Brain Damage from Alcohol Continues After Abstinence

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Damage to the brain caused by alcohol continues during the first few weeks of abstinence, a finding that refutes the notion that the brain begins to normalize immediately after individuals stop drinking.

“Until now, nobody could believe that in the absence of alcohol the damage in the brain would progress,” study investigator Santiago Canals, PhD, of the Institute of Neuroscience of Alicante, Consejo Superior de Investigaciones Científicas–Universidad Miguel Hernández, Spain, said in a news release.

The study was published online April 3 in JAMA Psychiatry.

A Look Inside the Brain

Using diffusion tensor imaging, the researchers assessed microstructural alterations in white matter after long-term alcohol exposure and during early abstinence in 91 men (mean age, 46) who had alcohol use disorder (AUD).

The men were hospitalized and were undergoing detoxification treatment, which guaranteed that they did not drink alcohol. Thirty-six healthy men of similar age who did not have AUD served as control persons.

The researchers found diffuse microstructural changes in white matter in the men with AUD compared with the control persons. These changes primarily affected the right hemisphere and the frontal region of the brain. These changes progressed during 2 to 6 weeks of abstinence.

“The study was not designed to look further in time, also due to the fact that our results were unexpected,” study coinvestigator Wolfgang Sommer, MD, PhD, of the University of Heidelberg, Germany, said.

“Other studies looked at a longer time horizon and typically found signs of recovery, both of the brain structure and its function. Nevertheless, we need more research to understand what is going on here and what are the temporal aspects of the underlying phenomena,” said Sommer.

The researchers replicated their observations in an established rat model of excessive alcohol consumption.

“The fact that the findings in humans mirror those in rats may establish a relationship between the observed changes and alcohol consumption, which is difficult to verify based on human results only, given the large heterogeneity of the abuse patterns, medication for relief of withdrawal symptoms, and comorbidities among patients with AUD,” the researchers write.

“This result establishes the utility of diffusion imaging for monitoring the brain status as a possible noninvasive biomarker of AUD progression and, potentially, of treatment response,” they add.

Important Translational Study

“These types of translational studies are crucial to help fill in gaps in addiction research,” Marisa Silveri, PhD, director of the Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital, Belmont, Massachusetts, and associate professor of psychiatry at Harvard Medical School, Boston, said.

“The findings do fly a little in the face of what we know, because when people become abstinent, it usually doesn’t take them long for things like brain chemistry and cognition to improve, somewhat after abstinence. But it’s studies like these that uncover some more micro level cellular indicators that tell us that just because you can recover some function, it doesn’t necessarily mean the brain is returned to a healthy state,” said Silveri.

“That’s an important message because people often think that when they no longer feel the acute intoxicating effects of alcohol, that it’s not still having an effect, and we do know from many studies that there are residual effects of alcohol intoxication on neurobiology.

“The brain is a fantastic orchestra of networks, and understanding some of the subtler changes and what they mean is work that is most needed,” she added.

Alcohol and the Electric Atrium: How Drinking Promotes AFIB

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Regular alcohol intake at moderate levels was associated with electrical and structural changes in atrial myocardium in patients who underwent electrophysiologic mapping studies prior to catheter ablation for atrial fibrillation (AF) in a small cross-sectional study.

Moderate alcohol consumption, defined as eight to 21 drinks per week, was an independent predictor of the atrial remodeling, characterized by significantly reduced atrial voltage and conduction velocities and increased atrial dimensions, reported a group January 9 in Heart Rhythm.

The same was not found for mild alcohol intake levels, defined as two to seven drinks per week.

The findings suggest that moderate alcohol intake has “direct effects on atrial substrate” that are consistent with myocardial fibrosis, although the association can’t prove it causes AF, observed senior author Peter M. Kistler, MBBS, PhD, Alfred Hospital, Melbourne, Australia.

However, “this study adds to the growing evidence base that excessive alcohol consumption is implicated in AF pathogenesis and as such is a potentially modifiable risk factor,” Kistler told us by email.

The study enrolled 75 otherwise mostly healthy patients with paroxysmal or persistent AF who were scheduled for catheter ablation at two hospitals from 2016 to 2018.

