Treatment Of Opioid Dependence Research Articles

Getting ready for AATOD: If you want to learn, go to Las Vegas

This week the American Association for the Treatment of Opioid Dependence (AATOD) holds its conference in Las Vegas, at the Planet Hollywood Resort and Casino. The meeting theme is “Treating Opioid Use Disorder: So much more than medication.” That is very timely, considering that there is a move to make treatment with methadone, what opioid treatment programs are allowed to prescribe and dispense, medication‐only by office‐based physicians. This move is codified in proposed legislation. As we have pointed out many times, only rarely in this country has methadone been prescribed for OUD outside of an OTP, and when it is, only highly qualified methadone‐experienced physicians have been allowed to do it. We will be at AATOD looking at how the organization and its members are working to improve treatment for patients.

More on methadone take‐home changes in SAMHSA final rule

The American Association for the Treatment of Opioid Dependence (AATOD) hosted two webinars on the final rule for opioid treatment programs, both of which we covered (see tk and tk). One of the key provisions is changes in take‐homes. The changes incorporate flexibilities of the COVID‐19 era, in which more take‐homes were allowed to limit the exposure of patients and staff to the virus. The new rule allows for up to seven days of take home doses during the first 14 days of treatments, and up to 14 doses up from 15 days of treatment and 28 take home doses from 31 days in treatment.” This month AATOD president Mark Parrino commented on various aspects of the rule, which he supports in general, to clarify the role of the OTP. Always the undercurrent exists that the OTP has full liability for any mishaps. And this is codified in the rule, which states: “The requirement that OTPs maintain procedures to protect take home from theft and diversion is finalized as well as patient education on safe transport and storage of take home doses, including documentation of the provision of this education and the patient's clinical record.” Parrino says: “To be clear, the OTP clinician makes the final determinations of who is eligible to receive take home medication. While toxicology reports should not be used punitively, they should be employed in providing objective information to the clinician within the OTP as to best ascertain who is most capable of handling take home medication at such early stages of treatment. We have stated this throughout our commentary on regulatory oversight of take home medication. There must be a balance in providing flexibility to the patients in order to retain the patients in treatment against the safety of providing such take home medication to an unsupervised individual. While we have learned that there is increased safety in providing such take home to patients as a result of the COVID‐19 experience, it does not relieve the OTP using careful balancing standards in order to provide safety and flexibility.”

ASAM features harm reduction, methadone, OTPs at conference

Not surprisingly, last week'k American Society of Addiction Medicine (ASAM) conference was sold out, with its big focus on moving methadone out of the opioid treatment program (OTP) system and into general office‐based care (preferably by only ASAM‐boarded physicians), and also considerable attention paid to the value of high‐quality treatment with methadone. A track called “Methadone in the Modern Era” included Ruth Potee, M.D., in an impassioned speech focused on the need for more access to methadone, and on the for‐profit OTPs that are out there. That track also featured Yngvild Olsen, M.D., director of the Center for Substance Abuse Treatment at the Substance Abuse and Mental Health Services Administration (SAMHSA) who talked about the other modern (aka, real world) era in which OTP regulations have been completely updated and revised. Aaron Ferguson, who said at a public conference last fall that he owed his life to diverted methadone (see https://onlinelibrary.wiley.com/doi/10.1002/adaw.33908) despite being a patient advocate, also presented at the conference, this time on harm reduction, which is beneficial to keeping people alive. Many OTPs, especially the large chain for‐profit OTPs, have been a target of ASAM members for years; most are also members of the American Association for the Treatment of Opioid Dependence, and some are members of the National Association for Behavioral Healthcare.

Schorr and Hurley to receive AATOD'D Nyswander‐Dole award

Allegra Schorr and Linda Hurley will each receive the Nyswander/Dole “Marie” Award during the conference of the American Association for the Treatment of Opioid Dependence (AATOD) next month. Schorr, president of the Coalition of Medication‐Assisted Treatment Providers and Advocates of New York State (COMPA), and Hurley, president and CEO of CODAC Behavioral Healthcare in Rhode Island, will accept the awards from AATOD. The award, the highest accolade AATOD can bestow upon someone in recognition for having made significant contributions in the field of opioid use disorder treatment, is named after Vincent Dole, M.D., and Marie Nyswander, M.D., two pioneers in the research of medication‐assisted treatment for addiction. Dole and Nyswander were the first recipients of this award in 1983.

