It is vital that physicians-particularly psychiatrists who are on the frontlines with patients who struggle with cannabis use-are able to identify and characterize cannabis use disorders; provide education; and offer effective, evidence-based treatments. This article provides a brief overview of each of these topics by walking through clinical decision-making with a case vignette that touches on common experiences in treating a patient with cannabis use disorder.

A separate and important issue is screening for emerging drugs of abuse, including synthetic “marijuana” products such as K2 and spice. Although these products are chemically distinct from the psychoactive compounds in the traditional cannabis plant, some cannabis users have tried synthetic “marijuana” products because of their gross physical similarity to cannabis plant matter.

Mr. M is a 43-year-old legal clerk who has been working in the same office for 20 years. He presents as a referral from his primary care physician to your outpatient psychiatry office for an initial evaluation regarding “managing some mid-life issues.” He states that while he likes his job, it is the only job he has had since graduating college and he finds the work boring, noting that most of his co-workers have gone on to law school or more senior positions in the firm. When asked what factors have prevented him from seeking different career opportunities, he states that he would “fail a drug test.” Upon further inquiry, Mr. M says he has been smoking 2 or 3 “joints” or taking a few hits off of his “vaping pen” of cannabis daily for many years, for which he spends approximately $70 to $100 a week.

He first used cannabis in college and initially only smoked “a couple hits” in social settings. Over time, he has needed more cannabis to “take the edge off” and has strong cravings to use daily. He reports liking how cannabis decreases his anxiety and helps him fall asleep, although he thinks the cannabis sometimes makes him “paranoid,” which results in his avoidance of family and friends.

More recently, he identifies conflict and regular arguments with his wife over his cannabis use-she feels it prevents him from being present with his family and is a financial burden. He admits missing an important awards ceremony for her work and sporting events for his children, for which he had to “come up with excuses,” but the truth is that he ended up smoking more than he had intended and lost track of the time.

Mr. M reports multiple previous unsuccessful attempts to reduce his use and 2 days when he stopped completely, which resulted in “terrible dreams,” poor sleep, sweating, no appetite, anxiety, irritability, and strong cravings for cannabis. Resumption of his cannabis use relieved these symptoms. He denies tobacco or other drug use, including use of synthetic marijuana products such as K2 or spice, and reports having a glass of wine or champagne once or twice a year for special occasions.

In the transition from DSM IV-TR to DSM-5, cannabis use disorders, along with all substance use disorders, have been redefined in line with characterizing a spectrum of pathology and impairment. The criteria to qualify for a cannabis use disorder remain the same except for the following:

 The criterion for recurrent legal problems has been removed.

 A new criterion for craving or a strong desire or urge to use cannabis has been added, and the terms abuse and dependence were eliminated.

To qualify as having a cannabis use disorder, a threshold of 2 criteria must be met. Severity of the disorder is characterized as “mild” if 2 or 3 criteria are met, “moderate” if 4 or 5 criteria are met, and “severe” if 6 or more criteria are met. Mr. M demonstrates 3 symptoms of impaired control: using longer than intended, unsuccessful efforts to cut back, and craving; 3 symptoms of social impairment: failure to fulfill home obligations, persistent problems with his wife, and reduced pursuit of occupational opportunities; 1 symptom of risky use: continued use despite paranoia; and 2 symptoms of pharmacological properties: tolerance and withdrawal. As such, he meets 9 criteria, which qualify him for a diagnosis of severe cannabis use disorder.

You summarize Mr. M’s 9 symptoms and counsel him about severe cannabis use disorder. He becomes upset and states that he was not aware one could develop an “addiction” to cannabis. He expresses an interest in treatment and asks what options are available.

Psychotherapeutic treatments, including motivational enhancement treatment (MET), cognitive behavioral therapy (CBT), and contingency management (CM), have demonstrated effectiveness in reducing frequency and quantity of cannabis use, but abstinence rates remain modest and decline after treatment. Generally, MET is effective at engaging individuals who are ambivalent about treatment; CM can lead to longer periods of abstinence during treatment by incentivizing abstinence; and CBT can work to enhance abstinence following treatment (preventing relapse). Longer duration of psychotherapy is associated with better outcomes. However, access to evidence-based psychotherapy is frequently limited, and poor adherence to evidence-based psychotherapy is common.

In conjunction with psychotherapy, medication strategies should be considered. Because there are no FDA-approved pharmacological agents for cannabis use disorder, patients should understand during the informed consent process that all pharmacotherapies used to treat this disorder are off-label. A number of clinical trials provide evidence for the off-label use of medications in the treatment of cannabis use disorder. The current strategies for the off-label treatment of cannabis use disorder target withdrawal symptoms, aim to initiate abstinence and prevent relapse or reduce use depending on the patient’s goals, and treat psychiatric comorbidity and symptoms that may be driving cannabis use. Here we focus on the evidence supporting these key strategies.

Cannabis withdrawal is defined by DSM-5 as having 3 or more of the following signs and symptoms that develop after the cessation of prolonged cannabis use:

• At least one of the following physical symptoms that causes discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache

Withdrawal symptoms may be present within the first 24 hours. Overall, they peak within the first week and persist up to 1 month following the last use of cannabis. In the case of Mr. M, insomnia, poor appetite, and irritability as well as sweating are identified, which meet DSM-5 criteria for cannabis withdrawal during the 2 days he abstained from use. He also identifies strong craving and vivid dreams, which are additional withdrawal symptoms included on marijuana withdrawal checklists in research studies, although not included in DSM-5 criteria. These and other symptoms should be considered in clinical treatment.

Medication treatment studies for cannabis withdrawal have hypothesized that if withdrawal symptoms can be reduced or alleviated during cessation from regular cannabis use, people will be less likely to resume cannabis use and will have better treatment outcomes. Studies have shown that dronabinol and nabilone improved multiple withdrawal symptoms, including craving; and quetiapine, zolpidem, and mirtazapine help with withdrawal-induced sleep disturbances.

