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Cannabidiol (CBD) for schizophrenia: Promise or pipe dream?
Over the past few decades, it has become increasingly clear that cannabis use can increase the risk of developing a psychotic disorder and worsen the course of existing schizophrenia in a dose-dependent fashion.1-3 Beyond psychosis, although many patients with mental illness use cannabis for recreational purposes or as purported “self-medication,” currently available evidence suggests that marijuana is more likely to represent a harm than a benefit for psychiatric disorders4 (Box4-8). Our current state of knowledge therefore suggests that psychiatrists should caution their patients against using cannabis and prioritize interventions to reduce or discontinue use, especially among those with psychotic disorders.
Box
Data from California in 2006—a decade after the state’s legalization of “medical marijuana”—revealed that 23% of patients in a sample enrolled in medical marijuana clinics were receiving cannabis to treat a mental disorder.5 That was a striking statistic given the dearth of evidence to support a benefit of cannabis for psychiatric conditions at the time, leaving clinicians who provided the necessary recommendations to obtain medical marijuana largely unable to give informed consent about the risks and benefits, much less recommendations about specific products, routes of administration, or dosing. In 2019, we know considerably more about the interaction between cannabinoids and mental health, but research findings thus far warrant more caution than enthusiasm, with one recent review concluding that “whenever an association is observed between cannabis use and psychiatric disorders, the relationship is generally an adverse one.”4
Some critics have argued that the medical marijuana industry represents little more than a front for recreational use. In California and other states that have legalized recreational use, that claim has been rendered all but moot, although the public remains curious about the potential health benefits of cannabinoids and will likely continue to look to clinicians for advice. For those seeking guidance from evidence-based research, the existing state of knowledge can seem like a “Wild West” of anecdotal subjective reports, biased opinions, and uncontrolled clinical studies. Cannabis remains a Schedule I drug at the federal level, and quality clinical research has been limited to a relatively modest number of randomized controlled trials (RCTs), mostly involving FDA-approved cannabinoids rather than smoked cannabis. Randomized controlled trials that have involved smoked marijuana have generally involved low-potency delta-9-tetrahydrocannabinol (THC) cannabis that may not reflect the same therapeutic and adverse effects of the increasingly high potency cannabis now available on the street and in dispensaries.
In psychiatry, a few RCTs are underway exploring cannabis as a viable treatment for mental disorders (eg, posttraumatic stress disorder), but none have yet been completed or published. At best, retrospective studies to date have failed to support a consistent benefit of cannabis for any psychiatric disorder and at worst increasingly suggest a negative impact on psychotic, mood, and anxiety disorders.4,6 Meanwhile, synthetic cannabinoid receptor agonists (eg, “Spice” products) have come to represent a clear public health risk, with both medical and psychiatric toxicity.7
A more cautiously optimistic case for the therapeutic potential of cannabinoids in psychiatry could be made for cannabidiol (CBD), which may possess anxiolytic, antipsychotic, and neuroprotective properties.8 Based on its purported health benefits, it is possible that CBD may even gain widespread popularity as a food supplement. Because a pharmaceutically-manufactured form of CBD was recently FDA-approved for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, off-label prescribing of CBD for psychiatric disorders can be anticipated. While there is not yet sufficient evidence about risks and benefits to justify CBD being recommended broadly in psychiatry, that same informational vacuum has not stopped eager patients from seeking approval for cannabis, and some physicians from providing it.
Despite that conclusion, because cannabis is classified as a Schedule I drug by the US Drug Enforcement Agency, clinical research investigating the risks and benefits of cannabis has been limited. It therefore remains possible that cannabis, or individual cannabinoids such as cannabidiol (CBD), may yet find a therapeutic niche in psychiatry. This article reviews evidence on CBD for the treatment of schizophrenia.
Cannabinergic drugs as potential antipsychotics
Although the bulk of evidence indicates a harmful effect of cannabis in individuals with or at risk for psychosis, there have been a few published cases of schizophrenia improving with dronabinol, an FDA-approved, synthetic form of delta-9-tetrahydrocannabinol (THC).9,10 THC is the constituent of cannabis that produces euphoric effects. These provocative findings have not been replicated in controlled clinical trials, but suggest at least the theoretical possibility of idiosyncratic benefits from THC for some individuals within the psychotic spectrum.
Still, given that most available evidence supports that THC has a harmful effect on psychosis and psychosis risk, researchers have instead performed randomized controlled trials (RCTs) to investigate a possible therapeutic role for medications that oppose the agonist effects of THC at cannabinoid type 1 (CB1) receptors. To date, 2 RCTs comparing rimonabant, a CB1 inverse agonist, with placebo (PLB) in patients with schizophrenia have failed to demonstrate any benefit for psychotic symptoms or cognitive deficits.11,12 A third trial examining rimonabant for people diagnosed with schizophrenia who were overweight found significant benefits for anxiety and depressive symptoms, but none for positive symptoms or the primary outcome of weight loss.13 While these results are discouraging, the role of THC in precipitating psychosis suggests that novel agents opposing the actions of THC on the cannabinoid system could have antipsychotic properties.14
Cannabidiol: An antipsychotic medication?
In contrast to THC, CBD has minimal euphorigenic properties and has recently been heralded in the popular press as a “miracle drug” with benefits for medical and psychiatric disorders alike.15 It has even been speculated that it could become a popular food supplement.16 In 2018, the FDA gave full approval to a pharmaceutically manufactured form of CBD (brand name: Epidiolex) as a novel treatment for 2 rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome,17 based on RCTs supporting its efficacy for these often refractory and life-threatening conditions.18-20
In psychiatry, there have not yet been enough robust clinical studies to support broad therapeutic claims for CBD as a treatment for any mental disorder.21 However, there is growing evidence that CBD has potential as an antipsychotic medication. In 1995, the first case report was published describing the efficacy of CBD, 1,500 mg/d, as standalone therapy in a single individual with schizophrenia.22 In 2006, the same research group followed up with a case series in which only 1 out of 3 patients with treatment-refractory schizophrenia improved with flexible dosing of CBD to a maximum dose of 1,280 mg/d.23
There have been 3 published RCTs exploring the efficacy of CBD in schizophrenia (Table24-26). The first study, published in 2012, included 39 adults with schizophrenia who were randomized to 800 mg/d of CBD or amisulpride (AMS), a second-generation antipsychotic that is popular in Europe but is not available in the United States.24 Over 4 weeks of randomized treatment, CBD resulted in as much improvement in overall symptoms and positive symptoms as AMS, and improvement of negative symptoms was significantly greater with CBD. Compared with patients treated with antipsychotic medication, patients who were treated with CBD had fewer extrapyramidal symptoms, less weight gain, and less prolactin elevation. This initial trial suggests that CBD might be as efficacious in schizophrenia as antipsychotic medication, without its burdensome adverse effects. However, this is the only RCT of CBD monotherapy published to date.
Continue to: Two other recently published RCTs...
Two other recently published RCTs compared CBD with PLB as add-on therapy to antipsychotics. McGuire et al25 compared CBD, 1,000 mg/d, to PLB over 6 weeks in 88 patients with schizophrenia. Positive symptom improvement was statistically greater with CBD than with PLB, although the magnitude of clinical change was modest (using the Positive and Negative Syndrome Scale [PANSS] positive symptom subscale: −3.2 points for CBD vs −1.7 points for PLB). Changes in PANSS total score and subscales for general and negative symptoms were not significantly different between treatment groups. There was also no significant difference in overall change in neurocognitive symptoms, although post-hoc analysis revealed significantly greater improvement in motor speed for patients treated with CBD. More than twice the number of patients treated with CBD were rated as “much improved” by the Clinical Global Impressions scale compared with patients treated with PLB, but this was not a statistically significant finding, and most patients experienced only “minimal” or “no improvement.” In terms of adverse events, there were no significant differences between patients in the CBD and PLB groups. Although this study is technically “positive” for CBD and suggests minimal adverse effects, it is not clear whether the statistically significant positive symptom improvements (+1.5 PANSS points for CBD over PLB) were clinically significant.
The most recently published placebo-controlled RCT of CBD as add-on therapy to antipsychotic medication included 36 patients with schizophrenia treated over 6 weeks.26 In this study, there was no benefit of CBD, 600 mg/d, on any PANSS score outcome (total, general, positive, or negative symptoms). For the primary outcome of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, there were no significant drug × time effects, and post-hoc analyses showed that only patients treated with PLB improved with time. Sedation was more common among patients treated with CBD compared with PLB.
Making sense of the data
There have been mixed results from the few case reports and 3 RCTs of patients with schizophrenia who were treated with CBD. How can we resolve these disparate findings? A few possible interpretations of the data that warrant clarification through additional research include:
Dosing. In the first case report with positive results, CBD was dosed at 1,500 mg/d,22 whereas in the subsequent case series with mixed results, the maximum allowable dose of CBD was 1,280 mg/d.23 Likewise, in the RCTs, positive results were found when CBD was dosed at 800 to 1,000 mg/d,24,25 but not at 600 mg/d.26 The efficacy of CBD for schizophrenia might depend on higher doses.
Treatment resistance. In the second case series in which only 1 out of 3 patients responded to treatment with CBD,23 the patients had demonstrated previous nonresponse to at least 2 first-generation antipsychotics (FGAs) and risperidone, 6 mg/d. In the RCTs, all patients were antipsychotic-responsive.24-26 Cannabidiol may not be as effective for patients with treatment-refractory schizophrenia as it is for patients with schizophrenia who respond to antipsychotics.
Continue to: Clinical stability
Clinical stability. Within the RCTs, the greatest response was observed in the study that enrolled patients who were hospitalized with acute symptoms of schizophrenia.23 In the 2 studies that found either modest or no benefit with CBD, the patients had been stabilized on antipsychotic medications prior to randomization. Cannabidiol may offer limited benefit as add-on therapy to patients who have already responded to antipsychotic treatment, where there is “less room” for additional improvement.
Monotherapy. Both the case reports22,23 and the RCT with the most robust positive findings24 involved treatment with CBD as monotherapy. For some patients with schizophrenia, CBD might be effective as standalone therapy as an alternative to antipsychotics that is better tolerated. Adding CBD to antipsychotic therapy might be redundant and therefore less effective.
Answering questions about CBD
Cannabidiol is becoming increasingly popular for its purported health benefits. The mixed results of the few studies published on CBD for schizophrenia place clinicians in a difficult position when attempting to answer questions about how cannabinoids might fit into treatment of patients with psychosis. Consider the following:
Is cannabis helpful for patients with schizophrenia? No. Aside from the few case reports suggesting that FDA-approved THC (dronabinol) can improve symptoms in some patients,9,10 most of the evidence from anecdotal reports and both experimental and observational studies indicate that cannabis, THC, and synthetic cannabinoids have a harmful effect in patients with or at risk for psychosis.1-3
If you are considering recommending some form of cannabis to patients with schizophrenia, what kind should you recommend? Recommending or encouraging cannabis use for patients with psychosis is ill-advised. Although certain types of cannabis might contain more THC (eg, Cannabis indica vs Cannabis sativa) or variable amounts of CBD, in general the amount of CBD in whole leaf cannabis is minimal, with the ratio of THC to CBD increasingly significantly over the past decade.3,27 Most forms of cannabis should therefore be avoided by individuals with or at risk for psychotic disorders.
Continue to: What about CBD oil and other CBD products sold in dispensaries?
What about CBD oil and other CBD products sold in dispensaries? Cannabidiol is increasingly available in various forms based on its ability to be designated as a legal hemp product (containing <0.3% THC) at the federal level or as a cannabinoid in states where cannabis is legal. However, several studies have now shown that cannabis products sold online or in dispensaries are often labeled inaccurately, with both under- and over-reporting of THC and CBD content.28-30 Some CBD products have been found to have almost no CBD at all.29,30 The unreliability of product labeling makes it difficult to predict the effects of CBD products that are not subject to FDA purity standards for medications or dietary supplements. It also raises questions about the sources of CBD and the reliability of dosing in the studies discussed above.
Why might CBD work as an antipsychotic? Although CBD has minimal affinity for cannabinoid receptors, it appears to act as a partial agonist of dopamine D2 receptors and an agonist at 5-HT1A receptors, with overall effects that decrease mesolimbic dopamine activity.31,32 In addition, CBD increases the availability of the endogenous cannabinoid anandamide, which may have antipsychotic properties.14,33
Now that the FDA has approved CBD manufactured by a pharmaceutical company, should it be prescribed “off-label” for patients with schizophrenia? This is the “million dollar question,” with insufficient evidence to provide a clear answer. It should now be possible to prescribe FDA-approved CBD for off-label purposes, including the treatment of schizophrenia and other psychiatric disorders. No doubt, some clinicians are already doing so. This will predictably yield more anecdotal evidence about efficacy and adverse effects in the future, but there is not yet adequate evidence to support an FDA indication for CBD in schizophrenia. Additional studies of CBD for schizophrenia are ongoing.
Bottom Line
Cannabidiol (CBD) is becoming increasingly popular based on its purported health benefits, but the evidence supporting a therapeutic role in psychiatry is preliminary at best. Although CBD is now available by prescription as an FDA-approved drug for the treatment of 2 rare forms of epilepsy, its benefits in patients with schizophrenia are uncertain based on mixed results in clinical trials.
Related Resources
- Clinicaltrials.gov. Studies of “cannabidiol” and “schizophrenia.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=Schizophrenia&term=cannabidiol.
- Grinspoon P. Cannabidiol (CBD) – what we know and what we don’t. Harvard Health Blog. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-wedont-2018082414476. Published August 24, 2018.
Drug Brand Names
Cannabidiol • Epidiolex
Dronabinol • Marinol
Risperidone • Risperdal
1. Pierre JM. Cannabis, synthetic cannabinoids, and psychosis risk: what the evidence says. Current Psychiatry. 2011;10(9):49-58.
