<v ->Hello, I'm Edward "Ned" Nunes,</v> from the Columbia University Medical Center and New York State Psychiatric Institute. And on behalf of PCSS, I'm going to spend the next 40 minutes or so giving an overview of the management of substance use that co-occurs, other substance use, that co-occurs with opioid use disorder. Focusing specifically on benzodiazepines, cocaine and amphetamines, and cannabis. So I don't have any relevant financial relationships that are relevant to this talk. Target audience. The goal of PCSS is to train healthcare professionals of all stripes in evidence-based practices for the prevention and treatment of opioid use disorders, particularly in prescribing medications, as well as for the prevention and treatment of substance use disorders in general. The educational objectives for this talk. At the conclusion of this activity, you should be able to diagnose and formulate a treatment plan for misuse and use disorders for the following substances, with emphasis on when they co-occur with opioid use disorder, benzodiazepines, cocaine and methamphetamine, and cannabis. Presentation will provide an overview of the evaluation and treatment of each of these substances with opioid use disorder. We'll also talk a little bit about alcohol use disorder. Alcohol use disorder is covered in detail in another substance use disorder core and PCSS core curriculum talk presentation, but it will be mentioned here. to highlight the common evaluation and treatment strategies across substance use disorders, and particularly in combination with opioid use disorder. Polysubstance use, comorbidity of opioid use disorder, and other substance use disorder. So general rule, the presence of one substance use disorder increases the likelihood of other concurrent substance use disorders. So people with opioid use disorder are at risk for using and misusing other substances. Especially, benzodiazepines, but also cocaine, methamphetamine, cannabis, and alcohol. Alcohol is also an important problem in people with opioid use disorder. So when one substance is present, look for others. So the general overview of diagnosis and treatment. Evaluate the DSM-5 criteria for a substance use disorder, for each of the other substances that a patient may be using in addition to opioids. General principles of intervention, screening, ask, ascertain the extent of the problem, and whether there's a use disorder there. Brief intervention and then treatment planning, pharmacological interventions, behavioral interventions, and think also about levels of care. Screening for co-occurring psychiatric disorders. So co-occurring psychiatric disorders in addition to co-occurring substance use disorders. We're talking about depression, PTSD, ADHD, this sort of thing. These are common among patients with opioid use disorder, and other substance use disorders, and they have often specific behavioral or pharmacological treatment indications. So if you can identify a mood disorder such as major depression or PTSD, other anxiety disorders like social anxiety or agoraphobia, or attention deficit hyperactivity disorder, these are treatable. And when a patient's using substances, this may signal the presence of psychiatric comorbidity. The substance use may reflect to some extent an effort to self-treat the disorder. And I like to particularly emphasize reviewing the childhood and developmental history for ADHD, anxiety, depression, trauma, and adverse childhood experiences. When I take a history, I like to spend quite a bit of time on this to get a sense of what may have been going on in childhood, and whether disorders like ADHD, or depression or anxiety may already have been brewing. So here's a case vignette that we'll visit as we go through the talk. It's a patient on buprenorphine who has benzodiazepine and alcohol use. That's a 35-year-old man with opioid use disorder, prescription opioids, which has now progressed to illicit opioids. He's initiated office-based treatment with buprenorphine, the dose has been advanced to 16 milligrams per day. He reports ceasing opioid use and his urine toxicologists are consistently positive for buprenorphine as prescribed, with intermittent positive results for benzodiazepines. He also describes drinking alcohol two days per week sometimes to intoxication. What is the most appropriate next step in this man's treatment? A. Increase buprenorphine to 24 milligrams. B. Refer to methadone maintenance. C. Admit to inpatient detoxification. D. Start outpatient long-acting benzodiazepine taper. Or E. Obtain more history. I would argue the answer is E, obtain more history. Why? I don't see that there's much of any evidence that increasing the buprenorphine dose or switching to methadone maintenance would be effective in addressing the sedative or alcohol use. Especially since the patient has stopped using illicit opioids, suggesting an adequate dose of buprenorphine may have been reached. I'd say