Combining dronabinol and lofexidine (an alpha-2 agonist) was superior to placebo in reducing craving, withdrawal, and self-administration during abstinence in a laboratory model. However, in a subsequent treatment trial, the combined medication treatment was not superior to placebo in reducing cannabis use or promoting abstinence.

Six double-blind placebo-controlled pharmacotherapy trials in adults with cannabis use disorder have looked at withdrawal as an outcome.

 Of these studies, only dronabinol, bupropion, and gabapentin reduced withdrawal symptoms.

 In addition to reducing withdrawal symptoms, nabiximols/Sativex (a combination tetrahydrocannabinol [THC] and cannabidiol nasal spray not available in the US) increased retention (while actively on the medication in an inpatient setting) but did not reduce outpatient cannabis use at follow-up.

All of the medications available for prescription in the US can be monitored reliably with urine drug screening to assess for illicit cannabis use except dronabinol, which will result in a positive screen for cannabis. When using urine drug screening, remember that for heavy cannabis users the qualitative urine drug screen can be positive for cannabis up to a month following cessation. When selecting a medication, take into account the cost of the medication, particularly since insurance will likely not cover THC agonists such as dronabinol for this indication, and possible misuse or diversion of scheduled substances (eg, dronabinol, nabilone). In addition, monitoring for reductions in substance use and withdrawal symptoms is key.

Abstinence initiation and relapse prevention

Other clinical trials have looked at medications to promote abstinence by reducing stress-induced relapse, craving (not as a component of withdrawal), and the reinforcing aspects of cannabis. Of these trials, the following results show potential promise with positive findings: gabapentin reduced quantitative THC urine levels and improved cognitive functioning (in addition to decreasing withdrawal), and buspirone led to more negative urine drug screens for cannabis (although the difference was not significant compared with placebo).

 However, in a follow-up larger study, no differences were seen compared with placebo and women had worse cannabis use outcomes on buspirone.

-acetylcysteine resulted in twice the odds of a negative urine drug screen in young adults and adolescents (although there was no difference between adolescent groups in self-report of cannabis use).

 reported that no differences were seen between 

-acetylcysteine and placebo (results of the trial are soon to be published). Topiramate resulted in significantly decreased grams of cannabis used but no difference in percent days used or proportion of positive urine drug screens.

 In a recent small clinical trial, reductions in cannabis use were seen with oxytocin in combination with MET.

 Studies with nabilone and long-term naltrexone administration reduced relapse and cannabis self-administration and subjective effects, respectively, which suggests promising avenues yet to be explored by clinical trials.

Other studies have looked at the effects of treating common comorbid psychiatric disorders in adults with cannabis use disorder, postulating that if the psychiatric disorder is treated, the individual may be more likely to abstain or reduce his or her cannabis use. For example, if a person is less depressed, he may better engage in CBT for relapse prevention.

Fluoxetine for depression and cannabis use disorder in adolescents decreased cannabis use and depression, although there was no difference compared with placebo.

 A trial of venlafaxine for adults with depression and cannabis use disorder demonstrated less abstinence with greater withdrawal-like symptoms compared with placebo.

 These findings suggest that this antidepressant might not be beneficial for treatment-seeking individuals with cannabis use disorder and may actually negatively affect outcomes.

After discussing and presenting the different psychotherapy and medication treatment options to Mr. M, you and he decide to start CBT to help with abstinence initiation. In addition, you prescribe 20 mg of dronabinol up to 2 times daily in combination with 50 mg of naltrexone daily, to help globally target Mr. M’s withdrawal symptoms and prevent relapse once abstinence is achieved. However, a few days later, Mr. M calls to say that his insurance will not cover the prescription for dronabinol and he cannot afford the high cost. Given his main concerns of cannabis withdrawal symptoms, you select gabapentin up to 400 mg 3 times daily and continue weekly individual CBT.

Mr. M calls back several days later and reports that he has made some improvements in reducing the frequency of his cannabis use, which he attributes to the medication, but he thinks he needs additional assistance. After reviewing the treatment options again, he gives informed consent to start 1200 mg of 

-acetylcysteine twice daily. After 10 weeks of this medication, his urine screens are negative.

You continue to provide relapse prevention CBT. He reports to you that his anxiety and insomnia are almost resolved, and you suspect that withdrawal was the cause of these symptoms. He reports significant improvement in his relationship with his family and recently received a promotion at work for “going above and beyond” on a project he was given the lead.

Over the next 6 months, he has 2 relapses that in functional analysis with you are determined to be triggered by unsolicited contact from his former drug dealer. Together, you develop a plan to block any further contact from the drug dealer. After several months, both the gabapentin and N-acetylcysteine are tapered and discontinued. Mr. M continues to see you for biweekly therapy sessions with random drug screens every 4 to 6 weeks.

Based on the available evidence, gabapentin, THC agonists, naltrexone, and possibly 

-acetylcysteine show the greatest promise in the off-label treatment of cannabis use disorders. System considerations, such as medication cost, need to be factored into the decision-making as well as combination medication and psychotherapy approaches, which-as demonstrated in the case of Mr. M-may ultimately work best. Until further research elucidates the standard of medication practices for cannabis use disorder, the best off-label medication strategy should target any co-occurring disorders as well as any identified problematic symptoms related to cannabis use and cessation of use. When available, referral for evidence-based psychotherapy should be made.

This article was originally published on June 30, 2017 and has since been updated.

Dr. Brezing is a Fellow in Addiction Psychiatry at the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons in New York City; Dr. Levin is Kennedy-Leavy Professor of Clinical Psychiatry, Columbia University College of Physicians and Surgeons, Chief of the Division on Substance Abuse, and Director of the Addiction Psychiatry Fellowship Program at New York Presbyterian Hospital.

