all people convicted of simple marijuana possession under federal law and urged governors to take similar action. Then on August 29th 2023 Politico reported the HHS Assistant Secretary wrote a letter to the DEA recommending that marijuana be moved from Schedule I to Schedule III. The letter is the last step in the official review process initiated by the President last October. Significantly, the DEA is not required to follow HHS’s recommendation.

The HHS recommendation was the result of an almost yearlong federal review of all available marijuana research. But advocates for the legalization of recreational marijuana and some lawmakers didn’t think the recommendation went far enough. They wanted the president to completely remove cannabis from the Controlled Substances Act. A cannabis advocate told Politico, “Rescheduling cannabis from 1 to 3 does not end criminalization.” However, if approved, the rescheduling would permit cannabis businesses to take tax exemptions for business expenses like salaries and benefits, providing a huge benefit to the financially struggling industry.

The shift in federal cannabis policy would also make it easier to conduct research on the health effects of cannabis consumption and for pharmaceutical companies to bring cannabis-based drugs to market. Researchers have long chafed at restrictions that only allow them to procure cannabis from a single farm at the University of Mississippi that bears little resemblance to the high-potency products many consumers are purchasing in state-legal markets.

Both legalization advocates and anti-legalization advocates are not happy with the HHS recommendation. Pro-marijuana advocates say it does not end criminalization, but anti-legalization advocates see it as potentially detrimental to public health. They say the “addiction profiteers” have been exposed for their lies about the physical, mental and financial benefits of legalization in the wake of the cumulating evidence of the harm being done to millions of Americans. “It is regrettable that the Department of Health and Human Services move now appears to be a nod to those monied interests.”

In August, ABC News did a short, 7-minute video in their Group Chat on how the increase in marijuana use could affect federal legislation, the economy, and national health, “How the legalization of recreational cannabis use is on the rise.” It’s available on YouTube, here. One of the individuals participating in this “Chat” said there is a lot of money at stake here in the marijuana industry. “It’s estimated that the marijuana industry can pump a hundred billion dollars into the overall economy this year.”

The health concerns were mentioned with a reference to a CDC report on its effect on teen health and wellbeing. “There are a lot of unknowns about the long-term risk of any cannabis exposure to developing brains.” According to the CDC marijuana use beginning in teen years or younger can affect brain development, which may impair thinking memory, and learning.” There were mental health issues, including schizophrenia. “The association between marijuana and schizophrenia is stronger in people who start using marijuana frequently at an early age.”

The health expert went on to say he hears from both sides is that “policy changes seem to be happening faster than scientific research. Now potentially rescheduling this from a class one substance can actually help with that research, but there’s a lot more we need to know.” But until then, we know already that several states are growing more cannabis than they can sell because there aren’t enough legal retailers in the market. The impact is that “the illegal marijuana trade is actually stronger and outpacing legal sales in states where it is legal.” In California, where recreational marijuana has been legal for seven years, unlicensed marijuana sales were more than double that of licensed sales.

Returning to Parallel Cannabis closing down its Goodblend facilities in Pennsylvania, there’s more to it than just wanting to serve “patients” in other more established markets. In the Green Market Report, John Schroyer reported the Atlanta-based company Parallel Cannabis is closing its three Goodblend PA facilities and leaving the Pennsylvania medical marijuana market because financial troubles led to a lawsuit from its landlord, Innovative Industrial Properties Inc. Pennsylvania is not the only state Parallel has had problems paying its rent. Parallel also defaulted on its rent for a facility in Texas. Parallel is one of the largest privately held multistate cannabis operators in the US, with additional facilities in Florida, Massachusetts, and Nevada.

Goodblend is struggling to get its own shareholders to agree to liquidate the business, with another pending lawsuit filed by Surterra Holdings, a division of Parallel. That suit alleges that minority owner Medical Bloom, which holds a 25% stake in Goodblend, has refused to agree to a dissolution. Parallel is asking for a court order to force the liquidation in order to pay off Goodblend’s debts, given that the Pennsylvania subsidiary is insolvent, the Post-Gazette reported.

So, in Pennsylvania, let’s not be seduced by the lure of money in legalizing recreational marijuana. The federal government is poised to reschedule marijuana, which will help the cannabis industry without removing marijuana from FDA oversight as a drug. Let’s wait a few more years and see what the scientific research tells us about the benefits and adverse effects from marijuana use before we begin to craft our legalization policy at the state or federal level. And let’s slow down the marijuana lobbyists at the state level who seem to be trying to get a preponderance of states to legalize recreational marijuana before that research has a chance to be done and published. If it means some more companies like Goodblend leave the state for more profitable fields elsewhere—or go bankrupt—good riddance.

