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Objective: Few studies of prescription stimulant non-oral, non-medical use (NMU) (defined by use not as prescribed) have been conducted in adults beyond the college population. The purpose of this study was to characterize prescription stimulant non-oral use, specifically intranasal (IN) use (snorting) in young adults. Method: Amazon’s MTurk platform was used to recruit participants for an online survey. Data were collected from March to April 2020. Results: Thirty-two percent ( n = 157) of survey respondents ( N = 975), aged 18 to 30, reported IN prescription stimulant use (average of 32.1 episodes of lifetime IN use). Adderall was the most-reported prescription stimulant used intranasally (89.2%). Most IN users (82%; n = 68) reported spending no more than 5 minutes tampering with prescription stimulants. Intranasal users said they would take the medication orally if unable to tamper or manipulate medication for IN use. Conclusion: These data help quantify a complex public health issue of ongoing IN use of prescription stimulants and suggest a potential role for manipulation-deterrent medications.

Objective: The purpose of the present study was to characterize prescription stimulant non-medical use (NMU) in adolescents between the ages of 13 and 18 years seeking treatment for substance use disorder (SUD) with the Comprehensive Health Assessment Tool for Teens (CHAT™). Method: Adolescents being evaluated for SUD treatment between Q1 2010 and Q3 2017 ( n = 20,189) completed the CHAT™. Results: About 4.3% of the sample ( N = 867) of adolescents in SUD treatment reported past 30-day prescription stimulant NMU. Compared to those without past 30-day prescription stimulant NMU, more reported a lifetime diagnosis of learning disorder or ADHD, more took medication for emotional, behavioral, or learning disorders, received past-month inpatient treatment, or were currently not enrolled in school. Prescription stimulants were most often taken orally for NMU, however, approximately half reported using alternate routes of administration, the most prominent of which was intranasal use. Conclusion: About 4.3% of adolescents in SUD treatment evaluation reported past 30-day prescription stimulant NMU. Greater percentages of lifetime learning disorder, medication use, past-month inpatient treatment, school unenrollment, and overall substance misuse were associated with prescription stimulant NMU, as were alternate routes of administration. These data reveal an ongoing, persistent level of past-30-day NMU of prescription stimulants among adolescents being evaluated for SUD treatment.

Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an active pharmaceutical ingredient (API) when immediate-release as well as extended-release formulations were on the market together (fourth quarter of 2011 to second quarter of 2016). Tapentadol (API) was compared with tramadol, hydrocodone, morphine, oxycodone, hydromorphone, and oxymorphone across Poison Center, Drug Diversion, and Treatment Center Programs Combined data streams from the Researched Abuse, Diversion and Addiction-Related Surveillance system. Findings suggest the public health burden related to tapentadol to date is low, but present. Event rates of abuse per population-level denominators were significantly lower than all other opioids examined. However, when adjusted for drug availability, event rates of abuse were lower than most Schedule II opioids studied, but were not the lowest. Disentangling these 2 sets of findings further by examining various opioid formulations, such as extended-release and the role of abuse-deterrent formulations, is warranted. Perspective This article presents the results from an examination of tapentadol API across the Researched Abuse, Diversion and Addiction-Related Surveillance System: a broad and carefully designed postmarketing mosaic. Data to date from Poison Center, Drug Diversion, and Treatment Centers combined suggest a low, but present public health burden related to tapentadol.

Background and objectives Opioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA-approved medications is an evidence-based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone-based relapse-prevention treatment. Methods Literature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone. Results Emerging practices for extended-release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences. Conclusions and scientific significance Treatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended-release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. (© 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177-187).

