The NIH Announces a Commitment to Research on LGBT Health

lgbt-med

Every person has a right to live a healthy life. One part of that vision is equal access to health care for all. But unsurprisingly, not everyone have the same ability to receive health care due to things like socioeconomic status, race, gender, or even sexual orientation. Indeed, LGBT people often have less access to health care than their non-LGBT counterparts, most often due to discrimination and stigma [1].

The Director of the National Institute on Minority Health and Health Disparities, part of the National Institutes of Health (NIH), announced “the formal designation of sexual and gender minorities (SGMs) as a health disparity population for NIH research.” Read the full announcement here.

What does this mean? That the NIH is officially recognizing that LGBT people have less access to health care and that improved research on LGBT-specific (defined here broadly as sexual and gender minorities) health issues is essential to improved health care.

The long-overdue announcement was supported by an important report released by the non-partisan National Academies of Science (NAS) in 2011. The report identified gaps in the research on the health of LGBT persons and made recommendations for improving this research that could benefit not just LGBT people, but the health care system overall.

LGBT individuals have unique health challenges that many doctors do not understand or address. For example, certain types of cancer seem to be more prevalent among gay men compared to straight men, which means different cancer screenings would be important for gay men [2].

The new designation by NIMHD will hopefully increase research and knowledge about the health challenges of LGBT people and will hopefully result in improved health care for all people, regardless of sexual orientation, gender identity, or gender expression.

Selected References

  1. Hatzenbuehler ML, Bellatorre A, Lee Y, Finch BK, Muennig P, Fiscella K. Structural stigma and all-cause mortality in sexual minority populations. Social science & medicine. 2014;103:33-41. doi: 10.1016/j.socscimed.2013.06.005.
  2. Quinn GP, Sanchez JA, Sutton SK, Vadaparampil ST, Nguyen GT, Green BL, et al. Cancer and lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations. CA: a cancer journal for clinicians. 2015;65(5):384-400. doi: 10.3322/caac.21288.
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CDC Reports Zika Virus Causes Microcephaly

Aedes aegypti mosquitoes (commons.wikimedia.org)
Aedes aegypti mosquitoes (commons.wikimedia.org)

A few weeks ago I wrote a post All About Zika virus epidemic. The million-dollar question is does Zika cause microcephaly (or abnormally small heads and severe brain damage) in the fetus if a pregnant woman is infected with virus? At the time I wrote my first post, the evidence strongly suggested that it did but scientists were reluctant to declare a direct causal relationship.

Earlier this month, scientists at the CDC published in the New England Journal of Medicine that there is now enough evidence to confirm that:

Yes, Zika virus does cause microcephaly.

The team from the CDC examined all the available reports and studies on the Zika virus and microcephaly and did a systematic analysis of all the evidence using a strict set of criteria to determine causality.

Read the full study.

While no one report or piece of evidence is the “smoking gun” all of the pieces put together reveal the truth. Just like only when all the pieces of a puzzle are fit together is the whole picture clear.

This conclusion is extremely important because the risks for pregnant women are very real. The CDC has released important information for pregnant women or women who intend to become pregnant in areas were Aedes mosquitoes (Zika carrying mosquitoes) are prevalent.

Read the CDC’s Information for Pregnant Women.

It’s important to remember that while Zika does cause microcephaly is does not cause it in 100% of pregnancies. Some pregnant women bitten by Zika will have no problems with the developing fetus. One thing we still don’t know is what is the risk that the Zika will cause microcephaly and who are the mothers most in danger of this happening?

As more information is gathered on this epidemic and more scientific studies published, the more we will learn about how to fight it.

 

Methadone vs Buprenorphine: Which is Better for Treating Heroin Addiction?

Check out my new post for addictionblog!

The CDC Fights Back Against the Opioid Epidemic

2000px-US_CDC_logo.svg

The CDC has released important information on dealing with the prescription opioid pain medication and heroin epidemic. Opioids are a class of drugs that include pain medications such as morphine, oxycodone, hydrocodone, methadone, fentanyl and others and the illegal drug heroin. I’ve spoken a great deal about this problem in various other posts (see here here here and especially here and here). Just to summarize some of most disturbing trends: the US is experiencing a surge in deaths due to overdose on opioids (overdoses/year due to opioids are now greater than fatalities from car crashes), virtually all demographics (age groups, income levels, gender, race) are affected, and many people addicted to opioid pain pills transition to heroin and as such, a huge increase in heroin abuse is also occurring; teenagers and adolescents are especially hard hit. The CDC’s report, released on Friday, March 18 provides a thorough review of the clinical evidence around prescription opioid pain medications and makes 12 recommendations to help control the over-prescription of these powerful drugs in attempt to reduce the amount of overdose deaths and addiction.

Read the full report.