They included 25 self-reported lifelong nondrinkers, 25 who reported consuming two to seevn drinks per week (mean, 4.5), and 25 reporting intake of eight to 21 drinks per week (mean, 14.1) in the most recent 12 months. As defined, one drink contained 12 g of alcohol.

Excluded were patients with permanent AF or significant structural heart disease, and those meeting the study definition of occasional drinker or binge drinker.

Mean left atrial size was larger in moderate drinkers than in nondrinkers (28.0 vs 22.7 cm²; P = .008).

Before ablation, off antiarrhythmic drugs, and in sinus rhythm (after external cardioversion, if necessary), the patients underwent high-density left-atrial mapping studies using the CARTO (Biosense Webster) three-dimensional electroanatomic mapping system.

Moderate drinkers, compared with nondrinkers, had significantly lower mean global bipolar voltages, slower conduction velocities (CV), and a higher proportion of complex atrial potentials

Results of CARTO Electroanatomic Mapping Studies by Alcohol Intake Level
ParameterModerate DrinkersNondrinkersPValue
Global bipolar voltages (mV)1.531.89.02
Conduction velocities (cm/s)33.541.7.04
Proportion of complex atrial potentials (%)7.84.5.004

Mild drinkers, compared with nondrinkers, showed a larger proportion of complex atrial potentials, a difference that reached marginal significance (6.6% vs 4.5%; P = .047), but no corresponding significant difference in mean global voltage or CV.

AF was seen to recur in 37% of patients at 12-lead electrocardiography and Holter monitoring, performed at prespecified intervals or on development of symptoms, during the postablation follow-up, which averaged 18.7 months.

The 37% included nine moderate drinkers, 11 mild drinkers, and eight nondrinkers, for rates of 40% for moderate and mild drinkers and 32% for nondrinkers. Those numbers are not in the report; Kistler said the study is underpowered to detect differences in AF recurrence rate.

However, significant independent substrate-related predictors of recurrent AF included reduced mean global voltage, greater proportion of low-voltage electrograms, and greater prevalence of complex potentials.

“Our study was primarily focused on alcohol’s effects on the atrium’s electrophysiological properties, but numerous recently published studies have identified excessive alcohol consumption as a significant predictor of postablation recurrence,” Kistler said. “This emphasizes the importance of lifestyle modification in improving AF outcomes postablation.”

Big Alcohol Knocks Back Medical Clout on Drinking

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VIENNA — Alcohol should carry warning labels about health risks, the marketing of alcohol directly to the public should be banned, and it should be more expensive, according to specialists in liver disease.

“Cost is the only way you can reduce alcohol consumption,” said Roger Williams, MD, from the Foundation for Liver Research in London. “Everyone has tried education; nothing works.”

In the fifth report of the Lancet Standing Commission on Liver Disease in the UK, Williams and his coauthors ask the British government for a “reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place.” They also ask for “the introduction of minimum unit pricing in England, targeted at the heaviest drinkers.”

The government has been reluctant to introduce any taxes on alcohol, because the drinks-industry lobby is very powerful. In fact, “it appears the lobby has more sway over government than medical opinion,” Williams said.

The report and its recommendations, along with other strategies to reduce alcohol consumption, will be discussed at the upcoming International Liver Congress (ILC) 2019.

Alcohol is still the biggest contributor to liver disease in Europe, followed by obesity and hepatitis B and C infection, according to the European Association for the Study of the Liver (EASL) HEPAHEALTH project (J Hepatol2018;69:718-735).

Harmful Use of Alcohol Causes 3 Million Deaths Annually

Last September, the World Health Organization reported that alcohol causes 3 million deaths globally every year, which is one death every 10 seconds. To combat alcohol-related health risks, the WHO outlined five high-impact strategies to reduce alcohol consumption: restricting availability, raising taxes, banning advertising, enhancing drunk-driving laws, and facilitating treatment.

The heaviest drinkers are now “the 40- to 50- and 50- to 60-year olds,” Williams said, adding that the number of women who drink heavily is rising.

