Characterizing the Use of Healthcare Access Supports Among People Who Use Drugs in Vancouver, Canada, 2017 to 2020: A Cohort Study.

BACKGROUND: For structurally marginalized populations, including people who use drugs (PWUD), equitable access to healthcare can be achieved through healthcare access supports. However, few studies characterized utilization of formal (eg, outreach workers, healthcare professionals) and informal (eg, friends/family) supports. Therefore, we sought to estimate the prevalence of and factors associated with receiving each type of support among PWUD. METHODS: We used data from 2 prospective cohort studies of PWUD in Vancouver, Canada, in 2017 to 2020. We constructed separate multivariable generalized linear mixed-effects models to identify factors associated with receiving each of the 3 types of supports (ie, healthcare professionals, outreach workers/peer navigators, and informal supports) compared to no supports. RESULTS: Of 996 participants, 350 (35.1%) reported receiving supports in the past 6 months at baseline, through informal supports (6.2%), outreach workers (14.1%), and healthcare professionals (20.9%). In multivariable analyses, HIV positivity, chronic pain, and avoiding healthcare due to the past mistreatment were positively associated with receiving supports from each of healthcare professionals and outreach workers. Men were less likely to receive any types of the supports (all P < .05). CONCLUSIONS: Utilization of healthcare access supports was relatively low in this sample. However, formal supports appeared to have reached PWUD exhibiting more comorbidities and experiencing discrimination in healthcare. Further efforts to make formal supports more available would benefit PWUD with unmet healthcare needs, particularly men.

A perspective on psychedelics as treatments for addictions: Past, Present, and Future.

This Perspectives piece gives a brief overview on the last 70 years of psychedelic research in relation to the treatment of mental illness with a particular focus on addictions. We briefly precis the work in the 19650s/60s that started following the discovery of LSD. Then we overview research developments over the past twenty years driven by emerging neuroscience on these agents, the rise of MDMA use in psychotherapy and the emergence of ketamine as a treatment for mental illnesses. We then briefly outline new research on the brain mechanisms of these therapeutic effects. Finally the current status of research and future challenges in the field are reviewed.

Safety and Efficacy of Rapid Methadone Titration for Opioid Use Disorder in an Inpatient Setting: A Retrospective Cohort Study.

OBJECTIVES: Inpatient guidelines for methadone titration do not exist, whereas outpatient guidelines lack flexibility and do not consider individual opioid tolerance. The evaluation of rapid, adaptable titration protocols may allow more patient-centered and effective treatment for opioid use disorder in the fentanyl era. METHODS: This study performed a retrospective chart review of patients 18 years or older with opioid use disorder who were initiated on methadone at a single academic urban hospital using a rapid divided dose protocol between November 2019 and November 2020. The primary outcome was adverse events associated with methadone, specifically opioid toxicity or sedation requiring increased medical observation or intervention. The secondary outcome was total daily dose of methadone received on day 7 of titration. RESULTS: Ninety-eight patients were included for a total of 168 visits. Sixty-five (66%) were male, with a median age of 38 years (interquartile range, 31-42 years). Sedation occurred in 2 patients (1%), who required either naloxone administration or transfer to an intensive care unit for monitoring. Of the 135 visits where patients received at least 7 days of methadone, the mean dose on day 1 was 41 mg (SD, 9.6 mg) and on day 7 was 65 mg (SD, 20.9 mg). CONCLUSIONS: In this inpatient cohort, rapid methadone titration was well tolerated and resulted in patients reaching higher doses of methadone than would be possible with a standard schedule, with few adverse events. Given the known effective dose range, this approach may result in shorter time to clinical stabilization and suggests that alternative methadone titration schedules may be safe and effective in appropriately selected patients.

MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

Take-home drug checking as a novel harm reduction strategy in British Columbia, Canada.

BACKGROUND: Drug checking is a harm reduction strategy used to identify components of illicitly obtained drugs, including adulterants, to prevent overdose. This study evaluated the distribution of take-home fentanyl test strips to people who use drugs (PWUD) in British Columbia, Canada. The primary aim was to assess if the detection of fentanyl in opioid samples was concordant between a take-home model and testing by trained drug checking staff. METHODS: Take-home fentanyl test strips were distributed at ten sites providing drug checking services from April to July 2019. The fentanyl positivity of the aggregate take-home and on-site drug checking groups were compared by class of substance tested. An administered survey assessed acceptability and behaviour change. RESULTS: 1680 take-home results were obtained from 218 unique participants; 68% of samples (n=1142) were identified as opioids and 23% (n=382) were stimulant samples. During this period, 852 samples were tested using on-site drug checking. The fentanyl positivity of opioid samples was 90.0% for take-home samples and 89.1% for on-site samples (Difference 0.8% (95% CI -2.3% to 3.9%)). These results were not affected by previous experience with test strips. Fentanyl positivity of stimulants in the take-home group was higher than on-site (24.7% vs. 3.2%), but the study was underpowered to conduct statistical analysis on this sub-group. When fentanyl was detected, 27% of individuals reported behaviour change that was considered safer/positive. Greater than 95% of participants stated they would use fentanyl test strips again. CONCLUSIONS: Take-home fentanyl test strips used by PWUD on opioid samples can provide similar results to formal drug checking services and are a viable addition to existing overdose prevention strategies. Use of this strategy for detection of fentanyl in stimulant samples requires further evaluation. This intervention was well accepted and in some participants was associated with positive behaviour change.