I finally got around to reading the whole thing and am happy to summarize its main analyses and findings. While the report is intended for primary health care providers and clinicians, the report’s findings are important for anyone suffering from short or long-term pain and the risks vs benefits posed by opioids.

But before I dive into the meat of the report, I wanted to clarify an important issue about addiction to prescription opioids. A false narrative exists that those suffering from addiction are “drug seekers” and it is this group of people that is duping doctors in prescribing them too many opioids while good patients that take opioids as directed are not over dosing or becoming addicted. It’s important to remember that opioids are so powerful anyone that takes them runs the risk of overdosing or becoming addicted after repeated use. Most people suffering from addiction and overdoses during the current prescription opioid epidemic are people that used opioids medically and not for recreation. This is true for youths prescribed opioids for a high-school sports injury, and older patients prescribed opioids for chronic back pain, and many other “regular” people. The CDC released this report to help fight back against the over-prescription of opioids and the severe risks that accompany their use. Doctors and patients alike need to be aware of the risks vs benefits of opioids if they decide to use them for pain therapy.

Hydrocodone (wikimedia.org)
Hydrocodone (wikimedia.org)

The CDC’s report had three primary goals:

  1. Identify relevant clinical questions related to prescribing of opioid pain medications.
  2. Evaluate the clinical and contextual evidence that addresses these questions
  3. Prepare recommendations based on the evidence.

Two types of evidence were used in preparation of the report: direct clinical evidence and indirect evidence that supports various aspects of the clinical evidence (contextual evidence). Studies included in the analysis ranged from high quality randomized control studies (the gold standard for evaluating clinical effectiveness) to more observational studies (not strong, direct evidence but useful information nonetheless).

The report identified five central questions regarding the concerns over opioids:

  1. Is there evidence of effectiveness of opioid therapy in long-term treatment of chronic pain?
  2. What are the risks of opioids?
  3. What differences in effectiveness between different dosing strategies (immediate release versus long-acting/extended release)?
  4. How effective are the existing systems for predicting the risks of opioids (overdose, addiction, abuse or misuse) and assessing those risks in patients?
  5. What is the effect of prescribing opioids for acute pain on long-term use?

Based on a close examination of the clinical evidence from a number of published studies, the CDC found the following answer to these questions.

  1. There is no evidence supporting the benefits of opioids at managing chronic pain. Opioids are only useful for acute (less than 3 days) pain and for cancer pain or end-or-life pain treatment.
  2. Opioids have numerous risks such as abuse and addiction, overdose, fractures due to falling in some older patients, car crashes due to impairments, and other problems. The longer opioids are used the greater these risks.
  3. There is no difference in effectiveness between immediate release opioids and long-acting or extended release formulation. The evidence suggests the risk for overdose is greater with long-acting and extended-release opioids.
  4. No currently available monitoring methods or systems are capable of completely predicting or identifying risk for overdose, dependence, abuse, or addiction but severak methods may be effective at helping to evaluate these risk factors.
  5. The use of opioids for treating acute pain increases the likelihood that they will be sued long-term (most likely because of tolerance and dependence).
Oxycodone (wikimedia.org)
Oxycodone (wikimedia.org)

The CDC also examined what they called contextual evidence or studies that didn’t directly answer the primary clinical questions but still provided valuable, if indirect, information about treatment of pain with/without opioids.

  • Non-medication based therapies like physical therapy, exercise therapy, psychological therapies, etc. can be effective at treating chronic pain for a number of conditions.
  • Non-opioid pain medications such as acetaminophen, NSAIDs, Cox-2 inhibitors, anti-convulsants, and anti-depressants (in some instances) were also effective in treating chronic pain for various conditions and have fewer dangers than opioids.
  • Long-acting opioids increase the risk for overdose and addiction. Higher doses of opioids also increase the risk for overdose.
  • Co-prescription of opioids with benzodiazepines greatly increases the risk of overdoses.
  • Many doctors are unsure of how to talk to their patients about opioids and their benefits vs risks and most patients don’t know what opioids even are.
  • The opioid epidemic costs billions of dollars in medical and associated costs. Its estimated  costs due to treatment of overdose alone is $20.4 billion.

Many other findings and important pieces are information were reported but too many to list here.

Based on all results of the analysis the CDC came up with 12 recommendations in three broad categories. I’ll briefly discuss each recommendation.

Category 1: Determining when to initiate or continue opioids for chronic pain.