2. Radhakrishan R, Wilkinson ST, D’Souza DC. Gone to pot – a review of the association between cannabis and psychosis. Front Psychiatry. 2014;5:54.
3. Pierre JM. Risks of increasingly potent cannabis: joint effects of potency and frequency. Current Psychiatry. 2016;16(2):14-20.
4. Hanna RC, Perez JM, Ghose S. Cannabis and development of dual diagnoses: a literature review. Am J Drug Alcohol Abuse. 2017;43(4):442-255.
5. Nunberg H, Kilmer B, Pacula RL, et al. An analysis of applicants presenting to a medical marijuana specialty practice in California. J Drug Policy Anal. 2011;4(1):1.
6. Wilkinson ST, Radhakrishnan, D’Souza DC. A systematic review of the evidence for medical marijuana in psychiatric indications. J Clin Psychiatry. 2016;77(8):1050-1064.
7. Tournebize J, Gibaja V, Kahn JP. Acute effects of synthetic cannabinoids: Update 2015. Subst Abus. 2016;38(3):344-366.
8. Crippa JA, Guimarães FS, Campos A, et al. Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. Front Immunol. 2018;9:2009.
9. Schwarz G, Karajgi B. Improvement in refractory psychosis with dronabinol: four case reports. J Clin Psychiatry. 2010;71(11):1552-1553.
10. Schwarz G, Karajgi B, McCarthy R. Synthetic delta-9-tetrahydrocannabinol (dronabinol) can improve the symptoms of schizophrenia. J Clin Psychopharmacol. 2009;29(3):255-258.
11. Meltzer HY, Arvanitis L, Bauer D, et al. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry. 2004;161(6):975-984.
12. Boggs DL, Kelly DL, McMahon RP, et al. Rimonabant for neurocognition in schizophrenia: a 16-week double blind placebo controlled trial. Schizophr Res. 2012;134(2-3):207-210.
13. Kelly DL, Gorelick DA, Conley RR, et al. Effects of cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study. J Clin Psychopharmacol. 2011;31(1):86-91.
14. Leweke FM, Mueller JK, Lange B, et al. Therapeutic potential of cannabinoids in psychosis. Biol Psychiatry. 2016;79(7):604-612.
15. Halperin A. What is CBD? The ‘miracle’ cannabis compound that doesn’t get you high. The Guardian. https://www.theguardian.com/society/2018/may/28/what-is-cbd-cannabidiol-cannabis-medical-uses. Published May 28, 2018. Accessed April 3, 2019.
16. Pierre J. Coca, cola, and cannabis: psychoactive drugs as beverages. Psychology Today (blog) Psych Unseen. https://www.psychologytoday.com/us/blog/psych-unseen/201810/coca-cola-and-cannabis-psychoactive-drugs-beverages. Published October 1, 2018. Accessed April 3, 2019.
17. U.S. Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. FDA News Release. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Published June 25, 2018. Accessed April 3, 2019.
18. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011-2020.
19. Thiele EA, March ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096.
20. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378:1888-1897.
21. Khoury JM, Neves MCLD, Rogue MAV, et al. Is there a role of cannabidiol in psychiatry? World J Biol Psychiatry. 2017:1-16.
22. Zuardi AW, Morais SL, Guimares FS, et al. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995;56(10):485-486.
23. Zuardi AW, Hallak JEC, Dursun SM. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006;20(5):683-686.
24. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94. doi: 10.1038/tp.2012.15.
25. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175(3):225-231.
26. Boggs DL, Surti I, Gupta A, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacol. 2018;235(7):1923-1932.
27. ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States. Biol Psychiatry. 2016; 79(7):613-619.
28. Vandrey R, Raber JC, Raber ME, et al. Cannabinoid dose and label accuracy in edible medical cannabis products. JAMA. 2015;313(24):2491-2492.
29. Ruth AC, Gryniewicz-Ruzicka CM, Trehy ML, et al. Consistency of label claims of internet-purchased hemp oil and cannabis products as determined using IMS and LC-MS: a marketplace study. J Reg Sci. 2016;3:1-6.
30. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318(17):1708-1709.
31. Seeman P. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry. 2016;6(10):e920. doi: 10.1038/tp.2016.195.
32. Renard J, Norris C, Rushlow W, et al. Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: implications for novel schizophrenia treatments. Neurosci Biobehav Rev. 2017;157-165.
33. Gururajan A, Malone DT. Does cannabidiol have a role in the treatment of schizophrenia? Schizophr Res. 2016;176(2-3):281-290.
Over the past few decades, it has become increasingly clear that cannabis use can increase the risk of developing a psychotic disorder and worsen the course of existing schizophrenia in a dose-dependent fashion.1-3 Beyond psychosis, although many patients with mental illness use cannabis for recreational purposes or as purported “self-medication,” currently available evidence suggests that marijuana is more likely to represent a harm than a benefit for psychiatric disorders4 (Box4-8). Our current state of knowledge therefore suggests that psychiatrists should caution their patients against using cannabis and prioritize interventions to reduce or discontinue use, especially among those with psychotic disorders.
Box
Data from California in 2006—a decade after the state’s legalization of “medical marijuana”—revealed that 23% of patients in a sample enrolled in medical marijuana clinics were receiving cannabis to treat a mental disorder.5 That was a striking statistic given the dearth of evidence to support a benefit of cannabis for psychiatric conditions at the time, leaving clinicians who provided the necessary recommendations to obtain medical marijuana largely unable to give informed consent about the risks and benefits, much less recommendations about specific products, routes of administration, or dosing. In 2019, we know considerably more about the interaction between cannabinoids and mental health, but research findings thus far warrant more caution than enthusiasm, with one recent review concluding that “whenever an association is observed between cannabis use and psychiatric disorders, the relationship is generally an adverse one.”4
Some critics have argued that the medical marijuana industry represents little more than a front for recreational use. In California and other states that have legalized recreational use, that claim has been rendered all but moot, although the public remains curious about the potential health benefits of cannabinoids and will likely continue to look to clinicians for advice. For those seeking guidance from evidence-based research, the existing state of knowledge can seem like a “Wild West” of anecdotal subjective reports, biased opinions, and uncontrolled clinical studies. Cannabis remains a Schedule I drug at the federal level, and quality clinical research has been limited to a relatively modest number of randomized controlled trials (RCTs), mostly involving FDA-approved cannabinoids rather than smoked cannabis. Randomized controlled trials that have involved smoked marijuana have generally involved low-potency delta-9-tetrahydrocannabinol (THC) cannabis that may not reflect the same therapeutic and adverse effects of the increasingly high potency cannabis now available on the street and in dispensaries.
In psychiatry, a few RCTs are underway exploring cannabis as a viable treatment for mental disorders (eg, posttraumatic stress disorder), but none have yet been completed or published. At best, retrospective studies to date have failed to support a consistent benefit of cannabis for any psychiatric disorder and at worst increasingly suggest a negative impact on psychotic, mood, and anxiety disorders.4,6 Meanwhile, synthetic cannabinoid receptor agonists (eg, “Spice” products) have come to represent a clear public health risk, with both medical and psychiatric toxicity.7
A more cautiously optimistic case for the therapeutic potential of cannabinoids in psychiatry could be made for cannabidiol (CBD), which may possess anxiolytic, antipsychotic, and neuroprotective properties.8 Based on its purported health benefits, it is possible that CBD may even gain widespread popularity as a food supplement. Because a pharmaceutically-manufactured form of CBD was recently FDA-approved for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, off-label prescribing of CBD for psychiatric disorders can be anticipated. While there is not yet sufficient evidence about risks and benefits to justify CBD being recommended broadly in psychiatry, that same informational vacuum has not stopped eager patients from seeking approval for cannabis, and some physicians from providing it.
Despite that conclusion, because cannabis is classified as a Schedule I drug by the US Drug Enforcement Agency, clinical research investigating the risks and benefits of cannabis has been limited. It therefore remains possible that cannabis, or individual cannabinoids such as cannabidiol (CBD), may yet find a therapeutic niche in psychiatry. This article reviews evidence on CBD for the treatment of schizophrenia.
Cannabinergic drugs as potential antipsychotics
Although the bulk of evidence indicates a harmful effect of cannabis in individuals with or at risk for psychosis, there have been a few published cases of schizophrenia improving with dronabinol, an FDA-approved, synthetic form of delta-9-tetrahydrocannabinol (THC).9,10 THC is the constituent of cannabis that produces euphoric effects. These provocative findings have not been replicated in controlled clinical trials, but suggest at least the theoretical possibility of idiosyncratic benefits from THC for some individuals within the psychotic spectrum.
Still, given that most available evidence supports that THC has a harmful effect on psychosis and psychosis risk, researchers have instead performed randomized controlled trials (RCTs) to investigate a possible therapeutic role for medications that oppose the agonist effects of THC at cannabinoid type 1 (CB1) receptors. To date, 2 RCTs comparing rimonabant, a CB1 inverse agonist, with placebo (PLB) in patients with schizophrenia have failed to demonstrate any benefit for psychotic symptoms or cognitive deficits.11,12 A third trial examining rimonabant for people diagnosed with schizophrenia who were overweight found significant benefits for anxiety and depressive symptoms, but none for positive symptoms or the primary outcome of weight loss.13 While these results are discouraging, the role of THC in precipitating psychosis suggests that novel agents opposing the actions of THC on the cannabinoid system could have antipsychotic properties.14
Cannabidiol: An antipsychotic medication?
In contrast to THC, CBD has minimal euphorigenic properties and has recently been heralded in the popular press as a “miracle drug” with benefits for medical and psychiatric disorders alike.15 It has even been speculated that it could become a popular food supplement.16 In 2018, the FDA gave full approval to a pharmaceutically manufactured form of CBD (brand name: Epidiolex) as a novel treatment for 2 rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome,17 based on RCTs supporting its efficacy for these often refractory and life-threatening conditions.18-20
In psychiatry, there have not yet been enough robust clinical studies to support broad therapeutic claims for CBD as a treatment for any mental disorder.21 However, there is growing evidence that CBD has potential as an antipsychotic medication. In 1995, the first case report was published describing the efficacy of CBD, 1,500 mg/d, as standalone therapy in a single individual with schizophrenia.22 In 2006, the same research group followed up with a case series in which only 1 out of 3 patients with treatment-refractory schizophrenia improved with flexible dosing of CBD to a maximum dose of 1,280 mg/d.23
There have been 3 published RCTs exploring the efficacy of CBD in schizophrenia (Table24-26). The first study, published in 2012, included 39 adults with schizophrenia who were randomized to 800 mg/d of CBD or amisulpride (AMS), a second-generation antipsychotic that is popular in Europe but is not available in the United States.24 Over 4 weeks of randomized treatment, CBD resulted in as much improvement in overall symptoms and positive symptoms as AMS, and improvement of negative symptoms was significantly greater with CBD. Compared with patients treated with antipsychotic medication, patients who were treated with CBD had fewer extrapyramidal symptoms, less weight gain, and less prolactin elevation. This initial trial suggests that CBD might be as efficacious in schizophrenia as antipsychotic medication, without its burdensome adverse effects. However, this is the only RCT of CBD monotherapy published to date.
Continue to: Two other recently published RCTs...
Two other recently published RCTs compared CBD with PLB as add-on therapy to antipsychotics. McGuire et al25 compared CBD, 1,000 mg/d, to PLB over 6 weeks in 88 patients with schizophrenia. Positive symptom improvement was statistically greater with CBD than with PLB, although the magnitude of clinical change was modest (using the Positive and Negative Syndrome Scale [PANSS] positive symptom subscale: −3.2 points for CBD vs −1.7 points for PLB). Changes in PANSS total score and subscales for general and negative symptoms were not significantly different between treatment groups. There was also no significant difference in overall change in neurocognitive symptoms, although post-hoc analysis revealed significantly greater improvement in motor speed for patients treated with CBD. More than twice the number of patients treated with CBD were rated as “much improved” by the Clinical Global Impressions scale compared with patients treated with PLB, but this was not a statistically significant finding, and most patients experienced only “minimal” or “no improvement.” In terms of adverse events, there were no significant differences between patients in the CBD and PLB groups. Although this study is technically “positive” for CBD and suggests minimal adverse effects, it is not clear whether the statistically significant positive symptom improvements (+1.5 PANSS points for CBD over PLB) were clinically significant.
The most recently published placebo-controlled RCT of CBD as add-on therapy to antipsychotic medication included 36 patients with schizophrenia treated over 6 weeks.26 In this study, there was no benefit of CBD, 600 mg/d, on any PANSS score outcome (total, general, positive, or negative symptoms). For the primary outcome of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, there were no significant drug × time effects, and post-hoc analyses showed that only patients treated with PLB improved with time. Sedation was more common among patients treated with CBD compared with PLB.
Making sense of the data
There have been mixed results from the few case reports and 3 RCTs of patients with schizophrenia who were treated with CBD. How can we resolve these disparate findings? A few possible interpretations of the data that warrant clarification through additional research include:
Dosing. In the first case report with positive results, CBD was dosed at 1,500 mg/d,22 whereas in the subsequent case series with mixed results, the maximum allowable dose of CBD was 1,280 mg/d.23 Likewise, in the RCTs, positive results were found when CBD was dosed at 800 to 1,000 mg/d,24,25 but not at 600 mg/d.26 The efficacy of CBD for schizophrenia might depend on higher doses.
Treatment resistance. In the second case series in which only 1 out of 3 patients responded to treatment with CBD,23 the patients had demonstrated previous nonresponse to at least 2 first-generation antipsychotics (FGAs) and risperidone, 6 mg/d. In the RCTs, all patients were antipsychotic-responsive.24-26 Cannabidiol may not be as effective for patients with treatment-refractory schizophrenia as it is for patients with schizophrenia who respond to antipsychotics.