more history is needed to determine the appropriate level of care in the treatment plan. Inpatient detoxification versus outpatient benzodiazepine taper might or might not be appropriate depending on the severity of the other substance use and other relevant dimensions. Psychiatric comorbidity, is there an anxiety or a mood disorder that might be present and needs specific treatment such as with an anti-depressant medication? Okay, let's talk a bit about alcohol and alcohol use disorder. Bearing in mind, again, that there's a whole another section in this series on alcohol and alcohol use disorder. So alcohol use disorder is the most common substance use disorder along with nicotine. Population prevalence, according to the NESARC, population survey is 30% lifetime, 8.5% current, that is past 12 months in the general population. Prevalence of alcohol use or use disorder among those with opioid use disorder is 30%. So a lot of alcohol use and use disorder among people with opioid use disorder. What are the main points about alcohol and opioid use disorder? Alcohol's a sedative on a broad continuum with benzodiazepines and other tranquilizers, so alcohol use and use disorder may commonly co-occur with other substances like benzodiazepines. Alcohol use disorder itself has been extensively studied, risk factors, genetics, stress, a lot of behavioral treatments, like motivational interviewing, 12-step facilitation, cognitive behavioral approaches. Importantly, alcohol will synergize with other sedatives, like benzodiazepines or opioids to increase the risk of intoxication, and the risk of respiratory depression and overdose and death. So a lot of drinking along with opioids is a dangerous combination. Screens for alcohol use and use disorders and treat when appropriate including considering medications for alcohol use disorder, so FDA approved are disulfiram, acamprosate, and naltrexone. Others that have some evidence for efficacy in clinical trials include gabapentin, topiramate, carbamazepine, varenicline, antidepressants if there's a co-occurring depression, and buspirone if there's a co-occurring anxiety disorder. Let's focus now on benzodiazepines and other sedatives. These are therapeutically very useful medications. They're highly effective for treating acute anxiety and insomnia. They act as GABA receptors, these are inhibitory and they have an inhibitory effect on neurons, they promote release of GABA and thereby have their inhibitory effect. They have potential for misuse or use in vulnerable individuals. The prevalence of benzodiazepines use disorders low in the general population but it's pretty common among patients with opioid use disorder, and it's potentially dangerous because opioids and benzodiazepines is another dangerous combination. The two can synergize to increase intoxication and increase the risk of respiratory depression and overdose. And overdose deaths often involve a combination of opioids and benzodiazepines or alcohol or other drugs, particularly sedatives like benzodiazepines or alcohol. How about benzodiazepine use among people without opioid use disorder? It's prevalent, as we said. It seems to be used to enhance the opioid euphoric effects. It may also be used to self-treat anxiety and insomnia or perhaps self-treat opioid withdrawal. I always think it's important when somebody's using benzodiazepines that has an opioid use disorder, maybe is under treatment for an opioid use disorder, to look for co-occurring mood and anxiety disorders because that may be part of what's driving it. PTSD, depression, they often involve a lot of anxiety and insomnia that respond to benzodiazepines, self-treatment can evolve into a use disorder, benzodiazepines may be prescribed and then evolve into a use disorder. So it's important to look for co-occurring disorders and institute more effective treatments. So for depression, for example, CBT or antidepressant medications. So what about benzodiazepines among patients on methadone maintenance treatment? While the prevalence of benzodiazepine use among patients in methadone maintenance treatment is very high, 20 to 60%, according to papers that report on this. And benzodiazepine use on methadone maintenance is associated with other drug use, high risk behavior, depression and anxiety disorders, remember to look for those, they're treatable, and unfortunately higher mortality. So what about benzodiazepines and buprenorphine treatment? What do we know? Well, we should always think about the French experience. Buprenorphine was introduced in France in the 1990s to combat opioid overdoses. And opioid overdoses were reduced dramatically overall in the population after buprenorphine was introduced and it was introduced in such a way that it was easy to prescribe without a lot of barriers. And the one exception to the reduction in overdoses was that overdoses that did occur seem to involve a combination of buprenorphine and benzodiazepines. Bearing