  • Recommendation 1: Non-pharmacologic (medication-based) therapy and non-opioid pharmacologic therapy are preferred for chronic pain.
    • The risks of overdose and addiction from long-term use of opioids is very high and benefits for actually treating pain are very low for most people. Therefore, other safer and more-effective treatments should be use first. The discussion of the risks vs benefits needs to be made clear by the patient’s doctor.
  • Recommendation 2: Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function
    • Opioids should be used for the shortest amount of time possible but if used for a long-term treatment, at the lowest effective dose.
    • If a patient suffers from an overdose or seems as if dependence or addiction is developing, a patient may need to be tapered off of opioids.
  • Recommendation 3: Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy.
    • The risks are high for the use of opioids and it is necessary for doctors to keep their patients informed about these risks.
    • Doctors should be “be explicit and realistic about expected benefits from opioids, explaining that while opioids can reduce pain during short-term use, there is no good evidence that opioids improve pain or function with long-term use, and that complete relief of pain is unlikely.”

Category 2: Opioid selection, dosage, duration, follow-up, and discontinuation.

  • Recommendation 4: When starting opioid therapy, clinicians should prescribe immediate-release opioids instead of extended-release or long-acting opioids.
    • There appears to be no difference in effectiveness at treating pain between the different types of opioids but the long-acting opioids come with a greater risk for overdose and dependence.
    • Long-acting opioids should be reserved for cancer pain or end-of-life pain.
    • It’s important to note that “abuse-deterrent” does not mean that there is no risk for abuse, dependence, or addiction. These types of formulations are generally to prevent intravenous use (shooting up with a needle) but most problems with opioids occur as a result of normal, oral use.
  • Recommendation 5: When opioids are started, clinicians should prescribe the lowest effective dosage.
    • The higher the dose the greater the risk. A low dose may be sufficient to control the pain without risk for overdose or the development of dependence.
    • Opioids are often most effective in the short-term and may not need to be continued after 3 days.
    • If dosage needs to be increased, changes in pain and function in the patient should be re-evaluated afterwards to determine if a benefit has occurred.
    • Patients currently on high-dose long-term opioids for chronic pain may want to consider tapering down their dosage.
      • Tapering opioids can be challenging can take a long-time due to the physical and psychological dependence. Tapering should be done slowly to and the best course of dosage should be determined specifically for the patient.
    • Recommendation 6: Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed.
      • Evidence suggests that using an opioid for acute pain can start a patient down a path of long-term use. This should attempted to be avoided by using a low dose if opioid is selected to treat acute pain.
      • Acute pain can often be effectively managed without opioids with non-medication-based therapies (like exercise, water aerobics, physical therapy, etc.) or non-opioid medications (like acetaminophen or NSAIDs).
    • Recommendation 7: Clinicians should evaluate benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation.
      • Opioids are most effective for the first three days and possible up to a week. If long-term therapy is decided upon, treatment should regularly be reassessed and reevaluated (at least every 3 months for long-term therapy).

Category 3: Assessing risks and addressing harms of opioid use.

  • Recommendation 8: Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone.
    • Specific risk factors for the specific condition that patient is using opioids for should be considered when developing the treatment plan.
    • Naloxone blocks the effects of opioids and can immediately revive someone that has experienced an overdose. Naloxone should be offered to patients if a patient is using opioids at high-dose for long-term therapy or previously suffered an overdose.
  • Recommendation 9: Clinicians should review the patient’s history of controlled substance prescription using state prescription drug monitoring program (PDMP) data to determine whether a patient is receive opioid dosages or dangerous combinations that put him or her at risk for overdose.
    • PDMPs are state-run databases that collect information on controlled prescription drugs dispensed by pharmacies and in some states, physicians too.
    • While the clinical evidence was unclear if PDMPs were accurate at predicting overdose or addiction, the contextual evidence supported that “most fatal overdoses were associated with patients receiving opioids from multiple prescribers and/or with patients receiving high total daily opioid dosage.”
    • PDMP should be consulted before beginning opioid therapy and during the course of treatment if used for long-term therapy and this data should be discussed with the patient.
    • However, PDMP data must be used cautiously as some patients are turned away from treatment that would otherwise have benefited.
  • Recommendation 10: (not a general recommendation but to be considered on a patient-by-patient basis) When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.
    • Urine drug tests can reveal information about potential risks due to combinations with other drugs not reported by the patient (e.g. benzodiazepines, heroin).
    • Urine testing should become standard practice and should be done prior to starting opioids for chronic therapy.
    • Clinicians should make it clear that testing is intended for patient safety and is not intended to deprive the patient of therapy unnecessarily.
  • Recommendation 11: Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.
    • Strong evidence suggests that many overdoses occurred in patients prescribed both benzodiazepines and opioids. The two should never be prescribed together if at all possible.
  • Recommendation 12: Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid abuse disorder (addiction).
    • Many patients using opioids for chronic pain now may have become physically and psychologically addicted to them and should be offered treatment (estimated at 3-26% of patients using opioids for chronic pain therapy).
    • Methadone and buprenorphine are proven, safe, and effective-treatments that retain patients in treatment and that satisfy an opioid addict’s cravings, prevent relapse to abusing opioids/heroin, and allow the patient to live a normal life (read my blog post on methadone).
    • Behavioral therapy/individual counseling in combination with medication-based treatment may improve positive benefits of treatment even further.
    • However, access to these medications can be extremely limited in some communities due to availability (methadone is restricted to clinics and clinicians need certification in order to prescribe buprenorphine) or cost (treatment often is not covered by insurance).
    • Urine testing or PDMP data may help to reveal if a patient has become addicted and if so, treatment should be arranged.