The authors report no conflicts of interest concerning the subject matter of this article.

 Bedi G, Cooper ZD, Haney M. Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers. 

 Haney M, Cooper ZD, Bedi G, et al. Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. 

 Cooper ZD, Foltin RW, Har CL, et al. A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers. 

 Herrmann ES, Cooper ZD, Bedi G, et al. Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users. 

 Haney M, Hart CL, Vosburg SK, et al. Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. 

 Levin FR, Mariani JJ, Pavlicova M, et al. Dronabinol and lofexidine for cannabis use disorder: a randomized, double-blind, placebo-controlled trial. 

 Sherman BJ, McRae-Clark AL. Treatment of cannabis use disorder: current science and future outlook. 

 Levin FR, Mariani JJ, Brooks DJ, et al. Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. 

 Penetar DM, Looby AR, Ryan ET, et al. Bupropion reduces some of the symptoms of marihuana withdrawal in chronic marihuana users: a pilot study. 

 Mason BJ, Crean R, Goodell V, et al. A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults. 

 Allsop DJ, Lintzeris N, Copeland J, et al. Cannabinoid replacement therapy (CRT): nabiximols (Sativex) as a novel treatment for cannabis withdrawal. 

 McRae AL, Brady KT, Carter RE. Buspirone for treatment of marijuana dependence: a pilot study. 

 McRae-Clark AL, Carter RE, Killeen TK, et al. A placebo-controlled trial of buspirone for the treatment of marijuana dependence. 

 Gray KM, Carpenter MJ, Baker NL, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. 

 Gray KM, Sonne SC, McClure EA, et al. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorders in adults. 

 Miranda R Jr, Treloar H, Blanchard A, et al. Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study. 

 Sherman BJ, Baker NL, McRae-Clark AL. Effect of oxytocin pretreatment on cannabis outcomes in a brief motivational intervention. 

 Haney M, Ramesh D, Glass A, et al. Naltrexone maintenance decreases cannabis self-administration and subjective effects in daily cannabis smokers. 

 Cornelius JR, Bukstein OG, Douaihy AB, et al. Double-blind fluoxetine trial in comorbid MDD-CUD youth and young adults. 

 Kelly MA, Pavlicova M, Glass A, et al. Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR? 

 Levin FR, Mariani J, Brooks DJ, et al. A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders. 

Articles

It is vital that psychiatrists are able to identify and characterize cannabis use disorders; provide education; and offer effective, evidence-based treatments. This article provides a brief overview of each of these topics.

Treatment for Cannabis Use Disorders: A Case Report

The presence of comorbid disorders is often the rule rather than the exception in individuals with ADHD. Of particular concern is problematic substance use; alcohol, cannabis, cocaine, and nicotine represent some of the most commonly abused substances. Elevated substance use significantly complicates a patient’s symptom presentation, making the accurate diagnosis, prognosis, and treatment of ADHD challenging even for the most skilled practitioners.

The link between ADHD and substance use disorders

Children with ADHD are at increased risk for alcohol use disorder as they get older, and they are more than twice as likely to develop nicotine dependence and marijuana or cocaine abuse or dependence (

). Approximately 15% of adolescents and young adults with ADHD have a comorbid substance use disorder (SUD), while 11% of individuals with an SUD also meet the criteria for ADHD.

 Findings indicate that the overlap between these disorders is not random, and several explanations have been posited for their link.

ADHD and SUD have been described as disorders of disinhibition, which suggests an underlying vulnerability that is shared by both disorders. Alternatively, features of ADHD, such as impulsivity, may increase the risk of initiating substance use. In fact, children with ADHD are significantly more likely to try a range of substances during their lifetime compared with their non- ADHD counterparts (see 

The mechanisms underlying the increased risk of SUD among those with a history or current diagnosis of ADHD are not well understood. Persistent ADHD, which might be a marker of increased vulnerability and/or of reduced access or responsiveness to intervention, is associated with much higher rates of SUD.

 The high co-occurrence between ADHD and SUD merits special consideration.

Assessment for ADHD requires the ability to distinguish between ADHD and other disorders that demonstrate significant symptomatic overlap. Among individuals who present with active substance abuse, it is critical to distinguish between a valid ADHD diagnosis and substance-induced impairments that can negatively affect attention, concentration, and impulsivity. Many psychoactive substances have acute effects that can mimic the symptoms of ADHD, such as chronic marijuana use, which has been associated with deficits in problem-solving, organization, and sustained attention that may persist even after 3 weeks of abstinence. Because of this, practitioners might want to prioritize the treatment of substance use and then re-evaluate patients for ADHD after a period of prolonged abstinence.

Unfortunately, this approach is sometimes not feasible, particularly for patients who present with significant and untreated ADHD symptoms that may impair the ability to engage in and benefit from SUD treatment. Thus, a comprehensive evaluation of ADHD symptoms during prior periods of abstinence may be the next best approach for assessing co-occurring SUD and ADHD, with a focus on whether the ADHD symptoms preceded the onset of substance use. While this is a reasonable recommendation, this approach is not without challenges, as it requires patients to recall the onset and severity of their initial symptoms. This may be especially challenging for patients with ADHD and substance abuse because both are associated with neurocognitive deficits.

Obtaining collateral information from parents and teachers, medical records, and psychological evaluations is recommended to elucidate the patient’s childhood functioning. Although it is not always feasible to access such corroborating information for adults with suspected ADHD, such data can be useful in determining whether ADHD symptoms were present in childhood and in differentiating primary from substance-induced ADHD symptoms.

Malingering, while uncommon, merits consideration in any diagnostic evaluation of co-occurring ADHD and SUD because stimulant medication may be sought for the treatment of ADHD. Methylphenidate and amphetamine salts have a high abuse potential and can produce a feeling of euphoria similar to illicit CNS stimulant drugs such as cocaine. Some individuals with SUDs may be motivated to feign a diagnosis of ADHD to gain access to stimulant medications.