in mind that we were talking about high dose intravenous benzodiazepine misuse, which is very unusual to see in the United States, it's unusual to see IV benzodiazepine misuse here. So keeping in mind that buprenorphine has less respiratory depression than full agonists, but that like with any other opioid, if you add benzodiazepines or other sedatives or alcohol to an opioid, even buprenorphine, you're going to increase the risk of respiratory depression. Clinical approach to this benzodiazepines at modest doses by the oral route can be a useful treatment for an appropriate patient. I would not consider co-occurring benzodiazepine use to be an absolute contraindication to buprenorphine treatment. The risk of not treating opioid use disorder, for example opioid overdose, far outweighs the likely risks of low dose benzodiazepines. And again, it's important to distinguish low dose benzodiazepine therapeutic use, again, looking for anxiety, mood, or sleep disorders, or misuse of relatively low doses versus higher dose misuse and binge use of benzodiazepines. So what about this spectrum of use, misuse and use disorder? Again, there's legitimate prescribed use, it's usually characterized by low dose, no escalation of the dose over time, a stable pattern taken as prescribed month in and month out and good therapeutic response, patients doing well, benefiting. Now, even if the use appears legitimate, it's important to closely monitor and seek non-addictive alternatives. For example, an antidepressant medication for depression or anxiety disorder or a sedating antidepressant for sleep. Trazodone is used a lot but beware of priapism in men, doxepin a sedating antidepressant, mirtazapine another sedating antidepressant can be considered. Okay, then there's misuse or risky use which is used not as prescribed or illicitly procured. Often higher doses taking more than prescribed. And then there's a use disorder where you're looking for a history of binge gross intoxication or overdose events, or you're looking for other forms of impairment that would add up to a use disorder. So when to consider misuse or use disorder or diversion, is diversion going on. So look for symptoms of intoxication or withdrawal. Beware of demands for a particular drug, usually a fast acting medication like alprazolam. Extended release doesn't work for me. The patient might say "Only Xanax works for me." Those are your warning signs. Repeated loss prescriptions, discordant pill counts. You ask the patient to bring back their pill bottle, and they've used more than they should have at this point, excessive preoccupation with securing medication supply, and multiple prescribers. Misuse potential of benzodiazepines depends in part on pharmacokinetics. So rapid absorption equals more rapid onset and more of a high or euphoria. Alprazolam and diazepam are two most rapidly absorbed benzodiazepines, and that produces more of this abuse potential. Clonazepam, lorazepam, chlordiazepoxide, and oxazepam are more solely absorbed, and those have arguably less abuse potential or misuse potential. Rapid absorption is also associated with more rapid onset of anxiolysis, which can be beneficial therapeutically. So not to rule out Xanax completely if it's been used at low dose to treat panic attacks, the occasional PRN dose for panic attacks. Another point. Shorter half-life is associated with greater risk of withdrawal effects. So benzodiazepine withdrawal resembles alcohol withdrawal, it can include risks of seizure and delirium so it can be quite serious. Withdrawal also drives drug seeking behavior and use disorder. Alprazolam with both rapid absorption and the short half-life is the most popular illicit or misused benzodiazepine, and it's also the one with the most, probably the most risk of problems with withdrawal. How about the benzodiazepine like sleep medications? The Z drugs like zolpidem, supposedly they have less misuse potential due to subunit selectivity at the GABA receptors, but in practice they're more similar to benzodiazepines than they are different. They have rapid absorption, they have a short half-life, you can get rebound insomnia, you can get sleep walking in the middle of the night. Patient says, "I woke up in the morning, and I realized that I'd been walking around all night. I went to the kitchen, I opened the refrigerator. I have no recollection of any of this." So, you know, you hear that, it's not uncommon, you can get withdrawal effects, so I would use this with caution in patients with opioid use disorder, these have also been implicated in opioid overdose deaths. So how about alternatives to benzodiazepines for sleep? So sleep hygiene and CBT for sleep. Sleep hygiene is very important. It's often disrupted in patients that are complaining of trouble sleeping, so you want to coach people on their sleep hygiene. Try to find and treat the underlying causes of the sleep disturbance. Is there a mood or anxiety