In Summary, the main takeaways from the report are:

  • Opioids are associated with many risks such as overdose, abuse, dependence, addiction, and others (e.g. fractures from falling or car-crashes due to impairment).
  • No evidence exists that opioids are effective for treatment of chronic pain (with the exception of cancer and end-of-life pain).
  • Opioids are most effective for short term (3-7 days) and in immediate-release formulations.
  • Non-medication based therapies and non-opioid medications are preferred for treatment of chronic pain.
  • Doctors need to clearly explain the risks vs benefits of opioid therapy with their patients.
  • If decided as the best course of action for a particular patient, opioid therapy needs to be repeated re-evaluated to make sure it is still working to alleviate pain.
  • The prescription drug monitoring programs are useful tools that should be consulted prior to beginning therapy in order to help determine a patient’s history with opioids and risk for abuse or overdose.
  • Naloxone should be made available to patients using opioids for long-term therapy in order to prevent possible overdoses.
  • Access to medication-based treatments (methadone or buprenorphine) for dependent individuals should be provided.

Concluding Thoughts

In 1995 Purdue pharmaceuticals released OxyContin (oxycodone, one of the most common prescription opioid pain medications) and launched an enormous push for doctors to use opioids as the primary treatment for chronic pain. The enormous surge in in prescriptions of oxycodone (500% increase from 1999-2011) followed this marketing campaign. One of the most disturbing aspects revealed by the CDC’s report is that despite this surge in prescriptions, there is a complete lack of data on the effectiveness of opioids for long-term chronic pain therapy.

To be fair though, “Big Pharma” is not the sole culprit in this crisis. One argument is that pharma was responding to the need of clinicians for an increased demand by patients for management of chronic pain. It is very disturbing though that the push for the use of opioids for long-term management was initiated without any supporting evidence. This is another example of how medicine must be guided by evidence-based principles and not on personal beliefs and values or medical tradition and culture.

It’s important to remember that some patients do tolerate opioids well and these patients may find them beneficial at treating their chronic pain condition. The guidelines do stress frequent reevaluation of the benefits vs risks of opioids and for some patients benefits will outweigh the risks.

Finally, the CDC’s guidelines are not legally binding. These are recommendations and not laws or regulations. This means no doctors are not legally required to comply with any of the CDC’s recommendations. Hopefully some or all of these recommendations will be formalized into formal laws and regulations because many of them are extremely important in regulating these powerful and potentially dangerous drugs.

(Also check out the Diane Rehm Show’s hour-long discussion of the report. As usual, the show offers a high quality analysis and discussion from a panel of experts.)

Top Scientific Leaders on Addiction Call for its Treatment as a Medical Disease

(© Alan Cleaver flickr https://www.flickr.com/photos/alancleaver/4104954991)
(© Alan Cleaver flickr https://www.flickr.com/photos/alancleaver/4104954991)

A new review article published in the prestigious New England Journal of Medicine highlights the importance of treatment of addiction as a medical disease and calls for a change in public health policy towards addiction. Written by several leaders in the addiction field including Nora Volkow, MD, the director of NIDA, and George Koob, PhD, the director of NIAAA, the article does a superb job at outlining the underlying biology of addiction and clearly explains why addiction is a disease of the brain that needs to be treated medically.

Read the full article here.

In fact, I also covered most of the points made in the article in my own post for Addiction Blog on “Why Addiction is a Brain Disease?”

However, when it comes to public health policy towards addiction, this is where the article fell short. While treatments for opioid addiction such as methadone and buprenorphine were briefly mentioned in the article, there was no call for a national effort to be made to increase access to these vital medications. The authors had a potential to increase awareness of the opioid epidemic and the treatments already on hand to fight it but failed to make a stronger case for this critical improvement.

Nevertheless, the article is well written and a great introduction to the neuroscience of addiction and why it is a disease of the brain.

Why is Addiction a Brain Disease?

I started as a contributor for the blog network addictionblog.org.

addiction blog logo copy

Read my first post, published today!

WHY IS ADDICTION A BRAIN DISEASE?