SAMHSA calls for “culture change” in methadone treatment

New regulations for opioid treatment programs (OTPs) create many new flexibilities for methadone practitioners and providers, and last month'h webinar for administrators focused on the key points. The Substance Abuse and Mental Health Services Administration (SAMHSA), which implements the 42 CFR Part 8 regulations, presented the information to about 800 attendees via a Zoom call on March 20 that was hosted by the American Association for the Treatment of Opioid Dependence (AATOD). Next week, ADAW will cover the March 27 webinar, which was for clinicians. For more on the new rule, see https://onlinelibrary.wiley.com/doi/10.1002/adaw.34023.

A multicomponent LC-MS/MS method for drugs of abuse testing using volumetric DBS and a clinical evaluation by comparison with urine

BackgroundDrug testing commonly use urine as a specimen and immunoassays for screening. The need for supervised urine collection has led to an interest in alternative specimens and a need for using mass spectrometry methods already for screening. In addition, mass spectrometry methods allow for broad multipanel screening which of great value because of the increased number of substances that needs to be covered has increased over time. One alternative specimen of interest for drugs of abuse testing is dried blood spots (DBS) and this work aimed at developing multipanel screening methods based on selected reaction monitoring liquid chromatography - mass spectrometry for both urine and dried finger blood as specimens. Materials and MethodsThe urine method comprised 37 analytes and utilised salted out liquid/liquid extraction in 96-well format, respectively, and the blood method comprised 35 analytes, a 10 µL volumetric DBS device and a two-step solvent extraction procedure. In both cases stable isotope labelled internal standards were used for almost all analytes. ResultsThe methods were validated according to forensic standard. The lowest reporting limits were generally set at 100 ng/mL for urine and 1 ng/mL for blood and the accuracy and imprecision were within limits of 15 and 20%. The methods were applied in a clinical study on patients receiving methadone maintenance treatment for opioid dependence. Methadone was detected in all urine and DBS samples, for urine sometimes below the commonly applied screening cutoff limit of 300 ng/mL. In 20 out of 99 cases no other drug was detected in any specimen. The most commonly other detected substances were pregabalin, amphetamine, alprazolam, zopiclone and THCCOOH. Findings in urine and DBS generally agreed well but more positives were detected in DBS. ConclusionMultipanel methods using liquid chromatography – mass spectrometry suitable for clinical drug screening were successfully developed for urine and blood collected by finger-pricking and stored as DBS.

Experience of patients on methadone maintenance treatment receiving take-home methadone doses during COVID-19 pandemic: A multi-site study from India

BackgroundMethadone take-home doses for opioid dependence treatment are strictly regulated due to diversion and overdose concerns, so patients must visit the clinic daily for dispensing. This was also done in India until the COVID-19 pandemic, when lockdown restriction compelled take- home dispensing of methadone. This study examined experience of patients who received take- home methadone during COVID-19 pandemic in India. MethodsObservational, cross-sectional design. We contacted all consenting methadone centres in India during the lockdown and selected those that provided take-home doses for the study. Patients who received daily methadone before the lockdown and take-home doses after were interviewed using a study-specific questionnaire. ResultsThe study had 210 participants. Take-home methadone was dispensed for 2.5 days on average in each dispensing. When taking methadone at home, 3.3% split their dose 25% took less than the prescribed dose to save it for a rainy days, and 3.3% reported an overdose episode. Adherence improved in 58.6% participants after take-home methadone. Participants perceived many benefits from take-home methadone such as reduced hospital visits and travel time to collect methadone, improvement in work, and financial savings. About 54.3% participants reported storing their take-home doses safely, and 1.9% reported that their family consumed methadone by mistake. ConclusionsTake-home methadone was found to be beneficial to most participants in terms of time saved and improved productivity. Preconceived concerns of providing take-home methadone in terms of its overdose, diversion, or accidental ingestion by others are not commonly seen when individuals are provided take-home doses of methadone.