Information regarding prototypical ADHD behavior is readily accessible via the Internet, which allows individuals who seek stimulants for non-medical purposes to be sufficiently “prepared” before a diagnostic evaluation. Unfortunately, neuropsychological evaluations, which are often used in conjunction with self-report to establish ADHD diagnoses, are also susceptible to feigned symptoms. Thus, incorporating ratings of patient functioning from other sources is advised, with particular attention to instances in which the client reports significantly more symptoms than other informants.

Many parents worry that stimulant medications will have iatrogenic effects and potentially increase a child’s susceptibility to subsequent drug use. Conversely, some caregivers, hoping for a rapid response to medication, may want to use stimulant medication as a first-line treatment-even for young children for whom pharmacological intervention should be considered only after appropriate behavioral interventions (eg, parent training). Parents clearly want to do what is best for their children, and psychiatrists and other clinicians should be prepared to provide evidence-based support for recommendations regarding treatment for ADHD in the context of potential risk of a later SUD.

There is little evidence for the sensitization hypothesis, in which the use of stimulant medication increases the risk of a later SUD. Findings from a meta-analysis indicate that the use of stimulant medications to treat childhood ADHD neither increases nor protects against the risk of later development of an SUD.

The American Academy of Child and Adolescent Psychiatry guidelines include psychoeducation regarding treatment options and the expected course of symptoms, adjunctive school support, and the use of FDA-approved medication if pharmacological intervention is selected. Treatment decisions should be made jointly with the patient and his or her family. The risk-to-benefit ratio of a particular stimulant and its adverse effects (eg, sleep disturbances, loss of appetite, growth stunting) should be discussed, and information provided about the flexibility that stimulant treatment allows for medication-free “holidays” on weekends and school breaks.

There is inconclusive evidence that stimulant medications are effective in reducing symptoms of ADHD and comorbid substance abuse in adults. While some studies have shown a reduction of ADHD and SUD symptoms following treatment with stimulant medications, others have documented improvements only in ADHD symptoms or no benefits at all.

 Unfortunately, the comorbidity of ADHD and SUD is associated with a poor prognosis for SUD treatment; therefore, prioritizing the treatment of ADHD merits consideration. Yet comorbid SUD is also associated with a poor prognosis for ADHD treatment, and it is often recommended that treatment of active substance abuse should precede the treatment of ADHD. Psychosocial interventions for SUD may need to be individualized to account for a patient’s ADHD symptoms, which may interfere with his or her ability to engage in treatment and increase the likelihood of treatment nonadherence.

Psychotherapy is always recommended for patients with comorbid ADHD and SUD. In addition, non-stimulants (eg, atomoxetine) or extended-release stimulants should be considered when treating co-occurring ADHD and SUD, as these medications are less subject to abuse and diversion and may be preferable for patients at risk for substance abuse. Although non-stimulants are less effective than stimulants in treating ADHD symptoms, they may represent an appropriate middle ground between no medication at all and stimulants.

Any psychoactive medication can be misused, so diligent documentation of all prescriptions must be maintained. Repetitive requests for an increase in dosage or early refills should be explored with the patient. For those with a history of substance abuse, medication decisions should ideally be reached through collaboration with the patient, family members, and spouses/partners, and it is critical to emphasize the importance of taking the medications as prescribed. For adolescents at high risk for diversion or misuse, parents can be encouraged to regulate their child’s medication use by storing all medications in locked cabinets.

ADHD is associated with increased risk of substance use initiation as well as abuse and dependence. There is no evidence that stimulant treatment for ADHD increases the subsequent risk of SUD; however, such medications are prone to misuse and diversion. In addition to thorough, multi-informant, and developmentally sensitive assessment, careful consideration of potential abuse of medication treatment for ADHD is warranted. Nonpharmacological or non-stimulant medications may be appropriate for treatment of ADHD for those at risk for SUD, or for those who have a current diagnosis of SUD. In addition, psychosocial intervention is recommended in conjunction with any medication treatment for individuals with comorbid ADHD and SUD.

Ms. GalÃ¡n is a graduate student in the joint clinical and developmental psychology PhD program at the University of Pittsburgh; Dr. Humphreys is Postdoctoral Fellow, Department of Psychology, Stanford University.

 Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. 

 Hechtman L, Swanson JM, Sibley MH, et al. Functional adult outcomes 16 years after childhood diagnosis of attention-deficit/hyperactivity disorder: MTA results. 

 Humphreys KL, Eng T, Lee SS. Stimulant medication and substance use outcomes: a meta-analysis. 

 Kalbag AS, Levin FR. Adult ADHD and substance abuse: diagnostic and treatment issues. 

 Riggs PD, Winhusen T, Davies RD, et al. Randomized controlled trial of osmotic-release methylphenidate with cognitive-behavioral therapy in adolescents with attention-deficit/hyperactivity disorder and substance use disorders. 

 Lee SS, Humphreys KL, Flory K, et al. Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review. 

Because comorbid substance abuse is the rule rather than the exception in individuals with ADHD, accurate diagnosis, prognosis, and management of ADHD is challenging even for the most skilled practitioners. 

ADHD and Substance Use: Current Evidence and Treatment Considerations

 During a routine return medication visit, your patient, a 45-year-old man with bipolar disorder, asks you about using an e-cigarette. You recall that he is a pack-a-day smoker, and when you last discussed his smoking about a year ago, he wanted to quit.

This clinical scenario is increasingly common for psychiatrists. Among people with mental illness, 15% have tried e-cigarettes compared with 7% of the general population, and use rates are on the rise.

 In a study comprising 956 cigarette smokers hospitalized for mental illness, trial use of e-cigarettes went from 0% in 2009 to 25% in 2013.

 In the general US population, among smokers, lifetime use of e-cigarettes increased from 10% in 2010 to 37% in 2013.