The effects of MDMA-assisted therapy on alcohol and substance use in a phase 3 trial for treatment of severe PTSD.

BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with alcohol and substance use disorders (ASUD). A randomized, placebo-controlled, phase 3 trial demonstrated the safety and efficacy of MDMA-assisted therapy (MDMA-AT) for the treatment of severe PTSD. This analysis explores patterns of alcohol and substance use in patients receiving MDMA-AT compared to placebo plus therapy (Placebo+Therapy). METHODS: Adult participants with severe PTSD (n = 90) were randomized to three blinded trauma-focused therapy sessions with either MDMA-AT or Placebo+Therapy. Eligible participants met DSM-5 criteria for severe PTSD and could meet criteria for mild (current) or moderate (early remission) alcohol or cannabis use disorder; other SUDs were excluded. The current analyses examined outcomes on standardized measures of hazardous alcohol (i.e., Alcohol Use Disorder Identification Test; AUDIT) and drug (i.e., Drug Use Disorder Identification Test; DUDIT) use at baseline prior to randomization and at study termination. RESULTS: There were no treatment group differences in AUDIT or DUDIT scores at baseline. Compared to Placebo+therapy, MDMA-AT was associated with a significantly greater reduction in mean (SD) AUDIT change scores (Δ = -1.02 (3.52) as compared to placebo (Δ = 0.40 (2.70), F (80, 1) = 4.20, p = 0.0436; Hedge's g= .45). Changes in DUDIT scores were not significantly different between treatment groups. CONCLUSIONS: MDMA-AT for severe PTSD may also lead to subclinical improvements in alcohol use. MDMA-AT does not appear to increase risk of illicit drug use. These data provide preliminary evidence to support the development of MDMA-AT as an integrated treatment for co-occurring PTSD and ASUD.

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

Rapid Transition From Methadone to Buprenorphine Utilizing a Micro-dosing Protocol in the Outpatient Veteran Affairs Setting.

OBJECTIVES: Alternative transition protocols from methadone to buprenorphine in the treatment of opioid use disorder (OUD) are needed to reduce the risk of precipitated withdrawal and opioid use during induction. METHODS: Case report (n = 1). RESULTS: One patient with OUD underwent a rapid microinduction outpatient protocol that did not cause precipitated withdrawal or require preceding taper before cessation of methadone. The induction was carried out safely in the outpatient setting. CONCLUSIONS: This report provides a patient-centered approach demonstrating feasibility and cost-effectiveness of rapid transition to buprenorphine in the US outpatient psychiatry setting. Barriers to adherence to opioid agonist therapy may be reduced using this protocol.

Rapid Induction of Buprenorphine/Naloxone for Chronic Pain Using a Microdosing Regimen: A Case Report.

Buprenorphine is an effective treatment for chronic pain and may reduce opioid-induced hyperalgesia. However, its pharmacological properties make its induction challenging, time-consuming, and can precipitate opioid withdrawal. We present the case of a 66-year-old woman with inadequately controlled postoperative pain despite escalating doses of oxycodone and methadone, who was successfully transitioned to buprenorphine/naloxone using a rapid microinduction technique without precipitating opioid withdrawal. Rapid induction provides an alternative method for transitioning patients from other opioids to buprenorphine/naloxone and facilitates transition of patients with chronic pain to buprenorphine therapy within a shorter window compared to currently existing protocols.

Rapid micro-induction of buprenorphine/naloxone for opioid use disorder in an inpatient setting: A case series.

BACKGROUND AND OBJECTIVES: Buprenorphine/naloxone has been shown to be effective in the treatment of opioid use disorder. Due to its pharmacological properties, induction can be challenging, time-consuming, and result in sudden onset of withdrawal symptoms. METHODS: Retrospective case series (n = 2). RESULTS: Two patients with opioid use disorder were successfully started on buprenorphine/naloxone using a rapid micro-induction technique that did not cause precipitated withdrawal or require preceding cessation of other opioids. DISCUSSION AND CONCLUSIONS: These cases provide an alternative method for starting buprenorphine/naloxone that offers unique benefits compared to protocols previously described in the literature. SCIENTIFIC SIGNIFICANCE: This method can be used to minimize barriers to opioid agonist therapy. (Am J Addict 2019;28:262-265).

Buprenorphine/naloxone induction for treatment of acute on chronic pain using a micro-dosing regimen: A case report.