09/5/23

Flesh Eating Tranq Dope

 

Image by Лечение Наркомании from Pixabay

A study published by the CDC , documented a new twist to drug overdose death rates, but it is about a non-opioid veterinary tranquilizer called xylazine. It said xylazine-related overdose deaths in 2021 were 35 times higher than the 2018 rate. The number of drug overdose deaths involving xylazine was 102 in 2018. That rose to 627 in 2019, then 1,499 in 2020 and 3,468 in 2021. Male deaths were double the rates for females over the 2018-2021 period. See the following graph from the study.

An NPR article reported the Biden administration declared illicit xylazine as an emergent threat. Rahul Gupta, the head of the White House Office of National Drug Control Policy said this was the first time a substance has been “designated as an emerging threat by any administration.” Known on the streets as tranq or tranq dope, it was first linked to overdose deaths in the North East, around Philadelphia, but has rapidly spread to Southern and Western states. The DEA reported it has seized xylazine and fentanyl mixtures in 48 of 50 states. See “Tranq Dope and Its Consequences.”

The CDC study indicated the rate of overdose deaths involving xylazine was highest in Region 3 (DC, Delaware, Maryland, Pennsylvania, Virginia and West Virginia), followed by Region 1 (Connecticut, Massachusetts, Maine, New Hampshire, Rhode Island and Vermont) and Region 2 (New Jersey and New York). Between 97.1% and 99.4% of drug overdose deaths involving xylazine also mentioned fentanyl. It has also been co-involved with cocaine, heroin and methamphetamine. See the following map from the CDC study.

Pennsylvania governor Josh Shapiro announced steps his Administration is taking to limit access to xylazine. Among the measures was a notice of intent to temporarily add xylazine to schedule III of Pennsylvania’s Controlled Substance, Drug Device and Cosmetic Act. The Acting Secretary of Health said, “Across the country and here in Pennsylvania we are seeing an alarming increase in the number of overdose deaths in which xylazine was a contributing factor.”

The FDA issued a warning about the risk of xylazine in humans to health care professionals on November 8, 2022. It said xylazine was originally approved in 1972 as a sedative and analgesic for use in veterinary medicine.  Its development for use in humans was discontinued because of adverse effects. Structurally, it is similar to clonidine and causes a rapid decrease in the release of norepinephrine and dopamine in the central nervous system. The effects appear similar to that of opioids, making it difficult to distinguish between opioid toxicity and xylazine.

On March 28, 2023, the Combating Illicit Xylazine Act was introduced with bipartisan, bicameral support. The legislation will address a gap in federal law by:

  1. Classifying its illicit use under Schedule III of the Controlled Substances Act;
  2. Enabling the DEA to track its manufacturing to ensure it is not diverted to the illicit market;
  3. Requiring a report on prevalence, risks, and recommendations to best regulate illicit use of xylazine;
  4. Ensuring all salts and isomers of xylazine are covered when restricting its illicit use;
  5. Declaring xylazine an emerging drug threat.

Unless you are a veterinarian, own large animals—or are familiar with the drug scene in places like the Kensington area of Philadelphia—you probably have not heard of xylazine before. “Xylazine—Medical and Public Health Imperatives” by Gupta et al in The New England Medical Journal said its first illicit use was reported in Puerto Rico around 2001. It began to appear intermittently in the continental U.A. between 2006 and 2018. The drug’s duration of effect is longer than fentanyl. Using them together enhances the euphoria and analgesia induced by fentanyl and seems to reduce the frequency of injections.

Xylazine is not easily detected by routine toxicology screens, and is likely under-detected and underdiagnosed. It is rapidly eliminated from the body, with a half-life of 23-50 minutes. Individuals with repeated use of xylazine can become physically dependent and experience withdrawal. “When xylazine is stopped abruptly, severe withdrawal symptoms may develop.” There are currently no FDA-approved medications to manage xylazine withdrawal. Repeated use also leads to severe, necrotic ulcerations.

Xylazine causes wounds that erupt with a scaly dead tissue called eschar; untreated, they can lead to amputation. It induces a blackout stupor for hours, rendering users vulnerable to rape and robbery. When people come to, the high from the fentanyl has long since faded and they immediately crave more.