Given the disproportionate burden of tobacco health harms in psychiatric patients, e-cigarettes are being considered as a potential tool for harm reduction. This article summarizes recent data on e-cigarettes, provides recommendations and resources to learn more, and emphasizes the evidence for treating tobacco (traditional cigarettes) addiction in people with mental illness.

E-cigarettes (ie, vaporizers, vape pens, e-hookah) are battery-operated devices that generate an aerosol from an e-liquid for inhalation. Consisting of a metal tube resembling a traditional cigarette, a battery, an atomizer, and a replaceable cartridge, e-cigarettes usually contain liquid nicotine, propylene glycol (an irritant in antifreeze), glycerin, flavoring, and other chemicals. A user puffs on an e-cigarette, and the heating element aerates the cartridge solution. Many of these are intended to simulate a cigarette. Tank or open systems, discussed below, allow users to fill the device with any substance of choice.

Developed and commercialized in China in 2003, e-cigarettes entered the US market in 2006; however, tobacco companies such as Philip Morris have been researching precursors to e-cigarettes since 1990. Over the past decade, advertising and sales of e-cigarettes have increased exponentially every year, and the major tobacco retailers now dominate the market. While tobacco advertising has been banned from television and radio since 1970, e-cigarettes are promoted widely on these media channels, on the web, and in social media, with many ads reaching youth. In August 2016-10 years after entering the US market-e-cigarettes came under the regulatory authority of the FDA, but regulatory evaluations of the products are still in progress.

 Nicotine is a psychoactive drug that can be addictive. Nicotine delivery with e-cigarettes varies by device (greater with the tank systems than with the cigarette-like products) and by experience level of the user. As the technology improves, the speed and the amount of nicotine absorbed are likely to increase over time, along with addiction. Mislabeling has been found with nicotine present in products labeled as nicotine-free or at higher concentrations than labeled.

 Flavored options (eg, candy, alcohol, unicorn vomit) can appeal to youth, whose brains are vulnerable to early addiction exposure. E-cigarettes are widely available for purchase online, in convenience stores, and in neighborhood vape shops. Past-month e-cigarette use nearly tripled from 2013 to 2014 among high school students (4.5% to 13.4%), surpassing all other tobacco use.

 For the first time in decades, the percentage of US youth exposed to any nicotine product increased, from 2013 to 2014 and again from 2014 to 2015. Moreover, e-cigarettes may be a gateway to conventional smoking. Two studies of adolescents who were never-smokers at baseline found that e-cigarette use predicted greater risk of cigarette smoking at follow-up.

 Modifications to e-cigarettes (“mods”) and open tank systems allow users to vape other substances, most commonly cannabis oil. In an anonymous study of more than 7000 high school students, nearly 1 in 5 adolescents who use e-cigarettes reported using the device to vape cannabis oil.

. Nicotine in high doses, especially in children, can be dangerous and even fatal. Poison control calls for nicotine poisoning have increased from one call in September 2010 to 215 calls per month related to e-cigarette exposure in February 2014.

Combustible cigarettes kill two-thirds of long-term smokers.

 E-cigarettes do not involve combustion; therefore, if a smoker switches to e-cigarettes, carbon monoxide exposure and health harms will be reduced. Yet, the evidence regarding e-cigarettes as a cessation aid is limited; dual use with combustible cigarettes is common; and the safety of e-cigarettes has not been established.

Half of current smokers report regular use of e-cigarettes.

 Any use of cigarettes is harmful, and the concern is that individuals who use e-cigarettes will continue to smoke conventional cigarettes rather than quit. The strongest evidence in support of e-cigarettes for quitting smoking has come from observational studies in the UK. One study, a time-trend analysis, concluded that for every 1% increase in e-cigarette use, the success rate of quit attempts increased by 0.098%.

 In contrast, a second study in the UK found that daily use of e-cigarettes was associated with increases in quit attempts and reductions in number of cigarettes smoked, but not with smoking cessation.

Meta-analyses have been conducted to synthesize the findings in the literature. A systematic review of 20 controlled studies concluded that the odds of quitting cigarettes was 28% lower in those who used e-cigarettes than in those who did not use e-cigarettes.

 Observational designs are challenged by confounding variables related to who self-selects to use an e-cigarette. Only 2 randomized controlled trials have evaluated e-cigarettes as a method for quitting conventional cigarettes. The quality of evidence was judged to be low grade, and in both trials, e-cigarettes with nicotine were no different in efficacy for quitting smoking than placebo (nicotine-free) e-cigarettes.

 To date, research does not support the use of e-cigarettes for cessation.

The American Heart Association’s (AHA) policy statement on e-cigarettes does not recommend their use; however, if a patient has tried and failed evidence-based tobacco cessation methods or is unwilling to try them, the AHA recommends

• No dual use of traditional cigarettes with e-cigarettes

• That a quit date is also set for the e-cigarettes

Smokers with mental illness consume nearly half the cigarettes sold in the US and die on average 25 years earlier than the general population, largely from chronic diseases, most tobacco-related. Tobacco use also creates a significant economic burden on patients, increases isolation, and affects the metabolism of a number of psychiatric medications.

Despite the obvious need to treat tobacco addiction, there has been a historic reluctance to do so out of concerns that mental health functioning may worsen with cessation. In a 2007 AAMC (Association of American Medical Colleges) Survey of more than 3000 physicians, psychiatrists were the least likely to address tobacco addiction-although findings indicate that psychiatric outcomes improve with tobacco cessation.

 The tobacco industry also plays a role by promoting the self-medication hypothesis (ie, that cigarettes reduce psychiatric symptoms). However, cigarettes reduce withdrawal symptoms of nicotine rather than psychiatric symptoms. Symptoms of nicotine withdrawal can mimic psychiatric symptoms (depression, insomnia, irritability, anxiety, restlessness).