disorder? Is there opioid withdrawal or stimulant intoxication going on or other substance effects? Consider sedating antidepressants. Again, Trazodone, but beware of the risk of priapism in men. Mirtazapine, tricyclic antidepressants that are sedating at low doses, like doxepin or amitriptyline, or even antihistamines, like Benadryl. Quetiapine and gabapentin can also be considered, they both have pretty good anxiolytic properties. Quetiapine can also have anti-depressant properties. Melatonin or melatonin agonists like ramelteon. And then there are the orexin antagonists like suvorexant. How do we evaluate benzodiazepine use disorder? Look for the quantity, pattern, and type, particularly, look for the high misuse potential drugs, like alprazolam. Evaluate the DSM-5 criteria, remembering that patients may tend to deny excessive use or impairment, so it's very useful to obtain collateral information from reliable significant others. Is the patient observed by others to be intoxicated or sedated or uncoordinated, suggesting that they're really taking too much and have a problem. And check the prescription monitoring program for multiple prescribers. How about urine toxicology evaluation of benzodiazepine use? So benzodiazepines are extensively metabolized, so detecting multiple benzodiazepines doesn't mean the patients necessarily using multiple benzodiazepines. But it's important to recognize these are metabolites, not assume the patients using multiple drugs. Another point to remember is the standard immunoassays are not very sensitive to all benzodiazepines. So standard assays test for nordiazepam and oxazepam, which are the main metabolites of many benzodiazepines including the older medications. But some of the newer high potency benzodiazepines, like alprazolam or clonazepam have different structures and metabolic and end products to which the assays are less sensitive. So it may be a question of lower concentration because these are high potency meds, may be related to structural differences. It's possible to request a lower threshold for detection or a more sensitive urine test assay. How about treatment of benzodiazepine use disorders? Evidence on treatments is limited advised to quit or cut down use motivational interviewing. CBT may be helpful. Taper or detoxification is a useful strategy. Evaluate for mood and anxiety disorders and substitute appropriate treatments for those disorders like SSRI's, antidepressants, et cetera, buspirone for anxiety. Consider the level of care, consider inpatient treatment if you've got high dose benzo use and it's out control, or you have a history of really complicated withdrawal delirium, seizures and so forth. Let's talk about discontinuation of benzodiazepines. The substitution and taper strategy. Substitute of benzodiazepine with lower misuse potential and a longer half-life. So for example, clonazepam, lorazepam or chlordiazepoxide, or phenobarbital can also be used. Choose an equivalent starting dose, and we'll show a table of equivalents on the next slide. Taper the dose slowly over a period of weeks to months. Oxazepam is a good choice if there's liver impairment. Anticonvulsants may be useful, Carbamazepine, pregabalin, gabapentin. And you may consider tapering the benzo the patient's currently taking. Here's an rough equivalency table. So a half or one milligram of alprazolam is equivalent to about one or so milligrams of clonazepam, five or 10 milligrams of diazepam, one to two milligrams of lorazepam, and 50 to 30 milligrams of oxazepam. So if you're using chlordiazepoxide, it's in a different dose range than if you're using clonazepam or lorazepam. So how about managing high doses of prescribed benzodiazepines? We see these patients, they come on very high doses of benzos. They may have been prescribed for anxiety or sleep and you can get tolerance to benzodiazepines, you get tolerance to the sedating or anxiolytic effects, and then the dose increases gradually over time. The rule of thumb, doses above three to four milligrams a day of lorazepam or above two milligrams a day of alprazolam or clonazepam, those are dangerous signs. And I think you want to encourage and help the patient to gradually reduce the benzodiazepines use over time. And it's a hard sell but you say to the patient, "You know, less is more with these medicines. You take more, you get tolerance, it stops working. Take less, the tolerance will be reduced, and you'll get more of the beneficial effects." So less risks of side effects and adverse events with a lower dose, and it may be more effective at helping sleep or anxiety, but it's often a long process coaching patients in reducing the doses of benzos. Let's go back to the case vignette, the patient on buprenorphine with benzo and alcohol use. Again, the 35-year-old man with opioid use disorder, buprenorphine 16 milligrams per day, abstinent from opioids, urines intermittently positive for benzodiazepines, drinks alcohol