OTPs gladly plan to implement new methadone rules

On Feb. 2 the Substance Abuse and Mental Health Services Administration (SAMHSA) released its final rule for opioid treatment programs and methadone, just as ADAW went to press (see SAMHSA issues final rule updating OTP methadone rules, ADAW Feb. 5; https://onlinelibrary.wiley.com/doi/10.1002/adaw.34023). The American Association for the Treatment of Opioid Dependence (AATOD), which represents more than 1,300 opioid treatment programs (OTPs) in the United States, last week commended SAMHSA for the guidance, which it called “enlightened and thoughtful.” In a Feb. 5 press statement, AATOD president Mark Parrino noted that the regulations have been reviewed by the Drug Enforcement Administration (DEA). For the final rule, go to https://www.federalregister.gov/documents/2024/02/02/2024‐01693/medications‐for‐the‐treatment‐of‐opioid‐use‐disorder.

Monitoring buprenorphine in patients on medication-assisted treatment.

Buprenorphine is used for medication-assisted treatment of opioid dependence. Monitoring of medication adherence involves testing of urine or oral fluid for the drug or its metabolite. Quantitative results using liquid chromatography tandem mass spectrometer testing defined the excretion pattern of the drug and its metabolites. Frequency distribution curves of buprenorphine and norbuprenorphine describe the expected drug concentrations of patients on this medication. Urine and oral fluid drug testing can be used to monitor adherence in this population.

The impact of changes in opioid dependency treatment upon COVID-19 transmission in Sydney, Australia: a retrospective longitudinal observational study

BackgroundIn April 2020, in response to the COVID-19 public health emergency, South Eastern Sydney Local Health District (SESLHD) Drug and Alcohol services modified their delivery of opioid dependency treatment (ODT) to reduce spread of COVID-19 and maintain continuity of care by increasing use of takeaway doses (TADs), transferring clients to local community pharmacies for dosing and encouraging the use of long-acting depot buprenorphine (LADB) which enabled once a month dosing.MethodsThis study was a retrospective longitudinal case–control study conducted from August 1st, to November 30th, 2021. Eligible clients were those admitted for treatment with SESLHD ODT Services prior to August 1st,2021 and who remained in treatment beyond November 30th, 2021. COVID-19 diagnoses were determined by a COVID-19 PCR and extracted from the electronic Medical Records (eMR) Discern Reporting Portal. Demographic, clinical and dosing related data were collected from eMR and the Australian Immunisation Register (AIR).ResultsClients attending SESLHD ODT services had significantly greater odds of acquiring COVID-19 than the NSW adult population at large (OR: 13.63, 95%CI: 9.64,18.88). Additionally, amongst SESLHD ODT clients, being of Aboriginal and Torres Strait Islander origin was associated with greater odds of acquiring COVID-19 (OR = 2.18, CI: 1.05,4.53); whilst being employed (OR = 0.06, CI:0.01,0.46), receiving doses at pharmacy (OR = 0.43, CI: 0.21,0.89), and being vaccinated (OR = 0.12, CI: 0.06,0.26) were associated with lower odds. Every additional day of attendance required for dosing was associated with a 5% increase in odds of acquiring COVID-19 (OR = 1.05, CI: 1.02,1.08).ConclusionsClients attending SESLHD ODT services are significantly more likely to acquire COVID-19 than the NSW population at large. Promoting vaccination uptake, transferring clients to pharmacy, and reducing the frequency of dosing (by use of takeaway doses or long-acting depot buprenorphine) are all potential methods to reduce this risk.