People in these age groups are also at risk for obesity. “If you’re overweight or obese, alcohol-related liver disease is worse,” he pointed out. “The two are synergistic.”

Fortunately, once government does take the lead, it really can be effective, he said. “Smoking is a good example of how policy can affect change.”

The duty escalator — introduced in the United Kingdom in 2008, but then repealed for beer in 2013 and for wine, cider, and spirits in 2014 — automatically increased alcohol duties by 2% above inflation every year.

The Duty Escalator, Minimum Unit Price

When the duty escalator was in place, rates of mortality related to alcohol consumption improved in Scotland and, to some extent, England, an analysis of the policy showed. Immediately after the repeals, however, rates started climbing.

Just 4% of the population accounts for almost one-quarter of the alcohol industry’s sales, and many of these people drink harmful quantities, according to the Lancet report.

“Then there’s the 5% of those who are poor and in a bad environmental situation and are drinking 100 units a day or more,” said Williams. “These are the ones we have to target with the minimum unit price; it stops them from drinking all those cheap ciders.”

In Scotland, legislation that established a minimum unit price was introduced in 2012, over legal challenges launched by the Scotch Whiskey Association.

Interventions should be targeted at higher-risk groups, said Peter Rice, MD, steering group chair of Scottish Health Action on Alcohol Problems (SHAAP), a project of the Royal College of Physicians of Edinburgh.

In fact, policy interventions that have the greatest effect on populations most in need “may be more useful than the traditional alcohol policy field conceptualizations of whole population and targeted measures,” he writes in a recent review of alcohol policies in Europe.

A minimum unit price specifically targeted at the extreme drinker who develops cirrhosis has a higher likelihood of being effective than tax or duty, Rice explains.

“If we can affect the heaviest drinkers, we can affect the rest of the population,” he said.

Policy is effective, he said. “We need restrictions on price, availability, and marketing; we cannot treat our way out of Scotland’s liver disease.”Clear advice from a physician is a powerful tool.

Rice, who will speak at the congress, said he hopes to inspire advocacy from medical professionals. He said he believes that having doctors get used to having direct conversations with patients about drinking is important.

“Clear advice from a physician is a powerful tool,” he said.

But nothing beats doctors getting involved in campaigning. “We need to get busy to advocate for effective prevention. Physicians have effective voices,” said Rice. Doctors, physiatrists, and hepatologists really made a difference “in our own debates in Scotland.”

He and his colleagues continue to work to ensure that the minimum price keeps up with inflation and market changes. “The government is now committed to reviewing price at a 2-year interval,” he reported.

Next, his team will look at pushing for a ban on alcohol marketing. “We increasingly see how sports sponsorship has an effect on people’s normalization of consumption,” he explained. “We would like to see regulations in sports.”

Today, outcomes for patients treated for liver disease are good. “Those who quit drinking do pretty well, as long as there is good support and treatment for them,” said Rice.

But, he added, “like most things in medicine, prevention is better than a cure.”

CDC: Rural-Urban Gap Persists in PCP Opioid Prescribing

Opioid prescribing rates are significantly higher in rural areas, though overall opioid prescribing has declined since 2016, according to the latest numbers from the Centers for Disease Control and Prevention (CDC).

Macarena C. García, DrPH, with the CDC’s Center for Surveillance,

epidemiology, and Laboratory Services, and colleagues report their findings in an article published online recently in Morbidity and Mortality Weekly Report.

García and colleagues analyzed national data from 31,422 primary care providers in the Athenahealth electronic health record (EHR) system from 2014 to 2017. They found that the prevalence of opioid prescriptions was 87% higher in the most rural counties compared with large metro counties (9.6% vs 5.2%).

The authors offered some context for the trend.

“Opioid prescribing in rural (nonmetropolitan) areas is strongly influenced by providers’ individual relationships with their patients, and can be inconsistent with opioid prescribing guidelines,” the authors write.

They also note that higher prescription rates in rural areas may be linked with higher use and misuse of prescription drugs at a younger age and higher prevalence of chronic pain among those in rural areas.

Rural areas also tend to have a higher percentage of older adults, a population with more conditions associated with pain, they note, and residents of rural areas may have less access to alternative treatments for pain.