Continue to: Clinical stability
Clinical stability. Within the RCTs, the greatest response was observed in the study that enrolled patients who were hospitalized with acute symptoms of schizophrenia.23 In the 2 studies that found either modest or no benefit with CBD, the patients had been stabilized on antipsychotic medications prior to randomization. Cannabidiol may offer limited benefit as add-on therapy to patients who have already responded to antipsychotic treatment, where there is “less room” for additional improvement.
Monotherapy. Both the case reports22,23 and the RCT with the most robust positive findings24 involved treatment with CBD as monotherapy. For some patients with schizophrenia, CBD might be effective as standalone therapy as an alternative to antipsychotics that is better tolerated. Adding CBD to antipsychotic therapy might be redundant and therefore less effective.
Answering questions about CBD
Cannabidiol is becoming increasingly popular for its purported health benefits. The mixed results of the few studies published on CBD for schizophrenia place clinicians in a difficult position when attempting to answer questions about how cannabinoids might fit into treatment of patients with psychosis. Consider the following:
Is cannabis helpful for patients with schizophrenia? No. Aside from the few case reports suggesting that FDA-approved THC (dronabinol) can improve symptoms in some patients,9,10 most of the evidence from anecdotal reports and both experimental and observational studies indicate that cannabis, THC, and synthetic cannabinoids have a harmful effect in patients with or at risk for psychosis.1-3
If you are considering recommending some form of cannabis to patients with schizophrenia, what kind should you recommend? Recommending or encouraging cannabis use for patients with psychosis is ill-advised. Although certain types of cannabis might contain more THC (eg, Cannabis indica vs Cannabis sativa) or variable amounts of CBD, in general the amount of CBD in whole leaf cannabis is minimal, with the ratio of THC to CBD increasingly significantly over the past decade.3,27 Most forms of cannabis should therefore be avoided by individuals with or at risk for psychotic disorders.
Continue to: What about CBD oil and other CBD products sold in dispensaries?
What about CBD oil and other CBD products sold in dispensaries? Cannabidiol is increasingly available in various forms based on its ability to be designated as a legal hemp product (containing <0.3% THC) at the federal level or as a cannabinoid in states where cannabis is legal. However, several studies have now shown that cannabis products sold online or in dispensaries are often labeled inaccurately, with both under- and over-reporting of THC and CBD content.28-30 Some CBD products have been found to have almost no CBD at all.29,30 The unreliability of product labeling makes it difficult to predict the effects of CBD products that are not subject to FDA purity standards for medications or dietary supplements. It also raises questions about the sources of CBD and the reliability of dosing in the studies discussed above.
Why might CBD work as an antipsychotic? Although CBD has minimal affinity for cannabinoid receptors, it appears to act as a partial agonist of dopamine D2 receptors and an agonist at 5-HT1A receptors, with overall effects that decrease mesolimbic dopamine activity.31,32 In addition, CBD increases the availability of the endogenous cannabinoid anandamide, which may have antipsychotic properties.14,33
Now that the FDA has approved CBD manufactured by a pharmaceutical company, should it be prescribed “off-label” for patients with schizophrenia? This is the “million dollar question,” with insufficient evidence to provide a clear answer. It should now be possible to prescribe FDA-approved CBD for off-label purposes, including the treatment of schizophrenia and other psychiatric disorders. No doubt, some clinicians are already doing so. This will predictably yield more anecdotal evidence about efficacy and adverse effects in the future, but there is not yet adequate evidence to support an FDA indication for CBD in schizophrenia. Additional studies of CBD for schizophrenia are ongoing.
Bottom Line
Cannabidiol (CBD) is becoming increasingly popular based on its purported health benefits, but the evidence supporting a therapeutic role in psychiatry is preliminary at best. Although CBD is now available by prescription as an FDA-approved drug for the treatment of 2 rare forms of epilepsy, its benefits in patients with schizophrenia are uncertain based on mixed results in clinical trials.
Related Resources
- Clinicaltrials.gov. Studies of “cannabidiol” and “schizophrenia.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=Schizophrenia&term=cannabidiol.
- Grinspoon P. Cannabidiol (CBD) – what we know and what we don’t. Harvard Health Blog. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-wedont-2018082414476. Published August 24, 2018.
Drug Brand Names
Cannabidiol • Epidiolex
Dronabinol • Marinol
Risperidone • Risperdal
Over the past few decades, it has become increasingly clear that cannabis use can increase the risk of developing a psychotic disorder and worsen the course of existing schizophrenia in a dose-dependent fashion.1-3 Beyond psychosis, although many patients with mental illness use cannabis for recreational purposes or as purported “self-medication,” currently available evidence suggests that marijuana is more likely to represent a harm than a benefit for psychiatric disorders4 (Box4-8). Our current state of knowledge therefore suggests that psychiatrists should caution their patients against using cannabis and prioritize interventions to reduce or discontinue use, especially among those with psychotic disorders.
Box
Data from California in 2006—a decade after the state’s legalization of “medical marijuana”—revealed that 23% of patients in a sample enrolled in medical marijuana clinics were receiving cannabis to treat a mental disorder.5 That was a striking statistic given the dearth of evidence to support a benefit of cannabis for psychiatric conditions at the time, leaving clinicians who provided the necessary recommendations to obtain medical marijuana largely unable to give informed consent about the risks and benefits, much less recommendations about specific products, routes of administration, or dosing. In 2019, we know considerably more about the interaction between cannabinoids and mental health, but research findings thus far warrant more caution than enthusiasm, with one recent review concluding that “whenever an association is observed between cannabis use and psychiatric disorders, the relationship is generally an adverse one.”4
Some critics have argued that the medical marijuana industry represents little more than a front for recreational use. In California and other states that have legalized recreational use, that claim has been rendered all but moot, although the public remains curious about the potential health benefits of cannabinoids and will likely continue to look to clinicians for advice. For those seeking guidance from evidence-based research, the existing state of knowledge can seem like a “Wild West” of anecdotal subjective reports, biased opinions, and uncontrolled clinical studies. Cannabis remains a Schedule I drug at the federal level, and quality clinical research has been limited to a relatively modest number of randomized controlled trials (RCTs), mostly involving FDA-approved cannabinoids rather than smoked cannabis. Randomized controlled trials that have involved smoked marijuana have generally involved low-potency delta-9-tetrahydrocannabinol (THC) cannabis that may not reflect the same therapeutic and adverse effects of the increasingly high potency cannabis now available on the street and in dispensaries.
In psychiatry, a few RCTs are underway exploring cannabis as a viable treatment for mental disorders (eg, posttraumatic stress disorder), but none have yet been completed or published. At best, retrospective studies to date have failed to support a consistent benefit of cannabis for any psychiatric disorder and at worst increasingly suggest a negative impact on psychotic, mood, and anxiety disorders.4,6 Meanwhile, synthetic cannabinoid receptor agonists (eg, “Spice” products) have come to represent a clear public health risk, with both medical and psychiatric toxicity.7
A more cautiously optimistic case for the therapeutic potential of cannabinoids in psychiatry could be made for cannabidiol (CBD), which may possess anxiolytic, antipsychotic, and neuroprotective properties.8 Based on its purported health benefits, it is possible that CBD may even gain widespread popularity as a food supplement. Because a pharmaceutically-manufactured form of CBD was recently FDA-approved for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, off-label prescribing of CBD for psychiatric disorders can be anticipated. While there is not yet sufficient evidence about risks and benefits to justify CBD being recommended broadly in psychiatry, that same informational vacuum has not stopped eager patients from seeking approval for cannabis, and some physicians from providing it.
Despite that conclusion, because cannabis is classified as a Schedule I drug by the US Drug Enforcement Agency, clinical research investigating the risks and benefits of cannabis has been limited. It therefore remains possible that cannabis, or individual cannabinoids such as cannabidiol (CBD), may yet find a therapeutic niche in psychiatry. This article reviews evidence on CBD for the treatment of schizophrenia.
Cannabinergic drugs as potential antipsychotics
Although the bulk of evidence indicates a harmful effect of cannabis in individuals with or at risk for psychosis, there have been a few published cases of schizophrenia improving with dronabinol, an FDA-approved, synthetic form of delta-9-tetrahydrocannabinol (THC).9,10 THC is the constituent of cannabis that produces euphoric effects. These provocative findings have not been replicated in controlled clinical trials, but suggest at least the theoretical possibility of idiosyncratic benefits from THC for some individuals within the psychotic spectrum.
Still, given that most available evidence supports that THC has a harmful effect on psychosis and psychosis risk, researchers have instead performed randomized controlled trials (RCTs) to investigate a possible therapeutic role for medications that oppose the agonist effects of THC at cannabinoid type 1 (CB1) receptors. To date, 2 RCTs comparing rimonabant, a CB1 inverse agonist, with placebo (PLB) in patients with schizophrenia have failed to demonstrate any benefit for psychotic symptoms or cognitive deficits.11,12 A third trial examining rimonabant for people diagnosed with schizophrenia who were overweight found significant benefits for anxiety and depressive symptoms, but none for positive symptoms or the primary outcome of weight loss.13 While these results are discouraging, the role of THC in precipitating psychosis suggests that novel agents opposing the actions of THC on the cannabinoid system could have antipsychotic properties.14
Cannabidiol: An antipsychotic medication?
In contrast to THC, CBD has minimal euphorigenic properties and has recently been heralded in the popular press as a “miracle drug” with benefits for medical and psychiatric disorders alike.15 It has even been speculated that it could become a popular food supplement.16 In 2018, the FDA gave full approval to a pharmaceutically manufactured form of CBD (brand name: Epidiolex) as a novel treatment for 2 rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome,17 based on RCTs supporting its efficacy for these often refractory and life-threatening conditions.18-20
In psychiatry, there have not yet been enough robust clinical studies to support broad therapeutic claims for CBD as a treatment for any mental disorder.21 However, there is growing evidence that CBD has potential as an antipsychotic medication. In 1995, the first case report was published describing the efficacy of CBD, 1,500 mg/d, as standalone therapy in a single individual with schizophrenia.22 In 2006, the same research group followed up with a case series in which only 1 out of 3 patients with treatment-refractory schizophrenia improved with flexible dosing of CBD to a maximum dose of 1,280 mg/d.23
There have been 3 published RCTs exploring the efficacy of CBD in schizophrenia (Table24-26). The first study, published in 2012, included 39 adults with schizophrenia who were randomized to 800 mg/d of CBD or amisulpride (AMS), a second-generation antipsychotic that is popular in Europe but is not available in the United States.24 Over 4 weeks of randomized treatment, CBD resulted in as much improvement in overall symptoms and positive symptoms as AMS, and improvement of negative symptoms was significantly greater with CBD. Compared with patients treated with antipsychotic medication, patients who were treated with CBD had fewer extrapyramidal symptoms, less weight gain, and less prolactin elevation. This initial trial suggests that CBD might be as efficacious in schizophrenia as antipsychotic medication, without its burdensome adverse effects. However, this is the only RCT of CBD monotherapy published to date.
Continue to: Two other recently published RCTs...
Two other recently published RCTs compared CBD with PLB as add-on therapy to antipsychotics. McGuire et al25 compared CBD, 1,000 mg/d, to PLB over 6 weeks in 88 patients with schizophrenia. Positive symptom improvement was statistically greater with CBD than with PLB, although the magnitude of clinical change was modest (using the Positive and Negative Syndrome Scale [PANSS] positive symptom subscale: −3.2 points for CBD vs −1.7 points for PLB). Changes in PANSS total score and subscales for general and negative symptoms were not significantly different between treatment groups. There was also no significant difference in overall change in neurocognitive symptoms, although post-hoc analysis revealed significantly greater improvement in motor speed for patients treated with CBD. More than twice the number of patients treated with CBD were rated as “much improved” by the Clinical Global Impressions scale compared with patients treated with PLB, but this was not a statistically significant finding, and most patients experienced only “minimal” or “no improvement.” In terms of adverse events, there were no significant differences between patients in the CBD and PLB groups. Although this study is technically “positive” for CBD and suggests minimal adverse effects, it is not clear whether the statistically significant positive symptom improvements (+1.5 PANSS points for CBD over PLB) were clinically significant.
The most recently published placebo-controlled RCT of CBD as add-on therapy to antipsychotic medication included 36 patients with schizophrenia treated over 6 weeks.26 In this study, there was no benefit of CBD, 600 mg/d, on any PANSS score outcome (total, general, positive, or negative symptoms). For the primary outcome of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, there were no significant drug × time effects, and post-hoc analyses showed that only patients treated with PLB improved with time. Sedation was more common among patients treated with CBD compared with PLB.
Making sense of the data
There have been mixed results from the few case reports and 3 RCTs of patients with schizophrenia who were treated with CBD. How can we resolve these disparate findings? A few possible interpretations of the data that warrant clarification through additional research include:
Dosing. In the first case report with positive results, CBD was dosed at 1,500 mg/d,22 whereas in the subsequent case series with mixed results, the maximum allowable dose of CBD was 1,280 mg/d.23 Likewise, in the RCTs, positive results were found when CBD was dosed at 800 to 1,000 mg/d,24,25 but not at 600 mg/d.26 The efficacy of CBD for schizophrenia might depend on higher doses.
Treatment resistance. In the second case series in which only 1 out of 3 patients responded to treatment with CBD,23 the patients had demonstrated previous nonresponse to at least 2 first-generation antipsychotics (FGAs) and risperidone, 6 mg/d. In the RCTs, all patients were antipsychotic-responsive.24-26 Cannabidiol may not be as effective for patients with treatment-refractory schizophrenia as it is for patients with schizophrenia who respond to antipsychotics.
Continue to: Clinical stability
Clinical stability. Within the RCTs, the greatest response was observed in the study that enrolled patients who were hospitalized with acute symptoms of schizophrenia.23 In the 2 studies that found either modest or no benefit with CBD, the patients had been stabilized on antipsychotic medications prior to randomization. Cannabidiol may offer limited benefit as add-on therapy to patients who have already responded to antipsychotic treatment, where there is “less room” for additional improvement.