NMU of prescription stimulant medications (RxStim) intended for treatment of attention deficit/hyperactivity disorder (ADHD) is a growing public health concern, particularly when used via non-oral routes of administration. However, the role of non-oral routes of administration for RxStim NMU in the larger substance abuse pathway is less well studied. The purpose of this study was to characterize RxStim NMU and investigate substance use trajectories among adults who reported non-oral RxStim NMU recruited from Reddit.Eligible participants must have been located in the US, English speaking, age 18 y, and have reported RxStim NMU via a non-oral route (any route other than ingestion) within the past 5 y. Participants were recruited from Feb-Sep 2019 using banner ads on Reddit, the 5th most visited website in the US. Participants completed an online survey which captured demographics, lifetime RxStim NMU and illicit substance use; they were compensated for their time. For purposes of this study, NMU included ANY of the following: (1) use for any reason, even once, without their own prescription, (2) use in ways other than prescribed, and (3) use for the feeling or experience the medication caused.Respondents (n=225) were primarily male (86.2%), 18–24 (48.0%) or 25–34 (43.1%) years of age, and Caucasian (78.2%), Black (7.1%) or Hispanic (5.3%). Lifetime diagnosis of ADHD was reported by 27.6%, with 53.2% diagnosed at age 11–19 and 35.5% at age 20+ years. RxStim NMU via snorting was reported by 99.1%, smoking 3.6% and injecting 6.2% (multiple routes could be reported). Almost all (n=222; 98.7%) also reported lifetime illicit drug use, among whom 182 (82.0%) initiated substance use by using an illicit drug (77.9% marijuana, 1.8% cocaine/crack, 0.9% inhalants, 0.9% hallucinogens, 0.5% methamphetamine/amphetamines) prior to RxStim NMU. Forty (18.0%) respondents initiated with RxStim NMU; 14.4% then initiated marijuana use, 0.9% initiated cocaine/crack use, 0.9% initiated barbiturate use, and 0.5% initiated heroin, inhalant, methamphetamine/amphetamine, and hallucinogen use. Average age of initial RxStim NMU was 18.7 (SD 3.7) years and most often was via swallowing (89.1%) followed by snorting (10.9%). Respondents began using marijuana at age 15.9 (SD 2.5), cocaine or crack at 19.7 (SD 3.3), and heroin at 20.9 (SD 5.5).Engagement in RxStim NMU via a non-oral route of administration is most often preceded by marijuana use. Among this Reddit-recruited population of non-oral RxStim nonmedical users, only 1 in 4 reported an ADHD diagnosis and Funding. Arbor Pharmaceuticals, LLC

Objective: Studies have suggested that the N-methyl-D-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence.Design: This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers.Participants: Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days.Interventions: Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants.Results: Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving.Conclusions: In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence.

This qualitative study summarizes information that individuals shared online about use of OxyContin following the August 2010 introduction of the abuse deterrent formulation (ADF). Purpose The primary objective was to study online posts that endorsed continued use of OxyContin or a switch from OxyContin to another formulation of oxycodone or another substance altogether following the introduction of the ADF. A secondary objective was to determine whether posts revealed that the ADF led to cessation of OxyContin use. Methods Data were collected with the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program, an online surveillance system that collects and organizes posts about prescription drugs from social media websites, blogs, and forums from 3Q2009 to 4Q2014 using a commercially available web platform. Results Posts were categorized by whether they conveyed a switch to drugs other than reformulated OxyContin or a continuation of reformulated OxyContin abuse. “Switch posts” primarily discussed switching to immediate-release opioids. “Continue abusing” posts identified tampering strategies for alternate routes of administration, oral use, and continued use although post authors were generally unhappy with the experience. No reference to OxyContin cessation as a function of the introduction of the ADF was found; however, discontinued use was discussed. Conclusions Web Monitoring data are useful for capturing cross sections of Internet conversation reflecting reactions to new drug formulations. These data support the notion that users will gravitate to non-ADFs generally, and to immediate-release non-ADF opioid formulations, specifically, as long as these options remain on the market.

