Christina Brezing, MD

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

Over the past 10 years, the prevalence of heroin and prescription opioid misuse has significantly increased, in large part because of the increased prescribing of opioid analgesics in the US. As a result, there has been an unparalleled rise in the number of people affected with opioid use disorders and great concerns about the associated morbidity and mortality-including opioid-related overdoses and deaths in conjunction with the spread of infectious diseases, such as HIV infection and hepatitis C.

In this environment, it is imperative that physicians, particularly psychiatrists, are able to identify opioid use disorders; provide education and strategies for harm reduction; and offer effective, evidence-based treatments.

In this brief overview, we provide a step-by-step process for clinical decision making with 2 common-scenario case vignettes.

Mr Gordon is a 45-year-old construction worker who had been injured a year earlier when picking up a heavy piece of equipment. His primary care physician (PCP) prescribed oxycodone for the pain. After 3 months, the original dose prescribed no longer controlled his pain, and Mr Gordon began gradually increasing the dose and subsequently running out of his medication earlier than anticipated. After multiple discussions about his increasing use of oxycodone and his failed attempts to cut down on his use, Mr Gordon’s PCP stopped prescribing the medication.

After using the last dose of oxycodone, Mr Gordon woke up sweating profusely, with diarrhea, nausea, bone aches and pains, and anxiety. The next morning, he experienced very strong urges to use oxycodone, and he made 3 appointments with different physicians and managed to obtain prescriptions from each of them. In addition, he began buying “blue roxies” (colloquial term for oxycodone 30-mg tablets) from a neighbor, and learned to crush and use 5 to 8 tablets intranasally daily, noting a faster onset of effect.

In a short time, Mr Gordon found himself frequently calling in sick to work so he could continue using the pain-killers. He felt sick on the mornings when he did not have enough pills. He also became depressed and uninterested in socializing, and he had poor appetite and no sex drive. He stopped going to the gym, which had previously been his passion.

After missing work for the third time in a week, he was fired. Out of work and with only a few tablets of oxycodone left, Mr Gordon feels that his use of oxycodone is out of control and that he has become “a different person.”

In DSM-5, opioid use disorders, like all substance use disorders, have been redefined as a spectrum of pathology and impairment. The criteria for an opioid use disorder are generally the same as in DSM-IV. The diagnostic criteria for DSM-IV abuse and dependence were combined in DSM-5 except for 2 changes: (1) the criterion for recurrent legal problems has been removed and (2) a new criterion for craving, or a strong desire or urge, to use opioids has been added (see 

In DSM-5, the two disorders of opioid abuse and opioid dependence are replaced by a category of opioid use disorder. A patient must meet at least 2 diagnostic criteria to qualify as having an opioid use disorder. Severity 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 Gordon meets 7 criteria, which qualifies him for a severe opioid use disorder. He demonstrates tolerance to oxycodone; is using more and for longer than intended; has had multiple failed attempts to decrease his use, withdrawal, and craving; has increased time spent obtaining opioids; and has failed to fulfill work obligations.

Mr Gordon also meets criteria for a DSM-5 category of opioid-induced depressive disorder. For that diagnosis, the onset of depressive disorder needs to be temporally connected with the substance use (ie, within 1 month as opposed to before the initiation of substance use or during a prolonged period of abstinence). Moreover, the opioids need to be capable of producing the specific syndrome, which is certainly the case with the depressive disorder.

"While opioid dependence is among the most severe and lethal of addictions, it also has the most effective medication treatments."

In the US, there are 3 FDA-approved medication treatments for opioid use disorders, all of which engage the Î¼-opioid receptor: methadone, a full agonist; buprenorphine, a partial agonist; and naltrexone, an antagonist. 

 compares the different properties of each medication. While methadone is an effective pharmacological option, because of federal regulations, it is only available at designated methadone administration sites (methadone maintenance treatment programs) and is not available for the treatment of opioid use disorders by prescription.