Monotherapy. Both the case reports22,23 and the RCT with the most robust positive findings24 involved treatment with CBD as monotherapy. For some patients with schizophrenia, CBD might be effective as standalone therapy as an alternative to antipsychotics that is better tolerated. Adding CBD to antipsychotic therapy might be redundant and therefore less effective.
Answering questions about CBD
Cannabidiol is becoming increasingly popular for its purported health benefits. The mixed results of the few studies published on CBD for schizophrenia place clinicians in a difficult position when attempting to answer questions about how cannabinoids might fit into treatment of patients with psychosis. Consider the following:
Is cannabis helpful for patients with schizophrenia? No. Aside from the few case reports suggesting that FDA-approved THC (dronabinol) can improve symptoms in some patients,9,10 most of the evidence from anecdotal reports and both experimental and observational studies indicate that cannabis, THC, and synthetic cannabinoids have a harmful effect in patients with or at risk for psychosis.1-3
If you are considering recommending some form of cannabis to patients with schizophrenia, what kind should you recommend? Recommending or encouraging cannabis use for patients with psychosis is ill-advised. Although certain types of cannabis might contain more THC (eg, Cannabis indica vs Cannabis sativa) or variable amounts of CBD, in general the amount of CBD in whole leaf cannabis is minimal, with the ratio of THC to CBD increasingly significantly over the past decade.3,27 Most forms of cannabis should therefore be avoided by individuals with or at risk for psychotic disorders.
Continue to: What about CBD oil and other CBD products sold in dispensaries?
What about CBD oil and other CBD products sold in dispensaries? Cannabidiol is increasingly available in various forms based on its ability to be designated as a legal hemp product (containing <0.3% THC) at the federal level or as a cannabinoid in states where cannabis is legal. However, several studies have now shown that cannabis products sold online or in dispensaries are often labeled inaccurately, with both under- and over-reporting of THC and CBD content.28-30 Some CBD products have been found to have almost no CBD at all.29,30 The unreliability of product labeling makes it difficult to predict the effects of CBD products that are not subject to FDA purity standards for medications or dietary supplements. It also raises questions about the sources of CBD and the reliability of dosing in the studies discussed above.
Why might CBD work as an antipsychotic? Although CBD has minimal affinity for cannabinoid receptors, it appears to act as a partial agonist of dopamine D2 receptors and an agonist at 5-HT1A receptors, with overall effects that decrease mesolimbic dopamine activity.31,32 In addition, CBD increases the availability of the endogenous cannabinoid anandamide, which may have antipsychotic properties.14,33
Now that the FDA has approved CBD manufactured by a pharmaceutical company, should it be prescribed “off-label” for patients with schizophrenia? This is the “million dollar question,” with insufficient evidence to provide a clear answer. It should now be possible to prescribe FDA-approved CBD for off-label purposes, including the treatment of schizophrenia and other psychiatric disorders. No doubt, some clinicians are already doing so. This will predictably yield more anecdotal evidence about efficacy and adverse effects in the future, but there is not yet adequate evidence to support an FDA indication for CBD in schizophrenia. Additional studies of CBD for schizophrenia are ongoing.
Bottom Line
Cannabidiol (CBD) is becoming increasingly popular based on its purported health benefits, but the evidence supporting a therapeutic role in psychiatry is preliminary at best. Although CBD is now available by prescription as an FDA-approved drug for the treatment of 2 rare forms of epilepsy, its benefits in patients with schizophrenia are uncertain based on mixed results in clinical trials.
Related Resources
- Clinicaltrials.gov. Studies of “cannabidiol” and “schizophrenia.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=Schizophrenia&term=cannabidiol.
- Grinspoon P. Cannabidiol (CBD) – what we know and what we don’t. Harvard Health Blog. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-wedont-2018082414476. Published August 24, 2018.
Drug Brand Names
Cannabidiol • Epidiolex
Dronabinol • Marinol
Risperidone • Risperdal
1. Pierre JM. Cannabis, synthetic cannabinoids, and psychosis risk: what the evidence says. Current Psychiatry. 2011;10(9):49-58.
2. Radhakrishan R, Wilkinson ST, D’Souza DC. Gone to pot – a review of the association between cannabis and psychosis. Front Psychiatry. 2014;5:54.
3. Pierre JM. Risks of increasingly potent cannabis: joint effects of potency and frequency. Current Psychiatry. 2016;16(2):14-20.
4. Hanna RC, Perez JM, Ghose S. Cannabis and development of dual diagnoses: a literature review. Am J Drug Alcohol Abuse. 2017;43(4):442-255.
5. Nunberg H, Kilmer B, Pacula RL, et al. An analysis of applicants presenting to a medical marijuana specialty practice in California. J Drug Policy Anal. 2011;4(1):1.
6. Wilkinson ST, Radhakrishnan, D’Souza DC. A systematic review of the evidence for medical marijuana in psychiatric indications. J Clin Psychiatry. 2016;77(8):1050-1064.
7. Tournebize J, Gibaja V, Kahn JP. Acute effects of synthetic cannabinoids: Update 2015. Subst Abus. 2016;38(3):344-366.
8. Crippa JA, Guimarães FS, Campos A, et al. Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. Front Immunol. 2018;9:2009.
9. Schwarz G, Karajgi B. Improvement in refractory psychosis with dronabinol: four case reports. J Clin Psychiatry. 2010;71(11):1552-1553.
10. Schwarz G, Karajgi B, McCarthy R. Synthetic delta-9-tetrahydrocannabinol (dronabinol) can improve the symptoms of schizophrenia. J Clin Psychopharmacol. 2009;29(3):255-258.
11. Meltzer HY, Arvanitis L, Bauer D, et al. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry. 2004;161(6):975-984.
12. Boggs DL, Kelly DL, McMahon RP, et al. Rimonabant for neurocognition in schizophrenia: a 16-week double blind placebo controlled trial. Schizophr Res. 2012;134(2-3):207-210.
13. Kelly DL, Gorelick DA, Conley RR, et al. Effects of cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study. J Clin Psychopharmacol. 2011;31(1):86-91.
14. Leweke FM, Mueller JK, Lange B, et al. Therapeutic potential of cannabinoids in psychosis. Biol Psychiatry. 2016;79(7):604-612.
15. Halperin A. What is CBD? The ‘miracle’ cannabis compound that doesn’t get you high. The Guardian. https://www.theguardian.com/society/2018/may/28/what-is-cbd-cannabidiol-cannabis-medical-uses. Published May 28, 2018. Accessed April 3, 2019.
16. Pierre J. Coca, cola, and cannabis: psychoactive drugs as beverages. Psychology Today (blog) Psych Unseen. https://www.psychologytoday.com/us/blog/psych-unseen/201810/coca-cola-and-cannabis-psychoactive-drugs-beverages. Published October 1, 2018. Accessed April 3, 2019.
17. U.S. Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. FDA News Release. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Published June 25, 2018. Accessed April 3, 2019.
18. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011-2020.
19. Thiele EA, March ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096.
20. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378:1888-1897.
21. Khoury JM, Neves MCLD, Rogue MAV, et al. Is there a role of cannabidiol in psychiatry? World J Biol Psychiatry. 2017:1-16.
22. Zuardi AW, Morais SL, Guimares FS, et al. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995;56(10):485-486.
23. Zuardi AW, Hallak JEC, Dursun SM. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006;20(5):683-686.
24. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94. doi: 10.1038/tp.2012.15.
25. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175(3):225-231.
26. Boggs DL, Surti I, Gupta A, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacol. 2018;235(7):1923-1932.
27. ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States. Biol Psychiatry. 2016; 79(7):613-619.
28. Vandrey R, Raber JC, Raber ME, et al. Cannabinoid dose and label accuracy in edible medical cannabis products. JAMA. 2015;313(24):2491-2492.
29. Ruth AC, Gryniewicz-Ruzicka CM, Trehy ML, et al. Consistency of label claims of internet-purchased hemp oil and cannabis products as determined using IMS and LC-MS: a marketplace study. J Reg Sci. 2016;3:1-6.
30. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318(17):1708-1709.
31. Seeman P. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry. 2016;6(10):e920. doi: 10.1038/tp.2016.195.
32. Renard J, Norris C, Rushlow W, et al. Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: implications for novel schizophrenia treatments. Neurosci Biobehav Rev. 2017;157-165.
33. Gururajan A, Malone DT. Does cannabidiol have a role in the treatment of schizophrenia? Schizophr Res. 2016;176(2-3):281-290.
1. Pierre JM. Cannabis, synthetic cannabinoids, and psychosis risk: what the evidence says. Current Psychiatry. 2011;10(9):49-58.
2. Radhakrishan R, Wilkinson ST, D’Souza DC. Gone to pot – a review of the association between cannabis and psychosis. Front Psychiatry. 2014;5:54.
3. Pierre JM. Risks of increasingly potent cannabis: joint effects of potency and frequency. Current Psychiatry. 2016;16(2):14-20.
4. Hanna RC, Perez JM, Ghose S. Cannabis and development of dual diagnoses: a literature review. Am J Drug Alcohol Abuse. 2017;43(4):442-255.
5. Nunberg H, Kilmer B, Pacula RL, et al. An analysis of applicants presenting to a medical marijuana specialty practice in California. J Drug Policy Anal. 2011;4(1):1.
6. Wilkinson ST, Radhakrishnan, D’Souza DC. A systematic review of the evidence for medical marijuana in psychiatric indications. J Clin Psychiatry. 2016;77(8):1050-1064.
7. Tournebize J, Gibaja V, Kahn JP. Acute effects of synthetic cannabinoids: Update 2015. Subst Abus. 2016;38(3):344-366.
8. Crippa JA, Guimarães FS, Campos A, et al. Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. Front Immunol. 2018;9:2009.
9. Schwarz G, Karajgi B. Improvement in refractory psychosis with dronabinol: four case reports. J Clin Psychiatry. 2010;71(11):1552-1553.
10. Schwarz G, Karajgi B, McCarthy R. Synthetic delta-9-tetrahydrocannabinol (dronabinol) can improve the symptoms of schizophrenia. J Clin Psychopharmacol. 2009;29(3):255-258.
11. Meltzer HY, Arvanitis L, Bauer D, et al. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry. 2004;161(6):975-984.
12. Boggs DL, Kelly DL, McMahon RP, et al. Rimonabant for neurocognition in schizophrenia: a 16-week double blind placebo controlled trial. Schizophr Res. 2012;134(2-3):207-210.
13. Kelly DL, Gorelick DA, Conley RR, et al. Effects of cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study. J Clin Psychopharmacol. 2011;31(1):86-91.
14. Leweke FM, Mueller JK, Lange B, et al. Therapeutic potential of cannabinoids in psychosis. Biol Psychiatry. 2016;79(7):604-612.
15. Halperin A. What is CBD? The ‘miracle’ cannabis compound that doesn’t get you high. The Guardian. https://www.theguardian.com/society/2018/may/28/what-is-cbd-cannabidiol-cannabis-medical-uses. Published May 28, 2018. Accessed April 3, 2019.
16. Pierre J. Coca, cola, and cannabis: psychoactive drugs as beverages. Psychology Today (blog) Psych Unseen. https://www.psychologytoday.com/us/blog/psych-unseen/201810/coca-cola-and-cannabis-psychoactive-drugs-beverages. Published October 1, 2018. Accessed April 3, 2019.
17. U.S. Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. FDA News Release. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Published June 25, 2018. Accessed April 3, 2019.
18. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011-2020.
19. Thiele EA, March ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10125):1085-1096.
20. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378:1888-1897.
21. Khoury JM, Neves MCLD, Rogue MAV, et al. Is there a role of cannabidiol in psychiatry? World J Biol Psychiatry. 2017:1-16.
22. Zuardi AW, Morais SL, Guimares FS, et al. Antipsychotic effect of cannabidiol. J Clin Psychiatry. 1995;56(10):485-486.
23. Zuardi AW, Hallak JEC, Dursun SM. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006;20(5):683-686.
24. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94. doi: 10.1038/tp.2012.15.
25. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175(3):225-231.
26. Boggs DL, Surti I, Gupta A, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacol. 2018;235(7):1923-1932.
27. ElSohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995-2014): analysis of current data in the United States. Biol Psychiatry. 2016; 79(7):613-619.
28. Vandrey R, Raber JC, Raber ME, et al. Cannabinoid dose and label accuracy in edible medical cannabis products. JAMA. 2015;313(24):2491-2492.
29. Ruth AC, Gryniewicz-Ruzicka CM, Trehy ML, et al. Consistency of label claims of internet-purchased hemp oil and cannabis products as determined using IMS and LC-MS: a marketplace study. J Reg Sci. 2016;3:1-6.
30. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318(17):1708-1709.
31. Seeman P. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry. 2016;6(10):e920. doi: 10.1038/tp.2016.195.
32. Renard J, Norris C, Rushlow W, et al. Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: implications for novel schizophrenia treatments. Neurosci Biobehav Rev. 2017;157-165.
33. Gururajan A, Malone DT. Does cannabidiol have a role in the treatment of schizophrenia? Schizophr Res. 2016;176(2-3):281-290.
Marijuana during prenatal OUD treatment increases premature birth
BALTIMORE – Marijuana is a not a good idea during pregnancy, and it’s an even worse idea when women are being treated for opioid addiction, according to an investigation from East Tennessee State University, Mountain Home.
Marijuana use may become more common as legalization rolls out across the country, and legalization, in turn, may add to the perception that pot is harmless, and maybe a good way to take the edge off during pregnancy and prevent morning sickness, said neonatologist Darshan Shaw, MD, of the department of pediatrics at the university.