Marijuana has Long-term Effects on the Brains of Adolescents

(from wikipedia.org)
(from wikipedia.org)

After alcohol, marijuana is the most widely used illegal drug in the United States (I mean seriously, who hasn’t smoked up at least once? According to Pew Research Center, half of the country) But pot laws are rapidly changing in many parts of the country and soon it may be as ubiquitous as alcohol. Four states in the US have legalized marijuana for recreational use and 23 total states have some form of legal marijuana use (including D.C.). While the health effects of alcohol have been well studied and are significant (some 88,000 deaths/year, the third highest cause of preventable death in the US, according to the CDC and NIAAA), little is known how this shifting trend in marijuana use will affect the country. Another important trend is the amount of THC (Δ-9-tetrohydrocannabinol, the chemical that is primarily responsible for the psychoactive effects of marijuana) in marijuana strains has been steadily increasing over the past few decades [1, 2]. The big question that researchers are asking themselves is if legal marijuana use drastically increases, what are the long-term personal and public health consequences of marijuana use? Of course, this is a huge question with many complexities.

Significantly, Marijuana is the also the most widely used illegal substance amongst youths. Adolescence (ages 12-17) is an extremely critical period for brain development [3, 4] yet the effects of marijuana on the brains of kids have not been thoroughly studied. A recent paper out of Dr. Steven R. Laviolette’s laboratory at the University of Ontario sought to answer this question: what happens to brains of adolescent and adult rats that have been exposed to THC?

Renard et al. 2016 abstract

Why was the research done? What is the hypothesis?

 There have been a number of studies published that suggest there might be an association between prolonged marijuana use (especially of high-potency strains) and schizophrenic-like or psychotic-like symptoms [5, 6] although there is disagreement in the scientific community on the evidence [7, 8] (I may write a blog post discussing this issue in the future). It is has even been suggested that youths that smoke marijuana are more at risk for psychotic symptoms as adults [9, 10]. The author’s sought to test this directly by injecting adolescent and adult rats with THC for a number of days, waiting a period of time after the injections, then measuring the long-term effects on the rats. The team hypothesized THC would have induced long-term changes in the brains of adolescent but not adults rats, and subsequent changes in psychotic-like behavior.

How was it done?

Adolescent and adult rats were injected with THC twice daily for 11 days. The dose of THC administered was increased (escalating dose) to account for any tolerance that may occur. As an important control, separate groups of adolescent and adult rats were injected with vehicle (the solution that THC was dissolved in but minus the THC itself). Following a 30-day abstinence period after the last injection, THC-adolescent, control-adolescent, THC-adult, and control-adult rat groups were subjected to number of behavioral and molecular tests to see what effect the drug had on the animals. I need to point out that the 30-day abstinence period is significant in the rat life-span. This is enough time for the adolescent rats to become adults so what the scientists are primarily studying is the long-term effects of THC on adolescents vs adults in adulthood.

In the behavioral neuroscience field, we have devised another of tests to measure various aspects of animal behavior. Obviously we can’t inject humans with THC and see what happens so we have to use rodents and identify behaviors that approximate a similar behavior in humans. Of course, rodent behavior is no where near as complex as humans but rats are remarkably sophisticated animals (ask anyone living in New York) and scientists have developed a number of ways to measure things from motivation to social behavior to anxiety to depression.

In this experiment, a social test was used, two different types of anxiety tests and a motor activity test. The tests measured effects on motivation, exploratory-behavior (another indicator of how motivated rats are), social interaction, and anxiety.

The scientists also measured the activity of dopamine-releasing neurons in the living animal using a technique called in vivo electrophysiology. Recall from my post I am Neuron! that when activated, brain cells (called neurons) conduct an electrical current that results in the release of neurotransmitters onto another neuron. This electrical current is called an action potential and we can measure this by inserting a special probe into the those neurons in the animals brain (the probe measures electrical currents). Therefore, with in vivo electrophysiology we can measure every time a neuron fires (i.e. an action potential is generated) in a specific part of the brain. Using this technique, the scientists measured dopamine neurons in an important region of the brain called the VTA and how often these neurons fire in THC vs control rats. Check out this video for more details on in vivo electrophysiology.

Finally, brains from animals were dissected and a number of protein molecules were studied using a common technique in molecular biology called a Western blot (or known as an immunoblot). A Western blot takes advantage of antibodies that are able to recognize and stick to one specific type of protein. Therefore, this assay can tell you two main things 1) if your protein of interest is present in your sample and 2) approximately how much of your protein there is compared to other samples. In this paper, tissue from a specific brain region is used and the protein is analyzed by Western blots in order to comparing quantities of proteins between the different experimental groups. Of course, the limitation of a Western blot is if you have a good antibody for your protein of interest. Luckily there are many biotech companies such as Cell Signaling that specialize in making and testing reliable antibodies. The scientists used the Western blots to study many proteins in a region of the brain called the prefrontal cortex (PFC), which is believed to be important in self-control and other high-function brain processes. Check out this video for more details on Western Blots.