Patients who desire office-based treatment for opioid use disorders have the 2 remaining options: buprenorphine and naltrexone. When selecting which medication is best suited for your patient, there are several factors to consider, includ-ing clinical history, treatment preferences, available support system, and access to resources. Each of these pharmacotherapies has a potential to decrease or eliminate craving for heroin or a prescription opioid, which helps the patient engage and benefit from a behavioral, abstinence-oriented treatment to achieve recovery-a voluntarily maintained lifestyle characterized by sobriety with care for personal health and relationships.

Buprenorphine partially activates the Î¼-opioid receptor, at approximately 50% the maximum effect produced by an agonist. At lower doses (16 mg or less), its agonist effect is directly correlated with the dose; however, at higher doses (more than 16 mg), its pharmacological and clinical effects decrease and plateau, with the increasing dose reaching a ceiling above which no further agonist effect is possible. The agonist effects of buprenorphine prevent opioid withdrawal and reduce or eliminate the craving for opioids. In addition to its agonist properties, bupre-norphine has a higher affinity for the Î¼-opioid receptor than commonly used opioids. As a result, buprenorphine functionally acts as an antagonist, preventing other opioids from binding to the receptor.

Buprenorphine is available in 2 sublingual formulations-as pure buprenorphine (Subutex) and as a buprenorphine/naloxone combination (Suboxone, Zubsolv)-and in a buccal film formulation (Bunavail).

Naloxone is a short-acting opioid antagonist, which is mostly inactive by the sublingual route. The addition of naloxone to the formulation is designed to deter misuse of the medication, since naloxone becomes active and exerts antagonist effects when used intravenously.

Physicians who are interested in using buprenorphine to treat patients with opioid use disorders can obtain a DATA 2000 (Drug Addiction Treatment Act of 2000) waiver by completing training and submitting their waiver of intent as outlined by the Substance Abuse and Mental Health Services Administration (SAMHSA). Training can be completed in person or online (pcssmat.org). The Drug Enforcement Administration will subsequently provide the physician with a separate license number (X-number) to be used when writing buprenorphine prescriptions.

Naltrexone binds to the Î¼-opioid receptor with a high affinity but does not exert any activity; rather, it prevents binding of agonists or displaces agonists at the receptor. Naltrexone can be administered after detoxification to prevent relapse, when it provides a complete blockade of opioid effects.

Naltrexone is available in an oral tablet formulation that requires daily administration or a once-monthly, long-acting intramuscular injection (Vivitrol) to bypass the difficulties with adherence to daily medication that many patients have at treatment outset. No additional training or licensure is required to prescribe naltrexone for opioid use disorders, but training materials are available (pcssmat.org).

All 3 of these medications should be considered in Mr Gordon’s treatment.

After the benefits and limitations of different medication options are explained to Mr Gordon, a decision is made for outpatient buprenorphine induction and maintenance treatment. This choice of treatment is made on the basis of his unwillingness to go through the detoxification and his preference for office-based treatment.

During the first month of treatment, he is maintained on buprenorphine 12 mg/d: he has no cravings and maintains abstinence from opioids as confirmed with weekly urine drug screens. After 2 months of treatment, he requests a dose decrease and the medication is gradually tapered to 4 mg/d. After 1 month of stabilization with buprenorphine, he reports that his depressed mood is resolved, his appetite is improved, and he is going to the gym daily. He is hired by another construction company; he goes to work every day, reengages with his friends, and resumes dating.

He feels that he is “cured” and decides to stop coming to treatment; he self-tapers off buprenorphine and notes minimal withdrawal symptoms. After about 6 months, he begins to casually use oxycodone again because he thinks that he is now able to control use, which he does in the first few weeks. However, his use gradually escalates and after 2 months of using, he admits that he needs help and reengages in treatment.

Given that he had an excellent response with buprenorphine, treatment is re-induced at a dosage of 8 mg/d, which, over 2 to 3 months, is gradually tapered to 4 mg/d. At this point, he has been stable and in recovery from opioids for 3 years. He plans to continue on buprenorphine maintenance indefinitely. He has no mood problems and is very happy with his current health and life situation.

Mr Gordon’s case highlights the chronic and potentially exacerbating nature of opioid use disorders, which is similar to other chronic psychiatric disorders, such as bipolar disorder. A long-term focus on medication adherence is needed as well as regular office visits to monitor stability, work on relapse prevention strategies, recognizing destabilizing events, and developing other health-promoting activities.