Assessment of Toxicity and Biological Effects of α-Pinene on Morphine Tolerance and Dependence in Mice

Background: Research shows that α-Pinene interacts with the opioidergic system. Objectives: This study aims to examine the toxicity and the effects of α-Pinene on morphine tolerance and dependence in mice. Methods: Guidelines No. 423 and No. 407 were used to investigate acute and sub-chronic toxicity, respectively. For sub-chronic toxicity analysis, the animals were sacrificed on day 28, and blood and tissue samples were collected. After inducing morphine tolerance or dependence, in both phases, animals received i.p. vehicle, diazepam (5 mg/kg), and α-Pinene (3.125, 6.25, and 12.5 mg/kg). Withdrawal signs were recorded for 30 minutes. Results: Only the acute dose of α-Pinene showed mortality in animals, but mild lesions were seen in the brain, liver, and kidneys in the mice receiving its subchronic dose. Moreover, ALT, AST, ALP, and TG levels increased (P < 0.05) in female mice. Besides, 6.25 and 12.5 mg/kg (P < 0.001) of α-Pinene and only its high dose (12.5 mg/kg) (P < 0.001) reduced the number of jumps in the tolerance and dependence phases, respectively. Diarrhea (P < 0.001), writhing (P < 0.001), rearing, and climbing (P < 0.05 and P < 0.001, respectively) behaviors decreased in the tolerance phase, and grooming, climbing, and teeth chattering declined in the dependence phase (P < 0.001). Conclusions: The LD50 of α-Pinene was lower than 2000 mg/kg, but its subchronic dose caused mild tissue toxicities and biochemical changes. Moreover, α-Pinene decreased morphine tolerance and dependence and possibly was useful for the treatment of opioid dependence after complimentary trials.

AATOD CEO on state of affairs of OTPs today

Mark Parrino, founder and President of the American Association for the Treatment of Opioid Dependence (AATOD), highlighted some of the reasons for the current outlook on opioid treatment programs (OTPs) – which for a few months or years, depending on your perspective, has not been great. The main reason is the American Society of Addiction Medicine (ASAM), which used to be a solid partner of AATOD and OTPs (see https://onlinelibrary.wiley.com/doi/10.1002/adaw.30330), but which in recent years has had a change in leadership and advocacy. What ASAM wants now is for MOTAA to pass – a bill which would allow ASAM‐certified physicians to prescribe methadone for opioid use disorder (OUD) to their patients. Under current federal law and regulation, only federally certified OTPs can provide (prescribe and dispense) methadone, and they do a lot more than just provide the medication.

Review: Retention is better with methadone than buprenorphine

In “Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta‐analysis of randomized and observational studies,” authors Louisa Degenhardt and colleagues reviewed studies to compare the effectiveness of methadone with buprenorphine. Their study, published in the June 2023 issue of Lancet Psychiatry, found that treatment retention was better with methadone than buprenorphine. The study was a meta‐analysis that identified 32 randomized controlled trials (RCTs) of 5,800 participants and 69 observational studies of 323,340 participants. Primary outcomes were.

'Planning for a healthy baby and a healthy pregnancy': A critical analysis of Canadian clinical practice guidelines for the treatment of opioid dependence during pregnancy.

As opioid fatalities rise in North America, the need to improve the supports available to those who are dependent on opioids and pregnant has become more urgent. This paper discusses the social organisation of drug treatment supports for those who are pregnant, using Canadian clinical practice guidelines (CPGs) for methadone maintenance treatment (MMT) as a case study. Pregnant patients are a priority population for MMT, both in Canada and internationally; the regulatory bodies that oversee MMT in Canada are the provincial Colleges of Physician and Surgeons and Health Canada. The paper analyses MMT CPGs published by these agencies, comparing their general recommendations to those specific to pregnant patients. We demonstrate that the guidelines address few treatment considerations for pregnant patients, other than improved birth outcomes and child welfare, despite acknowledging their more complex needs. Drawing on social science studies of gender and drugs, we argue that MMT CPGs therefore perpetuate the intensified surveillance and foetal prioritisation that have long generated barriers to care for opiate-dependent pregnant patients. We also discuss how and why the CPGs ultimately only reinforced these current limitations in the drug treatment sector.