twice a week. Further history, he's been under financial stress and maybe depressed. He buys alprazolam two milligram sticks from his former heroin dealer and takes half at night to sleep, it's one milligram. He drinks two to four beers to relax and acknowledges feeling high. His wife who does not drink or take drugs and seems reliable. Says she's aware of his alprazolam use for sleep, but she's worried about his alcohol use. But she has not witnessed severe intoxication or loss of consciousness while drinking. He is holding down a job with no lateness or absences. He wants to stop drinking and buying drugs from the dealer, but he says he's tried, and he's been unable to stop either alcohol or alprazolam. Which medication treatment would be the most appropriate first choice to help him stop drinking? Naltrexone? Disulfiram? Acamprosate? Or Gabapentin? I would argue for a disulfiram, although it's arguable. Disulfiram is a powerful treatment, it helps most people stop drinking. He has a wife, a significant other who can witness his daily ingestion of disulfiram which can get around the adherence problems. Patients should be of course educated about the disulfiram reaction. Naltrexone, of course would be contraindicated because he's on buprenorphine. You would precipitate withdrawal and that would be quite unpleasant and bad. Acamprosate's been shown to be modestly effective in reducing relapse to drinking after detoxification, but it's not really been shown effective among outpatients that are actively drinking. Gabapentin's a good thought. It's not FDA approved for treatment of alcohol or benzo use disorder, but it has low misuse potential. There are some clinical trials showing it's helpful for alcohol use disorder, although it's probably not as powerful as disulfiram. Really want to get the patient to stop drinking and they're willing to take it, and somebody will give them the disulfiram. Disulfiram, they're not likely to drink. Disulfiram, you also have to screen the patient medically and make sure that they're healthy enough to tolerate a disulfiram reaction if it occurs. Another question about the same vignette, What would be the most appropriate next step in managing his benzodiazepine use? A. Admit for inpatient benzodiazepine detoxification. B. Prescribe alprazolam one milligram at bedtime with a taper schedule. C. Prescribe clonazepam one milligram at bedtime and continue until the cause of the insomnia is better understood. Or D. Prescribe low dose doxepin and taper the clonazepam. I would argue D, low dose doxepin and taper the clonazepam. Why? Well, you want to get the patient off benzos, particularly alprazolam because of the misuse potential. Doxepin at low doses is non-addictive, relatively safe, may help with sleep. Ideally engage his wife to supervise the clonazepam taper. The inpatient detoxification is probably an overreaction, he's not that severe. The alprazolam taper might work but it's more advisable to get him away from the alprazolam because of the misuse potential. And clonazepam has less misuse potential than alprazolam due to the slower absorption and elimination. Okay, let's switch gears now and talk about cocaine, methamphetamine and prescription stimulants. So cocaine and amphetamines, and by amphetamines I mean prescribed stimulants, and also methamphetamine are indirecting acting sympathomimetics. They promote release of dopamine, and norepinephrine and serotonin from their respective neurons in the CNS. Cocaine blocks the reuptake pump on cell surfaces and is also a local anesthetic. Amphetamines promote release of catecholamines in part by blocking uptake into storage vesicles. So they have a little amphetamines and cocaine, have a little bit different pharmacology. They have stronger rewarding effects and addictive potential stemming mainly from their potent release of dopamine in the ventral striatum, brain reward system. So it's been shown that it's the dopamine release that's primarily driving the addictive potential. There are also milder stimulus like bupropion, which is an antidepressant, acts mainly at norepinephrine, but also promotes modest dopamine release. It's mildly energizing but very little euphoria, it's rarely misused. There's modafinil Provigil or R-modafinil, These are FDA approved to combat daytime sleepiness, in sleep apnea or narcolepsy or shift work, they're also used off label for ADHD or chronic fatigue, or depression. How about the prescription stimulant? So you've got dexedrine, which is d-amphetamine, where you've got d and l-amphetamine salts, the most common brand name there being Adderall. You've got methylphenidate which is cocaine like, in that it's not an amphetamine, rather it blocks dopamine reuptake on the surface of the cell. These are effective treatments for ADHD, and they can be effective adjunctive medications in treatment resistant depression. The extended-release formulations are available and these are the ones