Ms Derbin is a 26-year-old bartender who self-presents for outpatient treatment after injecting heroin for the past month. She first used nonprescribed oxycodone at age 19, when someone introduced her to snorting it at a party. Initially, she used it 1 or 2 times a week, usually on weekends; but over the next 2 years, her use progressed to daily snorting. She is no longer experiencing euphoria with use and is now using primarily to avoid withdrawal symptoms.

When oxycodone became increasingly more difficult to obtain, a boyfriend introduced her to injecting heroin to reduce daily expense and to have greater and faster euphoric effects. In addition to using opioids, Ms Derbin has been a daily marijuana smoker for 10 years and regularly uses intranasal cocaine (14 of the past 30 days), alcohol (weekend binge drinking), and benzodiazepines (mainly alprazolam for 5 of the past 30 days). She also reports a history of ADHD, for which she took stimulant medication from age 13 through 19.

She reports that this is not her first time coming to treatment for opioid use. At age 22, she had an inpatient methadone-assisted detox from opioids; treatment was tapered and discontinued before discharge. She remembers “not feeling well” following her discharge and relapsing 2 days after leaving the facility.

She went to her second detox 6 months later, and this time was discharged to a residential treatment center that followed a therapeutic community model. She stayed there for 3 months and was instructed to “become personally responsible for her behavior to be drug-free.” Medication-assisted treatment was not offered, but she was instructed to seek out Alcoholics Anonymous to maintain sobriety.

After her discharge and a total of 6 months abstaining from opioids, she relapsed with oxycodone and benzodiazepines-she notes that she felt “bored” at work and was seeking excitement. She overdosed during the first week, and a friend called an ambulance after she became nonresponsive.

This overdose prompted Ms Derbin to seek treatment again-this time as an outpatient with buprenorphine induction and maintenance. She did well for 2 months while taking buprenorphine, using heroin only occasionally, but she continued to use cocaine and alprazolam. Eventually she began diverting the buprenorphine and attempting to inject it. After 1 month, she stopped injecting buprenorphine and resumed daily injections of heroin. She presents to you with concerns about her injection use. She wants to be detoxified because she does not want to be “dependent on any substance ever again.”

Ms Derbin’s previous experience with multiple and varied treatment settings is quite common for many patients struggling with opioid use disorders. Her first two experiences of detoxification without the offer of medication-assisted treatment to prevent relapse is still the most frequently used strategy. However, as demonstrated in this case, patients whose detoxification is not followed by relapse-prevention treatment are at high risk for relapse. As many as 90% of such patients relapse, usually in 1 to 2 months, and unfortunately many will overdose given that they no longer have physiological tolerance to opioids once detoxified.

Detoxified individuals are at greater risk for overdose than those who avoid treatment and continue to use opioids regularly. Individuals who use opioids in the context of sedative and alcohol use are at the highest risk for respiratory suppression and overdose. All opioid users, especially those who decline further treatment following detoxification, should be counseled about the high risk of overdose with relapse and provided with a naloxone rescue kit. Their friends and family need to be educated about how to obtain a rescue kit (SAMHSA Opioid Overdose Toolkit; projectlazarus.org) and about how to administer the naloxone in the event of an overdose. Patients who inject opioids should also be informed about clean needle exchanges.

Ms Derbin’s history indicates a past trial of buprenorphine maintenance with a poor treatment response. While many patients do well with agonist or partial agonist maintenance treatment for opioid use disorder, others do not respond and continue to have cravings and illicit opioid use. Others, such as those engaged in recovery in the 12-step community, find it difficult to accept the idea of being “dependent” on another type of drug/opioid. Given Ms Derbin’s personal preference and interest, a trial of antagonist treatment with naltrexone in conjunction with relapse-prevention therapy and psychosocial interventions was agreed on, and her parents were brought in to be a part of treatment.