B-325 Retrospective Study Comparing Immunoassay Screen and Mass Spectrometry Confirmation Results in an Opioid Dependant Population

Abstract Background Retrospective analysis of clinical laboratory data is employed to monitor the performance of instruments, evaluate test utilization and support operational changes. Urine drug testing in the context of opioid use disorder is used to assist in the management of patients. This testing is typically performed by an immunoassay screen followed by mass spectrometry confirmation. Immunoassay screens identify drug class and can cross-react with off-target substances to produce false-positive or false-negative results. Mass spectrometry confirmations provide more sensitive and specific results. The objective of this study was to utilize historical data to determine the concordance between immunoassay and mass spectrometry results from patients in an opioid dependency treatment program. Methods Urine drug screening results spanning a 3-year period (2020–2023) were mined to identify samples that screened positive for amphetamines, benzodiazepines, opiates, fentanyl/carfentanil, oxycodone/oxymorphone, and cocaine. These results were compared to the mass spectrometry confirmation results. The immunoassay results were collected on an Olympus AU480 instrument and the mass spectrometry results were collected using an in-house developed dynamic multiple reaction monitoring method on both Agilent 6470 and 6460 triple quadrupole instruments. Results Of the 15 850 urine drug records reviewed, 28.8% screened positive for amphetamines, 23.5% screened positive for benzodiazepines, 14.2% screened positive for opiates, 23.8% screened positive for fentanyl/carfentanil, 4.2% screened positive for oxycodone/oxymorphone, and 11.2% screened positive for cocaine. Of the amphetamine class samples that screened positive, 95.3% confirmed positive and 4.7% confirmed negative. Of the benzodiazepine class samples that screened positive, 50.8% confirmed positive and 49.2% confirmed negative. Of the opiate class samples that screened positive, 79.8% confirmed positive and 20.2% confirmed negative. Of the fentanyl/carfentanil samples that screened positive, 97.2% confirmed positive and 2.8% confirmed negative. Of the oxycodone/oxymorphone samples that screened positive, 58.5% were confirmed positive and 41.5% confirmed negative. Of the cocaine samples that screened positive, 99.8% confirmed positive and 0.2% confirmed negative. Conclusion Our findings determined there were discrepancies among all classes when comparing immunoassay vs mass spectrometry results. There was good agreement between immunoassay and mass spectrometry results in the detection of fentanyl/carfentanil, cocaine and amphetamines. The differences between methods were most significant in the benzodiazepine, opiate and semi-synthetic opioid classes. This may be due to different cut-off levels between methods, specificity limitations of immunoassays and/or changing drug use patterns resulting in mass spectrometry multiple reaction monitoring false negative results.

Long-Acting Buprenorphine Formulations as a New Strategy for the Treatment of Opioid Use Disorder.

Long-acting buprenorphine formulations have been recently marketed for the Opioid Agonist Treatment (OAT) of opioid use disorder (OUD) associated with medical, social, and psychological support. Their duration of action ranges from one week up to 6 months. The non-medical use of opioids is increasing with a parallel rise in lethal overdoses. Methadone and buprenorphine are the standard treatment for opioid dependence. Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing the risks of overdose, crime, and transmission of HIV (Human Immunodeficiency Virus) in people who use opioids; however, its effectiveness has been hindered by low rates of uptake and retention in treatment. Furthermore, both methadone and buprenorphine are widely diverted and misused. Thus, a crucial aspect of treating OUD is facilitating patients' access to treatment while minimizing substance-related harm and improving quality of life. The newly developed long-acting buprenorphine formulations represent a significant change in the paradigm of OUD treatment, allowing an approach individualized to patients' needs. Strengths of this individualized approach are improved adherence (lack of peaks and troughs in blood concentrations) and a reduced stigma since the patient doesn't need to attend their clinic daily or nearly daily, thus facilitating social and occupational integrations as the quality of life. However, less frequent attendance at the clinic should not affect the patient-physician relationship. Therefore, teleconsulting or digital therapeutic services should be developed in parallel. In addition, diversion and intravenous misuse of buprenorphine are unlikely due to the characteristics of these formulations. These features make this approach of interest for treating OUD in particular settings, such as subjects staying or when released from prison or those receiving long-term residential treatment for OUD in the therapeutic communities. The long-lasting formulations of buprenorphine can positively impact the OUD treatment and suggest future medical and logistic developments to maximize their personalized management and impact.

'I went for rehab many times and it never worked, but the harm reduction process has given me renewed hope'. Perceptions on the effectiveness of harm reduction and community-based opioid substitution therapy.