What did they find?

THC-adolescent rats exhibited deficits in numerous behavioral experiments compared to controls while THC-adult rats did not appear to have any behavioral changes.

*Recall that these experiments were conducted 30 days after the last THC dose so the author’s show that these are long-term effects of THC on the brain of adolescent rats.

In the social activity test, rats showed little interest in interacting with a stranger rat (normal rats are usually curious about the novel stranger). THC-adolescents also did not walk around or explore a new cage as much. In the two different anxiety tests, THC-rats appeared to have be more anxious (demonstrated more anxiety-like behavior).

In the electrophysiology experiment, VTA DA neurons fired more frequently for some reason in THC-adolescents compared to the other groups.

Finally, numerous protein changes in the PFC were observed in a number of important signaling pathways such as Wnt and mTOR pathways. Interestingly, THC-adolescents vs THC-adults seemed to have opposite effects on this proteins.

Limitations to the study?

  1.  The behavioral changes observed were statistically significant (meaning, most likely a real effect and not some kind of fluke of random chance) but were modest changes in some of the tests performed. Would the changes last beyond the 30 days post injection in this study?
  2. There are impressive arrays of behavioral tests that rats can perform to measure numerous aspects of cognition (for example, memory and learning) but none of these experiments were performed. A far greater range of behavioral experiments would have made this study more compelling.
  3. While the electrophysiology and Western blot data are intriguing, the author’s performed no experiments to determine if these changes are responsible for the difference in behavior (association vs causation). These changes could merely be an incidental change and have nothing to do with the behaviors studies.
  4. The doses that the mice were injected with, while based on a previous study, are somewhat arbitrary. Would the changes be more pronounced or less pronounced with higher/lower doses or a shorter/longer dosing regimen?
  5. Only male rats were studied. Would the same behavioral and molecular changes occur in female rats?

What does it mean?

Based on the behavioral and molecular data presented, this data paper suggests that adolescent rats (but not adults) exposed to THC have long-lasting changes in the brain. The author’s argue that these effects recapitulate schizophrenia-like symptoms but I am not entirely convinced. Also, THC given to rats is not the same thing as marijuana smoked by human teenagers. So it’s important to keep in mind that this is one study. In science, we never draw grand conclusions about anything based on one study. Nevertheless, several other reports have corroborated these findings (see this review paper for a summary of many of them [11]). Indeed, it does seem that marijuana use can cause long-term deficiencies in human and rodent brains. The results of this paper are certainly intriguing and, if true, a whole host of stricter regulations on marijuana use in states that have legalized it may need to put in place to help curb increasing marijuana abuse amongst youths.

References

  1. Cascini F, et al. Increasing delta-9-tetrahydrocannabinol (Delta-9-THC) content in herbal cannabis over time: systematic review and meta-analysis. Current drug abuse reviews. 2012;5(1):32-40.
  1. Mehmedic Z, et al. Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. Journal of forensic sciences. 2010;55(5):1209-17.
  1. Keshavan MS, et al. Changes in the adolescent brain and the pathophysiology of psychotic disorders. The lancet Psychiatry. 2014;1(7):549-58.
  1. Spear LP. The adolescent brain and age-related behavioral manifestations. Neuroscience and biobehavioral reviews. 2000;24(4):417-63.
  1. Arseneault L, et al. Causal association between cannabis and psychosis: examination of the evidence. The British journal of psychiatry : the journal of mental science. 2004;184:110-7.
  1. Di Forti M, et al. Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. Schizophrenia bulletin. 2014;40(6):1509-17.
  1. Moore TH, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370(9584):319-28.
  1. Gage SH, et al. Association Between Cannabis and Psychosis: Epidemiologic Evidence. Biological psychiatry. 2015.
  1. Rubino T, Parolaro D. Long lasting consequences of cannabis exposure in adolescence. Molecular and cellular endocrinology. 2008;286(1-2 Suppl 1):S108-13.
  1. Stefanis NC, et al. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction. 2004;99(10):1333-41.
  1. Renard J, et al. Long-term consequences of adolescent cannabinoid exposure in adult psychopathology. Frontiers in neuroscience. 2014;8:361.

Personality-targeted Interventions Can Reduce Alcohol and Marijuana Use Among Adolescents

Cover-Photo-for-Conrod-post

Let me state the obvious: alcohol and marijuana are the two most widely used drugs of abuse in the United States. According to the annual National Survey on Drug Use and Health (NSDUH), (the most comprehensive survey of drug use and abuse in the United States conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA)) as of 2013, 86.8% of the population aged 18 or older have reported having consumed alcohol during their lifetime with over 16.6 million adults diagnosed with alcohol abuse disorder.