The NYT noted that xylazine can cause wounds so severe that some result in amputation. The article said a 38-year-old tattoo artist known as the Hood Grandma rolled her wheelchair in to the exchange check-in for Prevention Point Philadelphia, a 30-year-old health services center in Kensington, the neighborhood at the ‘epicenter’ of Philadelphia’s drug trade. Her mother, sister and partner all died of overdoses. Last year her right leg had to be amputated because of an infection from tranq bore into the bone. She said, “the tranq dope literally eats your flesh.”

She unrolled a bandage from elbow to palm. Beneath patches of blackened tissue, exposed white tendons and pus, the sheared flesh was hot and red. To stave off xylazine’s excruciating withdrawal, she said, she injects tranq dope several times a day. Fearful that injecting in a fresh site could create a new wound, she reluctantly shoots into her festering forearm.

Another woman developed a dependence on pain killers prescribed after a serious car crash. She began using heroin and eventually fentanyl, chasing the cheaper and more potent high. She watched in horror as the bruises she was accustomed to “from injecting fentanyl began hardening into an armor of crusty, blackened tissue.” People told her everyone’s dope was being cut with something that caused the grisly, painful sores. She said, “I’d wake up in the morning crying because my arms were dying.”

STAT News described how Savage Sisters, a harm reduction group in Philadelphia, has increased how often it offers wound care in the community. The executive director of Savage Sisters said she has been jumping up and down for three years, trying to get attention to the danger of xylazine infiltrating heroin and fentanyl. She said, “what we’re doing is a Band-Aid on a bullet hole.”

Drug users are reluctant to seek help until their medical condition had advanced to a dangerous point. One man waited until the wound on his wrist became so swollen and painful, he couldn’t move his hand. “The hospital told him that if he hadn’t come in then, he would have lost his hand.” Another man who had his wounds cleaned and wrapped was reluctant to consider going to a hospital for more advanced care because he was worried about getting “sick” in the hospital and being unable to use when he begins to experience withdrawal.

At this time, there has been minimal study of the xylazine drug scene. “Experts and advocates are still trying to understand just how dangerous xylazine is and how it works.” While presentations with images of the gruesome wounds from necrosis or dead tissue illustrate the serious adverse health effects from xylazine, medical professionals aren’t even sure what’s causing the necrosis, the wounds. Xylazine-related wounds can be healed with proper care, but many doctors aren’t aware that’s possible. It’s also changing what recovering from an overdose looks like after being given naloxone.

Someone who overdoses on tranq dope might start to breathe again after receiving naloxone, but still be unconscious from the sedative effect of xylaxzine. Giving them another dose of naloxone still won’t wake them up. “When it was just fentanyl, it was more straightforward. . . These kinds of unholy mixtures that bring down the level of consciousness in different ways are really making the overdose response picture tricky.” Although there are protocols for easing someone off illicit opioids, there is nothing for xylazine.

Savage Sisters provides drug users with cards they can give to medical providers that say, “Test me for xylazine.” The card also gives suggestions to medical professionals for treating the symptoms of xylazine withdrawal, which include anxiety. See the graphic below, taken from the STAT article.

It seemed that after fentanyl hit the streets, the drug scene couldn’t get any worse. But then drug entrepreneurs discovered xylazine mixed with fentanyl extends the fentanyl high and is cost-effective. Sure, your arms may feel like they’re dying, like tranq dope is eating your flesh. But isn’t the high worth it?

07/4/23

PREPARING to Legalize Cannabis

© Kindel media | pexels.com

Marijuana legalization in the US has been steadily moving forward in a piecemeal, state-by-state way for several years now. According to the National Conference of State Legislators, as of April 24, 2023 38 states and the District of Columbia have legalized cannabis products for medical use, and 22 states and the District of Columbia have legalized the recreational use of marijuana. Apparently anticipating the inevitability of legalization on a national level, Congressman Dave Joyce introduced H.R. 2598, the PREPARE (Post-Prohibition Adult Use Regulated Environment) Act on April 13, 2023, “To establish a Commission on the Federal Regulation of Cannabis to study a prompt and plausible pathway to the Federal regulation of cannabis.” Hakeem Jefferies, the Minority Leader of the House of Representatives, told Forbes: “The PREPARE Act will give lawmakers a bipartisan platform to legislate not only a fair and responsible end to prohibition but also a safer future for our communities.” However, two studies published in May of 2023 suggest that ending the so-called “prohibition” of marijuana may not be a responsible or safe action for some members of our communities.