BACKGROUND The prevalence of abuse, diversion, and web-based endorsement of tapentadol (extended-release [ER], immediate-release [IR]) has been characterized as low compared with other prescription opioids. Little is known about individual experience with tapentadol nonmedical use (NMU). OBJECTIVE This study aims to pilot web-based survey technologies to investigate the motivation for tapentadol NMU, sources of procurement, routes of administration, tampering methods, doses used, and impressions of tapentadol products (Nucynta and Nucynta ER). METHODS Recruitment flyers and banner advertisements were placed on the Bluelight website [DragonByte Technologies Ltd] with a link to a web-based survey (Qualtrics) designed to query about individuals’ lifetime tapentadol NMU. This web-based survey was followed by an interactive web-based chat (Cryptocat) with respondents who were willing to be contacted. Respondents were queried about sources for obtaining tapentadol, motives for use, routes of administration, tampering methods, drugs used in combination, tablet strengths and dosages, and reasons for continued or discontinued use. Desirability and attractiveness for NMU was rated. RESULTS Web-based recruitment successfully attracted difficult-to-find study participants. A total of 78 participants reported that tapentadol was obtained from friends and family (ER 11/30, 37%; IR 18/67, 27%), the internet (ER 11/30, 37%; IR 12/67, 18%) or participants’ own prescriptions from a doctor (ER 9/30, 30%; IR 17/67, 25%). It was used nonmedically for pain relief (ER 18/30, 60%; IR 33/67, 49%) and multiple psychotropic effects, including relaxation (ER 13/30, 43%; IR 29/67, 43%), reduction in depression or anxiety (ER 7/30, 23%; IR 30/67, 45%), or getting high (ER 12/30, 40%; IR 33/67, 49%). Tapentadol was primarily swallowed (ER 22/30, 73%; IR 55/67, 82%), although snorting (ER 2/30, 7%; IR 8/67, 12%) and injection (ER 2/30, 7%; IR 5/67, 8%) were also reported. The preferred dose for NMU was 100 mg (both ER and IR). The participants reported tapentadol use with benzodiazepines (ER 12/21, 57%; IR 28/47, 60%). Most participants had discontinued tapentadol NMU at the time of survey completion (ER 22/30, 73%; IR 55/67, 82%). Reasons for discontinued ER NMU included side effects (10/22, 46%) and lack of effective treatment (10/22, 46%). Reasons for discontinued IR NMU included lack of access (26/55, 47%) and better NMU options (IR 21/55, 38%). Few individuals were willing to divulge identifying information about themselves for the interactive chat (8/78, 10%), demonstrating the strength of anonymous, web-based surveys. Interactive chat supported the survey findings. A subgroup of participants (4/78, 5%) reported hallucinogenic side effects with high doses. CONCLUSIONS Web-based surveys can successfully recruit individuals who report drug NMU and those who are difficult to find. Tapentadol NMU appears to occur primarily for pain relief and for its psychotropic effects. Although it was liked by some, tapentadol did not receive a robust pattern of endorsement for NMU.