Of course, we all know the prevalence and extent of underage drinking, and the damage alcohol has on the developing brain has been heavily researched, not to mention all the significant secondary problems associated with alcohol abuse (car crashes, sexual assault on college campuses, falling off of balconies… ).

But here’s some numbers anyways: as of 2013, 8.7 million youths aged 12-20 reported past month alcohol use, a shockingly high number for an age group this is not legally allowed to drink alcohol…

Similarly, marijuana, which is still illegal in the vast majority of the US, is nearly as ubiquitous. According to the NSDUH 2013 survey, 19.8 million adults aged 18 or older reported past month marijuana use.

And with marijuana legalization in Colorado and Washington, a significant concern raised by many is that abuse of the drug among youths will dramatically increase even higher than it is now. The research supporting the damage marijuana can inflict on brain development is also significant.

But what if the risk of use of alcohol and marijuana by youths could be reduced? What if a teacher could be given the tools to not only identify certain risky personality traits in their students but also use that knowledge to help those at-risk students from trying and using drugs such as alcohol and marijuana? A series of studies coming out of the laboratory of Dr. Patricia A Conrod of King’s College London report having done exactly that.

SFN 2015 LogoI had the pleasure of seeing Dr. Conrod speak at the recent Society for Neuroscience Conference as part of a satellite meeting jointly organized by the National Institute on Drug Abuse (NIDA) and National Institute on Alcohol Abuse and Alcoholism (NIAAA). Dr. Conrod presented a compelling story spanning over a decade of her and her colleague’s work, in which certain personality traits amongst high risk youths, can actually be used to predict drug abuse amongst those kids. Dr. Conrod argues that by identifying different risk factors in different adolescents, a specific behavioral intervention can be designed to help reduce alcohol drinking and marijuana use in these youths. And who is best to administer such an intervention? Teachers and counselors, of course: educators that spend a great deal of time interacting with students and are in the best position to help them.

The Teacher-Delivered Personality Targeted Interventions For Substance Misuse Trial, also known as the Adventure Trial, was conducted in London during 2008-2009 and the results were first published in 2010.

This ambitious study recruited 2,643 students (between 13 and 14 years old) from 21 secondary schools in London (20 of the 21 schools were state-funded schools). Importantly, this study was a cluster-randomized control trial, which means the schools were randomly assigned to two groups: one group received the intervention while the other did not. The researchers identified four personality traits in high-risk (HR) youths that increase the risk of engaging in substance abuse. The four traits are:

  1. Anxiety sensitivity,
  2. Hopelessness
  3. Impulsivity
  4. Sensation seeking.

A specific intervention based on cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET) was developed to target each of these personality traits. Teacher, mentors, counselors, and educational specialists in each school that were recruited for the study were trained in the specific interventions. In general, CBT is an approach used in psychotherapy to change negative or harmful thoughts or the patient’s relationship to these thoughts, which in turn can change the patient’s behavior. CBT has been effective in a treating a number of mental disorders such anxiety, personality disorders, and depression. MET is an approach used to augment a patient’s motivation in achieving a goal and has mostly been employed in treating alcohol abuse.

The CBT and MET interventions in this study were designed to target one of the four personality traits (for example, anxiety reduction) and were administered in two 90-minute group sessions. The specific lesson plans for these interventions were not reported in the studies but included workbooks and such activities as goal-setting exercises and CBT therapies to help students to dissect their own personal experiences through identifying and dealing with negative/harmful thoughts and how those thoughts can result in negative behaviors. Interestingly, alcohol and drug use were only a minor focus of the interventions.

The success of the interventions was determined through self-reporting. The student’s completed the Reckless Behavior Questionnaire (RBQ), which is based on a six-point scale (“never” to “daily or almost daily”) to report substance use. Obviously due to the sensitive nature of these questionnaires and need for honesty by the students, measures were taken to ensure accuracy in the self-reporting, such as strong emphasis on the anonymity and confidentiality of the reports and inclusion of several “sham” items designed to gauge accuracy of reporting over time. Surveys were completed every 6-months for 24-months (two years) which is a sufficient time frame to assess the effect of the interventions.

Most importantly, schools were blinded to which group they were placed in and teachers and students not involved in the study were not aware of the trial occurring at the school. The students involved were unaware of the real purpose and scope of the study. These factors are important to consider because it held eliminate secondary effects and helps support the direct efficacy of the interventions themselves.

The results were impressive: reduced frequency and quantity of drinking occurred in the high-risk students that received the intervention compared to the control students that did not. While HR students were overall more likely to report drinking than low-risk (LR) students, the HR students saw a significant effect of the personality-targeted interventions on drinking behavior.

Conrod et al.2013 abstract

A study of this size is incredibly complex and the statistics involved are equally complex. The author’s analyzed the data in a number of ways and published the results in several papers. A recent study modeled the data over time (the 24-months in which the surveys were collected) and used these models to predict the odds that the students would engage in risky drinking behavior. The authors reported a 29% reduction in odds of frequency of drinking by HR students receiving the interventions and a 43% reduction in odds of binge drinking  when compared to HR students not receiving the interventions.