“As less densely populated areas appear to indicate both substantial progress in decreasing opioid prescribing and ongoing need for reduction, community health care practices and intervention programs must continue to be tailored to community characteristics,” the authors write.

The report points out that overall opioid prescribing rates have been declining since March 2016 after the release of the CDC Guideline for Prescribing Opioids for Chronic Pain.

Among other findings in the report:

  • Of 70,237 fatal drug overdoses in 2017, prescription opioids were involved in 17,029 (24.2%);
  • In 2017, 14 rural counties were among the 15 counties with the highest opioid prescribing rates, which put patients at greater risk for addiction and overdose.
  • Drug overdose is the leading cause of unintentional injury–associated death in the United States.

Among limitations of the study are that the data did not indicate the circumstances of the prescribing, such as whether a patient had chronic or acute pain, or whether prescriptions were filled and taken as the provider prescribed.

The authors write that this study shows that EHRs can help supplement traditional surveillance.

They add, “The lag between the collection of the data and this analysis could potentially be reduced to a matter of weeks with optimized workflows.

Opioid-Related Deaths Up Threefold in Children


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The mortality rate from opioid poisoning among children and adolescents in the United States increased almost threefold between 1999 and 2016, a new study shows.

The increase was most profound among those aged 15 to 19 years, a group that sustained a substantial rise in deaths from heroin and synthetic opioids.

The study found that opioids were responsible for almost 9000 deaths among children and adolescents during the period studied and that almost 40% of them died at home.

The opioid crisis should be viewed as a “family problem,” where “everyone is affected and likely exposed” when these drugs are brought into the home, lead author Julie R. Gaither, PhD, an epidemiologist and instructor, Department of Pediatrics, Yale School of Medicine.

“I would love it if physicians who treat adults with opioids would consider who else is in the household, whether it’s an elderly family member or children.”

Gaither stressed that although the opioid epidemic is complex, some of the answers to it “are just common sense,” and these include “basic safety measures” such as telling patients that an opioid can kill a child.

The study was published online December 28 in JAMA Network Open.

The authors report that almost 5000 children under age 6 years are evaluated every year for opioid exposure in emergency departments across the United States. Hospitalizations for opioid poisonings increased almost twofold among children and adolescents between 1997 and 2012.

However, it’s unclear how many children die each year from opioid poisonings and how mortality rates have changed over time since the opioid epidemic began in the late 1990s.

For this new study, researchers used the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER). This database includes US county-level death certificate data from the National Center for Health Statistics.

Investigators identified poisonings from prescription and illicit opioids between January 1, 1999, and December 31, 2016. They used International Statistical Classification of Diseases, 10th revision (ICD-10) codes to categorize deaths from any opioid.

Under the label “prescription opioids,” Gaither and colleagues grouped all but synthetic opioids. The exception was methadone, a synthetic opioid that was included in the prescription category.

The other synthetic opioids (including pharmaceutically and illicitly manufactured fentanyl) and heroin were assessed separately and only in adolescents aged 15 to 19 years.

Researchers classified deaths as unintentional, suicide, homicide, or undetermined.

They categorized children and adolescents by age group: 0 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 19 years.

In the oldest age group, researchers also examined deaths involving one or more other drugs.

Researchers used a generalized smoothing spline Poisson regression model to estimate mortality rates and assess temporal changes in rates over time (time effect).

They found that 8986 children and adolescents died from prescription and illicit opioid poisonings between 1999 and 2016. Of these, 88.1%, were aged 15 to 19 years, and 6.7% were under 5 years. Most deaths were among non-Hispanic whites (79.9%) and males (73.1%).

During the study period, the annual estimated mortality rate for all children and adolescents rose from 0.22 (95% CI, 0.19 – 0.25) to 0.81 (95% CI, 0.76 – 0.88) per 100,000, an increase of 268.2% (for time effect < .001).