To transition to antagonist treatment, the patient must first go through detoxification. One of 3 detox strategies can be used: agonist-assisted detoxification, symptomatic treatment only with non-opioid medication, or antagonist-assisted detoxification with symptomatic treatment. The main difference between agonist-assisted detoxification and the other two strategies is that withdrawal symptoms tend to be more severe toward the later part of treatment with agonists, while withdrawal symptoms are more severe earlier in treatment with the other two methods. Also, agonist detoxification requires a 7- to 10-day washout period before administration of naltrexone to prevent precipitated withdrawal. Because of this prolonged detoxification period and delay in starting naltrexone, some patients may drop out of treatment and relapse.

Once a patient completes detoxification, a urine drug screen should be obtained to confirm abstinence from all opioids (including buprenorphine). Administering naltrexone to a patient who is still physically dependent on opioids will precipitate a severe withdrawal reaction. If long-acting injectable naltrexone is selected, a trial of oral naltrexone may be given first to ensure that the patient tolerates the medication and withdrawal is not precipitated. If the patient has been abstinent (eg, in residential treatment), naltrexone injection can be given at treatment outset. Monthly injection of a long-acting intramuscular naltrexone is generally preferable to a daily oral administration, especially at treatment outset, because rates of treatment response tend to be twice as high with the long-acting prepa-ration (for more information, see pcssmat.org or SAMHSA’s 

Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorders: A Brief Guide

Often the psychiatrist is the only health care professional who has regular contact with a patient who has an opioid use disorder. This should be seen as an opportunity to provide prevention strategies, screening, counseling, and possible referrals for co-occurring medical problems commonly seen in this patient population. Given Ms Derbin’s recent injection drug use, HIV and hepatitis C and B status should be obtained with routine blood work in addition to referral for hepatitis B vaccinations if she has not already received them.

Ms Derbin was successfully detoxified with small ascending doses of oral naltrexone and supportive medications, including clonidine, zolpidem, and clonazepam. Subsequently, monthly injections of a long-acting intramuscular naltrexone were started. Her parents were instrumental early in treatment in reminding her of and bringing her to appointments and arranging for her to meet with a physician to better understand the nature of her condition and the role that medication plays in recovery.

As she became more engaged in the relapse-prevention behavioral therapy over time, she lost cravings for the drugs and now only uses marijuana with decreased frequency (from daily use down to 4 times a week). She has been abstinent from opioids for 18 months with ongoing monthly injections of naltrexone. At present, Ms Derbin reports much greater stability than with previous treatment attempts. When she started working, her PCP prescribed extended-release stimulants to treat symptoms of her ADHD. Ms Derbin reports improvement in work and life satisfaction. She broke up with the heroin-using boyfriend and began attending regular Narcotics Anonymous meetings, at which she has found a community of people she identifies with in recovery.

Many advances have been made in the treatment of opioid use disorders over the past decade. While opioid dependence is among the most severe and lethal of addictions, it also has the most effective medication treatments. Treatment is the most important strategy to reduce death due to opioid overdose-pharmacological treatments reduce the risk by 90%. The challenge now comes with implementing medication-assisted treatment into a widespread community practice to allow easier access to evidence-based care for patients. The medication-free approach cannot be justified as the only treatment for opioid addiction: overwhelming evidence exists to support the greater success of a medication-assisted approach.

Psychiatrists are in a prime position to launch a campaign in their communities to inform those seeking help and their families about the gap between what is being offered to patients and what is actually known to be effective at preventing relapse and death. Patients deserve the opportunity to make a well-informed choice about which path they take to recovery.

We should shift the focus away from discussing the superiority of one medication approach over another toward having thoughtful, tailored discussions to better understand which medication treatment option can best match an individual patient’s needs. Ultimately, as more evidence-based medication treatments are provided to patients with opioid use disorders, overdose deaths and other significant morbidity can be decreased.

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. Dr Bisaga is a Professor of Psychiatry at Columbia University College of Physicians and Surgeons and a Chair of the mentoring program “Physicians’ Clinical Support Service for Medication-Assisted Treatment.” (PCSS-MAT). The authors report no conflicts of interest concerning the subject matter of this article.