The movement towards recreational marijuana legalization is promoted by a widespread sense that casual cannabis use is benign. However, a Columbia University study by Sultan et al, “Nondisordered Cannabis Use Among Adolescents,” found that teens who used marijuana recreationally were 2 to 4 times more likely to develop depression and suicidality than teens who didn’t use it at all. The lead study author, Ryan Sultan, said in a Columbia University press release, “We were surprised to see that cannabis use had such strong associations to adverse mental health and life outcomes for teens who did not meet the criteria for having a substance use condition.”

Their study found that adolescents with nondisordered cannabis use (NDCU) and cannabis use disorder (CUD) had increased odds of adverse psychosocial events. Both were significantly associated with adverse psychosocial events in a stepwise gradient manner. Sultan said their study was the first to identify that subclinical, nondisordered cannabis use has “clear adverse and impairing associations for adolescents.”

In line with past studies, cannabis use among adolescents was associated with greater odds of depression and suicidal ideation. These in turn were associated with long-term adverse educational and occupational attainment outcomes “and increased risk of harmful substance use in adulthood.” There was also evidence of worse executive control, decreased attention and deficits in episodic memory. Compared to nonusers, adolescents in NDCU and CUD groups were around 2-3 times more likely to experience cognitive deficits.

We observed a stepwise severity gradient for the odds of psychosocial associations among nonuse, NDCU, and CUD. This severity gradient was also observed in prevalence values for adverse psychosocial events across all degrees of cannabis use. Furthermore, this observation was corroborated by a stepwise cannabis use frequency trend between NDCU and CUD.

The researchers thought their findings were particularly concerning given the increasing popularity of marijuana as states continue to move toward making the drug legal. They concluded that with the growing acceptance of both medicinal and recreational cannabis use in the US, “clinicians should be vigilant to screen, evaluate, and treat cannabis use in adolescents.”

The second study was a huge Danish study of over 6 million people that discovered a strong association between cannabis use disorder and schizophrenia. The research team included Nora Volkow, the Director of the National Institute on Drug Abuse (NIDA). The study, “Association between cannabis use disorder and schizophrenia stronger in young males than in females,” analyzed health records spanning over 5 decades in order to estimate the fraction of schizophrenia cases that could be attributed to cannabis use disorder. A Scientific American review of the study said it found up to 30% of the schizophrenia diagnoses—around 3,000 in total—could have been prevented if men between the ages of 21 and 30 had not developed cannabis use disorder. The Scientific American review said:

The Danish epidemiology study does not offer hard-and-fast proof of the cannabis-schizophrenia connection, which could be accomplished only through randomized controlled trials. But this link is supported by the fact that marijuana use and potency have risen markedly—from 13 percent THC content in Denmark in 2006 to 30 percent in 2016—alongside a rising rate in schizophrenia diagnoses. “While this isn’t proving causality, it’s showing that the numbers behave exactly the way they should, under the assumption of causality,” says Carsten Hjorthøj, the study’s lead author and an associate professor at the Mental Health Services in the Capital Region of Denmark and the University of Copenhagen.

This study won’t resolve the long-running debate over the statistical cause-and-effect relationship between cannabis and schizophrenia. For example, David Nutt thought the research was intriguing, but it also raised more questions. He asked whether some of the cases may have been misdiagnosed with schizophrenia rather than an alternative diagnosis—like cannabis-induced psychosis. Along with the researchers, he pointed to the lack of data on the participants’ frequency of cannabis use or age of first use or the amount of THC in the products they used.

However, Robin Murray, a professor of psychiatric research at the Institute of Psychiatry at King’s College London and co-editor in chief of the medical journal Psychological Medicine said the Danish study examined specific factors more closely—gender and age—than previous investigations of the possible link between cannabis and schizophrenia. He thought it added to the growing body of research that has gradually discounted other factors to cannabis as a trigger for schizophrenia, making the connection more plausible, “So causal effect is almost certain.” For more on cannabis and schizophrenia, and Robin Murray’s own research into marijuana, see “Gambling with Cannabis and Psychosis” and “Cannabis and Psychosis: More Reality Than Satire.”

Psychiatric Times periodically published articles to educate its readers on cannabis and its association with schizophrenia. In “Cannabis Confusion” John Miller noted that he’s read numerous articles in the psychiatric literature that made conflicting conclusions about the effects of cannabis on cognition, its risk of psychosis, addictive potential, and its effects on suicidality, depression, anxiety, and pain relief. He thought there was only one consistent finding: Heavy cannabis use during brain development increases the risk of psychosis and cognitive impairment.