In contrast to the unknowns regarding e-cigarettes, there are evidence-based and well-established cessation treatments that are underutilized.

 There are 7 FDA-approved nicotine replacement therapies (NRTs) that significantly improve quit rates: 3 over-the-counter NRTs (patch, gum, lozenge); 2 prescription NRTs (spray, inhaler); and 2 oral pills (bupropion, varenicline). NRT reduces nicotine cravings and withdrawal without the reinforcing effects of smoked nicotine. It is important to educate the patient on the proper use of NRTs. For example, people use the gum like normal chewing gum, when in fact nicotine in the gum is best absorbed in the oral mucosa by parking the gum in the cheek.

Bupropion is well known in psychiatry and acts on dopamine, norepinephrine, and nicotinic-cholinergic receptors to decrease cravings and withdrawal symptoms. Varenicline is a partial agonist at the Î±4Î²2 neuronal nicotinic acetylcholine receptor; it relieves craving and withdrawal and reduces the reinforcing effects of nicotine by blocking dopaminergic stimulation. The best evidence is for varenicline and combination NRT (eg, a patch plus gum or lozenge). The choice of medication depends on history, patient input, cost, previous attempts, and severity of dependence/withdrawal and breakthrough symptoms.

 Cessation medications are most effective when combined with counseling. Integrating the Public Health Service guidelines of the 5 As-Ask, Advise, Assess, Assist, Arrange-into regular practice for treating smoking is an evidence-based approach. The AAR method is also effective and takes less than 5 minutes: Asking about smoking, Advising to quit, and Referring to a program.

The national toll-free quit line (1-800-QUIT-NOW) and the National Cancer Institute’s smokefree.gov website offer evidence-based resources. For patients who are not yet ready to quit smoking, empathy and a focus on the benefits of quitting (health, financial, social) are recommended to maintain rapport and raise motivation.

In the clinical scenario presented at the start, the psychiatrist had not inquired about tobacco use for a year. It is recommended that psychiatrists assess tobacco use at every visit. Since tobacco use can affect clinical presentation (withdrawal symptoms) and medication levels, asking about tobacco use is clinically indicated. Systems changes (eg, including tobacco use in a standard assessment, providing clinician prompts) can help integrate tobacco treatment within clinical practice. Furthermore, supporting a culture of health where facilities are smoke-free fosters the best outcomes for smoking cessation. Smoke breaks should not be promoted nor should clinicians engage in smoking with patients. Treating patients with empathy and encouraging the use of NRT can be extremely helpful.

The Sidebar highlights 3 evidence-based accessible clinician resources on e-cigarettes and tobacco cessation treatment. We encourage psychiatrists and other mental health care providers to continue to follow the growing fields of research and regulation on e-cigarettes and tobacco.

 Dr. Prochaska’s research is funded by the NCI (grant R01CA204356), the NHLBI (grant R01HL117736), and the TRDRP (grants 24RT-0035 and 25IR-0032).

Dr. Das is Clinical Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine; Dr. Prochaska is Associate Professor of Medicine at the Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA.

Dr. Prochaska has been a consultant for Pfizer, which makes smoking cessation medications, and has been an expert witness for plaintiffs’ counsel in court cases against the tobacco companies.

 Cummins SE, Zhu SH, Tedeschi GJ, et al. Use of e-cigarettes by individuals with mental health conditions. 

 Prochaska JJ, Grana RA. E-cigarette use among smokers with serious mental illness. 

 King BA, Alam S, Promoff G, et al. Awareness and ever-use of electronic cigarettes among U.S. adults, 2010-2011. 

 Goniewicz ML, Gupta R, Lee YH, et al. Nicotine levels in electronic cigarette refill solutions: a comparative analysis of products from the U.S., Korea, and Poland. 

 Leventhal AM, Strong DR, Kirkpatrick MG, et al. Association of electronic cigarette use with initiation of combustible tobacco product smoking in early adolescence. 

 Miech R, Patrick ME, O’Malley PM, Johnston LD. E-cigarette use as a predictor of cigarette smoking: results from a 1-year follow-up of a national sample of 12th grade students. 

 Morean ME, Kong G, Camenga DR, et al. High school students’ use of electronic cigarettes to vaporize cannabis. 

 Rigotti NA. e-Cigarette use and subsequent tobacco use by adolescents: new evidence about a potential risk of e-cigarettes. 

 Chatham-Stephens K, Law R, Taylor E, et al. Exposure calls to US poison centers involving electronic cigarettes and conventional cigarettes: September 2010 to December 2014. 

 Pirie K, Peto R, Reeves GK, et al. The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. 

 Population Assessment of Tobacco and Health (PATH) Study Public-Use Files. Inter-University Consortium for Political and Social Research (ICPSR). 2017. 

 Beard E, West R, Michie S, Brown J. Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends. 

 Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. 

 Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. 

 Hartmann-Boyce J, McRobbie H, Bullen C, et al. Electronic cigarettes for smoking cessation. 

 Bhatnagar A, Whitsel LP, Ribisl KM, et al. Electronic cigarettes: a policy statement from the American Heart Association. 

 American Association of Medical Colleges. Physician behavior and practice patterns related to smoking cessation, summary report. Washington, DC: Association of American Medical Colleges; 2007.

 Hall SM, Prochaska JJ. Treatment of smokers with co-occurring disorders: emphasis on integration in mental health and addiction treatment settings. 

This article summarizes data on e-cigarettes, provides recommendations and resources to learn more, and emphasizes the evidence for treating tobacco (traditional cigarettes) addiction in people with mental illness.

E-Cigarettes, Vaping, and Other Electronic Nicotine Products: Harm Reduction Pathways or New Avenues for Addiction?

Dual diagnosis is a term commonly employed in substance use disorder (SUD) treatment. What is less recognizable is the concept of disturbed sleep as a co-occurring disorder in need of management.