The PCSS-MAT is a national training and mentoring project developed in response to the prescription opioid misuse epidemic and the availability of newer pharmacotherapies to address opioid dependence. The overarching goal of PCSS-MAT is to make available the most effective evidence-based education and training resources about medication-assisted treatments to serve patients in a variety of settings, including primary care, psychiatry, and pain management. The PCSS-MAT mentors are a national network of trained providers with expertise in medication-assisted treatment and who are skilled in clinical education. The PCSS-MAT mentoring program is available at no cost to providers. Funding for this initiative was made possible by a grant from SAMHSA (Substance Abuse and Mental Health Services Administration).

While opioid dependence is among the most severe and lethal of addictions, it also has the most effective medication treatments. The authors provide 2 case vignettes and a step-by-step process for clinical decision making.

Opioid Use Disorder: Update on Diagnosis and Treatment

 (AAAP) meeting assembled a fantastic group of presenters who put on high-quality, high-yield workshops and symposia, shining the light on current hot topics within the field of substance use disorders. The information provided is relevant not only for addiction psychiatrists, but all providers within mental health, given the pervasiveness of these disorders.

From reviewing the debate on electronic cigarettes to providing important new ways of thinking about substance abuse treatment in the context of co-occurring disorders, such as traumatic brain injury and chronic pain, the scope of the conference was broad and rich and those in attendance walked away with a wealth of knowledge (and a nice tan!).

A few major themes emerged from the meeting and include

(1) changes in US drug policies that ultimately impact the clinical scenarios we see, particularly with regards to marijuana and the impact these new laws will have on its citizens, which include in large part our patients

(2) novel treatment approaches of those “dually diagnosed”

(3) special populations that require integration of many individuals and disciplines in order to optimize patient outcomes. I had the pleasure to attend many of the workshops, symposia, paper, and poster sessions.

Here are some brief selected summaries from the many highlights at the meeting for the readers of 


In a presentation titled “Legalization of Marijuana: Are We Ready?”, Drs Kevin Hill from McLean Hospital, Richard Ries from the University of Washington, and Herb Kleber from Columbia University outlined the main points that every mental health care provider should have in their repertoire to allow for participation in the debate on legalization of marijuana. The presenters provided both the pros (tax revenue, decreased incarceration, and greater individual freedom) and the cons (increased health related costs, difficulty with determining safe levels for driving, fewer barriers to more users) of legalization of marijuana.

Interestingly, they reported that current polls identify that the majority (51%) of Americans are in favor of legalization of marijuana, which will include and capture our patients’ views. Knowing the issues will allow clinicians to have a dialogue with patients and colleagues outside of mental health and substance abuse on this growing trend.

A complement to this topic was a paper presentation by Dr Samuel Wilkinson, Gerrit van Schalkwyk, and Dr Cyril D’Souza from Yale on veterans’ attitudes about marijuana. Their interviews captured many of the misperceptions that patients have about marijuana including myths that it is not addictive, not associated with withdrawal, is natural, and overall has less of an effect on behavior than other substances.

This fast-growing trend of decreasing perception of harm leading to endorsements of legalization and ultimately more widespread use of marijuana was even further expanded by the symposium titled “What Is the Evidence of Harm to Adolescents Using Cannabis? A Critical Review of the Data.” Drs David Atkinson from the University of Texas-Southwestern, Christopher Hammond from Yale University, Kevin Gray from Medical University of South Carolina, Scott Krakower from Zucker Hillside Hospital, and Greg Tau from Columbia University honed in on the adverse health effects on one of the most vulnerable populations engaging in increased, regular cannabis use-adolescents. The symposium thoughtfully laid out the neurobiology of cannabis as an addiction in the young and developing brain, and the evidence of the role of cannabis in affective disorders, psychosis, and cognitive deficits in adolescents.

These adverse brain changes argue for the integration of care and sharing of knowledge among child and adolescent psychiatrists, addiction psychiatrists, pediatricians, and any other mental health or medical providers of care to this population, in addition to a call for more research into the impact of cannabis on this special population of youth.


Shifting focus to new treatment strategies for substance abuse and in particular for dual diagnosis patients, or patients diagnosed with both a substance use disorder and another co-occurring primary psychiatric disorder, Columbia faculty members Drs Adam Bisaga, Frances Levin, and John Mariani presented the workshop titled “Psychostimulant Treatment of Cocaine and Other Stimulant Use Disorders: Is It Time Yet?”