Broken down by age group, the increases in mortality rates (all for time effect < .001) were:

  • Ages 0 to 4 years: From 0.08 (95% CI, 0.06 – 0.10) to 0.26 (95% CI, 0.22 – 0.31) per 100,000, an increase of 225.0%.
  • Ages 5 to 9 years: From 0.02 (95% CI, 0.01 – 0.03) to 0.04 (95% CI, 0.03 – 0.06) per 100,000, an increase of 100.0%.
  • Ages 10 to 14 years: From 0.04 (95% CI, 0.03 – 0.06) to 0.10 (95% CI, 0.07 – 0.13) per 100,000, an increase of 150.0%.
  • Ages 15 to 19 years: From 0.78 (95% CI, 0.68 – 0.88) to 2.75 (95% CI, 2.55 – 2.96) per 100,000, an increase of 252.6%.

The authors noted that children under 5 years, who they called “a highly vulnerable group for which the consequence of the opioid crisis has been somewhat overshadowed by opioid-related morbidity among neonates and older teens,” had the second highest mortality rate.

Systemic Problem

The overall mortality rate for males increased by 241.9%, compared with 323.1% for females (all for time effect < .001).

“Most poisonings are still in males, and in white males in particular, but rates are rising at a faster rate among girls as well as among Hispanics and blacks,” commented Gaither. Black children had almost a fourfold increase in rates.

“This is indicative of the fact that this is a systemic problem and it’s continuing to spread to all segments of society,” she said.

Among non-Hispanic white children and adolescents, mortality rates increased by 289.3%.

About 80.8% of deaths were unintentional, 5.0% were because of suicide, and 2.4% were attributed to homicide.

But the manner of death varied significantly by age group. Among those 15 to 19 years, 85.3% of deaths were unintentional and 4.8% were attributed to suicide, while among children under 5 years, 38.0% of deaths were unintentional, 24.5% were because of homicide, and the manner of death could not be determined in 37.5% of cases.

The percentage of deaths because of homicide was highest in those younger than 1 year (34.5%).

Anecdotal evidence suggests parents may be giving their child an opioid to sedate them or help get them to sleep, commented Gaither.

Prescription opioids were implicated in 73.0% of deaths. Methadone alone caused 35.9% of prescription opioid deaths; however, the mortality rate for methadone peaked in 2007 and by 2016 had decreased by 76.7%.

Heroin was responsible for 23.6% of deaths among adolescents aged 15 to 19 years. Rates for fatal heroin poisonings in this group increased by 404.8%, whereas rates for prescription opioids increased by 94.7% (all for time effect < .001).

Huge Surge

In this age group, mortality rates for synthetic opioids increased by 2925.0% (for time effect < .001).

“For synthetic opioids, the rates were essentially flat until about 2014, and then there was a huge surge,” said Gaither. “Over time, there was this almost 3000% increase in deaths from synthetic opioids, and since 2014, a third of all poisoning deaths — so prescription, everything — were due to synthetic opioids.”

Among older adolescents, 38.5% of deaths involved another prescription or illicit substances in addition to an opioid. These included benzodiazepines (19.6%), cocaine (11.6%), alcohol (6.6%), antidepressants (4.1%), psychostimulants (4.0%), cannabis (1.6%), antipsychotics/neuroleptics (1.2%), or barbiturates (0.3%).

Almost two thirds of deaths (61.6%) occurred outside of a medical facility, with 38.0% occurring at home or other residential se

Gaither said she was surprised at the high number of opioid poisonings every year in kids. “There has been a perception that few kids actually die from opioid poisoning.”

Contributing to the surge in opioid-related deaths in kids is the sheer number of these drugs now available, which increases the chances that children will be somehow exposed.

Teens, for example, may find the drugs in the medicine cabinet or in their mother’s purse, while younger children may come across part of a drug strip on the floor or counter and put it in their mouth.

“We don’t have child-proof packaging on all opioids, including the fentanylpatch [Duragesic] and Suboxone,” the combination form of buprenorphine and naloxone used to treat opioid addiction, said Gaither.

Duragesic comes in foil wrappers that can be easily opened by a child, and Suboxone, now sold in brightly colored film strips, also poses a danger to children, she said.

The rate of opioid poisoning among young people could increase further with initiatives aimed at increasing the availability of naloxone in homes and communities, especially given that most pediatric deaths occur outside a medical setting.