Background: Due to its unique pharmacologic properties, efficacy as an analgesic, and role as a first-line medication for the treatment of opioid use disorder, sublingual buprenorphine has emerged as a treatment for patients with concurrent chronic pain and opioid use disorders. One challenge to utilizing buprenorphine is that precipitated opioid withdrawal can result if this medication is initiated in the presence of other opiates with lesser binding affinities. Micro-dosing induction regimens utilize a slower titration to avoid the need for a period of abstinence from other opiates and decrease the risk of precipitated withdrawal. Aims: The aim of this article is to present a case where a standardized micro-dosing induction regimen was used to transition a patient from other opiate analgesia to a sublingual formulation of buprenorphine/naloxone. Methods: This case took place on an inpatient neurosurgical unit of a Canadian tertiary-care city hospital. Written informed consent was collected prior to a detailed chart review. Results: Here we present a case of a postoperative neurosurgical inpatient who was referred to our team for pain management in the context of chronic pain and a past history of opioid use disorder. She was successfully transitioned to buprenorphine/naloxone, replacing all other opioid analgesia, without a period of opioid withdrawal using a micro-dosing induction regimen. Conclusions: Sublingual buprenorphine/naloxone can be safe and effective for treatment of chronic pain, particularly for those with past or current opioid use disorder. Micro-dosing provides a preferable induction strategy for patients who are not able to tolerate the requirement for moderate opioid withdrawal prior to initiation with existing regimens.

Contexte: En raison de ses propriétés pharmacologiques uniques, de son efficacité en tant qu'analgésique et de son rôle de médication de première ligne pour le traitement du trouble de l'usage d'opioïdes, la buprénorphine sublinguale s'est imposée comme traitement pour les patients qui souffrent simultanément de douleur chronique et d'un trouble de l'usage d'opioïdes. L'un des défis liés à l'utilisation de la buprénorphine est qu'elle peut donner lieu à un sevrage précipité des opioïdes si l'usage de cette médication est initié en présence d'autres opiacés dont les affinités de liaison sont moindres. Les traitements d'induction par microdosage utilisent un titrage plus lent afin d'éviter qu'une période d'abstinences des autres opiacés soit nécessaire et diminuer le risque de sevrage précipité.Objectifs: Présenter un cas où un traitement d'induction par microdosage a été utilisé pour assurer la transition d'une patiente utilisant d'autres d'autres analgésiques opiacés vers une formulation sublinguale de buprénorphine/naloxone.Méthodes: Ce cas s'est déroulé dans l'unité d'hospitalisation en neurochirurgie d'un hôpital de soins tertiaires d'une ville canadienne. Un consentement éclairé signifié par écrit a été recueilli avant l'examen approfondi des dossiers.Résultats: Nous présentons ici le cas d'une patiente hospitalisée en neurochirurgie qui a été référée à notre équipe après son opération, pour la prise en charge de la douleur dans un contexte de douleur chronique et d'antécédents d'usage d'opioïdes. En ayant recours à un traitement d'induction par microdosage, elle a fait la transition vers la buprénorphine/naloxone et a remplacé tous les autres analgésiques opioïdes sans période de sevrage des opioïdes.Conclusions: La buprénorphine/naloxone sublinguale peut être sécuritaire et efficace pour le traitement de la douleur chronique, particulièrement pour les personnes qui ont un trouble de consommation d'opiacés passé ou actuel. Le microdosage constitue une stratégie d'induction préférable pour les patients qui ne peuvent pas tolérer la nécessité d'un sevrage modéré des opioïdes avant de débuter les traitements existants.

α-linolenic acid and docosahexaenoic acid, alone and combined with trastuzumab, reduce HER2-overexpressing breast cancer cell growth but differentially regulate HER2 signaling pathways.

BACKGROUND: Diets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2-targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA). METHODS: The ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty acids was determined by measurement of phospholipid fatty acids by gas chromatography following treatment with 100 µM ALA. The effects of 96 h treatment with ALA or DHA, at serum levels seen in mice (50-100 µM), alone and combined with TRAS (10 µg/ml), on BT-474 cell growth measured by trypan blue exclusion, apoptosis measured by flow cytometric analysis of Annexin-V/7-AAD stained cells (ALA and TRAS treatment only) and protein biomarkers HER2 signaling measured by western blot were determined. RESULTS: ALA-treated BT-474 cells had higher phospholipid ALA but no increase in downstream n-3 metabolites including DHA. Both ALA and DHA reduced cell growth with and without TRAS. ALA had no effect on apoptosis. ALA and DHA showed opposite effects on Akt and MAPK phosphorylation; ALA increased and DHA decreased phosphorylation. CONCLUSIONS: Together these data suggest that, while both ALA and its DHA metabolite can reduce HER2-overexpressing breast cancer growth with and without TRAS, they demonstrate for the first time that DHA is responsible for the effects of ALA-rich diets on HER2 signaling pathways.