Dr. Shaw wondered how that trend might impact treatment of opioid use disorder (OUD) during pregnancy, which has also become more common. The take-home is that “if you have a pregnant patient on medically assistant therapy” for opioid addition, “you should warn them against use of marijuana. It increases the risk of prematurity and low birth weight,” he said at the Pediatric Academic Societies annual meeting.
He and his team reviewed 2,375 opioid-exposed pregnancies at six hospitals in south-central Appalachia from July 2011 to June 2016. All of the women had used opioids during pregnancy, some illegally and others for opioid use disorder (OUD) treatment or other medical issues; 108 had urine screens that were positive for tetrahydrocannabinol (THC) at the time of delivery.
Infants were born a mean of 3 days earlier in the marijuana group, and a mean of 265 g lighter. They were also more likely to be born before 37 weeks’ gestation (14% versus 6.5%); born weighing less than 2,500 g (17.6% versus 7.3%); and more likely to be admitted to the neonatal ICU (17.5% versus 7.1%).
On logistic regression to control for parity, maternal status, and tobacco and benzodiazepine use, prenatal marijuana exposure more than doubled the risk of prematurity (odds ratio, 2.35; 95% confidence interval, 1.3-4.23); tobacco and benzodiazepines did not increase the risk. Marijuana also doubled the risk of low birth weight (OR, 2.02; 95% CI, 1.18-3.47), about the same as tobacco and benzodiazepines.
The study had limitations. There was no controlling for a major confounder: the amount of opioids woman took while pregnant. These data were not available, Dr. Shaw said.
Neonatal abstinence syndrome was more common in the marijuana group (33.3% versus 18.1%), so it’s possible that women who used marijuana also used more opioids. “We suspect that opioid exposure was not uniform among all infants,” he said. There were also no data on the amount or way marijuana was used.
Marijuana-positive women were more likely to be unmarried, nulliparous, and use tobacco and benzodiazepines.
There was no industry funding for the work, and Dr. Shaw had no disclosures.
BALTIMORE – Marijuana is a not a good idea during pregnancy, and it’s an even worse idea when women are being treated for opioid addiction, according to an investigation from East Tennessee State University, Mountain Home.
Marijuana use may become more common as legalization rolls out across the country, and legalization, in turn, may add to the perception that pot is harmless, and maybe a good way to take the edge off during pregnancy and prevent morning sickness, said neonatologist Darshan Shaw, MD, of the department of pediatrics at the university.
Dr. Shaw wondered how that trend might impact treatment of opioid use disorder (OUD) during pregnancy, which has also become more common. The take-home is that “if you have a pregnant patient on medically assistant therapy” for opioid addition, “you should warn them against use of marijuana. It increases the risk of prematurity and low birth weight,” he said at the Pediatric Academic Societies annual meeting.
He and his team reviewed 2,375 opioid-exposed pregnancies at six hospitals in south-central Appalachia from July 2011 to June 2016. All of the women had used opioids during pregnancy, some illegally and others for opioid use disorder (OUD) treatment or other medical issues; 108 had urine screens that were positive for tetrahydrocannabinol (THC) at the time of delivery.
Infants were born a mean of 3 days earlier in the marijuana group, and a mean of 265 g lighter. They were also more likely to be born before 37 weeks’ gestation (14% versus 6.5%); born weighing less than 2,500 g (17.6% versus 7.3%); and more likely to be admitted to the neonatal ICU (17.5% versus 7.1%).
On logistic regression to control for parity, maternal status, and tobacco and benzodiazepine use, prenatal marijuana exposure more than doubled the risk of prematurity (odds ratio, 2.35; 95% confidence interval, 1.3-4.23); tobacco and benzodiazepines did not increase the risk. Marijuana also doubled the risk of low birth weight (OR, 2.02; 95% CI, 1.18-3.47), about the same as tobacco and benzodiazepines.
The study had limitations. There was no controlling for a major confounder: the amount of opioids woman took while pregnant. These data were not available, Dr. Shaw said.
Neonatal abstinence syndrome was more common in the marijuana group (33.3% versus 18.1%), so it’s possible that women who used marijuana also used more opioids. “We suspect that opioid exposure was not uniform among all infants,” he said. There were also no data on the amount or way marijuana was used.
Marijuana-positive women were more likely to be unmarried, nulliparous, and use tobacco and benzodiazepines.
There was no industry funding for the work, and Dr. Shaw had no disclosures.
BALTIMORE – Marijuana is a not a good idea during pregnancy, and it’s an even worse idea when women are being treated for opioid addiction, according to an investigation from East Tennessee State University, Mountain Home.
Marijuana use may become more common as legalization rolls out across the country, and legalization, in turn, may add to the perception that pot is harmless, and maybe a good way to take the edge off during pregnancy and prevent morning sickness, said neonatologist Darshan Shaw, MD, of the department of pediatrics at the university.
Dr. Shaw wondered how that trend might impact treatment of opioid use disorder (OUD) during pregnancy, which has also become more common. The take-home is that “if you have a pregnant patient on medically assistant therapy” for opioid addition, “you should warn them against use of marijuana. It increases the risk of prematurity and low birth weight,” he said at the Pediatric Academic Societies annual meeting.
He and his team reviewed 2,375 opioid-exposed pregnancies at six hospitals in south-central Appalachia from July 2011 to June 2016. All of the women had used opioids during pregnancy, some illegally and others for opioid use disorder (OUD) treatment or other medical issues; 108 had urine screens that were positive for tetrahydrocannabinol (THC) at the time of delivery.
Infants were born a mean of 3 days earlier in the marijuana group, and a mean of 265 g lighter. They were also more likely to be born before 37 weeks’ gestation (14% versus 6.5%); born weighing less than 2,500 g (17.6% versus 7.3%); and more likely to be admitted to the neonatal ICU (17.5% versus 7.1%).
On logistic regression to control for parity, maternal status, and tobacco and benzodiazepine use, prenatal marijuana exposure more than doubled the risk of prematurity (odds ratio, 2.35; 95% confidence interval, 1.3-4.23); tobacco and benzodiazepines did not increase the risk. Marijuana also doubled the risk of low birth weight (OR, 2.02; 95% CI, 1.18-3.47), about the same as tobacco and benzodiazepines.
The study had limitations. There was no controlling for a major confounder: the amount of opioids woman took while pregnant. These data were not available, Dr. Shaw said.
Neonatal abstinence syndrome was more common in the marijuana group (33.3% versus 18.1%), so it’s possible that women who used marijuana also used more opioids. “We suspect that opioid exposure was not uniform among all infants,” he said. There were also no data on the amount or way marijuana was used.
Marijuana-positive women were more likely to be unmarried, nulliparous, and use tobacco and benzodiazepines.
There was no industry funding for the work, and Dr. Shaw had no disclosures.
REPORTING FROM PAS 2019
Key clinical point: Warn pregnant women being treated for opioid use disorder to stay away from marijuana.
Major finding: Marijuana use more than doubled the risk of prematurity and low birth weight.
Study details: Review of 2,375 opioid-exposed pregnancies at six hospitals
Disclosures: There was no industry funding for the work, and the lead investigator had no disclosures.
EU authorization recommended for buprenorphine implant
The European Medicines Agency announced April 26 that its human medicines committee has recommended granting a marketing authorization for Sixmo, a long-lasting implant delivering buprenorphine as treatment for opioid use disorder (OUD).
This recommendation is a step toward making the product available to patients with OUD in the European Union, according to a press release from the EMA. Safety and efficacy of the implant were studied in three trials with a total of 628 patients.
Standard treatment of OUD includes psychological and social counseling, as well as substitution opioid therapy – such as methadone or buprenorphine. The Sixmo implant involves four small rods implanted in the patient’s upper arm under local anesthetic.
The most common adverse events associated with the medicine were in keeping with the known events associated with buprenorphine – headache, constipation, and insomnia. Insertion and removal were associated with pain, severe itching, and hematoma at the implant site.
The full release can be found on the EMA website.
The European Medicines Agency announced April 26 that its human medicines committee has recommended granting a marketing authorization for Sixmo, a long-lasting implant delivering buprenorphine as treatment for opioid use disorder (OUD).
This recommendation is a step toward making the product available to patients with OUD in the European Union, according to a press release from the EMA. Safety and efficacy of the implant were studied in three trials with a total of 628 patients.
Standard treatment of OUD includes psychological and social counseling, as well as substitution opioid therapy – such as methadone or buprenorphine. The Sixmo implant involves four small rods implanted in the patient’s upper arm under local anesthetic.
The most common adverse events associated with the medicine were in keeping with the known events associated with buprenorphine – headache, constipation, and insomnia. Insertion and removal were associated with pain, severe itching, and hematoma at the implant site.
The full release can be found on the EMA website.
The European Medicines Agency announced April 26 that its human medicines committee has recommended granting a marketing authorization for Sixmo, a long-lasting implant delivering buprenorphine as treatment for opioid use disorder (OUD).
This recommendation is a step toward making the product available to patients with OUD in the European Union, according to a press release from the EMA. Safety and efficacy of the implant were studied in three trials with a total of 628 patients.
Standard treatment of OUD includes psychological and social counseling, as well as substitution opioid therapy – such as methadone or buprenorphine. The Sixmo implant involves four small rods implanted in the patient’s upper arm under local anesthetic.
The most common adverse events associated with the medicine were in keeping with the known events associated with buprenorphine – headache, constipation, and insomnia. Insertion and removal were associated with pain, severe itching, and hematoma at the implant site.
The full release can be found on the EMA website.
Deadly overlap of fentanyl and stimulants on the rise
Rates of a potentially deadly overlap between use of nonprescribed fentanyl and use of either cocaine or methamphetamine have been increasing, a cross-sectional study of 1 million urine drug tests shows.
Leah LaRue, PharmD, of Millennium Health in San Diego, and colleagues performed the study, which sampled 1 million urine drug tests submitted by health care professionals “as part of routine care” during Jan. 1, 2013–Sept. 30, 2018. They isolated tests that were positive for either cocaine or methamphetamine – but not positive for both – and then determined how many in each group were also positive for nonprescribed fentanyl. Their analyses showed that the rate of cocaine-positive tests that also were positive for nonprescribed fentanyl increased from 0.9% in 2013 (n = 84; 95% confidence interval, 0.7%-1.1%) to 17.6% in 2018 (n = 427; 95% CI, 16.1%-19.1%), an increase of 1,850% (P less than .001). The rate of methamphetamine-positive tests that also were positive for nonprescribed fentanyl also started at 0.9% in 2013 (n = 29; 95% CI, 0.6%-1.2%) but rose to 7.9% in 2018 (n = 344; 95% CI, 7.1%-8.7%, a 798% increase (P less than .001). The study was published in JAMA Network Open.
The investigators suggested two explanations for these increases: intentional combination of drugs for “speedball effects” of combining stimulants and depressants and/or unintentional exposure on the part of users through contamination of substances. There have been increases in both cocaine-related and methamphetamine-related deaths, and the investigators of this study suspect these increases could be explained in part by overlap with opioids such as fentanyl. Part of the overdose risk inherent in these combinations is that, as the stimulant wears off, the fentanyl increasingly depresses the respiratory system, according to investigators; alternatively, opioid-naive stimulant users might be exposed to high levels of fentanyl with no opioid tolerance, which also can lead to overdose.
The study’s limitations include how samples were submitted – by health care professionals as part of routine care – and the possibility that individuals’ list of prescribed medications could have been incomplete or inaccurate such that the presence of prescribed fentanyl was counted as nonprescribed.
“The combination of nonprescribed fentanyl with cocaine or methamphetamine places an individual at increased risk of overdose,” they concluded.
cpalmer@mdedge.com
SOURCE: LaRue L et al. JAMA Netw Open. 2019 Apr 26. doi: 10.1001/jamanetworkopen.2019.2851.
Rates of a potentially deadly overlap between use of nonprescribed fentanyl and use of either cocaine or methamphetamine have been increasing, a cross-sectional study of 1 million urine drug tests shows.
Leah LaRue, PharmD, of Millennium Health in San Diego, and colleagues performed the study, which sampled 1 million urine drug tests submitted by health care professionals “as part of routine care” during Jan. 1, 2013–Sept. 30, 2018. They isolated tests that were positive for either cocaine or methamphetamine – but not positive for both – and then determined how many in each group were also positive for nonprescribed fentanyl. Their analyses showed that the rate of cocaine-positive tests that also were positive for nonprescribed fentanyl increased from 0.9% in 2013 (n = 84; 95% confidence interval, 0.7%-1.1%) to 17.6% in 2018 (n = 427; 95% CI, 16.1%-19.1%), an increase of 1,850% (P less than .001). The rate of methamphetamine-positive tests that also were positive for nonprescribed fentanyl also started at 0.9% in 2013 (n = 29; 95% CI, 0.6%-1.2%) but rose to 7.9% in 2018 (n = 344; 95% CI, 7.1%-8.7%, a 798% increase (P less than .001). The study was published in JAMA Network Open.
The investigators suggested two explanations for these increases: intentional combination of drugs for “speedball effects” of combining stimulants and depressants and/or unintentional exposure on the part of users through contamination of substances. There have been increases in both cocaine-related and methamphetamine-related deaths, and the investigators of this study suspect these increases could be explained in part by overlap with opioids such as fentanyl. Part of the overdose risk inherent in these combinations is that, as the stimulant wears off, the fentanyl increasingly depresses the respiratory system, according to investigators; alternatively, opioid-naive stimulant users might be exposed to high levels of fentanyl with no opioid tolerance, which also can lead to overdose.
The study’s limitations include how samples were submitted – by health care professionals as part of routine care – and the possibility that individuals’ list of prescribed medications could have been incomplete or inaccurate such that the presence of prescribed fentanyl was counted as nonprescribed.