A likely explanation for the wide-ranging discrepancies is that cannabis is the product of a plant that is not a single molecule or pure substance. Many articles with the word cannabis in the title can be discarded as meaningless unless the authors took the additional step of testing all of the cannabis used by their study subjects for the quantitative and qualitative molecules present.

He noted that as more states legalize cannabis for medical or recreational use, it is likely that federal laws will eventually make cannabis use legal on a national level. “That will create an opportunity to require a comprehensive analysis and disclosure of all the components of the numerous strains of cannabis currently being sold in state dispensaries or on the streets.”

Fuller Torrey, a research psychiatrist specializing in schizophrenia, commented in “Is Cannabis Use Increasing Schizophrenia?” on an earlier Danish study that claimed the use of cannabis was a likely cause of the increasing incidence of schizophrenia over the past two decades. He noted that an increasing incidence of schizophrenia, or psychosis in general has also been reported in England, Switzerland and Canada. Torrey also gave citations and links to the various studies that supported his statement. He also thought the move towards legalizing recreational use in the US meant that “a possible relationship between cannabis use and increasing schizophrenia is potentially very important and needs to be confirmed.” He said:

It is an embarrassment to American medicine that NIMH has so little to contribute on such an important question. At a minimum, NIMH should issue a request for proposals to try and confirm the Danish study in another country which has appropriate data so that we will have a definitive answer to this question.

In “Does Cannabis Cause Psychosis?” Brian Miller reviewed several research studies of the relationship between cannabis and psychosis and concluded there was a robust association between cannabis use and the risk of psychosis, with evidence of a dose-response relationship, “which supports the plausibility of a causal association.”

Comorbid cannabis use is highly prevalent in psychosis (especially FEP [first episode of psychosis], with declining use over time), with strong evidence for an earlier age of onset of illness, as well as effects of psychopathology and cognition. In patients with psychosis, continued cannabis use is associated with antipsychotic nonadherence, illness relapse, and longer hospitalizations. These findings raise the possibility of a dose-response relationship between current cannabis use and transition to psychosis. Findings suggest that targeting cannabis use during the UHR [ultra-high risk] period may confer significant benefits on long-term outcomes. Continued cannabis use is also a potential target for intervention to improve antipsychotic adherence and other outcomes in patients with psychosis. Future research in this area is clearly warranted to elucidate mechanisms and novel treatment strategies for relevant populations.

Further research is needed to clarify the potential harms and adverse effects from using cannabis and marijuana products. While not yet proved conclusively, it does seem that there is a causative connection between schizophrenia and using marijuana for some people, but not for all people. Although this is more evident with heavy users (those who could be classified as having a cannabis use disorder), the Sultan et al study found there were even adverse mental health and life outcomes for teens that used marijuana, but did not meet the criteria for a substance use condition.

Cannabis use among adolescents increased the odds of depression and suicidal ideation among adolescents. Consistent with past research, there was also evidence of worse executive control, decreased attention and problems with episodic memory. When compared to nonusers, adolescents who used marijuana were 2 to 3 times more likely to experience cognitive deficits.

Heather Baccus spoke to America Reports on Fox News of how she believes her son’s marijuana use led to his psychotic break a few months before he committed suicide in July of 2021. Randy began using marijuana when he was 15 and had a cannabis user disorder within a year. By the time he was 21, he was experiencing delusions and paranoia. Heather said he thought it was helping him with his anxiety and depression, which she said he did not have until after he began using marijuana.

He knew that he would manage and function fairly well in life, but he was paranoid. He thought his roommates were out to get him. He thought that people at work were out to get him. He would quit a job quickly. He accused one of his employers of being in the mob. When he had a full-blown attack in March of 2021, he called us and said the mob was coming after him, that they were coming after us, and he just was out of sorts.

There is a video clip of a short interview with Nora Volkow, the director of NIDA and a coauthor of the above cited Danish study in the Fox News article. She said marijuana is not as benign as we would like it to be and is associated with psychosis. “High doses, regular use can be harmful.” She said there were likely three possibilities. Marijuana use triggers an episode in some individuals that have a latent risk for psychosis. In others, it may just accelerate the timing of the psychosis. Finally, it may also trigger a psychotic event that would not otherwise happen.