As is the case with affective and anxiety disorders, a growing body of evidence is emerging that SUDs share a complicated relationship with sleep that is bidirectional. Findings suggest that a history of baseline insomnia may be predictive of disordered substance use.

 It is also interesting that abstinent adolescents with a family history of substance dependence are more likely to experience difficulties sleeping-a fact that may illustrate psychosocial factors or the presence of a genetic association between sleep and SUDs.

Recent evaluations indicate that polymorphisms of clock genes elucidate this association. Clock genes encode for proteins that form part of an auto-regulatory feedback loop that cycles over a 24-hour period. Variations in certain Clock genes appear to influence sleep drive and circadian preferences; one such gene, 

, has been linked to insomnia severity in alcoholic patients.

 New frontiers in addiction research have also implicated neuropeptides such as orexin in the dual role of sleep and reward circuitry.

 The lateral hypothalamus contains many of the neurotransmitters and neural networks involved in alertness, concentration, mood, and regulation of the sleep-wake cycle; many of these networks extend to the reward center that is manipulated by substances of abuse.

It may not come as a surprise that while 10% to 15% of the general population experiences insomnia, reports for subjects with active alcohol use disorders and comorbid sleep disturbance range from 30% to 80%.

 Sleep disruption complicates acute withdrawal as well-upwards of 50% of patients report sleep disturbance during acute withdrawal from alcohol.

 Sleep disturbance in early recovery also represents a formidable obstacle for patients with alcohol use disorder; a subset of patients experiences first-episode insomnia with sobriety. While recovery of restorative sleep is possible with sobriety, it has been suggested that disordered sleep may persist for years in people with a history of chronic alcohol use and increases vulnerability to relapse.

Users who perceive their substance of abuse as soporific may be at increased risk for sleep disturbances and relapse. This perception may be based on early experiences of the substance, when moderate use of alcohol may indeed have conferred subjective sleep benefits such as reduced onset to sleep. A recent analysis that looked at the link between sleep disturbance and alcohol relapse in a residential treatment facility suggests that patients who reported use of alcohol as a sleep aid were more than 3-fold more likely to relapse at 12 months (odds ratio [OR] = 3.26; 95% confidence interval [CI] = 1.33-7.95; 

 Study findings also indicate a significant association between patients’ use of hypnotics at admission and alcohol relapse at 12 months (OR = 4.03; 95% CI = 1.63-9.97; 

 queried alcohol-dependent subjects in an inpatient setting and found a subjective sense of sleep latency to be a predictor of relapse. Other studies also support this association between subjective perceptions of increased awakenings and difficulty falling asleep and relapse risk in early alcohol recovery.

Objective evidence of sleep disturbance exists in alcohol use disorders as well. Polysomnography studies suggest that chronic alcohol use increases sleep latency (defined as the amount of time from lights out to sleep onset) throughout the vacillating stages of use, including active drinking periods, acute withdrawal, post-withdrawal, and early and late recovery. In their review, Angarita and colleagues

conclude that total sleep time (the amount of sleep in one complete episode of sleeping) is uniformly adversely affected by alcohol in all of its use stages from active drinking to later recovery.

Persons with alcohol use disorders also appear to suffer from slow wave sleep deficits (stage N3), which may correspond to difficulty with learning, memory, and cognitive performance. Use of alcohol results in suppression of REM sleep. Following 2 to 3 weeks of abstinence, there appears to be a REM rebound, which some patients describe as an increase in vivid dreams.

Polysomnography for the purpose of diagnosing sleep disorders is not practical for many patients and is unnecessary for a diagnosis of insomnia. A clinical diagnosis of insomnia is obtained by meeting the following criteria outlined by the American Academy of Sleep Medicine

: dissatisfaction with sleep quantity or quality, with one or more of the following symptoms: difficulty initiating sleep, difficulty maintaining sleep, waking up earlier than desired, resistance to going to bed on an appropriate schedule, or difficulty sleeping without parent or caregiver. In addition, the sleep disturbance may cause impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning. These criteria are detailed in 

Other sleep disorders such as obstructive sleep apnea may co-occur with alcohol dependence and can be differentiated from insomnia by screening for factors such as obesity, hypertension, snoring, daytime somnolence, and retrognathia. Periodic limb movement disorder may disturb sleep and may be more prevalent in chronic alcohol users; it is diagnosed by polysomnography.

Circadian rhythm abnormalities have also been linked with alcohol use disorders. Research has implicated melatonin deficiency and delay as a potential culprit for sleep-onset difficulty. Recovering alcohol-dependent men and women demonstrate lower melatonin levels in early evening and delayed melatonin peaks compared with controls. Although melatonin assays are commercially available, the practical applicability of such investigations in sleep disturbances in alcohol recovery is limited. Insomnia remains the most common sleep disturbance encountered in alcoholics: a good history is the cornerstone of accurate diagnosis.

Treatment of sleep disorders in previously substance-abusing patients is complicated. Clinicians remain appropriately circumspect about prescribing medications with potential abuse liability, and sleep disturbance may often be perceived by clinicians and patients alike as a natural consequence of substance withdrawal that should remit in time. Whether sleep disturbance is a residue of substance use or substance use is a consequence of historically complicated sleep patterns is up for debate. What has been shown, however, is that a failure to treat the comorbid sleep disorder may predict relapse.

Nonpharmacological interventions such as cognitive behavioral therapy for insomnia (CBT-I) have been effective at minimizing sleep disturbance in recovery populations and may have positive effects on relapse. CBT-I consists of behavioral and cognitive strategies aimed at improving sleep quality and daytime functioning (

). A benefit of this intervention is its applicability to multiple SUDs and its minimal adverse effects. Limitations may include expense, time commitment, and availability of local qualified clinicians.