The accessibility of opioid substitution therapy (OST), one of the recommended treatments for opioid dependence, remains low. This study sought to explore the perceived effectiveness of OST from the perspectives of peer outreach workers and OST clients in a community-based harm reduction programme. The research was done within the Community-Oriented Substance Use Programme (COSUP) in Tshwane, South Africa. Fifteen peer educators (13 males and 2 females) took part in two focus group discussions. Thereafter, there were semi-structured interviews in which 15 OST clients (11 males and 4 females) participated. A convenience cross-sectional study was used. Interviews were audio-recorded. Using thematic analysis, themes were examined to evaluate how OST and the harm reduction approach were perceived to contribute to the improved health status of people with opioid dependence. Peer outreach workers and COSUP clients significantly endorsed OST as an effective treatment for opioid dependence. Participants perceived greater effectiveness of OST compared to abstinence-centred inpatient rehabilitation programmes. However, there were sentiments that more community education on OST was needed to motivate people with opioid dependence to access services and to address misconceptions about OST. There is a lack of multi-level and multi-sectoral engagement of various stakeholders in opioid dependence services, needed to accelerate utilisation of OST services. SO WHAT?: The research unpacks the need for an integrated approach to service use optimisation, and the need to evaluate the role that increased awareness and community education on harm reduction strategies can play in enhancing the utilisation of OST services.

The potential protective effect of melatonin and N-acetylcysteine alone and in combination on opioid-induced testicular dysfunction and degeneration in rat

Methadone (Met) is the most common treatment for opioid addiction. Although Met is effective for treatment of opioid dependence, sexual dysfunctions and infertility have been reported as a major problem in patients under Met treatment. The present study aimed to evaluate the effect of melatonin and N-acetylcysteine (N) on morphine and Met-induced oxidative stress, apoptosis, suppression of blood sexual hormones, impairment in sperm parameters, and sexual dysfunction. Adult male Wistar rats (n = 66) were randomly divided into 11 equal groups (n = 6) as follows: control, sham, morphine, Met, Met+N, Met+ melatonin, Met+melatonin+N, morphine+ Met, morphine+Met+ melatonin, morphine+Met+N, and morphine+Met+ melatonin+N groups. On day 56 post-treatment, the blood was collected from the tail and the serum levels of sex hormones were evaluated, then the rats were sacrificed, and their bilateral testes and epididymis were retrieved for histological, immunohistochemical, molecular, testicular tissue stress oxidative status, and sperm parameters assays. Exposure to morphine, Met, and shift of morphine to Met resulted in testicular degeneration that can be attributed to generating the stress oxidative-induced- apoptotic testicular cell death and impairing spermatogenesis. Melatonin and N alone and particularly, in combination with each other improved testicular degeneration, sex hormone suppression, and testicular function mediated by increasing the testicular antioxidant capacity and inhibition of the apoptosis pathway. It’s suggested that oral administration of antioxidants may be an effective treatment for attenuating some opioid-related testicular dysfunction and degeneration.

Editorial introductions.

Editorial introductions.

In Case You Haven't Heard…

At last week's COMPA symposium (see article, page 1), Mark Parrino delivered a quip that drew broad laughter from attendees. It was something a psychoanalyst friend told him years ago: “If you want to know the difference between a neurotic and a psychotic, the neurotic builds sandcastles in the sky. The psychotic moves in and pays rent.” He was cautioning against building a system of methadone reform which, in reality and practice, won't work. Some of the promoters of this new system are lawmakers, as his remarks indicated. Parrino, president of the American Association for the Treatment of Opioid Dependence, was also defending his position of opposing office‐based physician prescribing of methadone. Noting that many reporters have challenged him on this policy, saying it was just protecting opioid treatment program (OTP) turf, Parrino went on to discuss the origins of the OTP system in the 1970s. Nobody wanted to provide methadone to people with opioid addiction. And he added that many more services are needed for these patients, who have mental health disorders, HIV, hepatitis, homelessness, and trauma, just for example. Medication alone won't solve these problems, he said. Yet, when federal officials tell him that they are going to expand treatment, and he asks, “What is treatment?,” the response is, medication. Medication is important, but not the only part of treatment for addiction. Don't start furnishing that sandcastle, or it will be too late.