The PREPARE Act sounds like a responsible, proactive step to take before we move towards national legalization of marijuana. But I don’t believe we are thinking about the concurrent increase with adverse mental health concerns like depression, suicidal ideation and psychosis. What do we need to do to PREPARE for that?

06/20/23

Walk the Talk

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In his devotional thoughts in My Utmost for His Highest, for February 19th, Oswald Chambers made the following statement: “We have to take the first step as though there were no God. It is no use to wait for God to help us, He will not; but immediately we arise we find He is there. Whenever God inspires, the initiative is a moral one. We must do the thing and not lie like a log.”

The thought applies equally to the real psychological and spiritual drudgery of progressive sanctification and the “progress not perfection” component of change in recovery. Chambers is not advocating a self-willed “pull yourself up by your bootstraps” spirituality, but pointing to how faith and works come together. After quoting from Isaiah 60:1 (“Arise, shine, for your light has come, and the glory of the Lord has risen upon you.”), he said: “It requires the inspiration of God to go through drudgery with the light of God upon it.”

We start with a clear recognition of our powerlessness over sin (or addiction), we have faith that God is more powerful than our sin (or addiction), we surrender our lives to God and then we begin to align our lives with His will. Our initial belief in who God is and what He promises is manifested in our ongoing efforts to live as we believe He has called us to live. After we believe in our hearts and confess with our mouth, we are called to walk the talk. We must do the thing and not lie like a log. “Be holy, for I am holy” (1 Pet. 1:16). Interestingly, this call to holiness in First Peter also includes the exhortation to be sober-minded:

Therefore, preparing your minds for action, and being sober-minded, set your hope fully on the grace that will be brought to you at the revelation of Jesus Christ. As obedient children, do not be conformed to the passions of your former ignorance, but as he who called you is holy, you also be holy in all your conduct, since it is written, “You shall be holy, for I am holy. (1 Pe 1:13-16)

While the Greek term for sober-minded, nēphō, in verse 13 can have the literal sense of abstinent, here it means to be in control of one’s thought processes and not fall into irrational thinking. However, for the addict and alcoholic the term does have a literal sense: be free from every form of mental and spiritual drunkenness (i.e., passion, excess, rashness, confusion). In other words, don’t continue in your former way of life. Resist the craving to once again drink or use drugs. Be holy; walk the talk.

There is a threefold aspect to holiness that corresponds to the three tenses of salvation noted in Romans 5:1-2. That is, because we are justified by faith (a past completed action), we now have (present tense) peace with God through our Lord Jesus Christ. We also have access by faith into the grace in which we stand (present tense). Therefore, we rejoice in hope of the still-future glory of God.

All believers are positionally holy by virtue of their calling and they are summoned to live out their lives in a manner befitting their new position in Christ. With God’s help, they grow and mature “with the life of Christ as their pattern.” The third and final phase of holiness will only be reached when Christ completes the process of salvation upon His return, “when all His own will be like Him, seeing Him as He is, the perfect and glorious Son of God (1 Jn. 3:2).”

Although a believer in Christ must become engaged in this process, his involvement is not something praiseworthy. It is not a contributing factor to his acceptance by God, which is already his as a gift by God’s grace. It’s more that when he is adopted into the family of God, he should reproduce the family likeness and be like his older brother, Jesus. According to The International Standard Bible Encyclopedia, the starting point for this character development is realizing that the mercies of God call for an adequate response: presenting one’s body as a living sacrifice (Rom. 12:1). During this character development we will be tempted to remain conformed to the things of this world, but we are to be transformed–by the renewing of our mind–into a growing likeness to Christ (2 Cor. 3:18).

Similarly, there is a threefold transformation process in recovery, where soberness corresponds to holiness. We would then alter the Scriptural command to be holy in a relationship with Christ to: Be sober for we are sober. Addicts and alcoholics become members of A.A./N.A. by their desire to stop drinking and using drugs. And they are challenged to live out their lives in conformity to the principles of abstinence and sobriety embodied in A.A./N.A. With God’s help, they grow and mature “with the Twelve Steps as their pattern.” The end goal of such a life is to die sober; to live life on life’s terms without turning to drugs or alcohol.

In 1961, Louis R. told the story in the AA Grapevine how President McKinley once gave him a tip for watering his horse. He hadn’t known who McKinley was until someone told him. But he didn’t care as long as the man had given him whiskey-money. Louis was around nineteen at the time.