that should be preferred therapeutically. So you've got extended release mixed amphetamine salts, brand name Adderall, you've got extended release methylphenidate in several different formulations, Concerta being one of them. And you've got lisdexamfetamine, otherwise known as Vyvanse the brand name, which is a pro-drug of amphetamine, also has slow absorption and slow elimination. So again, there's less potential for high, and less potential for misuse. Let's take a look at methamphetamine. It's a variation on amphetamine. It is pretty easy to synthesize in illicit laboratories. It's prevalent varies by region and by subculture, so there's geographic variation. It's associated in some settings with risky sex because of its sexual stimulating effects. Can be taken by mouth or intranasal or rectal, or smoked or injected. It has some neurotoxicity potentially if it's used in high doses for long enough, more so than other stimulants probably. Also, multiple other potential physical, and neuro, and psychological adverse effects. If you've seen patients with severe high dose methamphetamine use disorder, it can really be a disturbing picture. All the both physical and psychological damage that this does. Let's talk about stimulants in combination of opioid use disorder. Cocaine and methamphetamine commonly co-occur with opioid use disorder. There's casual occasional use, there's use to enhance the high or speed balling, and then there's use disorder. And other stimulant use may also be observed among patients with opioid use disorder, so you could see methamphetamine, you could see other stimulants. Sometimes these are prescribed for putative attention-deficit disorder, although the diagnosis is not always so clear. With prescribed stimulants, what are the signs to worry about of misuse or use disorder? It's similar to prescribed benzodiazepines. Consider misuse or use disorder when you've got symptoms of intoxication or withdrawal, this patient's demanding a particular medicine, usually immediate release, "Oh, extended release doesn't work for me. I need the immediate release pill." Or you know, "Only Adderall works for me." Repeated loss prescriptions, discordant pill counts, preoccupation with securing a medication supply, and also multiple prescribers. How do we evaluate cocaine or stimulant work? Well, it's difficult to quantify the dose, but I like to ask about days per week, route, smoked or intravenous, more severe than intranasal, quantify the hours per day using, look for DSM-5 use disorder symptoms like loss of control, impairment, tolerance and withdrawal. Ask about dollars spent, what's the dollar amount you're spending every day or what's the equivalent dollar value of the cocaine you're taking? Bear in mind that drugs may be obtained in exchange for services such as sex for drugs. Cocaine and stimulant acute effects. You've got intoxication that produces elevated mood, talkativeness, activity level, grandiosity, elevated vital signs, heavy use or overdose can produce agitation, elevated vital signs including hypothermia which can be quite dangerous, paranoia and psychosis, so there's a whole range. Cocaine stimulant withdrawal is like the opposite, it consists of fatigue, depression which may be severe, patients may even become suicidal during stimulant withdrawal. Insomnia then hypersomnia, and it may impair functioning for several days. Treatments for cocaine use disorder, behavioral treatment's the mainstay, advice, motivational interviewing, contingency management, CBT, cognitive behavioral therapy for relapse prevention, 12-step facilitation. There's evidence for effectiveness of all of these contingency management particularly. How about medications? Many medications have been tested for cocaine use disorder with some hints of effectiveness, but none clearly effective or FDA approved. Examples of what's been tested. Noradrenergic antidepressants, like tricyclic antidepressants or bupropion, disulfiram, topiramate, modafinil. And then you've got extended-release stimulant plus topiramate which is an interesting combination that's been tested by John Mariani and Frances Levin, and found to have some evidence of producing abstinence in actually two different clinical trials already, so that's an interesting combination to look at and think about stimulant plus topiramate. Mixed amphetamine salt slow release, so brand name Adderall slow release plus topiramate combination. So in cocaine use disorder, you want to look for attention-deficit disorder as a treatment strategy. It's common among patients with substance use disorders, including cocaine. 