Background The prevalence of abuse, diversion, and web-based endorsement of tapentadol (extended-release [ER], immediate-release [IR]) has been characterized as low compared with other prescription opioids. Little is known about individual experience with tapentadol nonmedical use (NMU). Objective This study aims to pilot web-based survey technologies to investigate the motivation for tapentadol NMU, sources of procurement, routes of administration, tampering methods, doses used, and impressions of tapentadol products (Nucynta and Nucynta ER). Methods Recruitment flyers and banner advertisements were placed on the Bluelight website [DragonByte Technologies Ltd] with a link to a web-based survey (Qualtrics) designed to query about individuals’ lifetime tapentadol NMU. This web-based survey was followed by an interactive web-based chat (Cryptocat) with respondents who were willing to be contacted. Respondents were queried about sources for obtaining tapentadol, motives for use, routes of administration, tampering methods, drugs used in combination, tablet strengths and dosages, and reasons for continued or discontinued use. Desirability and attractiveness for NMU was rated. Results Web-based recruitment successfully attracted difficult-to-find study participants. A total of 78 participants reported that tapentadol was obtained from friends and family (ER 11/30, 37%; IR 18/67, 27%), the internet (ER 11/30, 37%; IR 12/67, 18%) or participants’ own prescriptions from a doctor (ER 9/30, 30%; IR 17/67, 25%). It was used nonmedically for pain relief (ER 18/30, 60%; IR 33/67, 49%) and multiple psychotropic effects, including relaxation (ER 13/30, 43%; IR 29/67, 43%), reduction in depression or anxiety (ER 7/30, 23%; IR 30/67, 45%), or getting high (ER 12/30, 40%; IR 33/67, 49%). Tapentadol was primarily swallowed (ER 22/30, 73%; IR 55/67, 82%), although snorting (ER 2/30, 7%; IR 8/67, 12%) and injection (ER 2/30, 7%; IR 5/67, 8%) were also reported. The preferred dose for NMU was 100 mg (both ER and IR). The participants reported tapentadol use with benzodiazepines (ER 12/21, 57%; IR 28/47, 60%). Most participants had discontinued tapentadol NMU at the time of survey completion (ER 22/30, 73%; IR 55/67, 82%). Reasons for discontinued ER NMU included side effects (10/22, 46%) and lack of effective treatment (10/22, 46%). Reasons for discontinued IR NMU included lack of access (26/55, 47%) and better NMU options (IR 21/55, 38%). Few individuals were willing to divulge identifying information about themselves for the interactive chat (8/78, 10%), demonstrating the strength of anonymous, web-based surveys. Interactive chat supported the survey findings. A subgroup of participants (4/78, 5%) reported hallucinogenic side effects with high doses. Conclusions Web-based surveys can successfully recruit individuals who report drug NMU and those who are difficult to find. Tapentadol NMU appears to occur primarily for pain relief and for its psychotropic effects. Although it was liked by some, tapentadol did not receive a robust pattern of endorsement for NMU.

The progression from prescription opioid (RXO) abuse to RXO addiction is not well understood in adolescents, nor is the progression from RXO addiction to heroin abuse. The purpose of this pilot study was to characterize the development of RXO drug abuse, RXO drug addiction, and heroin abuse in a small cohort of adolescents recovering from opioid addiction at Massachusetts Recovery High Schools (RHS). A self-report questionnaire was administered to 31 adolescent, former RXO abusers across two Massachusetts RHS. RXO abuse was primarily initiated due to curiosity; RXOs were initially obtained through illicit and licit methods. Fifty-eight percent (N = 18) of the RXO abusers became addicted to RXOs. Many addicted adolescents initiated RXO abuse under the influence of marijuana, yet believed that they became addicted due to the stress from difficult life situations. A subgroup indicated they abused and became addicted to RXOs that had been obtained from legitimate prescriptions due to their pain. Sixte...

Glial activation is hypothesized to contribute directly to opioid withdrawal. This study investigated the dose-dependent effects of a glial cell modulator, ibudilast, on withdrawal symptoms in opioid-dependent volunteers after abrupt discontinuation of morphine administration. Non-treatment-seeking heroin-dependent volunteers (n = 31) completed the in-patient, double-blind, placebo-controlled, within-subject and between-group study. Volunteers were maintained on morphine (30 mg, QID) for 14 days and placebo (0 mg, QID) for the last 7 days of the 3-week study. Volunteers also received placebo (0 mg, PO, BID) capsules on days 1-7. On days 8-21, volunteers were randomized to receive ibudilast (20 or 40 mg, PO, BID) or placebo capsules. Subjective and clinical ratings of withdrawal symptoms were completed daily using daily using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opioid Withdrawal Scale (COWS). Medication side effects were also monitored. Relative to the first 2 weeks, all groups exhibited withdrawal during the third week as assessed by the SOWS and COWS (P ≤ 0.0001). Although overall SOWS scores did not differ between groups, exploratory analyses pooling the two ibudilast groups demonstrated that they had lower ratings of withdrawal symptoms on SOWS items ('anxious,' 'perspiring,' 'restless,' 'stomach cramps') during detoxification relative to the placebo group. Ibudilast was well tolerated; no serious adverse events occurred during the study. Pharmacological modulation of glial activity with ibudilast decreased some subjective ratings of opioid withdrawal symptoms. These exploratory findings are the first to demonstrate the potential clinical utility of glial modulators for treating opioid withdrawal in humans.