At an A.A. meeting on November 17, 1951 he raised his hand and asked the speaker if A.A. expected a man who had drunk all his life to stop drinking just like that. The speaker responded that if he’d done it, Louis could too. Louis said, “I figured maybe he was right, so I reached inside my shirt, took out the half pint of wine, and gave it to the man sitting next to me.” He never drank again. After ten years of sobriety, Louis realized he had a bad heart and knew he didn’t have too much longer to live, but he didn’t care. “The main thing I want is to die sober. And with the grace of God and the help of my good friends in Alcoholics Anonymous, I can do it.”

In the AA Grapevine article, “A Small Price to Pay,” an attorney reflected on his 28-year drinking career. With just a few years sober, he noted that some long timers he knew had slipped back into the mess from whence they came and died drunk and miserable. “I know I’ll die someday. But I prefer to die sober and happy, when my time comes.” He commented that eternal vigilance was the price of his freedom from the “thralldom” of his active addiction. “So if the form that my vigilance must take is active participation in AA and a continuing, honest attempt to work the program, that’s a small price to pay.”

Think of recovery as walking up a down escalator. The trick is to continue to walk up the escalator faster than it is moving down. It doesn’t matter how far up the escalator you have gone, even if you can no longer see the bottom from which you started. The moment you stop moving faster than the escalator is, you start going backwards; and eventually you will get to the bottom again. You have to walk the talk until the day you die.

If you’re interested, more articles from this series can be found under the link for “The Romans Road of Recovery.” “A Common Spiritual Path” (01) and “The Romans Road of Recovery” (02) will introduce this series of articles. If you began by reading one that came from the middle or the end of the series, try reading them before reading others. Follow the numerical listing of the articles (i.e., 01, 02, or 1st, 2nd, etc.), if you want to read them in the order they were originally intended. This article is 18th in the series. Enjoy.

05/23/23

The Loophole with Delta-8

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You may have seen storefront signs saying something like, “Delta-8 Sold Here”, and wondered what they could be selling. In states where recreational marijuana is not legal you would most likely think it certainly couldn’t be referring to that, and you would be right. It is technically not THC or delta-9-tetrahydrocannabinal, the main psychoactive ingredient in cannabis sativa. But according to the Agriculture Improvement Act of 2018, any part of the cannabis plant containing .3% or less of THC by dry weight is now defined as hemp. And there’s the loophole that has been exploited to permit delta-8 THC to be legally sold in markets that so far have restricted the legalization of marijuana.

In December of 2018, the Senate easily passed the Agriculture Improvement Act of 2018, 87 to 13. In, “How Delta-8 THC Works, and Why Experts Are Worried About It,” The New York Times reported that at the insistence of Mitch McConnell, the bill legalized industrial hemp as a crop. The hope was that hemp could be used for construction products and plastic composites and help vendors of CBD, a non-psychoactive compound found in cannabis sativa or “hemp.” But what happened was the 2018 Farm Bill allowed hemp to be used as a precursor for synthesizing delta-8-THC, which has a nearly identical chemical structure to delta-9-THC. And delta-8 is psychoactive, producing a “high” similar to delta-9. See the graphic below from “Marijuana Variant of Concern.”

Here is why designating hemp as cannabis sativa containing less than .3% in the 2018 Farm Bill was so significant. According to the pro-marijuana website Weedmaps, most cannabis plants contain negligible amounts of CBD, less than 1%. However, hemp plants average between 12% and 18% CBD. The Center for Disease Control and Prevention (CDC) noted that CBD does not produce a high as THC does. At this point in time, there is only one FDA approved medicine containing purified CBD from hemp, Epidiolex, which is approved to treat seizure disorders.

But the 2018 Farm Bill removed “hemp from the federal Controlled Substances Act, effectively legalizing CBD if it comes from hemp.” CBD is now marketed in many consumer products: foods, oils, lotions, capsules, and cosmetics. Science is still learning about CBD and the CDC said CBD products are not risk free. They can lead to liver damage, drowsiness or sleepiness, diarrhea or changes in appetite, and mood changes like irritability. They may also lead to serious side effects when used in combination with other medicines or drugs.

There is a lot we do not know about CBD. Currently, we do not know how CBD use affects a person over time. We also do not know how different modes of CBD use (smoking, vaping, eating, applying to skin, etc.) affect a person.

CDC released a Health Alert Network (HAN) Health Advisory in 2021 to inform consumers that CBD can be synthetically converted into Delta-8 THC, which is psychoactive and not well understood. This alert warns consumers about the potential for adverse events due to insufficient labeling of products containing THC and CBD.