“The combination of nonprescribed fentanyl with cocaine or methamphetamine places an individual at increased risk of overdose,” they concluded.
cpalmer@mdedge.com
SOURCE: LaRue L et al. JAMA Netw Open. 2019 Apr 26. doi: 10.1001/jamanetworkopen.2019.2851.
Rates of a potentially deadly overlap between use of nonprescribed fentanyl and use of either cocaine or methamphetamine have been increasing, a cross-sectional study of 1 million urine drug tests shows.
Leah LaRue, PharmD, of Millennium Health in San Diego, and colleagues performed the study, which sampled 1 million urine drug tests submitted by health care professionals “as part of routine care” during Jan. 1, 2013–Sept. 30, 2018. They isolated tests that were positive for either cocaine or methamphetamine – but not positive for both – and then determined how many in each group were also positive for nonprescribed fentanyl. Their analyses showed that the rate of cocaine-positive tests that also were positive for nonprescribed fentanyl increased from 0.9% in 2013 (n = 84; 95% confidence interval, 0.7%-1.1%) to 17.6% in 2018 (n = 427; 95% CI, 16.1%-19.1%), an increase of 1,850% (P less than .001). The rate of methamphetamine-positive tests that also were positive for nonprescribed fentanyl also started at 0.9% in 2013 (n = 29; 95% CI, 0.6%-1.2%) but rose to 7.9% in 2018 (n = 344; 95% CI, 7.1%-8.7%, a 798% increase (P less than .001). The study was published in JAMA Network Open.
The investigators suggested two explanations for these increases: intentional combination of drugs for “speedball effects” of combining stimulants and depressants and/or unintentional exposure on the part of users through contamination of substances. There have been increases in both cocaine-related and methamphetamine-related deaths, and the investigators of this study suspect these increases could be explained in part by overlap with opioids such as fentanyl. Part of the overdose risk inherent in these combinations is that, as the stimulant wears off, the fentanyl increasingly depresses the respiratory system, according to investigators; alternatively, opioid-naive stimulant users might be exposed to high levels of fentanyl with no opioid tolerance, which also can lead to overdose.
The study’s limitations include how samples were submitted – by health care professionals as part of routine care – and the possibility that individuals’ list of prescribed medications could have been incomplete or inaccurate such that the presence of prescribed fentanyl was counted as nonprescribed.
“The combination of nonprescribed fentanyl with cocaine or methamphetamine places an individual at increased risk of overdose,” they concluded.
cpalmer@mdedge.com
SOURCE: LaRue L et al. JAMA Netw Open. 2019 Apr 26. doi: 10.1001/jamanetworkopen.2019.2851.
FROM jama network open
CDC warns against misuse of opioid-prescribing guideline
Officials at the Centers for Disease Control and Prevention are warning against the misapplication of the agency’s 2016 guidelines on opioid prescribing, as well as clarifying dosage recommendations for patients starting or stopping pain medications.
In a perspective published in the New England Journal of Medicine on April 24, lead author Deborah Dowell, MD, chief medical officer for the CDC’s National Center for Injury Prevention and Control, conveyed concern that some policies and practices derived from the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain are inconsistent with the recommendations and often go beyond their scope.
Misapplication examples include inappropriately applying the guideline to patients in active cancer treatment, patients experiencing acute sickle cell crises, or patients experiencing postsurgical pain, Dr. Dowell wrote.
The guideline offers guidance to clinicians treating chronic pain in adults who are already receiving opioids long-term at high dosages, she noted. It includes advice on maximizing nonopioid treatment, reviewing risks associated with continuing high-dose opioids, and collaborating with patients who agree to taper dosage, among other guidance.
Any application of the guideline’s dosage recommendation that results in hard limits or “cutting off” opioids is also an incorrect use of the recommendations, according to Dr. Dowell.
While the guideline advises clinicians to start opioids at the lowest effective dosage and avoid increasing dosage to 90 morphine milligram equivalents per day or more, that statement does not suggest discontinuation of opioids already prescribed at high dosages, according to the CDC’s clarification.
The guidance also does not apply to patients receiving or starting medication-assisted treatment for opioid use disorder.
The commentary comes after a trio of organizations raised concerns that insurers are inappropriately applying the recommendations to active cancer patients when making coverage determinations.
The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American Society of Hematology, raised the issue in a letter to the CDC in February. In response, Dr. Dowell clarified that the recommendations are not intended to deny clinically appropriate opioid therapy to any patients who suffer chronic pain, but rather to ensure that physicians and patients consider all safe and effective treatment options.
In the perspective, Dr. Dowell wrote that the CDC is evaluating the intended and unintended impact of the 2016 opioid-prescribing guideline on clinician and patient outcomes and that the agency is committed to updating the recommendations when new evidence is available.
Officials at the Centers for Disease Control and Prevention are warning against the misapplication of the agency’s 2016 guidelines on opioid prescribing, as well as clarifying dosage recommendations for patients starting or stopping pain medications.
In a perspective published in the New England Journal of Medicine on April 24, lead author Deborah Dowell, MD, chief medical officer for the CDC’s National Center for Injury Prevention and Control, conveyed concern that some policies and practices derived from the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain are inconsistent with the recommendations and often go beyond their scope.
Misapplication examples include inappropriately applying the guideline to patients in active cancer treatment, patients experiencing acute sickle cell crises, or patients experiencing postsurgical pain, Dr. Dowell wrote.
The guideline offers guidance to clinicians treating chronic pain in adults who are already receiving opioids long-term at high dosages, she noted. It includes advice on maximizing nonopioid treatment, reviewing risks associated with continuing high-dose opioids, and collaborating with patients who agree to taper dosage, among other guidance.
Any application of the guideline’s dosage recommendation that results in hard limits or “cutting off” opioids is also an incorrect use of the recommendations, according to Dr. Dowell.
While the guideline advises clinicians to start opioids at the lowest effective dosage and avoid increasing dosage to 90 morphine milligram equivalents per day or more, that statement does not suggest discontinuation of opioids already prescribed at high dosages, according to the CDC’s clarification.
The guidance also does not apply to patients receiving or starting medication-assisted treatment for opioid use disorder.
The commentary comes after a trio of organizations raised concerns that insurers are inappropriately applying the recommendations to active cancer patients when making coverage determinations.
The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American Society of Hematology, raised the issue in a letter to the CDC in February. In response, Dr. Dowell clarified that the recommendations are not intended to deny clinically appropriate opioid therapy to any patients who suffer chronic pain, but rather to ensure that physicians and patients consider all safe and effective treatment options.
In the perspective, Dr. Dowell wrote that the CDC is evaluating the intended and unintended impact of the 2016 opioid-prescribing guideline on clinician and patient outcomes and that the agency is committed to updating the recommendations when new evidence is available.
Officials at the Centers for Disease Control and Prevention are warning against the misapplication of the agency’s 2016 guidelines on opioid prescribing, as well as clarifying dosage recommendations for patients starting or stopping pain medications.
In a perspective published in the New England Journal of Medicine on April 24, lead author Deborah Dowell, MD, chief medical officer for the CDC’s National Center for Injury Prevention and Control, conveyed concern that some policies and practices derived from the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain are inconsistent with the recommendations and often go beyond their scope.
Misapplication examples include inappropriately applying the guideline to patients in active cancer treatment, patients experiencing acute sickle cell crises, or patients experiencing postsurgical pain, Dr. Dowell wrote.
The guideline offers guidance to clinicians treating chronic pain in adults who are already receiving opioids long-term at high dosages, she noted. It includes advice on maximizing nonopioid treatment, reviewing risks associated with continuing high-dose opioids, and collaborating with patients who agree to taper dosage, among other guidance.
Any application of the guideline’s dosage recommendation that results in hard limits or “cutting off” opioids is also an incorrect use of the recommendations, according to Dr. Dowell.
While the guideline advises clinicians to start opioids at the lowest effective dosage and avoid increasing dosage to 90 morphine milligram equivalents per day or more, that statement does not suggest discontinuation of opioids already prescribed at high dosages, according to the CDC’s clarification.
The guidance also does not apply to patients receiving or starting medication-assisted treatment for opioid use disorder.
The commentary comes after a trio of organizations raised concerns that insurers are inappropriately applying the recommendations to active cancer patients when making coverage determinations.
The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the American Society of Hematology, raised the issue in a letter to the CDC in February. In response, Dr. Dowell clarified that the recommendations are not intended to deny clinically appropriate opioid therapy to any patients who suffer chronic pain, but rather to ensure that physicians and patients consider all safe and effective treatment options.
In the perspective, Dr. Dowell wrote that the CDC is evaluating the intended and unintended impact of the 2016 opioid-prescribing guideline on clinician and patient outcomes and that the agency is committed to updating the recommendations when new evidence is available.
Teen e-cigarette use: A public health crisis
After 2 decades of steady decline in adolescent and young adult use of tobacco products, e-cigarettes have dramatically altered the landscape of substance use in youth. E-cigarette use among teens has been on the rise for years but the recent exponential increase is unprecedented. From 2017 to 2018, adolescent e-cigarette use had the largest year-to-year increase (78%, from 12% to 21%) of any individual substance or class of substances at any time during the past 2 decades of nationwide monitoring.1 This has appropriately caught the nation’s attention. In 2016, Surgeon General Vivek H. Murthy, MD, commissioned an extensive report about electronic cigarettes, and in 2018 Surgeon General Jerome Adams, MD, MPH, issued an advisory declaring e-cigarettes a public health crisis for adolescents.2
E-cigarettes have received attention as a possible boon to adult cigarette smokers seeking a less hazardous product. We can consider the use of tobacco products along a continuum from smoked tobacco, dual use (both smoked tobacco and electronic nicotine delivery), electronic nicotine delivery only, and finally, nonuse. For some adults, transitioning from smoked tobacco products to electronic delivery systems has been a step toward less overall harm from substance use, with a small minority of that population going on to achieve abstinence from all nicotine products.3 For youth and teens, the story has been the opposite. With the rapid rise of e-cigarettes, adolescents overwhelmingly have been moving in the wrong direction at each potential step along this continuum.4 Less than 8% of teens who use e-cigarettes indicated that smoking cessation is a factor in their use.5 An estimated 1.3 million U.S. teens now are dependent or at high risk for dependence upon nicotine because of e-cigarette use. Furthermore, these teens are at a fourfold higher risk of progression to cigarette use, compared with their peers.6
One product in particular gives us information as to why this trend has accelerated so rapidly. Juul, now the sales leader among electronic nicotine delivery systems, rose from approximately 25% to a dominant 75% of market share in just over 1 fiscal year after a social media campaign targeted toward youth and young adults. The device is shaped like an elongated flash drive, is marketed as “sleek,” “looking cool,” and being “super easy” to use. This product touts its use of nicotine salts that can deliver higher concentrations of nicotine more rapidly to mimic the experience of smoking a cigarette as closely as possible. The fruity flavors in Juul “pods” and many other devices also appeal to teens. Many youth are left misinformed, thinking they are using a relatively harmless alternative to cigarettes.
E-cigarette use in youth carries many risks. Among the physical risks is exposure to harmful chemicals (even if less numerous than smoked tobacco products) such as diacetyl (a known cause of bronchiolitis obliterans, or “popcorn lung”), formaldehyde, acrolein, benzene, and metals such as nickel, tin and lead.7 “Safer than cigarettes” is a low bar indeed. Cognitive and emotional risks of early nicotine exposure include poor focus and attention, permanent lowering of impulse control, and a higher risk of mood and anxiety disorders.
Furthermore, nicotine is a gateway drug, with a clearly understood molecular basis for how it can potentiate the effects of later used substances, especially stimulants such as cocaine.8 The gateway and priming effect is compounded for youth because of ongoing brain development and plasticity during teen years. E-cigarette use also is associated with other risk behaviors including a manyfold higher likelihood of binge drinking, having multiple sexual partners in a short period of time, and using other substances such as cannabis, cocaine, methamphetamine, and heroin or nonprescribed opioids.9 An electronic system for vaporization also presents a risk for use of other substances. In just 1 year from 2017 to 2018, marijuana “vaping” increased by more than 50% among all ages surveyed.10
Pediatric health care providers are essential educators for both teens and parents regarding the risks of e-cigarette use. Many youth don’t know what they’re using; 66% of youth reported that the vapors they were inhaling contained only flavoring. Only 13% reported they were inhaling nicotine.10 In stark contrast to these self-reports, all Juul “pods” contain nicotine. As has been a pattern with nationwide surveys of substance use for decades, adolescent use is inversely correlated with perception of risk; 70% of 8th-12th graders do not foresee great harm in regular e-cigarette use. In addition, adolescents use substances less often when they know their parents disapprove. Parents also must be taught about the risks of e-cigarette use and can be provided with resources and taught effective strategies if they have difficulty communicating their disapproval to their children.
Age-appropriate screening in primary care settings must include specific language regarding the use of electronic cigarettes, with questions about “vaping” and “juuling.” Discussions with teens may be more effective with emphasis on issues that resonate with youth such as the financial cost, loss of freedom when dependence develops, and the fact that their generation is once again being targeted by the tobacco industry. Referral for further treatment, including individual and group therapy as well as family-focused interventions, should be considered for teens who use daily, use other substances regularly, or could benefit from treatment for co-occurring mental health disorders.
Electronic cigarette use should not be recommended as a smoking cessation strategy for teens.11 Pediatric health care providers must advocate for regulation of these products, including increasing the legal age of purchase and banning flavoring in e-cigarettes products, Internet sales, and advertisements targeted to youth.
The rapid rise in e-cigarette use among teens is of great concern. As with all classes of substances, early initiation of nicotine drastically increases the risk of developing a substance use disorder and portends a prolonged course and greater accumulation of adverse consequences. There is an urgent need for education, prevention, and early identification of e-cigarette use to protect the current and future well-being of children and adolescents.
Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington. He said he had no relevant financial disclosures. Email Dr. Jackson at pdnews@mdedge.com.