20% of patients seeking treatment for cocaine use disorder at least will have an attention-deficit disorder, it's very common. The diagnosis depends on a careful lifetime history to establish the ADHD diagnosis during childhood, and extended-release mixed amphetamine salts increased cocaine abstinence compared to placebo among outpatients with cocaine use disorder and co-occurring attention-deficit disorder. Dr. Levin showed that in a very nice large clinical trial. Now, among patients receiving methadone maintenance for opioid use disorder, extended-release methylphenidates been studied. It's been shown to be safe, it was not associated with misuse or diversion. However, it was very hard to see any beneficial effect in those trials, there wasn't much evidence of a benefit. Extended-release amphetamine as Adderall-XR combined with topiramate, again, has shown promise for cocaine use disorder not selected for ADHD, and it's not been tested in methadone patients or buprenorphine patients. How about treatment for amphetamine or methamphetamine use disorder? Remember that the withdrawal may be severe and require supportive treatment. Patient may be exhausted and depressed and not able to function much for several days after a binge. Contingency management's been shown to effect, be effective again, behavioral treatment, CBT for relapse prevention, 12-step facilitation. Medications. None yet FDA approved. Hints of effectiveness in some trials for naltrexone, bupropion, mirtazepine has two trials with small effects. Methylphenidate extended-release a small trial with some hints of effectiveness. There is a positive study for the combination of injection naltrexone plus bupropion, modestly effective in a large trial for methamphetamine for severe methamphetamine use disorder. And that was published in New England Journal in 2021. So how about levels of care for cocaine and other stimulant use disorders. There's limited evidence that these disorders can be managed on an outpatient basis, but studies demonstrate positive outcomes. Withdrawal does not usually require intensive medical supervision, so you don't need a hospitalization to manage withdrawal, generally, unless the patient becomes really suicidal. The level of care depends mainly on the level of psychosocial impairment. More severe impairment or disorganization. You want to think about either intensive outpatient or an inpatient residential, where inpatient residential would enforce abstinence, get the drugs out of the system, and buy some time to put into place a treatment plan. Back to our case vignette of our 35-year-old man on 16 milligrams a day of buprenorphine. The patient now begins to produce cocaine positive urines, he says he takes cocaine in the morning to combat fatigue and get to work on time. He also says his work is often tedious, the cocaine helps him stay focused. He denies all symptoms of cocaine use disorder. He asks for a prescription for Adderall, immediate release, mentioning that several years ago a doctor diagnosed him with ADHD and treated him with Adderall. Childhood history yields no indication of problems with performance or behavior at school. What would be the most appropriate next step in his treatment? A. Institute contingency management where cocaine positive urines trigger reductions in buprenorphine dose? B. Prescribe Adderall immediate release? C. Prescribe Adderall extended-release, and... I'm sorry, by Adderall, I mean, extended-release mixed amphetamine salts. D. Counsel that ongoing alprazolam and alcohol use may contribute to his fatigue. Or E. Obtain collateral history from his mother about his childhood years. I would argue both D and E. Counsel him that the ongoing alprazolam and alcohol use may be contributing to his fatigue, and why doesn't he Try stopping them and see what happens. But, and also, obtain collateral history from his mother. You always want to dig into the history as much as you can of childhood because the diagnosis of ADHD may not be obvious on initial history. Let's now talk about cannabis use and use disorder. Cannabis contains multiple potentially active compounds, THC, which is active at the cannabinoid receptor as a partial agonist. This is what's mainly responsible for the psychoactive effects, it promotes dopamine release which is what makes it addictive. Then there's cannabidiol, which is another cannabinoid, but it does not release dopamine, and it does not in itself appear to have potential for misuse, it doesn't produce psychoactive effects, particularly. It may be an anticonvulsant and it may have analgesic effects, and it's being studied for those indications. Different strains contain different concentrations. Contemporary strains may be highly potent, so contemporary strains with high concentrations of THC can cause severe intoxication that can be very unpleasant. It can engender a greater risk of a use disorder, and you can get cognitive impairment or the so-called amotivational syndrome. How about cannabis and opioid use disorder? Well, cannabis use is very common among patients with opioid use disorder, including those being treated with methadone or buprenorphine or naltrexone. And you've got some shared neuro pharmacologic mechanisms between cannabis and opioids. For example, cannabis withdrawal