THC most often refers to delta-9 THC, the most common THC isomer in cannabis. But there are several other isomers that occur naturally in cannabis, including delta-8 THC, which is estimated to be approximately 50-75% as psychoactive as delta-9 THC. The CBD-to delta-8 THC conversion process uses a solvent, acid, and heat to produce concentrations of delta-8 THC higher than those found naturally in the cannabis plant. “This conversion process, used to produce some marketed products, may create harmful by-products that presently are not well-characterized.”

The 2018 Farm Bill led to an expanding and unregulated market for delta-8-THC, according to Leas et al, which sought to measure public interest in delta-8. The researchers looked at the global rate of recommended searches that mentioned delta-8-THC from January 2011 through August 2021. The search trends were stable from 2011 through 2019. But they increased by 257% from 2019 to 2020 and 705% from 2020 to August 2021. The global trend of delta-8-THC searches was driven primarily by increases in the U.S., where the rate increased by 466% from 2019 to 2020 and by 850% from 2020 to August 2021. “By 2021, the rate of searches for delta-8THC in the US was at least 10 times higher than [the] rate of delta-8-THC searches in any other country or territory.”

The growth in searches following legalization of hemp in the US as well as the greater interest in US States with more restrictive delta-9-THC policies suggests that delta-8-THC may be meeting a demand for legal use of THC in markets that do not permit use of delta-9-THC. The one-year lag following the legalization of hemp could potentially be explained by a need for developing an infrastructure to produce and ship delta-8-THC products. For example, one manufacturer claims to have created “USA’s first federally legal THC-dominant product since cannabis prohibition started,” after it developed a method of synthesizing delta-8-THC in September of 2019. By 2021, hundreds of Delta-8-THC manufacturers existed throughout the US, and many offered to ship products to consumers and wholesale to retailers in states that did not permit use of delta-9-THC.

While public interest in delta-8-THC seemed to be concentrated in the US, some manufacturers have opened offices in Europe. One manufacturer, Just Delta, has offices in the UK. Leas et al said global and US jurisdictions should clarify whether methods of converting cannabinoids to THC compounds are legal under existing hemp and cannabis laws. They recommended a public-health-focused approach that clarifies definitions of THC compounds to include delta-8-THC and other THC isomers; and disallows the use of methods that convert CBD to THC, “at least until these can be determined to be safe.”

The NYT article, “How Delta-8 THC Works,” reported that a survey of delta-8 users said they were less anxious, less paranoid, and had a nicer high than with delta-9 THC. “The most common experiences when using delta-8 were relaxation, euphoria and pain relief.” There were reports of some difficulty concentrating, problems with short-term memory and an altered sense of time, but not to the same extent as with regular marijuana. The explanation for the differences between delta-8 THC and delta-9 THC is probably that there’s less delta-8 THC in the CB1 receptors, “so people are less likely to experience the more distressing symptoms” when they get too high.

Manufacturers of delta-8 products argue that delta-8 may chemically be THC, but legally it now is hemp. “Since you can extract CBD from hemp, and CBD is not THC, [then] it’s still considered hemp.” The lack of regulation around delta-8 in the US is the biggest concern of many public health experts. In a paper published in December of 2022, none of the delta-8 products tested contained the amount of delta-8 they claimed. All 27 had potentially harmful byproducts, presumably from the manufacturing process, including lead and mercury.

Between January 2021 and February 2022 national poison control centers handled over 2,000 calls about delta-8. Forty-one percent involved children accidentally ingesting products with delta-8. “One of those cases resulted in death.” Without federal regulation, 14 states have banned delta-8, or all unregulated forms of THC, including delta-10. Ironically, this includes several states where recreational marijuana is legal, including Colorado and New York. Delta-10 is illegal in Colorado and New York as well.

Eric Leas, the lead researcher in the above study that assessed public interest in delta-8-THC, said in “The Hemp Loophole,” that “the loopholes that allow THC compounds to be sold as hemp ought to be closed.” He said the regulatory system for recreational marijuana makes it a safer product than delta-8. The manufacturing quality checks and other regulatory requirements such as labeling rules about potency and licensing distributers act as important public health standards. None of these protections currently exist for delta-8. All the experts interviewed for “How Delta-8 THC Works,” including those supportive of legalizing marijuana, recommended against using delta-8. “There is no way to ensure its safety.”