Interestingly, the authors report a mild herd-effect in the LR students. Meaning that they believe the intervention slowed the onset of drinking in the LR students possibly due to the interactions between the HR student’s receiving the interventions and LR students. However, additional studies will need to be done in order to confirm this result.

Recall that the Reckless Behavior Questionnaire (RBQ) was utilized in this study to quantify drug-taking behavior. While the study was specifically designed to measure effects on alcohol, the RBQ also included questions about marijuana. So the authors reanalyzed their data and specifically looked at effects of the interventions on marijuana use.

Mahu et al. 2015

The found that the sensation seeking personality sub-type of HR students that received an intervention had a 75% reduction in marijuana use compared to the sensation seeking HR students that did not receive the intervention. However, unlike the findings found on alcohol use, the study was not able to detect any effect on marijuana use for the HR students in general. Nevertheless, the data suggest that the teacher/counselor administered interventions are effective at reduce marijuana use as well.

While you may be unconvinced by the modest reduction in drinking and marijuana frequency reported in these studies and may be skeptical of the long-term effect on drug use in these kids, keep in mind that the teachers and counselors that administered these interventions received only 2 or 3 days of training and the interventions themselves were very brief, only two 90-minute sessions. What I find remarkable is that such a brief, targeted program can have ANY effects at all. And most importantly, the effects well outlasted the course of the interventions for the full two-years of the follow-up interviews.

These targeted interventions have four main advantages:

  1. Administered in a real-world setting by teachers and counselors
  2. Brief (only two 90-minute group sessions)
  3. Cheap (the cost of training and materials for the group sessions)
  4. Effective!

The scope of this intervention needs to be tested on a much larger cohort of students in a larger variety of neighborhoods but it is extremely promising nonetheless. Also, it would be interesting to breakdown these data by race, socioeconomic status, and gender, all of which may impact the effectiveness of the treatments and was not considered in this analysis. Finally, how would you implement these interventions on a wide scale? I eagerly look forward to additional work on these topics.

Thanks for reading 🙂

See these other articles in Time and on King’s College for less detailed discussions of these studies.

Also see these related studies from Conrod’s group:

Castellanos-Ryan N, Conrod PJ, Vester JBK, Strain E,, Galanter M, Conrod PJ. Personality and substance misuse: evidence for a four-factor model of vulnerability. In: Vester JBK, Strain E, Galanter M, Conrod PJ, eds. Drug Abuse and Addiction in Medical Illness. Vols 1 and 2. New York, NY: Humana/Spring Press; 2012.

Conrod PJ, Pihl RO, Stewart SH, Dongier M. Validation of a system of classifying female substance abusers on the basis of personality and motivational risk factors for substance abuse. Psychol Addict Behav. 2000;14(3):243-256.

Conrod PJ, Stewart SH, Comeau N, Maclean AM. Efficacy of cognitive behavioral interventions targeting personality risk factors for youth alcohol misuse. J Clin Child Adolesc Psychol. 2006;35(4):550-563.

Conrod PJ, Castellanos-Ryan N, Strang J. Brief, personality-targeted coping skills interventions and survival as a non-drug user over a 2-year period during adolescence. Arch Gen Psychiatry. 2010;67(1):85-93.

O’Leary-Barrett M, Mackie CJ, Castellanos-Ryan N, Al-Khudhairy N, Conrod PJ. Personality-targeted interventions delay uptake of drinking and decrease risk of alcohol-related problems when delivered by teachers. J AmAcad Child Adol Psychiatry. 2010;49(9):954-963.

Important Considerations in Optogenetics Behavioral Experiments

Image credit NSF, Inbal Goshen, Karl Deisseroth.
Image credit NSF, Inbal Goshen, Karl Deisseroth.

The third and final part of my three part guest blog series on Optogenetics has been published on the Addgene blog. Addgene is a nonprofit organization dedicated to making it easier for scientists to share plasmids and I’m thrilled to be able to contribute to their blog! This post covers the running behavioral experiments utilizing optogenetics.

Check it out!

http://blog.addgene.org/important-consideration-in-optogenetics-behavioral-experiments

 

The Materials Science of Optogenetics Experiments

(blog.addgene.org)
(blog.addgene.org)

The second part of my three part guest blog series on Optogenetics has been published on the Addgene blog. Addgene is a nonprofit organization dedicated to making it easier for scientists to share plasmids and I’m thrilled to be able to contribute to their blog! This post covers the material science aspects of running optogenetic experiments.

Check it out!

http://blog.addgene.org/the-materials-science-of-optogenetics-experiments