References
1. MMWR Morb Mortal Wkly Rep. 2018;67:1276-7.
2. e-cigarettes.surgeongeneral.gov
3. N Engl J Med 2019;380:629-37.
4. Pediatrics. 2018 Dec; 142(6):e20180486.
5. MMWR Morb Mortal Wkly Rep 2018;67:196-200.
6. JAMA Pediatr. 2017 Aug 1;171(8):788-97.
7. “Public health consequences of e-cigarettes” (Washington, DC: National Academies Press, January 2018).
8. N Engl J Med 2014;371:932-43.
9. N Engl J Med 2019;380:689-90.
10. MMWR Morb Mortal Wkly Rep. 2016 Jan 8;64(52):1403-8.
11. Pediatrics. 2019 Feb;143(2). pii: e20183652.
After 2 decades of steady decline in adolescent and young adult use of tobacco products, e-cigarettes have dramatically altered the landscape of substance use in youth. E-cigarette use among teens has been on the rise for years but the recent exponential increase is unprecedented. From 2017 to 2018, adolescent e-cigarette use had the largest year-to-year increase (78%, from 12% to 21%) of any individual substance or class of substances at any time during the past 2 decades of nationwide monitoring.1 This has appropriately caught the nation’s attention. In 2016, Surgeon General Vivek H. Murthy, MD, commissioned an extensive report about electronic cigarettes, and in 2018 Surgeon General Jerome Adams, MD, MPH, issued an advisory declaring e-cigarettes a public health crisis for adolescents.2
E-cigarettes have received attention as a possible boon to adult cigarette smokers seeking a less hazardous product. We can consider the use of tobacco products along a continuum from smoked tobacco, dual use (both smoked tobacco and electronic nicotine delivery), electronic nicotine delivery only, and finally, nonuse. For some adults, transitioning from smoked tobacco products to electronic delivery systems has been a step toward less overall harm from substance use, with a small minority of that population going on to achieve abstinence from all nicotine products.3 For youth and teens, the story has been the opposite. With the rapid rise of e-cigarettes, adolescents overwhelmingly have been moving in the wrong direction at each potential step along this continuum.4 Less than 8% of teens who use e-cigarettes indicated that smoking cessation is a factor in their use.5 An estimated 1.3 million U.S. teens now are dependent or at high risk for dependence upon nicotine because of e-cigarette use. Furthermore, these teens are at a fourfold higher risk of progression to cigarette use, compared with their peers.6
One product in particular gives us information as to why this trend has accelerated so rapidly. Juul, now the sales leader among electronic nicotine delivery systems, rose from approximately 25% to a dominant 75% of market share in just over 1 fiscal year after a social media campaign targeted toward youth and young adults. The device is shaped like an elongated flash drive, is marketed as “sleek,” “looking cool,” and being “super easy” to use. This product touts its use of nicotine salts that can deliver higher concentrations of nicotine more rapidly to mimic the experience of smoking a cigarette as closely as possible. The fruity flavors in Juul “pods” and many other devices also appeal to teens. Many youth are left misinformed, thinking they are using a relatively harmless alternative to cigarettes.
E-cigarette use in youth carries many risks. Among the physical risks is exposure to harmful chemicals (even if less numerous than smoked tobacco products) such as diacetyl (a known cause of bronchiolitis obliterans, or “popcorn lung”), formaldehyde, acrolein, benzene, and metals such as nickel, tin and lead.7 “Safer than cigarettes” is a low bar indeed. Cognitive and emotional risks of early nicotine exposure include poor focus and attention, permanent lowering of impulse control, and a higher risk of mood and anxiety disorders.
Furthermore, nicotine is a gateway drug, with a clearly understood molecular basis for how it can potentiate the effects of later used substances, especially stimulants such as cocaine.8 The gateway and priming effect is compounded for youth because of ongoing brain development and plasticity during teen years. E-cigarette use also is associated with other risk behaviors including a manyfold higher likelihood of binge drinking, having multiple sexual partners in a short period of time, and using other substances such as cannabis, cocaine, methamphetamine, and heroin or nonprescribed opioids.9 An electronic system for vaporization also presents a risk for use of other substances. In just 1 year from 2017 to 2018, marijuana “vaping” increased by more than 50% among all ages surveyed.10
Pediatric health care providers are essential educators for both teens and parents regarding the risks of e-cigarette use. Many youth don’t know what they’re using; 66% of youth reported that the vapors they were inhaling contained only flavoring. Only 13% reported they were inhaling nicotine.10 In stark contrast to these self-reports, all Juul “pods” contain nicotine. As has been a pattern with nationwide surveys of substance use for decades, adolescent use is inversely correlated with perception of risk; 70% of 8th-12th graders do not foresee great harm in regular e-cigarette use. In addition, adolescents use substances less often when they know their parents disapprove. Parents also must be taught about the risks of e-cigarette use and can be provided with resources and taught effective strategies if they have difficulty communicating their disapproval to their children.
Age-appropriate screening in primary care settings must include specific language regarding the use of electronic cigarettes, with questions about “vaping” and “juuling.” Discussions with teens may be more effective with emphasis on issues that resonate with youth such as the financial cost, loss of freedom when dependence develops, and the fact that their generation is once again being targeted by the tobacco industry. Referral for further treatment, including individual and group therapy as well as family-focused interventions, should be considered for teens who use daily, use other substances regularly, or could benefit from treatment for co-occurring mental health disorders.
Electronic cigarette use should not be recommended as a smoking cessation strategy for teens.11 Pediatric health care providers must advocate for regulation of these products, including increasing the legal age of purchase and banning flavoring in e-cigarettes products, Internet sales, and advertisements targeted to youth.
The rapid rise in e-cigarette use among teens is of great concern. As with all classes of substances, early initiation of nicotine drastically increases the risk of developing a substance use disorder and portends a prolonged course and greater accumulation of adverse consequences. There is an urgent need for education, prevention, and early identification of e-cigarette use to protect the current and future well-being of children and adolescents.
Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington. He said he had no relevant financial disclosures. Email Dr. Jackson at pdnews@mdedge.com.
References
1. MMWR Morb Mortal Wkly Rep. 2018;67:1276-7.
2. e-cigarettes.surgeongeneral.gov
3. N Engl J Med 2019;380:629-37.
4. Pediatrics. 2018 Dec; 142(6):e20180486.
5. MMWR Morb Mortal Wkly Rep 2018;67:196-200.
6. JAMA Pediatr. 2017 Aug 1;171(8):788-97.
7. “Public health consequences of e-cigarettes” (Washington, DC: National Academies Press, January 2018).
8. N Engl J Med 2014;371:932-43.
9. N Engl J Med 2019;380:689-90.
10. MMWR Morb Mortal Wkly Rep. 2016 Jan 8;64(52):1403-8.
11. Pediatrics. 2019 Feb;143(2). pii: e20183652.
After 2 decades of steady decline in adolescent and young adult use of tobacco products, e-cigarettes have dramatically altered the landscape of substance use in youth. E-cigarette use among teens has been on the rise for years but the recent exponential increase is unprecedented. From 2017 to 2018, adolescent e-cigarette use had the largest year-to-year increase (78%, from 12% to 21%) of any individual substance or class of substances at any time during the past 2 decades of nationwide monitoring.1 This has appropriately caught the nation’s attention. In 2016, Surgeon General Vivek H. Murthy, MD, commissioned an extensive report about electronic cigarettes, and in 2018 Surgeon General Jerome Adams, MD, MPH, issued an advisory declaring e-cigarettes a public health crisis for adolescents.2
E-cigarettes have received attention as a possible boon to adult cigarette smokers seeking a less hazardous product. We can consider the use of tobacco products along a continuum from smoked tobacco, dual use (both smoked tobacco and electronic nicotine delivery), electronic nicotine delivery only, and finally, nonuse. For some adults, transitioning from smoked tobacco products to electronic delivery systems has been a step toward less overall harm from substance use, with a small minority of that population going on to achieve abstinence from all nicotine products.3 For youth and teens, the story has been the opposite. With the rapid rise of e-cigarettes, adolescents overwhelmingly have been moving in the wrong direction at each potential step along this continuum.4 Less than 8% of teens who use e-cigarettes indicated that smoking cessation is a factor in their use.5 An estimated 1.3 million U.S. teens now are dependent or at high risk for dependence upon nicotine because of e-cigarette use. Furthermore, these teens are at a fourfold higher risk of progression to cigarette use, compared with their peers.6
One product in particular gives us information as to why this trend has accelerated so rapidly. Juul, now the sales leader among electronic nicotine delivery systems, rose from approximately 25% to a dominant 75% of market share in just over 1 fiscal year after a social media campaign targeted toward youth and young adults. The device is shaped like an elongated flash drive, is marketed as “sleek,” “looking cool,” and being “super easy” to use. This product touts its use of nicotine salts that can deliver higher concentrations of nicotine more rapidly to mimic the experience of smoking a cigarette as closely as possible. The fruity flavors in Juul “pods” and many other devices also appeal to teens. Many youth are left misinformed, thinking they are using a relatively harmless alternative to cigarettes.
E-cigarette use in youth carries many risks. Among the physical risks is exposure to harmful chemicals (even if less numerous than smoked tobacco products) such as diacetyl (a known cause of bronchiolitis obliterans, or “popcorn lung”), formaldehyde, acrolein, benzene, and metals such as nickel, tin and lead.7 “Safer than cigarettes” is a low bar indeed. Cognitive and emotional risks of early nicotine exposure include poor focus and attention, permanent lowering of impulse control, and a higher risk of mood and anxiety disorders.
Furthermore, nicotine is a gateway drug, with a clearly understood molecular basis for how it can potentiate the effects of later used substances, especially stimulants such as cocaine.8 The gateway and priming effect is compounded for youth because of ongoing brain development and plasticity during teen years. E-cigarette use also is associated with other risk behaviors including a manyfold higher likelihood of binge drinking, having multiple sexual partners in a short period of time, and using other substances such as cannabis, cocaine, methamphetamine, and heroin or nonprescribed opioids.9 An electronic system for vaporization also presents a risk for use of other substances. In just 1 year from 2017 to 2018, marijuana “vaping” increased by more than 50% among all ages surveyed.10
Pediatric health care providers are essential educators for both teens and parents regarding the risks of e-cigarette use. Many youth don’t know what they’re using; 66% of youth reported that the vapors they were inhaling contained only flavoring. Only 13% reported they were inhaling nicotine.10 In stark contrast to these self-reports, all Juul “pods” contain nicotine. As has been a pattern with nationwide surveys of substance use for decades, adolescent use is inversely correlated with perception of risk; 70% of 8th-12th graders do not foresee great harm in regular e-cigarette use. In addition, adolescents use substances less often when they know their parents disapprove. Parents also must be taught about the risks of e-cigarette use and can be provided with resources and taught effective strategies if they have difficulty communicating their disapproval to their children.
Age-appropriate screening in primary care settings must include specific language regarding the use of electronic cigarettes, with questions about “vaping” and “juuling.” Discussions with teens may be more effective with emphasis on issues that resonate with youth such as the financial cost, loss of freedom when dependence develops, and the fact that their generation is once again being targeted by the tobacco industry. Referral for further treatment, including individual and group therapy as well as family-focused interventions, should be considered for teens who use daily, use other substances regularly, or could benefit from treatment for co-occurring mental health disorders.
Electronic cigarette use should not be recommended as a smoking cessation strategy for teens.11 Pediatric health care providers must advocate for regulation of these products, including increasing the legal age of purchase and banning flavoring in e-cigarettes products, Internet sales, and advertisements targeted to youth.
The rapid rise in e-cigarette use among teens is of great concern. As with all classes of substances, early initiation of nicotine drastically increases the risk of developing a substance use disorder and portends a prolonged course and greater accumulation of adverse consequences. There is an urgent need for education, prevention, and early identification of e-cigarette use to protect the current and future well-being of children and adolescents.
Dr. Jackson is assistant professor of psychiatry at the University of Vermont, Burlington. He said he had no relevant financial disclosures. Email Dr. Jackson at pdnews@mdedge.com.
References
1. MMWR Morb Mortal Wkly Rep. 2018;67:1276-7.
2. e-cigarettes.surgeongeneral.gov
3. N Engl J Med 2019;380:629-37.
4. Pediatrics. 2018 Dec; 142(6):e20180486.
5. MMWR Morb Mortal Wkly Rep 2018;67:196-200.
6. JAMA Pediatr. 2017 Aug 1;171(8):788-97.
7. “Public health consequences of e-cigarettes” (Washington, DC: National Academies Press, January 2018).
8. N Engl J Med 2014;371:932-43.
9. N Engl J Med 2019;380:689-90.
10. MMWR Morb Mortal Wkly Rep. 2016 Jan 8;64(52):1403-8.
11. Pediatrics. 2019 Feb;143(2). pii: e20183652.
FDA approves generic naloxone spray for opioid overdose treatment
The Food and Drug Administration on April 19 approved the first generic naloxone hydrochloride nasal spray (Narcan) as treatment for stopping or reversing an opioid overdose.
“In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible,” said Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, in a press release. “In addition to this approval of the first generic naloxone nasal spray, moving forward, we will prioritize our review of generic drug applications for naloxone.”
The agency said the naloxone nasal spray does not need assembly and can be used by anyone, regardless of medical training. If the spray is administered quickly after the overdose begins, the effect of the opioid will be countered, often within minutes. However, patients should still seek immediate medical attention.
The FDA cautioned that, when used on a patient with an opioid dependence, naloxone can cause severe opioid withdrawal, characterized by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.
Find the full press release on the FDA website.
lfranki@mdedge.com
The Food and Drug Administration on April 19 approved the first generic naloxone hydrochloride nasal spray (Narcan) as treatment for stopping or reversing an opioid overdose.