Background The characteristics of patients with co-occurring chronic pain and prescription opioid abuse have not been well described, and even less is known about differences between men and women in this population. Objectives This study evaluated sex differences in the demographic, diagnostic, and behavioral attributes of patients with chronic pain and opioid abuse. Methods Data were collected via self-report and semistructured clinical interviews from 162 patients (120 men and 42 women) who screened for a study investigating the abuse liability of prescription opioids. Results There were no differences between men and women in age, race, education, marital status, or employment status. Participants had used prescription opioids for 5.4 ± 6.7 years. The majority of participants (60%) had low back pain in addition to opioid dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. More women reported more arthritic pain than men, but otherwise there were no differences in types of pain. Pain exerted a greater effect in women on mood, walking ability, and social relations. Men reported more of certain aberrant behaviors, including abuse of alcohol or illicit drugs, unauthorized dose increases, contact with street culture, and being arrested by police. Women were more depressed than men. Conclusions The demographic profile of opioid-abusing patients with chronic pain presenting for treatment in a clinical trial was similar between sexes; however, some important differences were observed. Women reported more psychiatric comorbidity and endorsed greater pain-related physical and social impairment. Men reported more aberrant behaviors. These differences suggest that men with chronic pain and opioid abuse/dependence may benefit by closer monitoring of aberrant behaviors whereas women may benefit from closer attention paid to physical and psychological effects of pain.

OBJECTIVES Many adolescents and young adults report having chronic pain. Urine drug toxicology (UDT) is not routinely used in the pediatric pain management population, despite more routine use in adults with pain, particularly those prescribed opioids. As a first step toward establishing monitoring practices in pediatric and adolescent pain management, the present study evaluated the role of UDT in conjunction with a standard clinical interview in identifying the rate of adherence to an established analgesic regimen. The study also aimed to assess the use of UDT in identifying possible aberrant behaviors in this population. METHODS Data were acquired from a convenience sample of 50 pediatric and adolescent pain management initial consultations, during which a clinical interview and UDT were conducted. Data were analyzed to determine adherence to an established analgesic prescription regimen, and for identification of aberrant behaviors including concurrent use of illicit substances and prescription medication misuse. Other pertinent demographic and clinical factors were examined as factors in adherence. RESULTS Opioid medications were prescribed for 42% of the sample receiving pain medications, and 22% of the sample was nonadherent to their prescription analgesic regimen. Factors associated with a higher likelihood of nonadherence were an older age and having an opioid prescription. The majority (90%) of those nonadherent to their analgesic regimen displayed some form of aberrant behavior. Among the nonadherent patients, 50% were identified by UDT alone, and 50% were identified by self-report during the clinical encounter. CONCLUSIONS These results highlight the challenges of identifying nonadherence to a prescription regimen among adolescents with chronic pain. In addition, this preliminary work suggests that UDT could be used in conjunction with careful clinical interviewing to substantiate patient report and increase the likelihood of detecting analgesic nonadherence and aberrant behaviors.

This chapter reviews the conduct of the human abuse potential study from the regulatory perspective, as outlined in the Food and Drug Administration (FDA)'s 2010 Guidance for Industry: Assessment of Abuse Potential of Drugs. Using the guidance as an outline, the chapter describes how human abuse potential studies are conceived and conducted, how they are analyzed, how Adverse Events (AEs) are considered, and how abuse liability may continue to be monitored after drug approval. Human abuse potential trials by themselves are not sufficient to bring about drug scheduling; however, they are a critical piece of the abuse liability assessment submitted to the FDA as part of a New Drug Application (NDA). Thus, this chapter summarizes a critical piece of the regulatory package.