Before getting to the specifics of the topic at hand, the presenters did a wonderful job framing the key principles guiding the general use of medication assisted treatment of substance use disorders: (1) to reduce substance use and (2) to reduce the harms associated with substance use. These two ideas have fueled the use of agonist medication in the treatment of substance abuse, particularly opioids.

Using this concept and applying it to the treatment of cocaine use disorders, the faculty reviewed some preclinical and mostly clinical evidence for the use of oral psychostimulants, like D-amphetamine and methylphenidate in the treatment of cocaine use disorders. Notably, they highlighted the risks associated with this off-label use given the mixed and relatively limited literature on this topic. They made it clear that when considering this treatment for cocaine use disorder, the following treatment strategy should be used:

• include a thoughtful clinical evaluation of the risks and benefits
• assess trust between the physician and patient
• utilize a step-wise approach to medication selection first using reuptake inhibitors (such as modafinil, buproprion, and desipramine) that have less abuse potential
• if the above step-wise approach fails, then consider transitioning to monoamine enhancers, like methylphenidate and d-amphetamine with frequent monitoring and low supplies of medication provided at any given time

Dr Mariani encouraged the audience to think about their prescribing/treatment approaches on a spectrum of conservative to liberal, noting that conservative prescribers have less risk of misuse or diversion of their prescribed medications by patients but run the risk of under-treating their patients. In contrast, liberal prescribers would be much less likely to under-treat but ran a greater risk of their medication being misused or diverted. Ultimately, the goal is to find the “sweet spot” in prescribing practices to maximize treatment response and minimize misuse or diversion.

Following this concept of using psychostimulants for cocaine use disorder, Dr Levin showed new evidence from her soon-to-be published study looking at the use of higher dose monoamine enhancers, specifically d-amphetamine, in the treatment of cocaine use disorders in individuals with co-occurring ADHD. Not only did higher dose d-amphetamine improve ADHD symptoms as compared to placebo, it also led to greater abstinence from cocaine. Given the high co-occurrence of ADHD and substance use disorders and the negative bidirectional impact they have on health outcomes, she encouraged thoughtful screening to identify ADHD and substance use with appropriate interventions and treatment referrals.

Finally, on a similar note, Drs Denise Hien from City College of New York and Chaya Bhuvaneswaran from the University of Massachusetts-Worcester presented a workshop titled “Innovative Treatment Strategies for PTSD and Co-occurring Addictions.”Dr Hien emphasized the reciprocally reinforcing problem of PTSD and substance use disorders and the need to address both the effects of trauma and substance use in order to optimize patient-related outcomes. She reviewed a number of different evidence based psychotherapies including Seeking Safety, Concurrent Treatment with Prolonged Exposure (COPE), and Integrated CBT for PTSD-to to name a few-that have been found to synergistically improve PTSD symptoms and substance use when used in conjunction with medications like sertraline and prazosin.

Dr Bhuvaneswaran discussed the role of mindfulness training in the treatment of PTSD and substance use disorders with an emphasis on the attention to basic principles of mindfulness. She encouraged audience members to not feel compelled to spend large amounts of money on specialized mindfulness training, but rather to focus on the basic universal principles of mindfulness available to everyone for low cost and to take this into consideration when working with low socioeconomic patient groups.

It was an outstanding conference, and if readers find their interest piqued, I strongly encourage you to attend the AAAP Annual Meeting and/or the Addictions and Their Treatment Course next year in Huntington Beach, California-it will undoubtedly provide an in-depth perspective from the field of addiction psychiatry in the treatment of patients with substance use disorders within the context of mental health.

Dr Brezing is a clinical and research fellow in the Division of Substance Abuse, Department of Psychiatry at Columbia University and New York State Psychiatric Institute in New York City. The author reports no conflicts of interest concerning the subject matter of this article.

Given the pervasiveness of substance use disorders, the information provided here is relevant not only for addiction psychiatrists, but all mental health providers and primary care physicians.

Christina Brezing, MD

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