“I personally am not sure how that affects very young kids,” said Gaither. “I think we need further research to be able to say what parents of young child should be doing.”

She urged clinicians to consider the individual patient in the context of the family “and to think about how everyone in the home is affected and likely exposed to opioids.”

The study relied on data from death certificates, so it’s possible that misclassification of cause and manner of death occurred, the researchers noted.

Tip of the Iceberg

Asked to comment for, Lloyd Werk, MD, MPH, chief, Division of General Pediatrics, Department of Pediatrics, Nemours Children’s Health System, Orlando, Florida, said the new study “reveals the extent of opioid deaths that had not been known in pediatrics.”

But the surge in opioid deaths is just “the tip of the iceberg,” said Werk.

“With this study showing so many youth experiencing opioid deaths, that tells us there are even more youth experiencing mental and physical consequences from opioids, including depression, anxiety, school failure, risk for illnesses like hepatitis, and pregnancy.”

Such consequences can even include heart infections because of intravenous drug use and stroke, he added.

Because of the increased consequences of opioid use, it’s even more important to screen young people for drug use.

Several screening tools are available. Some of the more well-known are SBIRT (Screening, Brief Intervention, and Referral to Treatment) and HEADSS (Home, Education/Employment, Peer Group Activities, Drugs, Sexuality, and Suicide/Depression).

Results of screening can give youth positive reinforcement if they’re staying away from drugs, and if they’re struggling, support and referrals can be provided, said Werk.

Are kids likely to be honest about their drug use? “If it becomes a routine part of regular office visits and is done confidentially without the parents in the room, there is evidence that there is a decent response,” said Werk.

But the first step is to just ask youth about drug use. “If you ask the question early enough, you can potentially save a life.”

Primary care physicians generally start such screening at about age 11 or 12 years, said Werk.

Some research has linked drug use in youth, along with mental health problems and poor health, to earlier exposure to events such as divorce, abuse, and a parent being incarcerated. 

“If we can identify folks at risk, maybe we help them build resilience, build their ability to cope,” he said.

The fact that some prescribed opioids are still not in childproof packages is “crazy,” Werk added. “Here you have a substance that can cause you to stop breathing, especially if you’re a toddler, and that’s potentially fatal. We could do a better job of child-proofing containers that hold opioids.”

Endorsing Cannabis as an Opioid Substitute ‘Irresponsible’





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Even as two states have passed laws to encourage clinicians to use cannabis as a substitute for opioids, some experts are warning against this practice.

Two addiction experts — Keith Humphreys, PhD, professor of psychiatry and behavioral sciences at Stanford University, Palo Alto, California, and Richard Saitz, MD, professor and chair of the department of community health sciences, Boston University School of Public Health, Massachusetts — argue that “substituting cannabis for opioid addiction treatments is potentially harmful.”

Saitz, who is also a former director of Boston Medical Center’s Clinical Addiction Research and Education Unit, said he and Humphreys decided to write the article, which was published online February 1 in JAMA, because patients and physicians have been “chattering” about cannabis as an opioid substitute.

“The conversation has generally assumed cannabis to be safer and as effective as opioids, but it isn’t clear what the truth is.”

Thirty-three states, Washington, DC, Guam, and Puerto Rico have legalized cannabis for medical use, and 10 states and Washington, DC, have legalized it for recreational use, according to the National Council on State Legislatures.

Both New York and Illinois recently amended medical marijuana laws in favor of cannabis as a substitute, which was another factor in writing the article, said Saitz.

New York issued emergency regulations in July 2018 allowing opioid users to become certified to use medical marijuana instead. In August 2018, the Illinois governor signed a bill allowing individuals over age 21 with conditions for which opioids might be used to apply for the medical marijuana program.

“Irresponsible” Recommendation

“The suggestion that patients should self-substitute a drug (ie, cannabis) that has not been subjected to a single clinical trial for opioid addiction is irresponsible and should be reconsidered,” Saitz and Humphreys write.

“There are no randomized clinical trials of substituting cannabis for opioids in patients taking or misusing opioids for treatment of pain, or in patients with opioid addiction treated with methadone or buprenorphine,” they add.