and opioid withdrawal share many features in common, including irritability, insomnia, and anxiety. Cannabis may have analgesic properties. Patients report taking cannabis to help with sleep or anxiety, they sometimes also report taking cannabis to deal with opioid withdrawal. How do we evaluate cannabis use disorder? You want to try to quantify it, days of use, pattern of use, smoked versus edible products, joints and blunts with the rough formula. That one blunt, which is a cigar hollowed out and filled with cannabis is an equivalent of about three joints. But quantitation is difficult and also because of the variations in potency and concentration of the THC products that can be obtained. So look for DSM-5 use disorder symptoms, loss of control, impairment, tolerance and withdrawal, which do occur with cannabis. And bear in mind that with cannabis patients often deny impairment, so it's important to get a collateral report from significant others. Failure to perform to potential in school, career, use a motivational interviewing approach to try to give the patient a little time to come around to acknowledging some of the impairment that they may be experiencing. Treatment for cannabis use disorder. Well, behavioral treatment again is the mainstay advice to cut down motivational interviewing, CBT for relapse prevention, contingency management's also been tested and found to be effective. How about medications for cannabis use disorder? None is clearly effective. Some have shown promises. A little promise from trials for gabapentin, for Marinol which is oral THC used to treat anorexia and cancer chemotherapy. Quetiapine. And what about levels of care for cannabis use disorder? Most cannabis use disorder can be managed in the office or in any other outpatient setting. Inpatients rarely necessary for safety reasons, but it may be valuable to initiate absence. It can be very hard to get someone using cannabis to quit cannabis as an outpatient, but maybe they'd agree to go inpatient to get it out of their system. And let's see how they feel once the drug is washed out of their system. In summary, conclusions about co-occurring opioid and other substance use. Co-occurring substance use is common among patients with opioid use disorder, it's almost the rule rather than the exception. We're talking alcohol, benzodiazepines, cocaine, and other stimulants like methamphetamine and cannabis. The first step is of good evaluation. Ask about the substance use applying principles of MI in your interviewing, quantify the amount and frequency of use, seek collateral report from reliable significant others, evaluate per DSM-5 use disorder criteria, classify the disorder as mild, moderate, or severe, and consider safety concerns and especially overdose risk. Look for other co-occurring disorders that the substance use may signal, depression, anxiety, PST, ADHD, sleep, or don't forget pain. Consider behavioral or pharmacological treatments for other substance use disorders. And bear in mind that much co-occurring substance use is mild to moderate severity and can be managed in the office or outpatient setting. Indications for more intensive outpatient or in inpatient care would include serious risks such as overdose or gross intoxication, severe withdrawal, severe psychosocial impairment, or failure to improve at a lower level of care. The slide deck contains a list of key references that underlie the material that I've just presented. And I would like to put in a plug for the PCSS Mentoring Program. The PCSS Mentor Program is designed to offer both general information to clinicians about evidence-based clinical practices and prescribing medications for opioid use disorder, and treating other co-occurring substance use disorder. But in addition to didactic materials in which PCSS offers a great deal, PCSs also offers mentors. It's a national network of providers with expertise in addictions, pain, evidence-based treatment, including medications for opioid use disorder. And there's a three-tiered approach that allows every mentor/mentee relationship to be unique and cater to the specific needs of the mentee. And there's no cost, so go to pcssnow.org/mentoring, if you would be interested in connecting with a mentor who you could talk with about your cases and get some coaching in how to manage patients with opioid and other substance use disorders. There's a PCSS discussion forum where if you have a clinical question, you can ask a colleague, and it's a simple way to get direct answers or prompt discussion. And this is the link to the website here. PCSS is a collaboration of many professional organizations, each with a stake in the opioid problem. And with that, I would like to thank you for your attention. I hope you've found it helpful. And that concludes my talk.

substance use disorders

opioid use disorder

benzodiazepines

cocaine

amphetamines

cannabis

DSM-5 criteria

co-occurring psychiatric disorders