Light therapy may be helpful in patients recovering from alcohol use disorders who have circadian rhythm dysfunction. Benefits include ease of use and absence of medication interactions. Adverse effects may include activation with possible mania induction in susceptible patients.

Supplementation may also be considered in the treatment schema for patients with an SUD and co-occurring sleep disruption. It is reasonable to introduce melatonin as a potential intervention for patients with alcohol use disorders who have melatonin deficiencies. Studies that evaluated magnesium supplementation found improved subjective sleep scores and improved sleep latency on polysomnography, with total sleep time gains noted in groups with decreased periodic limb movement symptoms.

 lists available pharmacotherapeutic agents for alcohol use disorder comorbid with sleep disorders. A 2014 review by Conroy and Arnedt

 noted that gabapentin appeared to be safe and effective for treating insomnia in abstinent alcohol-dependent patients. This was corroborated by a study by Mason and colleagues,

 which showed significant improvement in sleep quality for alcohol-dependent patients treated with 1200 mg of gabapentin daily. Benefits of gabapentin include nonhepatic metabolism and inability to lower the seizure threshold; adverse effects include sedation, confusion, ataxia, and abuse potential.

Trazodone was also shown to significantly improve sleep at doses that averaged 100 mg nightly in a large placebo-controlled trial conducted in alcohol-dependent patients over 24 weeks.

 Although there were some initial concerns about an increased risk of relapse with the use of trazodone, subsequent studies have not borne that out. Benefits include tolerability; adverse effects may include priapism, oversedation, and GI disturbance due to serotonergic effects.

An investigation by Litten and colleagues

 demonstrated improved sleep quality with 400 mg of quetiapine extended release. This study extended earlier findings of Martinotti and colleagues,

 who reported significant correlations between the reduction in alcohol withdrawal and craving scores and HAM-D (Hamilton-Depression screen) insomnia items. Adverse effects include disruption of the metabolic profile, risk of movement disorders, and possible abuse potential.

A multicenter trial of 371 alcohol-dependent patients found a significant reduction in obsessional thoughts and compulsions about using alcohol and a reduction in sleep disturbance with topiramate use.

 Melatonin receptor agonists such as ramelteon and agomelatine have also shown some benefit in sleep improvement for alcohol-dependent patients, although further studies are warranted.

 Adverse effects of ramelteon include somnolence, dizziness, fatigue, and nausea as well as complex sleep behaviors such as sleep driving.

The following case vignettes highlight the complexity and individual nuances of patients who struggle with sleep and substances. These cases also illustrate the importance of asking about caffeine, nicotine, and high-sugar food intake in early-recovery patients with persistent sleep disturbance. Future investigations of substance use and sleep should incorporate an analysis of these features, as patients in recovery may exhibit a tendency toward cross-addiction and increased consumption of caffeine, nicotine, and sugar that may affect sleep quality.

Mr. P had a history of severe alcohol use disorder with 25 years of sobriety following successful chemical dependency treatment. He had a comorbid chronic insomnia disorder that was responsive to a stable 12.5-mg dose of zolpidem extended release. After his primary care provider retired, a new physician tapered off and discontinued zolpidem. Following several other unsuccessful medication trials and a year of disrupted sleep, Mr. P relapsed to alcohol to help fall asleep. He quickly reverted to previous abusive patterns, and he returned to his second alcohol use disorders treatment. After successful completion of treatment, zolpidem was re-instated and Mr. P has remained sober since that time.

Mr. S had a 10-year history of sleep disturbance and daytime fatigue as well as a history of opioid-use disorder that was in sustained remission. Zolpidem was prescribed to target his sleep disturbance, and within 1 year he escalated the dose to 30 mg nightly. He was referred for chemical dependency treatment for a sedative-hypnotic use disorder, and eventually zolpidem was tapered off. For more than a year, he had persistent sleep disturbance.

Mr. S reported that he was drinking more than 7 caffeinated beverages daily and was chewing 1 can of tobacco daily. He achieved restorative sleep with mirtazapine (15 mg nightly) and gabapentin (300 mg 3 times daily). He was able to taper and discontinue caffeinated beverages and transitioned from chewing tobacco to nicotine gum.

Dr. Schmidt is a Psychiatry Resident, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN; Dr. Kolla is Assistant Professor of Psychiatry and Psychology, Department of Psychiatry and Psychology, and Center for Sleep Medicine, Mayo Clinic, Rochester.

 Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? 

 Hasler BP, Martin CS, Wood DS, et al. A longitudinal study of insomnia and other sleep complaints in adolescents with and without alcohol use disorders. 

 Brower KJ, Wojnar M, Slwerska E, et al. PER3 polymorphism and insomnia severity in alcohol dependence. 

 Schmidt KA, Ho AMC, Frye MA, Choi DS. Association of plasma orexin A and ethanol-drinking behaviors in pregnant rats. 

 Brower KJ. Assessment and treatment of insomnia in adult patients with alcohol use disorders. 

 Brower KJ, Perron BE. Prevalence and correlates of withdrawal-related insomnia among adults with alcohol dependence: results from a national survey. 

This article reviews current literature on insomnia and alcohol use disorders and highlights assessment and treatment of sleep disorders in patients with comorbid alcohol abuse.

Vol 34 No 8

Treatment for Cannabis Use Disorders: A Case Report

ADHD and Substance Use: Current Evidence and Treatment Considerations

E-Cigarettes, Vaping, and Other Electronic Nicotine Products: Harm Reduction Pathways or New Avenues for Addiction?

Understanding and Addressing Sleep Disruptions in Alcohol Use Disorders

Improving Mental Health: Four Secrets in Plain Sight

Psychodynamic Psychiatry: A Case Report

The Healing Power of Photographs

Anti-NMDA Receptor Encephalitis: Diagnostic Issues for Psychiatrists

What a Long Strange Trip It’s Been

Frontotemporal Dementia: A Brain Disease That Challenges Definitions of Mental Illness

Musician Injuries