There is “low-strength” evidence showing that cannabis can alleviate neuropathic pain, and insufficient evidence for other types of pain, and the studies are of poor quality, said the authors.

Saitz and Humphreys noted that some have said that allowing cannabis use instead of opioids has led to fewer overdoses. But, they said, “correlation is not causation.”

The only individual-level study to look at this issue, published in the Journal of Addiction Medicine in 2018, found that “medical cannabis use was positively associated with greater use and misuse of prescription opioids,” they said. A regression model study published last fall in the American Journal of Psychiatry reached a similar conclusion: that cannabis use increased the risk of developing nonmedical prescription opioid use and opioid use disorder.

Saitz and Humphreys said proponents of substitution often overlook the risks of cannabis, which include motor vehicle crashes, cognitive impairment, structural brain changes, and psychotic symptoms. There is also a risk of cannabis addiction, they said.

The authors said that if cannabis is to be used as medicine, it should be subjected to the same types of trials and regulation as medical therapies.

“Cannabis and cannabis-derived medications merit further research, and such scientific work will likely yield useful results,” they said. “This does not mean that medical cannabis recommendations should be made without the evidence base demanded for other treatments,” they write.

Ineffective Pain Reliever

Asokumar Buvanendran, MD, chair of the American Society of Anesthesiologists (ASA) Committee on Pain Medicine and a professor of anesthesiology at Rush University Medical Center, Chicago, Illinois, agreed that “there is not enough research and science” on cannabis, but added, “we need to support further research.”

The ASA has supported moving marijuana to schedule II on the Drug Enforcement Administration’s list of controlled substances, which would facilitate more research, Buvanendran told Medscape Medical News.

Even though he practices in Illinois, he said that he does not believe awareness of the changes to the state’s medical marijuana law is widely known.

Buvanendran said he’d counsel patients seeking to substitute cannabis to consider alternatives — such as injection therapies and surgical procedures to modulate nerves causing pain — which have a larger evidence base.

Kevin Boehnke, PhD, a research investigator in the anesthesiology department and Chronic Pain and Fatigue Research Center at the University of Michigan, Ann Arbor, who has written a lot on cannabis and chronic pain, said that most cannabis trials have methodological flaws and “the evidence for opioids for chronic pain management is quite poor.”

He also notes that the studies generally do not distinguish between tetrahydrocannabinol (THC), which is psychoactive, and cannabidiol (CBD), the other most prevalent active ingredient. THC is associated with most of the health risk of cannabis, while CBD products have limited abuse potential, Boehnke said.

Boehnke believes cannabis offers less dangerous side effects and a lower risk of addiction — although he would advise against use in people with substance use disorders. Both opioids and cannabis are relatively ineffective pain relievers, “but one of them can kill you and one can’t,” said Boehnke, adding, “to me, the risk-benefit is obvious.”

Need for Better Evidence

He added that he is looking forward to a time when there is better evidence to guide clinicians, particularly given that he and his colleagues recently published data suggesting that potentially more than a million Americans are using medical marijuana.

In that study, published in the February edition of Health Affairs, the researchers queried states with medical marijuana laws in an attempt to gauge how many Americans have registered and what conditions they were treating with cannabis.

Data were available from 20 states and Washington, DC; Connecticut does not publish reports on users and did not respond to requests for data and 12 states said they don’t have statistics.

Chronic pain was the most common patient-reported condition, accounting for 62% of the total conditions reported, followed by multiple sclerosis spasticity. Those are also the two conditions with the largest evidence base and among the most common conditions required for medical marijuana certification in most states, Boehnke said.

And chronic pain affects some 100 million Americans, so it is no surprise that it is the most common condition that individuals are seeking to treat, he said.

Even though the lack of reports from some states likely underestimate the number of patients using medical marijuana, “our data show that the number of medical cannabis patients has risen dramatically over time as more states have legalized medical cannabis,” said Boehnke and colleagues.

The gap in statistics on the number of users and conditions they are treating highlights “the importance of compiling a nationwide database of medical cannabis users to evaluate the risks and benefits of using medical cannabis for different medical conditions and symptoms,” said the authors.