“In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible,” said Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, in a press release. “In addition to this approval of the first generic naloxone nasal spray, moving forward, we will prioritize our review of generic drug applications for naloxone.”
The agency said the naloxone nasal spray does not need assembly and can be used by anyone, regardless of medical training. If the spray is administered quickly after the overdose begins, the effect of the opioid will be countered, often within minutes. However, patients should still seek immediate medical attention.
The FDA cautioned that, when used on a patient with an opioid dependence, naloxone can cause severe opioid withdrawal, characterized by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.
Find the full press release on the FDA website.
lfranki@mdedge.com
The Food and Drug Administration on April 19 approved the first generic naloxone hydrochloride nasal spray (Narcan) as treatment for stopping or reversing an opioid overdose.
“In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible,” said Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, in a press release. “In addition to this approval of the first generic naloxone nasal spray, moving forward, we will prioritize our review of generic drug applications for naloxone.”
The agency said the naloxone nasal spray does not need assembly and can be used by anyone, regardless of medical training. If the spray is administered quickly after the overdose begins, the effect of the opioid will be countered, often within minutes. However, patients should still seek immediate medical attention.
The FDA cautioned that, when used on a patient with an opioid dependence, naloxone can cause severe opioid withdrawal, characterized by symptoms such as body aches, diarrhea, tachycardia, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.
Find the full press release on the FDA website.
lfranki@mdedge.com
FDA to expand opioid labeling with instructions on proper tapering
The Food and Drug Administration is making changes to opioid analgesic labeling to give better information to clinicians on how to properly taper patients dependent on opioid use, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.
, such as withdrawal symptoms, uncontrolled pain, and suicide. Both the FDA and the Centers for Disease Control and Prevention offer guidelines on how to properly taper opioids, Dr. Throckmorton said, but more needs to be done to ensure that patients are being provided with the correct advice and care.
The changes to the labels will include expanded information to health care clinicians and are intended to be used when both the clinician and patient have agreed to reduce the opioid dosage. When this is discussed, factors that should be considered include the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.
Other actions the FDA is pursuing to combat opioid use disorder include working with the National Academies of Sciences, Engineering, and Medicine on guidelines for the proper opioid analgesic prescribing for acute pain resulting from specific conditions or procedures, and advancing policies that make immediate-release opioid formulations available in fixed-quantity packaging for 1 or 2 days.
“The FDA remains committed to addressing the opioid crisis on all fronts, with a significant focus on decreasing unnecessary exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those involved in the illegal importation and sale of opioids,” Dr. Throckmorton said.
Find the full statement by Dr. Throckmorton on the FDA website.
The Food and Drug Administration is making changes to opioid analgesic labeling to give better information to clinicians on how to properly taper patients dependent on opioid use, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.
, such as withdrawal symptoms, uncontrolled pain, and suicide. Both the FDA and the Centers for Disease Control and Prevention offer guidelines on how to properly taper opioids, Dr. Throckmorton said, but more needs to be done to ensure that patients are being provided with the correct advice and care.
The changes to the labels will include expanded information to health care clinicians and are intended to be used when both the clinician and patient have agreed to reduce the opioid dosage. When this is discussed, factors that should be considered include the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.
Other actions the FDA is pursuing to combat opioid use disorder include working with the National Academies of Sciences, Engineering, and Medicine on guidelines for the proper opioid analgesic prescribing for acute pain resulting from specific conditions or procedures, and advancing policies that make immediate-release opioid formulations available in fixed-quantity packaging for 1 or 2 days.
“The FDA remains committed to addressing the opioid crisis on all fronts, with a significant focus on decreasing unnecessary exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those involved in the illegal importation and sale of opioids,” Dr. Throckmorton said.
Find the full statement by Dr. Throckmorton on the FDA website.
The Food and Drug Administration is making changes to opioid analgesic labeling to give better information to clinicians on how to properly taper patients dependent on opioid use, according to Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research.
, such as withdrawal symptoms, uncontrolled pain, and suicide. Both the FDA and the Centers for Disease Control and Prevention offer guidelines on how to properly taper opioids, Dr. Throckmorton said, but more needs to be done to ensure that patients are being provided with the correct advice and care.
The changes to the labels will include expanded information to health care clinicians and are intended to be used when both the clinician and patient have agreed to reduce the opioid dosage. When this is discussed, factors that should be considered include the dose of the drug, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.
Other actions the FDA is pursuing to combat opioid use disorder include working with the National Academies of Sciences, Engineering, and Medicine on guidelines for the proper opioid analgesic prescribing for acute pain resulting from specific conditions or procedures, and advancing policies that make immediate-release opioid formulations available in fixed-quantity packaging for 1 or 2 days.
“The FDA remains committed to addressing the opioid crisis on all fronts, with a significant focus on decreasing unnecessary exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies and opioids more resistant to abuse and misuse; and taking action against those involved in the illegal importation and sale of opioids,” Dr. Throckmorton said.
Find the full statement by Dr. Throckmorton on the FDA website.
NIH’s HEAL initiative seeks coordinated effort to tackle pain, addiction
MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.
The , said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.
In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.
The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.
First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”
Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”
The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.
The initiative also aims to promote discovery of new biologic targets for safe and effective pain treatment. New understanding of the physiology of pain has led to a multitude of candidate targets, said Dr. Koroshetz: “The good news is that there are so many potential targets. When I started in neurology in the ‘90s, I wouldn’t have said there were many, but now I’d say the list is long.”
Support for this work will require the development of human cell and tissue models, such as induced pluripotent stem cells, 3D printed organoids, and tissue chips. Several HEAL-funded grant mechanisms also seek research-industry collaboration to move investigational drugs for new targets through the pipeline quickly. The agency is hoping to see grantees apply new technologies, such as artificial intelligence, which can help identify new chemical structures and pinpoint new therapeutic targets for drug repurposing.
In addition to rapid drug discovery and accelerated clinical trials, Dr. Koroshetz said that HEAL leaders are hoping to see cross-pollination from two other NIH initiatives to boost pain-targeted medical device development. Both the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiatives have already shown promise in identifying targets for effective, noninvasive pain relief devices, he said. Technologies being developed from these programs are “truly amazing,” he added.
A new focus on data and asset sharing among industry, academia, and NIH will “improve the quality, consistency, and efficiency of early-phase pain clinical trials,” Dr. Koroshetz continued. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will coordinate data and biosample hosting.
Through a competitive submission process, EPPIC-net will review dossiers from institutions or consortia that can serve as assets around which clinical trials can be designed and executed. These early-phase trials will focus on well-defined pain conditions with unmet need, such as chronic regional pain syndrome and tic douloureux, he said.
“We want to find patients who have well-defined conditions. We know the phenotypes, we know the natural history. We’re looking for clinical sites to work on these projects as part of one large team to bring new therapies to patients,” noted Dr. Koroshetz.
Further along the spectrum of research, comparative effectiveness research networks will provide a reality check to compare both pharmacologic and nonpharmacologic interventions all along the spectrum from acute to chronic pain. Here, data elements and storage will also be coordinated through EPPIC-Net.
Implementation science research will fine-tune the practicalities of bringing research to practice as the final piece of the puzzle, said Dr. Koroshetz.
Under NIH director Francis Collins, MD, PhD, Dr. Koroshetz is co-leading the HEAL initiative, along with Nora Volkow, MD, director of the National Institute on Drug Abuse. They wrote about the initiative in JAMA last year (JAMA. 2018 Jul 10;320[2]:129-30).
Dr. Koroshetz reported no conflicts of interest.
MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.
The , said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.
In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.
The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.
First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”
Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”
The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.
The initiative also aims to promote discovery of new biologic targets for safe and effective pain treatment. New understanding of the physiology of pain has led to a multitude of candidate targets, said Dr. Koroshetz: “The good news is that there are so many potential targets. When I started in neurology in the ‘90s, I wouldn’t have said there were many, but now I’d say the list is long.”
Support for this work will require the development of human cell and tissue models, such as induced pluripotent stem cells, 3D printed organoids, and tissue chips. Several HEAL-funded grant mechanisms also seek research-industry collaboration to move investigational drugs for new targets through the pipeline quickly. The agency is hoping to see grantees apply new technologies, such as artificial intelligence, which can help identify new chemical structures and pinpoint new therapeutic targets for drug repurposing.
In addition to rapid drug discovery and accelerated clinical trials, Dr. Koroshetz said that HEAL leaders are hoping to see cross-pollination from two other NIH initiatives to boost pain-targeted medical device development. Both the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiatives have already shown promise in identifying targets for effective, noninvasive pain relief devices, he said. Technologies being developed from these programs are “truly amazing,” he added.
A new focus on data and asset sharing among industry, academia, and NIH will “improve the quality, consistency, and efficiency of early-phase pain clinical trials,” Dr. Koroshetz continued. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will coordinate data and biosample hosting.
Through a competitive submission process, EPPIC-net will review dossiers from institutions or consortia that can serve as assets around which clinical trials can be designed and executed. These early-phase trials will focus on well-defined pain conditions with unmet need, such as chronic regional pain syndrome and tic douloureux, he said.
“We want to find patients who have well-defined conditions. We know the phenotypes, we know the natural history. We’re looking for clinical sites to work on these projects as part of one large team to bring new therapies to patients,” noted Dr. Koroshetz.
Further along the spectrum of research, comparative effectiveness research networks will provide a reality check to compare both pharmacologic and nonpharmacologic interventions all along the spectrum from acute to chronic pain. Here, data elements and storage will also be coordinated through EPPIC-Net.
Implementation science research will fine-tune the practicalities of bringing research to practice as the final piece of the puzzle, said Dr. Koroshetz.
Under NIH director Francis Collins, MD, PhD, Dr. Koroshetz is co-leading the HEAL initiative, along with Nora Volkow, MD, director of the National Institute on Drug Abuse. They wrote about the initiative in JAMA last year (JAMA. 2018 Jul 10;320[2]:129-30).
Dr. Koroshetz reported no conflicts of interest.
MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.
The , said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.
In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.
The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.
First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”
Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”
The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.
The initiative also aims to promote discovery of new biologic targets for safe and effective pain treatment. New understanding of the physiology of pain has led to a multitude of candidate targets, said Dr. Koroshetz: “The good news is that there are so many potential targets. When I started in neurology in the ‘90s, I wouldn’t have said there were many, but now I’d say the list is long.”
Support for this work will require the development of human cell and tissue models, such as induced pluripotent stem cells, 3D printed organoids, and tissue chips. Several HEAL-funded grant mechanisms also seek research-industry collaboration to move investigational drugs for new targets through the pipeline quickly. The agency is hoping to see grantees apply new technologies, such as artificial intelligence, which can help identify new chemical structures and pinpoint new therapeutic targets for drug repurposing.
In addition to rapid drug discovery and accelerated clinical trials, Dr. Koroshetz said that HEAL leaders are hoping to see cross-pollination from two other NIH initiatives to boost pain-targeted medical device development. Both the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) and the Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiatives have already shown promise in identifying targets for effective, noninvasive pain relief devices, he said. Technologies being developed from these programs are “truly amazing,” he added.
A new focus on data and asset sharing among industry, academia, and NIH will “improve the quality, consistency, and efficiency of early-phase pain clinical trials,” Dr. Koroshetz continued. The Early Phase Pain Investigation Clinical Network (EPPIC-Net) will coordinate data and biosample hosting.
Through a competitive submission process, EPPIC-net will review dossiers from institutions or consortia that can serve as assets around which clinical trials can be designed and executed. These early-phase trials will focus on well-defined pain conditions with unmet need, such as chronic regional pain syndrome and tic douloureux, he said.
“We want to find patients who have well-defined conditions. We know the phenotypes, we know the natural history. We’re looking for clinical sites to work on these projects as part of one large team to bring new therapies to patients,” noted Dr. Koroshetz.
Further along the spectrum of research, comparative effectiveness research networks will provide a reality check to compare both pharmacologic and nonpharmacologic interventions all along the spectrum from acute to chronic pain. Here, data elements and storage will also be coordinated through EPPIC-Net.
Implementation science research will fine-tune the practicalities of bringing research to practice as the final piece of the puzzle, said Dr. Koroshetz.
Under NIH director Francis Collins, MD, PhD, Dr. Koroshetz is co-leading the HEAL initiative, along with Nora Volkow, MD, director of the National Institute on Drug Abuse. They wrote about the initiative in JAMA last year (JAMA. 2018 Jul 10;320[2]:129-30).
Dr. Koroshetz reported no conflicts of interest.
REPORTING FROM APS 2019
Trial Opens to Study New Drug for Opioid Cravings
Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.
The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.
At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.
The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.
Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.
The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.
At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.
The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.
Habitual use of opioids “rewires” the brain’s reward system. In the study, researchers will be testing ANS-6637 (Amygdala Neurosciences), a drug that may inhibit the dopamine surge of opioid use, without affecting the levels of dopamine needed for normal brain function.
The phase 1 trial will enroll up to 50 healthy adults aged 18 to 65 years. On the first day of the 10-day study, they will receive a single dose of midazolam, chosen to act as a template for liver metabolism. After a drug-free day 2, on days 3 through 7 they will receive 600 mg/d of ANS-6637. On day 8, the participants will be given the 2 drugs together to determine how the investigational drug affects midazolam levels, which also will help the researchers understand how ANS-6637 is processed in the body. The volunteers will return for a final outpatient visit after 1 week.
At present, few pharmacologic interventions target opioid-related cravings, says researcher Henry Masur, MD, chief of the Clinical Center’s Critical Care Medicine Department. If proven effective, the researchers say, ANS-6637 could be part of a comprehensive package of services, including harm reduction, opioid agonist therapy, and behavioral interventions.
The study is funded through NIH’s Helping to End Addiction Long-Term (HEAL) Initiative, an “aggressive, trans-agency effort to speed scientific solutions” to the opioid crisis.